Abstract:
An object of the present invention is to provide a medicinal drug much improved in anti tumor activity and excellent in safety. According to the present invention, there is provided a medicinal drug containing a compound represented by the following general formula (1) or a salt thereof as an active ingredient: [Formula 1] wherein X 1  represents a nitrogen atom or a group —CH═, R 1  represents a group -Z-R 6 , in which Z represents a group —CO—, a group —CH(OH)— or the like, R 6  represents a 5- to 15-membered monocyclic, dicyclic or tricyclic saturated or unsaturated heterocyclic group having 1 to 4 nitrogen atoms, oxygen atoms or sulfur atoms, R 2  represents a hydrogen atom or a halogen atom, Y represents a group —O—, a group —CO—, a group —CH(OH)— or a lower alkylene group, and A represents [Formula 2] wherein R 3  represents a hydrogen atom, a lower alkoxy group or the like, p represents 1 or 2, R 4  represents an imidazolyl lower alkyl group or the like.

Description:
BACKGROUND OF THE INVENTION 
       [0001]    (1) Field of the Invention 
         [0002]    The present invention relates to a medicinal drug. 
         [0003]    (2) Description of Related Art 
         [0004]    Since the clinical use of nitrogen mustard as an anticancer agent was started in the 1940s for the first time in the world, numerous anticancer drugs have ever been developed. Actually, for example, antimetabolites such as 5-fluorouracil, antitumor antibiotics such as adriamycin, platinum complex such as cisplatin, and plant-derived carcinostatics such as vindesine have been subjected to clinical use. 
         [0005]    However, most of these carcinostatics have significant side effects such as digestive disorders, myelosuppression and alopecia since they are cytotoxic also to normal cells. Due to the side effects, their range of application is limited. In addition, the therapeutic effects themselves are partial and short, in most cases. 
         [0006]    Developments of new carcinostatics in place of these has been made; however, satisfactory results have not yet been obtained. Patent documents 1 and 2 disclose that certain kinds of compounds have fibrosing inhibitory actions. However, it is not known whether the compounds have antitumor actions. 
       [Patent Document 1] WO/2006/014012 
     [Patent Document 2] JP-A-2004-35475 
     BRIEF SUMMARY OF THE INVENTION 
       [0007]    An object of the present invention is therefore to provide an excellent medicinal drug such as a therapeutic drug for a tumor, particularly, a therapeutic drug for a malignant tumor. 
         [0008]    The present inventors intensively conducted studies with the view to attaining the aforementioned object. As a result, they found that a compound represented by the general formula (1) below and a salt thereof have an excellent antitumor effect. The present invention has been achieved based on the finding. 
         [0009]    More specifically, the present invention provides medicinal drugs shown in items 1 to 58. 
         [0000]    Item 1: An antitumor agent comprising a compound represented by the general formula (1) below or a salt thereof as an active ingredient: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein X 1  represents a nitrogen atom or a group —CH═,
 
R 1  represents a group -Z-R 6 ,
 
Z represents a group —N(R 8 )—B—, a group —B—N(R 8 )—, a group —B 0 —O—, a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    a group —CO—, a group —CH(OH)—, a group N(R 9a —CO—N—(R 9b )—, a group —N═CH—, a group —N(R 10a )—SO 2 —(B 22a )e-, a lower alkenylene group, a group —NHCO—B 1 —, a group —NHCO—B 2 —(W)u-, a group —B 0 —B 19a —, a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    a group —SO 2 —N(R 10b )—, a group —S—, a lower alkynylene group, a lower alkylene group, a group —N(R 8d )— or a group —CO—NH—B 18a —,
 
R 8  represents a hydrogen atom, a lower alkyl group that may have a lower alkoxy group as a substituent, a lower alkanoyl group, a lower alkylsulfonyl group or a phenyl lower alkyl group,
 
B represents a group —CO— or a lower alkylene group,
 
B 0  represents a lower alkylene group,
 
         [0010]    B 1  represents a lower alkenylene group that may have a phenyl group as a substituent, 
         [0000]    B 2  represents a lower alkylene group that may be substituted by a group selected from the group consisting of a lower alkoxy group and a phenyl group,
 
R 9a  represents a hydrogen atom or a lower alkyl group,
 
R 9b  represents a hydrogen atom or a lower alkyl group,
 
R 10  represents a hydrogen atom or a lower alkyl group,
 
B 22a  represents a lower alkylene group or a lower alkenylene group,
 
e represents 0 or 1,
 
B 18  represents a lower alkylene group,
 
B 19a  represents a lower alkylene group,
 
B 20a  represents a lower alkylene group,
 
B 21a  represents a lower alkylene group,
 
k represents 2 or 3,
 
c represents 0 or 1,
 
d′ represents 0 or 1,
 
R 10b  represents a hydrogen atom or a lower alkyl group,
 
R 8d  represents a hydrogen atom or a lower alkyl group,
 
W represents an oxygen atom, a group —NH—, or a sulfur atom,
 
u represents 0 or 1,
 
R 6  represents 5- to 15-membered monocyclic, dicyclic or tricyclic saturated or unsaturated heterocyclic group having 1 to 4 nitrogen atoms, oxygen atoms or sulfur atoms (that may have 1 to 3 substituents, which are selected from the group consisting of an oxo group; a lower alkoxy group that may have a halogen atom as a substituent; a lower alkyl group that may have a halogen atom as a substituent; a halogen atom; a lower alkylsulfonyl group; a phenyl group that may be substituted by a lower alkyl group that may have a halogen atom on the phenyl ring; a lower alkylthio group, a pyrrolyl group, a benzoyl group; a lower alkanoyl group; lower alkoxycarbonyl group; and an amino group that may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent, on the heterocyclic ring), an adamantly group, a naphthyl group (that may have 1 to 3 groups selected from the group consisting of a lower alkyl group, a halogen atom, and an amino group that may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent, on the naphthalene ring), an alkyl group that may have a lower alkoxy group as a substituent, a cycloalkyl group that may be substituted by a group selected from the group consisting of an amino substituted lower alkyl group that may have a lower alkyl group and a lower alkyl group that may have a halogen atom as a substituent, on the cycloalkyl ring, a lower alkenyl group that may have a halogen atom as a substituent, a lower alkanoyl group, a benzoyl group (that may have 1 to 3 groups selected from the group consisting of a lower alkyl group that may have a halogen atom and halogen atom, as a substituents, on the phenyl ring), a halogen atom substituted lower alkyl group, cycloalkyl lower alkyl group or a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R 7  represents a hydrogen atom, a phenyl group, a carboxy group, a hydroxyl group, a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, a phenoxy group, a lower alkoxy group that may have a halogen atom as a substituent, a lower alkylenedioxy group, an amino group that may have, as a substituent, a group selected from the group consisting of a lower alkyl group, a lower alkanoyl group, a benzoyl group, and a cycloalkyl group, a cyano group, a lower alkanoyl group that may have a halogen atom as a substituent, a lower alkylsulfonyl group, an aminosulfonyl group, a lower alkoxycarbonyl group, a lower alkanoyloxy group, a lower alkoxycarbonyl lower alkyl group or a 5- or 6-membered saturated or unsaturated heterocyclic group having 1 to 4 nitrogen atoms, oxygen atoms, or sulfur atoms (that may have an oxo group on the heterocyclic ring),
 
m represents an integer from 1 to 5 (when m represents 2 to 5, two to five R 7 s may be identical or different) and
 
R 2  represents a hydrogen atom, a halogen atom, or a lower alkyl group,
 
Y represents a group —O—, a group —N(R 5 )—, a group —CO—, a group —CH(OH)—, a lower alkylene group, a group —
 
S(O)n-, or a group —C(═N—OH)—,
 
R 5  represents a hydrogen atom, a lower alkyl group, a lower alkanoyl group, a benzoyl group, a phenyl lower alkyl group, or a cycloalkyl group,
 
n represents 0, 1, or 2,
 
A represents a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    or a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    p represents 1 or 2,
 
R 3  represents a hydrogen atom, a lower alkoxy group, a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, a lower alkoxycarbonyl group, a carboxy group, a group —CONR 11 R 12 , or a cyano group,
 
wherein R 11  and R 12  may be identical or different and each represent a hydrogen atom, a lower alkyl group, a cycloalkyl group, or a phenyl group, and R 11  and R 12 , together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic ring,
 
R 4  represents an imidazolyl lower alkyl group, a 1,2,4-triazolyl lower alkyl group, a 1,2,3-triazolyl lower alkyl group, a 1,2,5-triazolyl lower alkyl group, a pyrazolyl lower alkyl group, a pyrimidinyl lower alkyl group that may have an oxo group as a substituent on the pyrimidine ring, a 3,5-dioxoisoxazolidin-4-ylidene lower alkyl group, a 1,2,4-oxadiazolyl lower alkyl group that may have a lower alkyl group as a substituent on the 1,2,4-oxadiazole ring, a thiazolidinyl lower alkyl group that may have an oxo group as a substituent on the thiazolidine ring, a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    or a group -(T) 1 -N(R 14 )R 15 ,
 
R 13  represents a hydrogen atom, a lower alkyl group that may have a halogen atom as a substituent, a lower alkanoyl group that may have a halogen atom as a substituent, a lower alkoxycarbonyl group, a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring, an imidazolyl lower alkyl group, a lower alkoxycarbonyl lower alkyl group, a carboxy lower alkyl group, a benzoyl group, a morpholino-substituted lower alkanoyl group, a piperazinyl carbonyl lower alkyl group that may be substituted, on the piperazine ring, by a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring, a piperazinyl lower alkanoyl group that may be substituted, on the piperazine ring, by a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring, a morpholinocarbonyl-substituted lower alkyl group, or an imidazolyl lower alkanoyl group,
 
R 13a  represents a hydrogen atom or a hydroxyl group,
 
T represents a lower alkylene group, a group —N(R 17 )—B 3 —CO—, a group —B 19 —N(R 18 )—CO—, a group —B 4 —CO—, a group -Q-B 5 —CO—, a group —B 6 —N(R 19 )—B 7 —CO—, a group —CO—B 8 —, a group —CH(OH)—B 9 —, a group —CO—B 10 —CO—, a group —CH(OH)—B 11 —CO—, a group —CO—, a group —SO 2 —, or a group —B 23a —CO—CO—,
 
wherein R 17  represents a hydrogen atom, a lower alkyl group, a cycloalkyl group, a cycloalkylcarbonyl group, a lower alkanoyl group that may have a halogen atom as a substituent, a lower alkenyl group, an amino-substituted lower alkanoyl group that may have a lower alkyl group as a substituent, or a lower alkylsulfonyl group,
 
B 3  represents a lower alkylene group,
 
B 19  represents a lower alkylene group,
 
R 18  represents a hydrogen atom or a lower alkyl group,
 
B 4  represents a lower alkenylene group or a lower alkylene group that may have a hydroxyl group as a substituent,
 
Q represents an oxygen atom or a group —S(O)n- (wherein
 
n is the same as described above),
 
B 5  represents a lower alkylene group,
 
B 6  represents a lower alkylene group,
 
R 19  represents a hydrogen atom or a lower alkanoyl group,
 
B 7  represents a lower alkylene group,
 
B 8  represents a lower alkylene group,
 
B 9  represents a lower alkylene group,
 
B 10  represents a lower alkylene group,
 
B 11  represents a lower alkylene group,
 
B 23a  represents a lower alkylene group,
 
l represents 0 or 1,
 
R 14  represents a hydrogen atom or an alkyl group that may have a hydroxyl group as a substituent,
 
R 15  represents (2) a hydroxyl group-substituted alkyl group, (3) a cycloalkyl group that may have a group selected from the group consisting of a hydroxyl group and a lower alkyl group as a substituent, (4) a phenoxy lower alkyl group, (5) a phenyl group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkyl group; a lower alkoxy group that may have a halogen atom as a substituent; a halogen atom; an amino lower alkoxy group that may have a lower alkyl group as a substituent; a hydroxyl group-substituted lower alkyl group; a phenyl lower alkyl group; a lower alkynyl group; an amino group that may have a lower alkylsulfonyl group as a substituent; a lower alkylthio group; a cycloalkyl group; a phenylthio group; an adamantyl group; an anilino group that may have a halogen atom as a substituent on the phenyl ring; a lower alkoxycarbonyl group; a piperazinyl group that may have a lower alkyl group as a substituent on the piperazine ring; a pyrrolidinyl group that may have an oxo group as a substituent on the pyrrolidine ring; a lower alkanoylamino group; a cyano group; and a phenoxy group, (6) a phenoxy group, (7) a phenyl lower alkyl group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a halogen atom, a lower alkoxy group that may have a halogen atom as a substituent, and a lower alkyl group, (8) a phenyl lower alkyl group that has a lower alkylenedioxy group as a substituent on the phenyl ring, (10) a lower alkoxycarbonyl-substituted lower alkyl group, (11) a carboxy-substituted lower alkyl group, (12) an amino group that may have a lower alkanoyl group as a substituent, (13) a 1,2,3,4-tetrahydroquinolyl group that may have 1 to 3 groups selected from the group consisting of an oxo group, a lower alkoxy group, and a lower alkylenedioxy group as a substituent(s) on the tetrahydroquinoline ring, (14) a cycloalkyl lower alkyl group, (15) a piperazinyl lower alkanoyl group that may be substituted, on the piperazine ring, by a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring, (16) a pyridyl lower alkyl group, (17) an amino group-substituted lower alkyl group that may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent, (18) a lower alkoxy lower alkyl group, (19) an imidazolyl group, (20) an imidazolyl lower alkyl group, (21) a 1,2,3,4-tetrahydroisoquinolylcarbonyl-substituted lower alkyl group, (22) a piperidinylcarbonyl group that may have a group selected from the group consisting of a lower alkoxycarbonyl group, a phenyl lower alkyl group, and a furyl lower alkyl group as a substituent on the piperidine ring, (23) a thiazolidinyl lower alkanoyl group that may have an oxo group as a substituent on the thiazolidine ring, (24) a piperidinyl group that may be substituted, on the piperidine ring, by a group selected from the group consisting of a lower alkoxycarbonyl group, a phenyl lower alkyl group, a lower alkyl group, a benzoyl group, and a furyl lower alkyl group, (25) a carbonyl lower alkyl group substituted by a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    (26) a carbonyl lower alkyl group substituted by a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    (27) a group —CO—B 20 —N(R 36 )R 37 , (26a) a pyrrolidinyl lower alkyl group, (27a) a morpholino lower alkyl group, (28a) a phenyl lower alkenyl group, (29a) an anilinocarbonyl lower alkyl group that may have a lower alkyl group as a substituent on the phenyl ring, (30a) an indolyl group, (31a) a piperazinyl lower alkyl group that may have, as a substituent on the piperazine ring, a group selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring, (32a) an amidino lower alkyl group that may have a lower alkyl group as a substituent, (33a) a fluorenyl group, (34a) a carbazolyl group that may have a lower alkyl group as a substituent on the carbazole ring, (35a) an amidino group that may have a lower alkyl group as a substituent, (36a) a piperazinyl-substituted oxalyl group that may have 1 to 3 groups selected from the group consisting of a phenyl lower alkyl group (that may have 1 to 3 groups selected from the group consisting of a lower alkylenedioxy group and a lower alkoxy group as a substituent(s) on the phenyl ring) and a pyridyl lower alkyl group as a substituent(s) on the piperazine ring, or (37a) a cyano-substituted lower alkyl group,
 
R 34  represents an oxo group or a phenyl group,
 
d represents an integer from 0 to 3,
 
B 20  represents a lower alkylene group,
 
R 36  and R 37 , together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic group, wherein, on the heterocyclic ring, 1 to 3 phenyl lower alkyl groups that may have a lower alkylenedioxy group on the phenyl ring, may be present as a substituent(s),
 
R 14  and R 15 , together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 10-membered saturated or unsaturated heterocyclic ring; or a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein, on the heterocyclic ring, 1 to 3 substituents may be present which are selected from the group consisting of (28) a phenyl-substituted lower alkyl group, which has 1 to 2 phenyl groups that may be substituted by 1 to 3 groups on the phenyl ring, selected from the group consisting of a lower alkanoyl group, an amino group that may have a lower alkanoyl group as a substituent, a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, a lower alkoxy group that may have a halogen atom as a substituent, a phenyl lower alkoxy group, a hydroxyl group, and a lower alkylenedioxy group, and that may have a pyridyl group on the lower alkyl group, (29) a carbamoyl group, (30) a pyridyl lower alkyl group that may have, as a substituent(s) on the pyridine ring, 1 to 3 groups selected from the group consisting of a hydroxyl group and a lower alkyl group that may have a hydroxyl group as a substituent, (31) a pyrrolyl lower alkyl group that may have 1 to 3 lower alkyl groups as a substituent(s) on the pyrrole ring, (32) a benzoxazolyl lower alkyl group, (33) a benzothiazolyl lower alkyl group, (34) a furyl lower alkyl group, (35) a benzoyl group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a cyano group, an amino group that may have a lower alkylsulfonyl group as a substituent, a halogen atom, a lower alkoxy group, a lower alkyl group that may have a halogen atom as a substituent, a thiazolidinyl lower alkyl group that may have an oxo group as a substituent on the thiazolidine ring, a thiazolidinylidene lower alkyl group that may have an oxo group as a substituent on the thiazolidine ring, and a lower alkylenedioxy group, (36) a pyrimidinyl group, (37) a pyrazinyl group, (38) a pyridyl group, (39) a lower alkoxycarbonyl group, (40) a thiazolidinyl lower alkanoyl group that may be substituted, on the thiazolidine ring, by a group selected from the group consisting of an oxo group and a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    (wherein R a  and R b  each represent a lower alkyl group), (41) a lower alkyl group that may have a group selected from the group consisting of a hydroxyl group and a halogen atom as a substituent, (42) a lower alkanoyl group that may have a halogen atom as a substituent, (43) a phenyl group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a carbamoyl group that may have a group selected from the group consisting of a lower alkoxy lower alkyl group and a lower alkyl group, a lower alkoxycarbonyl group, a carboxy group, a cyano group, a phenyl group, a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, a lower alkoxy group that may have a halogen atom as a substituent, a benzoyl group that may have a halogen atom as a substituent on the phenyl ring, a phenyl lower alkyl group that may have a halogen atom as a substituent on the phenyl ring, and a hydroxyl group, (44) a phenyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring, (45) a naphthyl lower alkyl group, (46) a phenoxy group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a cyano group, a lower alkyl group that may have a halogen atom as a substituent, and a lower alkoxy group that may have a halogen atom as a substituent, (47) a phenoxy lower alkyl group, (48) a phenyl lower alkoxy group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, and a lower alkoxy group that may have a halogen atom as a substituent, (49) a group —(B 12 CO)t-N(R 20 )R 21 , (50) a group —(CO)o-B 13 —N(R 22 )R 23 , (51) a 1,2,3,4-tetrahydronaphthyl-substituted lower alkyl group that may be substituted, on the 1,2,3,4-tetrahydronaphthalene ring, by 1 to 5 lower alkyl groups as a substituent(s), (52) a cycloalkyl group that may have a hydroxyl group as a substituent, (53) a piperidinyl group that may be substituted, on the piperidine ring, by 1 to 3 lower alkyl groups as a substituent(s), (54) a quinolyl lower alkyl group, (55) a 1,2,3,4-tetrazolyl lower alkyl group that may have a group selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group as a substituent on the tetrazole ring, (56) a thiazolyl lower alkyl group that may have a phenyl group as a substituent on the thiazole ring, (57) a benzoyl lower alkyl group that may have 1 to 3 groups selected from the group consisting of a lower alkoxy group and a halogen atom as a substituent(s) on the phenyl ring, (58) a piperidinyl lower alkyl group that may have a lower alkyl group as a substituent on the piperidine ring, (59) an imidazolyl group that may have 1 to 3 phenyl groups as a substituent(s) on the imidazole ring, (60) a benzimidazolyl group that may have 1 to 3 lower alkyl groups as a substituent(s) on the benzimidazole ring, (61) a pyridyl lower alkoxy group, (62) a 1,2,3,4-tetrahydroquinolyl lower alkyl group that may have an oxo group as a substituent on the tetrahydroquinoline ring, (63) a 1,3,4-oxadiazolyl lower alkyl group that may have an oxo group as a substituent on the 1,3,4-oxadizole ring, (64) a cycloalkyl lower alkyl group, (65) a tetrahydropyranyl group, (66) a thienyl lower alkyl group, (67) a pyrimidinylcarbonyl group that may have an oxo group as a substituent on the pyrimidine ring, (68) a hydroxyl group, (69) a carboxy group, (70) a lower alkoxy lower alkyl group, (71) a lower alkoxy lower alkoxy group, (72) a benzoyloxy group, (73) a lower alkoxycarbonyl lower alkoxy group, (74) a carboxy lower alkoxy group, (75) a phenoxy lower alkanoyl group, (76) a 1,2,3,4-tetrahydroquinolylcarbonyl group that may have an oxo group as a substituent on the tetrahydroquinoline ring, (77) a phenylsulfonyl group, (78) an imidazolyl lower alkanoyl group, (79) an imidazolyl lower alkyl group, (80) a pyridylcarbonyl group, (81) an imidazolylcarbonyl group, (82) a lower alkoxycarbonyl lower alkyl group, (83) a carboxy lower alkyl group, (84) a group —(O—B 15 )s-CO—N(R 26 )R 27 , (85) a group —N(R 28 )— CO—B 16 —N(R 29 )R 30 , (86) a group —N(R 31 )—B 17 —CO—N(R 32 )R 33 , (87) a benzoxazolyl group, (88a) a benzothienyl group, (89a) an oxo group, and (90a) a 1,2,3,4-tetrahydroquinolyl group that may have an oxo group as a substituent on the tetrahydroquinoline ring,
 
B 12  represents a lower alkylene group,
 
t represents 0 or 1,
 
R 20  and R 21  may be identical or different and each represent a hydrogen atom; an amino group that may have a lower alkoxycarbonyl group as a substituent; a benzoyl group that may have 1 to 3 lower alkoxy groups as a substituent(s) on the phenyl ring; a lower alkyl group; a lower alkyl group having 1 to 2 phenyl groups that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, a lower alkoxy group that may have a halogen atom as a substituent, and a lower alkylthio group; a phenyl group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkoxy group that may have a halogen atom as a substituent and a lower alkyl group that may have a halogen atom as a substituent; a lower alkoxycarbonyl group; a cycloalkyl lower alkyl group; a pyrrolidinyl lower alkyl group that may have 1 to 3 lower alkyl groups that may have a hydroxyl group as a substituent on the pyrrolidine ring; an amino-substituted lower alkyl group that may have a group selected from the group consisting of a phenyl group and a lower alkyl group as a substituent; a 1,2,3,4-tetrahydronaphthyl-substituted lower alkyl group that may have 1 to 5 lower alkyl groups as a substituent(s) on the 1,2,3,4-tetrahydronaphthalene ring; a naphthyl lower alkyl group; a pyridyl lower alkyl group; a quinolyl lower alkyl group; a 1,2,3,4-tetrazolyl lower alkyl group that may have 1 to 3 groups selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group as a substituent(s) on the tetrazole ring; a 1,2,4-triazolyl lower alkyl group; a tetrahydrofuryl lower alkyl group that may have a hydroxyl group as a substituent on the lower alkyl group; a phenoxy lower alkyl group that may have 1 to 3 groups selected from the group consisting of a lower alkyl group and a nitro group as a substituent(s) on the phenyl ring; a phenyl lower alkanoyl group; a lower alkanoyl group that may have a halogen atom as a substituent; an imidazolyl lower alkanoyl group; a lower alkoxycarbonyl lower alkyl group; a pyridyl group; or a carboxy lower alkyl group, or a cycloalkyl group; and R 20  and R 21 , together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic ring (wherein, on the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group consisting of a lower alkyl group, a phenyl group that may have 1 to 3 groups selected from the group consisting of a halogen atom and a lower alkyl group that may have a halogen atom as a substituent(s) on the phenyl ring, and a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring),
 
o represents 0 or 1,
 
B 13  represents a lower alkylene group,
 
R 22  and R 23  may be identical or different and each represent a hydrogen atom, a lower alkyl group, a benzoyl group that may have 1 to 3 lower alkoxy groups as a substituent(s) on the phenyl ring, a phenoxy lower alkyl group that may have a lower alkyl group as a substituent on the phenyl ring, a phenyl lower alkyl group, or a phenyl group, or R 22  and R 23 , together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic ring (wherein, on the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring),
 
B 15  represents a lower alkylene group,
 
s represents 0 or 1,
 
R 26  and R 27  may be identical or different and each represent a hydrogen atom, a lower alkyl group, a phenyl lower alkyl group, or an imidazolyl lower alkyl group, and R 26  and R 27 , together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic ring, (wherein, on the heterocyclic ring, 1 to 3 phenyl lower alkyl groups that may have a lower alkylenedioxy group as a substituent, may be present on the phenyl ring, as a substituent(s)),
 
R 28  represents a hydrogen atom or a lower alkyl group,
 
B 16  represents a lower alkylene group,
 
R 29  and R 30 , together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic group, wherein, on the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group consisting of a lower alkyl group, a phenyl group, and a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring,
 
R 31  represents a hydrogen atom or a lower alkyl group,
 
B 17  represents a lower alkylene group,
 
R 32  and R 33 , together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic group, (wherein, on the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group consisting of a lower alkyl group, a phenyl group, and a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring),
 
provided that the aforementioned compound or a salt thereof satisfies the following requirements (i) to (v):
 
         [0011]    (i) when X 1  represents a group —CH═, then R 3  represents a hydrogen atom; 
         [0012]    (ii) when X 1  represents a group —CH═, l represents 1, T represents —CO—, and R 14  represents a hydrogen atom or an alkyl group that may have a hydroxyl group as a substituent, R 15  represents the group (24); 
         [0013]    (iii) when X 1  represents a group —CH═, l represents 1, and T represents —N(R 17 )—B 3 —CO—, R 14  and R 15 , together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 10-membered saturated or unsaturated heterocyclic ring, wherein, on the heterocyclic ring, 1 to 3 groups of (28) are present as a substituent(s); 
         [0014]    (iv) when X 1  represents a nitrogen atom, and l represents 0, or when X 1  represents a nitrogen atom, l represents 1, and T represents —CO— or —SO 2 , R 15  is not a group (5), (7), (19), or (20); and 
         [0015]    (v) when R 6  represents a cycloalkyl group that may have on the cycloalkyl ring, a substituent selected from the group consisting of an amino-substituted lower alkyl group that may have a lower alkyl group and a lower alkyl group that may have a halogen atom as a substituent, R 4  represents a group -(T) l -N(R 14 )R 15  (wherein T and l are the same as described above, and R 14  and R 15 , together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 10-membered saturated heterocyclic ring; or R 14  and R 15  form a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    Item 2: The antitumor agent according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-1) to (1-7) below or a salt thereof as an active ingredient: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein Y 3  represents a lower alkylene group.
 
Item 3: The antitumor agent according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-8) to (1-14) below or a salt thereof as an active ingredient:
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein Y 3  represents a lower alkylene group.
 
Item 4: The antitumor agent according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-15) to (1-21) below or a salt thereof as an active ingredient:
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein Y 3  represents a lower alkylene group.
 
Item 5: The antitumor agent according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-22) to (1-28) below or a salt thereof as an active ingredient:
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein Y 3  represents a lower alkylene group.
 
Item 6: The antitumor agent according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-29) to (1-35) below or a salt thereof as an active ingredient:
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein Y 3  represents a lower alkylene group.
 
Item 7: The antitumor agent according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-36) to (1-42) below or a salt thereof as an active ingredient:
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein Y 3  represents a lower alkylene group.
 
Item 8: The antitumor agent according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-43) to (1-49) below or a salt thereof as an active ingredient:
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein Y 3  represents a lower alkylene group.
 
Item 9: The antitumor agent according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-50) to (1-56) below or a salt thereof as an active ingredient:
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein Y 3  represents a lower alkylene group.
 
Item 10: The antitumor agent according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-57) to (1-63) below or a salt thereof as an active ingredient:
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein Y 3  represents a lower alkylene group.
 
Item 11: the antitumor agent according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-64) to (1-70) below or a salt thereof as an active ingredient:
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein Y 3  represents a lower alkylene group, and Z 1  represents a lower alkenylene group.
 
Item 12: The antitumor agent according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-71) to (1-77) below or a salt thereof as an active ingredient:
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein Y 3  represents a lower alkylene group.
 
Item 13: The antitumor agent according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-78) to (1-84) below or a salt thereof as an active ingredient:
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein Y 3  represents a lower alkylene group.
 
Item 14: The antitumor agent according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-85) to (1-91) below or a salt thereof as an active ingredient:
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein Y 3  represents a lower alkylene group.
 
Item 15: The antitumor agent according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-92) to (1-98) below or a salt thereof as an active ingredient:
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein Y 3  represents a lower alkylene group.
 
Item 16: The antitumor agent according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-99) to (1-105) below or a salt thereof as an active ingredient:
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein Y 3  represents a lower alkylene group.
 
Item 17: The antitumor agent according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-106) to (1-112) below or a salt thereof as an active ingredient:
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein Y 3  represents a lower alkylene group.
 
Item: 18 The antitumor agent according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-113) to (1-119) below or a salt thereof as an active ingredient:
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein Y 3  represents a lower alkylene group.
 
Item: 19 The antitumor agent according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-120) to (1-126) below or a salt thereof as an active ingredient:
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein Y 3  represents a lower alkylene group, and Z 2  represents a lower alkynylene group.
 
Item: 20 The antitumor agent according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-127) to (1-133) below or a salt thereof as an active ingredient:
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein Y 3  represents a lower alkylene group.
 
Item: 21 The antitumor agent according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-134) to (1-140) below or a salt thereof as an active ingredient:
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein Y 3  represents a lower alkylene group, and
 
Z 3  represents a lower alkylene group or a group —N(R 8d )—.
 
Item 22: The antitumor agent according to any one of items 1 to 21, wherein Y is a group —O—.
 
Item 23: The antitumor agent according to any one of items 1 to 21, wherein Y is a group —N(R 5 )—.
 
Item 24: The antitumor agent according to any one of items 1 to 21, wherein Y is a group —CO—, a group —CH(OH)—, a lower alkylene group, a group —S(O)n-, or a group —C(═N—OH)—.
 
Item 25: The antitumor agent according to any one of items 1 to 21, wherein A is a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    Item 26: The antitumor agent according to any one of items 1 to 21, wherein A is a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    Item 27: The antitumor agent according to any one of items 1 to 21, wherein R 4  represents an imidazolyl lower alkyl group, a 1,2,4-triazolyl lower alkyl group, a 1,2,3-triazolyl lower alkyl group, a 1,2,5-triazolyl lower alkyl group, a pyrazolyl lower alkyl group, a pyrimidinyl lower alkyl group that may have an oxo group as a substituent on the pyrimidine ring, a 3,5-dioxoisoxazolidin-4-ylidene lower alkyl group, a 1,2,4-oxadiazolyl lower alkyl group that may have a lower alkyl group as a substituent on the 1,2,4-oxadiazole ring, a thiazolidinyl lower alkyl group that may have an oxo group as a substituent on the thiazolidine ring, a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    or a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    Item 28: The antitumor agent according to any one of items 1 to 21, wherein R 4  is a group -(T) l -N(R 14 )R 15 , and l is 0. 
         [0016]    Item 29: The antitumor agent according to any one of items 1 to 21, wherein R 4  is a group -(T) l -N(R 14 )R 14 R 15 , and l is 1. 
         [0000]    Item 30: The antitumor agent according to any one of items 1 to 21, wherein R 4  is a group -(T) l -N(R 14 )R 15 , l is 1, and T is a group —N(R 17 )—B 3 —CO—.
 
Item 31: The antitumor agent according to any one of items 1 to 21, wherein R 4  is a group -(T) l -N(R 14 )R 15 , l is 1, and T is a group —B 19 —N(R 18 )—CO—.
 
Item 32: The antitumor agent according to any one of items 1 to 21, wherein R 4  is a group -(T) l -N(R 14 )R 15 , l is 1, and T is a group —B 4 —CO—.
 
Item 33: The antitumor agent according to any one of items 1 to 21, wherein R 4  is a group -(T) l -N(R 14 )R 15 , l is 1, and T is a group -Q-B 5 —CO—.
 
Item 34: The antitumor agent according to any one of items 1 to 21, wherein R 4  is a group -(T) l -N(R 14 )R 15 , l is 1, and T is a group —B 6 —N(R 19 )—B 7 —.
 
Item 35: The antitumor agent according to any one of items 1 to 21, wherein R 4  is a group -(T) l -N(R 14 )R 15 , l is 1, and T is a group —CO—B 8 —.
 
Item 36: The antitumor agent according to any one of Items 1 to 21, wherein R 4  is a group -(T) l -N(R 14 )R 15 , l is 1, and T is a group —CH(OH)—B 9 —.
 
Item 37: The antitumor agent according to any one of items 1 to 21, wherein R 4  is a group -(T) l -N(R 14 )R 15 , l is 1, and T is a group —CO—B 10 —CO—.
 
Item 38: The antitumor agent according to any one of items 1 to 21, wherein R 4  is a group -(T) l -N(R 14 )R 15 , l is 1, and T is a group —CH(OH)—B 11 —CO—.
 
Item 39: The antitumor agent according to any one of items 1 to 21, wherein R 4  is a group -(T) l -N(R 14 )R 15 , l is 1, and T is a group —CO—.
 
Item 40: The antitumor agent according to any one of items 1 to 21, wherein R 4  is a group -(T) l -N(R 14 )R 15 , l is 1, and T is a group —SO 2 —.
 
Item 41: The antitumor agent according to any one of items 1 to 21, wherein R 4  is a group -(T) l -N(R 14 )R 15 , l is 1, and T is a group —B 23a —CO—CO—.
 
Item 42: The antitumor agent according to any one of items 1 to 21, wherein R 4  is a group -(T) l -N(R 14 )R 15 , l is 1, and T is a lower alkylene group.
 
Item 43: The antitumor agent according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-1), (1-2), (1-8), (1-9), (1-15), (1-16), (1-29), (1-30), (1-43), (1-44), (1-57), (1-58), (1-64) and (1-65) or a salt thereof as an active ingredient, wherein Y is a group —O— or a group —N(R 5 )—, A is a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    and
 
R 4  is a group -(T) l -N(R 14 )R 15 .
 
         [0017]    Item 44: The antitumor agent according to item 43, wherein l is 1, and T is a group —N(R 7 )—B 3 —CO—. 
         [0000]    Item 45: The antitumor agent according to item 43, wherein l is 1, and T is a group —B 4 —CO—.
 
Item 46: The antitumor agent according to item 43, wherein l is 1, and T is a group —CO—.
 
Item 47: The antitumor agent according to item 43, wherein l is 0.
 
Item 48: The antitumor agent according to item 1, comprising a compound selected from the group consisting of N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]ethylamino}-2-methoxyphenoxy)pyridin-3-yl]-3,4-dichlorobenzamide, N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]ethylamino}phenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide, N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]ethylamino}-2-fluorophenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide, N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-fluorophenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide, N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-methoxyphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide, N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]ethylamino}-2-methoxyphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide, N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]ethylamino}-2-methylphenoxy)pyridin-3-yl]-3,4-dichlorobenzamide, N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-methylphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide, N-(6-{4-[3-(4-piperonylpiperazin-1-yl)-3-oxopropyl]phenoxy}pyridin-3-yl)-3,4-dichlorobenzenesulfonamide, N-[6-(4-{4-[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]piperazin-1-yl}phenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide, N-[6-(4-{4-[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}phenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide, N-{6-[(4-{4-[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}phenyl)methylamino]pyridin-3-yl}-4-trifluoromethylbenzamide, N-[6-(4-{4′-[2-(4-benzylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}-2-methylphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide, N-[6-(4-{4-[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}-2-methylphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide, N-[6-(4-{4-[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}-2-methylphenoxy)pyridin-3-yl]-3,4-dichlorobenzamide, N-{6-[4-(4-benzylpiperazine-1-carbonyl)phenoxy]pyridin-3-yl}-4-trifluoromethylbenzamide, N-{6-[4-(4-benzylpiperazine-1-carbonyl)phenoxy]pyridin-3-yl}-3,4-dichlorobenzamide, N-[6-({4-[3-(4-piperonylpiperazin-1-yl)-3-oxopropyl]phenyl}methylamino)pyridin-3-yl]-4-trifluoromethylbenzamide, N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]ethylamino}-2-fluorophenoxy)pyridin-3-yl]-3,4-dichlorobenzamide, N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-fluorophenoxy)pyridin-3-yl]-3,4-dichlorobenzamide, N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-methoxyphenoxy)pyridin-3-yl]-3,4-dichlorobenzamide, N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}phenoxy)pyridin-3-yl]-3,4-dichlorobenzamide, 1-(6-{4-[3-(4-piperonylpiperazin-1-yl)-3-oxopropyl]phenoxy}pyridin-3-yl)-3-(3,4-dichlorophenyl)-1-ethylurea, N-(6-{4-[3-(4-piperonylpiperazin-1-yl)-3-oxopropyl]phenoxy}pyridin-3-yl)-4-trifluoromethylbenzamide, N-[6-(4-{[2-(4-benzylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-methylphenoxy)pyridin-3-yl]-4-trifluoromethylrobenzamide, N-[6-(4-{4-[2-(4-benzylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}phenoxy)pyridin-3-yl]-3,4-dichlorobenzamide, N-(6-{4-[3-(4-piperonylpiperazine-1-carbonyl)piperidin-1-yl]phenoxy}pyridin-3-yl)-3,4-dichlorobenzamide, N-[6-(4-{4-[2-(4-benzylrupiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}phenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide, N-{6-[(4-{4-[2-(4-benzylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}phenyl)methylamino]pyridin-3-yl}-4-trifluoromethylbenzamide, N-(6-{4-[(2-{4-[4-(4-fluorobenzoyl)phenyl]piperazin-1-yl}-2-oxoethyl)methylamino]-2-methoxyphenoxy}pyridin-3-yl)-4-trifluoromethylbenzamide, 2-(4-piperonylpiperazin-1-yl)-N-{3-methyl-4-[5-(4-trifluoromethylphenoxymethyl)pyridin-2-yloxy]phenyl}-2-oxoacetamide, N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-methylphenoxy)pyridin-3-yl]-2-fluoro-4-trifluoromethylbenzamide, N-[6-(4-{4-[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}-2-methoxyphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide and 4-(3-{3-methyl-4-[5-(4-trifluoromethylbenzoylamino)-pyridin-2-yloxy]phenyl}-2-oxohexahydropyrimidin-1-yl)benzoic acid ethyl ester, or a salt thereof as an active ingredient.
 
Item 49: The antitumor agent according to any one of items 1 to 48, wherein a target of the antitumor agent is a malignant tumor.
 
Item 50: The antitumor agent according to item 49, wherein the malignant tumor is a solid tumor.
 
Item 51: The antitumor agent according to item 49, wherein the malignant tumor is a hematological cancer.
 
Item 52: The antitumor agent according to item 49, wherein the malignant tumor is lymphoma, leukemia, or myeloma.
 
Item 53: A method for treating or preventing tumor comprising an administration of a compound represented by the general formula (1) below or a salt thereof:
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein X 1  represents a nitrogen atom or a group —CH═,
 
R 1  represents a group -Z-R 6 ,
 
Z represents a group —N(R 8 )—B—, a group —B—N(R 8 )—, a group —B 0 —O—, a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    a group —CO—, a group —CH(OH)—, a group —N(R 9a )—CO—N—(R 9b )—, a group —N═CH—, a group —N(R 10a )—SO 2 —(B 22a ) e-, a lower alkenylene group, a group —NHCO—B 1 —, a group —NHCO—B 2 —(W)u-, a group —BO—O—B 19a —, a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    a group —SO 2 —N(R 10b )—, a group —S—, a lower alkynylene group, a lower alkylene group, a group —N(R 8d )— or a group —CO—NH—B 18a —.
 
R 8  represents a hydrogen atom, a lower alkyl group that may have a lower alkoxy group as a substituent, a lower alkanoyl group, a lower alkylsulfonyl group or a phenyl lower alkyl group,
 
B represents a group —CO— or a lower alkylene group,
 
B 0  represents a lower alkylene group,
 
B 1  represents a lower alkenylene group that may have a phenyl group as a substituent,
 
B 2  represents a lower alkylene group that may be substituted by a group selected from the group consisting of a lower alkoxy group and a phenyl group,
 
R 9a  represents a hydrogen atom or a lower alkyl group,
 
R 9b  represents a hydrogen atom or a lower alkyl group,
 
R 10a  represents a hydrogen atom or a lower alkyl group,
 
B 22a  represents a lower alkylene group or a lower alkenylene group,
 
e represents 0 or 1,
 
B 18a  represents a lower alkylene group,
 
B 19a  represents a lower alkylene group,
 
B 20a  represents a lower alkylene group,
 
B 21a  represents a lower alkylene group,
 
k represents 2 or 3,
 
c represents 0 or 1,
 
d′ represents 0 or 1,
 
         [0018]    R 10b  represents a hydrogen atom or a lower alkyl group, 
         [0000]    R 8d  represents a hydrogen atom or a lower alkyl group,
 
W represents an oxygen atom, a group —NH—, or a sulfur atom,
 
u represents 0 or 1,
 
R 6  represents 5- to 15-membered monocyclic, dicyclic or tricyclic saturated or unsaturated heterocyclic group having 1 to 4 nitrogen atoms, oxygen atoms or sulfur atoms (that may have 1 to 3 substituents, which are selected from the group consisting of an oxo group; a lower alkoxy group that may have a halogen atom as a substituent; a lower alkyl group that may have a halogen atom as a substituent; a halogen atom; a lower alkylsulfonyl group; a phenyl group that may be substituted by a lower alkyl group that may have a halogen atom on the phenyl ring; a lower alkylthio group, a pyrrolyl group, a benzoyl group; a lower alkanoyl group; lower alkoxycarbonyl group; and an amino group that may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent, on the heterocyclic ring), an adamantly group, a naphthyl group (that may have 1 to 3 groups selected from the group consisting of a lower alkyl group, a halogen atom, and an amino group that may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent, on the naphthalene ring), an alkyl group that may have a lower alkoxy group as a substituent, a cycloalkyl group that may be substituted by a group selected from the group consisting of an amino substituted lower alkyl group that may have a lower alkyl group and a lower alkyl group that may have a halogen atom as a substituent, on the cycloalkyl ring, a lower alkenyl group that may have a halogen atom as a substituent, a lower alkanoyl group, a benzoyl group (that may have 1 to 3 groups selected from the group consisting of a lower alkyl group that may have a halogen atom and halogen atom, as a substituents, on the phenyl ring), a halogen atom substituted lower alkyl group, cycloalkyl lower alkyl group or a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R 7  represents a hydrogen atom, a phenyl group, a carboxy group, a hydroxyl group, a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, a phenoxy group, a lower alkoxy group that may have a halogen atom as a substituent, a lower alkylenedioxy group, an amino group that may have, as a substituent, a group selected from the group consisting of a lower alkyl group, a lower alkanoyl group, a benzoyl group, and a cycloalkyl group, a cyano group, a lower alkanoyl group that may have a halogen atom as a substituent, a lower alkylsulfonyl group, an aminosulfonyl group, a lower alkoxycarbonyl group, a lower alkanoyloxy group, a lower alkoxycarbonyl lower alkyl group or a 5- or 6-membered saturated or unsaturated heterocyclic group having 1 to 4 nitrogen atoms, oxygen atoms, or sulfur atoms (that may have an oxo group on the heterocyclic ring),
 
m represents an integer from 1 to 5 (when m represents 2 to 5, two to five R 7 s may be identical or different) and
 
R 2  represents a hydrogen atom, a halogen atom, or a lower alkyl group,
 
Y represents a group —O—, a group —N(R 5 )—, a group —CO—, a group —CH(OH)—, a lower alkylene group, a group —S(O)n-, or a group —C(═N—OH)—,
 
R 5  represents a hydrogen atom, a lower alkyl group, a lower alkanoyl group, a benzoyl group, a phenyl lower alkyl group, or a cycloalkyl group,
 
n represents 0, 1, or 2,
 
A represents a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    or a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    p represents 1 or 2,
 
R 3  represents a hydrogen atom, a lower alkoxy group, a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, a lower alkoxycarbonyl group, a carboxy group, a group —CONR 11 R 12 , or a cyano group,
 
wherein R 11  and R 12  may be identical or different and each represent a hydrogen atom, a lower alkyl group, a cycloalkyl group, or a phenyl group, and R 11  and R 12 , together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic ring,
 
R 4  represents an imidazolyl lower alkyl group, a 1,2,4-triazolyl lower alkyl group, a 1,2,3-triazolyl lower alkyl group, a 1,2,5-triazolyl lower alkyl group, a pyrazolyl lower alkyl group, a pyrimidinyl lower alkyl group that may have an oxo group as a substituent on the pyrimidine ring, a 3,5-dioxoisoxazolidin-4-ylidene lower alkyl group, a 1,2,4-oxadiazolyl lower alkyl group that may have a lower alkyl group as a substituent on the 1,2,4-oxadiazole ring, a thiazolidinyl lower alkyl group that may have an oxo group as a substituent on the thiazolidine ring, a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    or a group -(T) 1 -N(R 14 )R 15 ,
 
R 13  represents a hydrogen atom, a lower alkyl group that may have a halogen atom as a substituent, a lower alkanoyl group that may have a halogen atom as a substituent, a lower alkoxycarbonyl group, a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring, an imidazolyl lower alkyl group, a lower alkoxycarbonyl lower alkyl group, a carboxy lower alkyl group, a benzoyl group, a morpholino-substituted lower alkanoyl group, a piperazinyl carbonyl lower alkyl group that may be substituted, on the piperazine ring, by a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring, a piperazinyl lower alkanoyl group that may be substituted, on the piperazine ring, by a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring, a morpholinocarbonyl-substituted lower alkyl group, or an imidazolyl lower alkanoyl group,
 
R 13a  represents a hydrogen atom or a hydroxyl group,
 
T represents a lower alkylene group, a group —N(R 17 )—B 3 —CO—, a group —B 19 —N(R 18 )—CO—, a group —B 4 —CO—, a group -Q-B 5 —CO—, a group —B 6 —N(R 19 )—B 7 —CO—, a group —CO—B 8 —, a group —CH(OH)—B 9 —, a group —CO—B 10 —CO—, a group —CH(OH)—B 11 —CO—, a group —CO—, a group —SO 2 —, or a group —B 23a —CO—CO—,
 
wherein R 17  represents a hydrogen atom, a lower alkyl group, a cycloalkyl group, a cycloalkylcarbonyl group, a lower alkanoyl group that may have a halogen atom as a substituent, a lower alkenyl group, an amino-substituted lower alkanoyl group that may have a lower alkyl group as a substituent, or a lower alkylsulfonyl group,
 
B 3  represents a lower alkylene group,
 
B 19  represents a lower alkylene group,
 
R 18  represents a hydrogen atom or a lower alkyl group,
 
B 4  represents a lower alkenylene group or a lower alkylene group that may have a hydroxyl group as a substituent,
 
Q represents an oxygen atom or a group —S(O)n- (wherein
 
n is the same as described above),
 
B 5  represents a lower alkylene group,
 
B 6  represents a lower alkylene group,
 
R 19  represents a hydrogen atom or a lower alkanoyl group,
 
B 7  represents a lower alkylene group,
 
B 8  represents a lower alkylene group,
 
B 9  represents a lower alkylene group,
 
B 10  represents a lower alkylene group,
 
B 11  represents a lower alkylene group,
 
B 23a  represents a lower alkylene group,
 
l represents 0 or 1,
 
R 14  represents a hydrogen atom or an alkyl group that may have a hydroxyl group as a substituent,
 
R 15  represents (2) a hydroxyl group-substituted alkyl group, (3) a cycloalkyl group that may have a group selected from the group consisting of a hydroxyl group and a lower alkyl group as a substituent, (4) a phenoxy lower alkyl group, (5) a phenyl group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkyl group; a lower alkoxy group that may have a halogen atom as a substituent; a halogen atom; an amino lower alkoxy group that may have a lower alkyl group as a substituent; a hydroxyl group-substituted lower alkyl group; a phenyl lower alkyl group; a lower alkynyl group; an amino group that may have a lower alkylsulfonyl group as a substituent; a lower alkylthio group; a cycloalkyl group; a phenylthio group; an adamantyl group; an anilino group that may have a halogen atom as a substituent on the phenyl ring; a lower alkoxycarbonyl group; a piperazinyl group that may have a lower alkyl group as a substituent on the piperazine ring; a pyrrolidinyl group that may have an oxo group as a substituent on the pyrrolidine ring; a lower alkanoylamino group; a cyano group; and a phenoxy group, (6) a phenoxy group, (7) a phenyl lower alkyl group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a halogen atom, a lower alkoxy group that may have a halogen atom as a substituent, and a lower alkyl group, (8) a phenyl lower alkyl group that has a lower alkylenedioxy group as a substituent on the phenyl ring, (10) a lower alkoxycarbonyl-substituted lower alkyl group, (11) a carboxy-substituted lower alkyl group, (12) an amino group that may have a lower alkanoyl group as a substituent, (13) a 1,2,3,4-tetrahydroquinolyl group that may have 1 to 3 groups selected from the group consisting of an oxo group, a lower alkoxy group, and a lower alkylenedioxy group as a substituent(s) on the tetrahydroquinoline ring, (14) a cycloalkyl lower alkyl group, (15) a piperazinyl lower alkanoyl group that may be substituted, on the piperazine ring, by a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring, (16) a pyridyl lower alkyl group, (17) an amino group-substituted lower alkyl group that may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent, (18) a lower alkoxy lower alkyl group, (19) an imidazolyl group, (20) an imidazolyl lower alkyl group, (21) a 1,2,3,4-tetrahydroisoquinolylcarbonyl-substituted lower alkyl group, (22) a piperidinylcarbonyl group that may have a group selected from the group consisting of a lower alkoxycarbonyl group, a phenyl lower alkyl group, and a furyl lower alkyl group as a substituent on the piperidine ring, (23) a thiazolidinyl lower alkanoyl group that may have an oxo group as a substituent on the thiazolidine ring, (24) a piperidinyl group that may be substituted, on the piperidine ring, by a group selected from the group consisting of a lower alkoxycarbonyl group, a phenyl lower alkyl group, a lower alkyl group, a benzoyl group, and a furyl lower alkyl group, (25) a carbonyl lower alkyl group substituted by a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    (26) a carbonyl lower alkyl group substituted by a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    27) a group —CO—B 2 O—N(R 36 )R 37 , (26a) a pyrrolidinyl lower alkyl group, (27a) a morpholino lower alkyl group, (28a) a phenyl lower alkenyl group, (29a) an anilinocarbonyl lower alkyl group that may have a lower alkyl group as a substituent on the phenyl ring, (30a) an indolyl group, (31a) a piperazinyl lower alkyl group that may have, as a substituent on the piperazine ring, a group selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring, (32a) an amidino lower alkyl group that may have a lower alkyl group as a substituent, (33a) a fluorenyl group, (34a) a carbazolyl group that may have a lower alkyl group as a substituent on the carbazole ring, (35a) an amidino group that may have a lower alkyl group as a substituent, (36a) a piperazinyl-substituted oxalyl group that may have 1 to 3 groups selected from the group consisting of a phenyl lower alkyl group (that may have 1 to 3 groups selected from the group consisting of a lower alkylenedioxy group and a lower alkoxy group as a substituent(s) on the phenyl ring) and a pyridyl lower alkyl group as a substituent(s) on the piperazine ring, or (37a) a cyano-substituted lower alkyl group,
 
R 34  represents an oxo group or a phenyl group,
 
d represents an integer from 0 to 3,
 
B 20  represents a lower alkylene group,
 
R 36  and R 37 , together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic group, wherein, on the heterocyclic ring, 1 to 3 phenyl lower alkyl groups that may have a lower alkylenedioxy group on the phenyl ring, may be present as a substituent(s),
 
R 14  and R 15 , together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 10-membered saturated or unsaturated heterocyclic ring; or a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein, on the heterocyclic ring, 1 to 3 substituents may be present which are selected from the group consisting of (28) a phenyl-substituted lower alkyl group, which has 1 to 2 phenyl groups that may be substituted by 1 to 3 groups on the phenyl ring, selected from the group consisting of a lower alkanoyl group, an amino group that may have a lower alkanoyl group as a substituent, a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, a lower alkoxy group that may have a halogen atom as a substituent, a phenyl lower alkoxy group, a hydroxyl group, and a lower alkylenedioxy group, and that may have a pyridyl group on the lower alkyl group, (29) a carbamoyl group, (30) a pyridyl lower alkyl group that may have, as a substituent(s) on the pyridine ring, 1 to 3 groups selected from the group consisting of a hydroxyl group and a lower alkyl group that may have a hydroxyl group as a substituent, (31) a pyrrolyl lower alkyl group that may have 1 to 3 lower alkyl groups as a substituent(s) on the pyrrole ring, (32) a benzoxazolyl lower alkyl group, (33) a benzothiazolyl lower alkyl group, (34) a furyl lower alkyl group, (35) a benzoyl group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a cyano group, an amino group that may have a lower alkylsulfonyl group as a substituent, a halogen atom, a lower alkoxy group, a lower alkyl group that may have a halogen atom as a substituent, a thiazolidinyl lower alkyl group that may have an oxo group as a substituent on the thiazolidine ring, a thiazolidinylidene lower alkyl group that may have an oxo group as a substituent on the thiazolidine ring, and a lower alkylenedioxy group, (36) a pyrimidinyl group, (37) a pyrazinyl group, (38) a pyridyl group, (39) a lower alkoxycarbonyl group, (40) a thiazolidinyl lower alkanoyl group that may be substituted, on the thiazolidine ring, by a group selected from the group consisting of an oxo group and a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    (wherein R a  and R b  each represent a lower alkyl group), (41) a lower alkyl group that may have a group selected from the group consisting of a hydroxyl group and a halogen atom as a substituent, (42) a lower alkanoyl group that may have a halogen atom as a substituent, (43) a phenyl group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a carbamoyl group that may have a group selected from the group consisting of a lower alkoxy lower alkyl group and a lower alkyl group, a lower alkoxycarbonyl group, a carboxy group, a cyano group, a phenyl group, a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, a lower alkoxy group that may have a halogen atom as a substituent, a benzoyl group that may have a halogen atom as a substituent on the phenyl ring, a phenyl lower alkyl group that may have a halogen atom as a substituent on the phenyl ring, and a hydroxyl group, (44) a phenyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring, (45) a naphthyl lower alkyl group, (46) a phenoxy group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a cyano group, a lower alkyl group that may have a halogen atom as a substituent, and a lower alkoxy group that may have a halogen atom as a substituent, (47) a phenoxy lower alkyl group, (48) a phenyl lower alkoxy group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, and a lower alkoxy group that may have a halogen atom as a substituent, (49) a group —(B 12 CO)t-N(R 20 )R 21 , (50) a group —(CO)o-B 13 —N(R 22 )R 22 , (51) a 1,2,3,4-tetrahydronaphthyl-substituted lower alkyl group that may be substituted, on the 1,2,3,4-tetrahydronaphthalene ring, by 1 to 5 lower alkyl groups as a substituent(s), (52) a cycloalkyl group that may have a hydroxyl group as a substituent, (53) a piperidinyl group that may be substituted, on the piperidine ring, by 1 to 3 lower alkyl groups as a substituent(s), (54) a quinolyl lower alkyl group, (55) a 1,2,3,4-tetrazolyl lower alkyl group that may have a group selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group as a substituent on the tetrazole ring, (56) a thiazolyl lower alkyl group that may have a phenyl group as a substituent on the thiazole ring, (57) a benzoyl lower alkyl group that may have 1 to 3 groups selected from the group consisting of a lower alkoxy group and a halogen atom as a substituent(s) on the phenyl ring, (58) a piperidinyl lower alkyl group that may have a lower alkyl group as a substituent on the piperidine ring, (59) an imidazolyl group that may have 1 to 3 phenyl groups as a substituent(s) on the imidazole ring, (60) a benzimidazolyl group that may have 1 to 3 lower alkyl groups as a substituent(s) on the benzimidazole ring, (61) a pyridyl lower alkoxy group, (62) a 1,2,3,4-tetrahydroquinolyl lower alkyl group that may have an oxo group as a substituent on the tetrahydroquinoline ring, (63) a 1,3,4-oxadiazolyl lower alkyl group that may have an oxo group as a substituent on the 1,3,4-oxadizole ring, (64) a cycloalkyl lower alkyl group, (65) a tetrahydropyranyl group, (66) a thienyl lower alkyl group, (67) a pyrimidinylcarbonyl group that may have an oxo group as a substituent on the pyrimidine ring, (68) a hydroxyl group, (69) a carboxy group, (70) a lower alkoxy lower alkyl group, (71) a lower alkoxy lower alkoxy group, (72) a benzoyloxy group, (73) a lower alkoxycarbonyl lower alkoxy group, (74) a carboxy lower alkoxy group, (75) a phenoxy lower alkanoyl group, (76) a 1,2,3,4-tetrahydroquinolylcarbonyl group that may have an oxo group as a substituent on the tetrahydroquinoline ring, (77) a phenylsulfonyl group, (78) an imidazolyl lower alkanoyl group, (79) an imidazolyl lower alkyl group, (80) a pyridylcarbonyl group, (81) an imidazolylcarbonyl group, (82) a lower alkoxycarbonyl lower alkyl group, (83) a carboxy lower alkyl group, (84) a group —(O—B 15 )s-CO—N(R 26 )R 27 , (85) a group —N(R 28 )—CO—B 16 —N(R 29 )R 30 , (86) a group —N(R 31 )—B 17 —CO—N(R 32 )R 33 , (87) a benzoxazolyl group, (88a) a benzothienyl group, (89a) an oxo group, and (90a) a 1,2,3,4-tetrahydroquinolyl group that may have an oxo group as a substituent on the tetrahydroquinoline ring,
 
B 12  represents a lower alkylene group,
 
t represents 0 or 1,
 
R 20  and R 21  may be identical or different and each represent a hydrogen atom; an amino group that may have a lower alkoxycarbonyl group as a substituent; a benzoyl group that may have 1 to 3 lower alkoxy groups as a substituent(s) on the phenyl ring; a lower alkyl group; a lower alkyl group having 1 to 2 phenyl groups that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, a lower alkoxy group that may have a halogen atom as a substituent, and a lower alkylthio group; a phenyl group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkoxy group that may have a halogen atom as a substituent and a lower alkyl group that may have a halogen atom as a substituent; a lower alkoxycarbonyl group; a cycloalkyl lower alkyl group; a pyrrolidinyl lower alkyl group that may have 1 to 3 lower alkyl groups that may have a hydroxyl group as a substituent on the pyrrolidine ring; an amino-substituted lower alkyl group that may have a group selected from the group consisting of a phenyl group and a lower alkyl group as a substituent; a 1,2,3,4-tetrahydronaphthyl-substituted lower alkyl group that may have 1 to 5 lower alkyl groups as a substituent(s) on the 1,2,3,4-tetrahydronaphthalene ring; a naphthyl lower alkyl group; a pyridyl lower alkyl group; a quinolyl lower alkyl group; a 1,2,3,4-tetrazolyl lower alkyl group that may have 1 to 3 groups selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group as a substituent(s) on the tetrazole ring; a 1,2,4-triazolyl lower alkyl group; a tetrahydrofuryl lower alkyl group that may have a hydroxyl group as a substituent on the lower alkyl group; a phenoxy lower alkyl group that may have 1 to 3 groups selected from the group consisting of a lower alkyl group and a nitro group as a substituent(s) on the phenyl ring; a phenyl lower alkanoyl group; a lower alkanoyl group that may have a halogen atom as a substituent; an imidazolyl lower alkanoyl group; a lower alkoxycarbonyl lower alkyl group; a pyridyl group; or a carboxy lower alkyl group, or a cycloalkyl group; and R 20  and R 21 , together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic ring (wherein, on the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group consisting of a lower alkyl group, a phenyl group that may have 1 to 3 groups selected from the group consisting of a halogen atom and a lower alkyl group that may have a halogen atom as a substituent(s) on the phenyl ring, and a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring),
 
o represents 0 or 1,
 
B 13  represents a lower alkylene group,
 
R 22  and R 23  may be identical or different and each represent a hydrogen atom, a lower alkyl group, a benzoyl group that may have 1 to 3 lower alkoxy groups as a substituent(s) on the phenyl ring, a phenoxy lower alkyl group that may have a lower alkyl group as a substituent on the phenyl ring, a phenyl lower alkyl group, or a phenyl group, or R 22  and R 23 , together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic ring (wherein, on the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring),
 
B 15  represents a lower alkylene group,
 
s represents 0 or 1,
 
R 26  and R 27  may be identical or different and each represent a hydrogen atom, a lower alkyl group, a phenyl lower alkyl group, or an imidazolyl lower alkyl group, and R 26  and R 27 , together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic ring, (wherein, on the heterocyclic ring, 1 to 3 phenyl lower alkyl groups that may have a lower alkylenedioxy group as a substituent, may be present on the phenyl ring, as a substituent(s)),
 
R 27  represents a hydrogen atom or a lower alkyl group,
 
B 16  represents a lower alkylene group,
 
R 29  and R 30 , together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic group, wherein, on the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group consisting of a lower alkyl group, a phenyl group, and a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring,
 
R 31  represents a hydrogen atom or a lower alkyl group,
 
         [0019]    B 17  represents a lower alkylene group, 
         [0000]    R 32  and R 33 , together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic group, (wherein, on the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group consisting of a lower alkyl group, a phenyl group, and a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring),
 
provided that the aforementioned compound or a salt thereof satisfies the following requirements (i) to (v):
 
         [0020]    (i) when X 1  represents a group —CH═, then R 3  represents a hydrogen atom; 
         [0021]    (ii) when X 1  represents a group —CH═, l represents 1, T represents —CO—, and R 14  represents a hydrogen atom or an alkyl group that may have a hydroxyl group as a substituent, R 15  represents the group (24); 
         [0022]    (iii) when X 1  represents a group —CH═, l represents 1, and T represents —N(R 17 )—B 3 —CO—, R 14  and R 15 , together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 10-membered saturated or unsaturated heterocyclic ring, wherein, on the heterocyclic ring, 1 to 3 groups of (28) are present as a substituent(s); 
         [0023]    (iv) when X 1  represents a nitrogen atom, and l represents 0, or when X 1  represents a nitrogen atom, l represents 1, and T represents —CO— or —SO 2 , R 15  is not a group (5), (7), (19), or (20); and 
         [0024]    (v) when R 6  represents a cycloalkyl group that may have on the cycloalkyl ring, a substituent selected from the group consisting of an amino-substituted lower alkyl group that may have a lower alkyl group and a lower alkyl group that may have a halogen atom as a substituent, R 4  represents a group -(T) l -N(R 14 )R 15  (wherein T and l are the same as described above, and R 14  and R 15 , together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 10-membered saturated heterocyclic ring; or R 14  and R 15  form a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    Item 54: Use of a compound represented by the general formula (1) below or a salt thereof for manufacturing an antitumor agent: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein X 1  represents a nitrogen atom or a group —CH═,
 
R 1  represents a group -Z-R 6 ,
 
Z represents a group —N(R 8 )—B—, a group —B—N(R 8 )—, a group —B 0 —O—, a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    a group —CO—, a group —CH(OH)—, a group —N(R 9a )—CO—N—(R 9b )—, a group —N═CH—, a group —N(R 10a )—SO 2 —(B 22a )e-, a lower alkenylene group, a group —NHCO—B 1 —, a group —NHCO—B 2 —(W)u-, a group —BO—O—B 19a —, a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    a group —SO 2 —N(R 10b )—, a group —S—, a lower alkynylene group, a lower alkylene group, a group —N(R 8d )— or a group —CO—NH—B 18a —.
 
R 8  represents a hydrogen atom, a lower alkyl group that may have a lower alkoxy group as a substituent, a lower alkanoyl group, a lower alkylsulfonyl group or a phenyl lower alkyl group,
 
B represents a group —CO— or a lower alkylene group,
 
B 0  represents a lower alkylene group,
 
B 1  represents a lower alkenylene group that may have a phenyl group as a substituent,
 
B 2  represents a lower alkylene group that may be substituted by a group selected from the group consisting of a lower alkoxy group and a phenyl group,
 
R 9a  represents a hydrogen atom or a lower alkyl group,
 
R 9b  represents a hydrogen atom or a lower alkyl group,
 
R 10a  represents a hydrogen atom or a lower alkyl group,
 
B 22a  represents a lower alkylene group or a lower alkenylene group,
 
e represents 0 or 1,
 
B 18a  represents a lower alkylene group,
 
B 19a  represents a lower alkylene group,
 
B 20a  represents a lower alkylene group,
 
B 21a  represents a lower alkylene group,
 
k represents 2 or 3,
 
c represents 0 or 1,
 
d′ represents 0 or 1,
 
R 10b  represents a hydrogen atom or a lower alkyl group,
 
R 8d  represents a hydrogen atom or a lower alkyl group,
 
W represents an oxygen atom, a group —NH—, or a sulfur atom,
 
u represents 0 or 1,
 
R 6  represents 5- to 15-membered monocyclic, dicyclic or tricyclic saturated or unsaturated heterocyclic group having 1 to 4 nitrogen atoms, oxygen atoms or sulfur atoms (that may have 1 to 3 substituents, which are selected from the group consisting of an oxo group; a lower alkoxy group that may have a halogen atom as a substituent; a lower alkyl group that may have a halogen atom as a substituent; a halogen atom; a lower alkylsulfonyl group; a phenyl group that may be substituted by a lower alkyl group that may have a halogen atom on the phenyl ring; a lower alkylthio group, a pyrrolyl group, a benzoyl group; a lower alkanoyl group; lower alkoxycarbonyl group; and an amino group that may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent, on the heterocyclic ring), an adamantly group, a naphthyl group (that may have 1 to 3 groups selected from the group consisting of a lower alkyl group, a halogen atom, and an amino group that may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent, on the naphthalene ring), an alkyl group that may have a lower alkoxy group as a substituent, a cycloalkyl group that may be substituted by a group selected from the group consisting of an amino substituted lower alkyl group that may have a lower alkyl group and a lower alkyl group that may have a halogen atom as a substituent, on the cycloalkyl ring, a lower alkenyl group that may have a halogen atom as a substituent, a lower alkanoyl group, a benzoyl group (that may have 1 to 3 groups selected from the group consisting of a lower alkyl group that may have a halogen atom and halogen atom, as a substituents, on the phenyl ring), a halogen atom substituted lower alkyl group, cycloalkyl lower alkyl group or a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R 7  represents a hydrogen atom, a phenyl group, a carboxy group, a hydroxyl group, a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, a phenoxy group, a lower alkoxy group that may have a halogen atom as a substituent, a lower alkylenedioxy group, an amino group that may have, as a substituent, a group selected from the group consisting of a lower alkyl group, a lower alkanoyl group, a benzoyl group, and a cycloalkyl group, a cyano group, a lower alkanoyl group that may have a halogen atom as a substituent, a lower alkylsulfonyl group, an aminosulfonyl group, a lower alkoxycarbonyl group, a lower alkanoyloxy group, a lower alkoxycarbonyl lower alkyl group or a 5- or 6-membered saturated or unsaturated heterocyclic group having 1 to 4 nitrogen atoms, oxygen atoms, or sulfur atoms (that may have an oxo group on the heterocyclic ring),
 
m represents an integer from 1 to 5 (when m represents 2 to 5, two to five R 7 s may be identical or different) and
 
R 2  represents a hydrogen atom, a halogen atom, or a lower alkyl group,
 
Y represents a group —O—, a group —N(R 5 )—, a group —CO—, a group —CH(OH)—, a lower alkylene group, a group —S(O)n-, or a group —C(═N—OH)—,
 
R 5  represents a hydrogen atom, a lower alkyl group, a lower alkanoyl group, a benzoyl group, a phenyl lower alkyl group, or a cycloalkyl group,
 
n represents 0, 1, or 2,
 
A represents a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    or a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    p represents 1 or 2,
 
R 3  represents a hydrogen atom, a lower alkoxy group, a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, a lower alkoxycarbonyl group, a carboxy group, a group —CONR 11 R 12 , or a cyano group,
 
wherein R 11  and R 12  may be identical or different and each represent a hydrogen atom, a lower alkyl group, a cycloalkyl group, or a phenyl group, and R 11  and R 12 , together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic ring,
 
R 4  represents an imidazolyl lower alkyl group, a 1,2,4-triazolyl lower alkyl group, a 1,2,3-triazolyl lower alkyl group, a 1,2,5-triazolyl lower alkyl group, a pyrazolyl lower alkyl group, a pyrimidinyl lower alkyl group that may have an oxo group as a substituent on the pyrimidine ring, a 3,5-dioxoisoxazolidin-4-ylidene lower alkyl group, a 1,2,4-oxadiazolyl lower alkyl group that may have a lower alkyl group as a substituent on the 1,2,4-oxadiazole ring, a thiazolidinyl lower alkyl group that may have an oxo group as a substituent on the thiazolidine ring, a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    or a group -(T) l -N(R 14 )R 15 ,
 
R 13  represents a hydrogen atom, a lower alkyl group that may have a halogen atom as a substituent, a lower alkanoyl group that may have a halogen atom as a substituent, a lower alkoxycarbonyl group, a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring, an imidazolyl lower alkyl group, a lower alkoxycarbonyl lower alkyl group, a carboxy lower alkyl group, a benzoyl group, a morpholino-substituted lower alkanoyl group, a piperazinyl carbonyl lower alkyl group that may be substituted, on the piperazine ring, by a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring, a piperazinyl lower alkanoyl group that may be substituted, on the piperazine ring, by a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring, a morpholinocarbonyl-substituted lower alkyl group, or an imidazolyl lower alkanoyl group,
 
R 13a  represents a hydrogen atom or a hydroxyl group,
 
T represents a lower alkylene group, a group —N(R 17 )—B 3 —CO—, a group —B 19 —N(R 18 )—CO—, a group —B 4 —CO—, a group Q-B 5 —CO—, a group —B 6 —N(R 19 )—B 7 —CO—, a group —CO—B 8 —, a group —CH(OH)—B 9 —, a group —CO—B 10 —CO—, a group —CH(OH)—B 11 —CO—, a group —CO—, a group —SO 2 —, or a group —B 23a —CO—CO—,
 
wherein R 17  represents a hydrogen atom, a lower alkyl group, a cycloalkyl group, a cycloalkylcarbonyl group, a lower alkanoyl group that may have a halogen atom as a substituent, a lower alkenyl group, an amino-substituted lower alkanoyl group that may have a lower alkyl group as a substituent, or a lower alkylsulfonyl group,
 
B 3  represents a lower alkylene group,
 
B 19  represents a lower alkylene group,
 
R 18  represents a hydrogen atom or a lower alkyl group,
 
B 4  represents a lower alkenylene group or a lower alkylene group that may have a hydroxyl group as a substituent,
 
Q represents an oxygen atom or a group —S(O)n- (wherein
 
n is the same as described above),
 
B 5  represents a lower alkylene group,
 
B 6  represents a lower alkylene group,
 
R 19  represents a hydrogen atom or a lower alkanoyl group,
 
B 7  represents a lower alkylene group,
 
B 8  represents a lower alkylene group,
 
B 9  represents a lower alkylene group,
 
B 10  represents a lower alkylene group,
 
B 11  represents a lower alkylene group,
 
B 23a  represents a lower alkylene group,
 
l represents 0 or 1,
 
R 14  represents a hydrogen atom or an alkyl group that may have a hydroxyl group as a substituent,
 
R 15  represents (2) a hydroxyl group-substituted alkyl group, (3) a cycloalkyl group that may have a group selected from the group consisting of a hydroxyl group and a lower alkyl group as a substituent, (4) a phenoxy lower alkyl group, (5) a phenyl group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkyl group; a lower alkoxy group that may have a halogen atom as a substituent; a halogen atom; an amino lower alkoxy group that may have a lower alkyl group as a substituent; a hydroxyl group-substituted lower alkyl group; a phenyl lower alkyl group; a lower alkynyl group; an amino group that may have a lower alkylsulfonyl group as a substituent; a lower alkylthio group; a cycloalkyl group; a phenylthio group; an adamantyl group; an anilino group that may have a halogen atom as a substituent on the phenyl ring; a lower alkoxycarbonyl group; a piperazinyl group that may have a lower alkyl group as a substituent on the piperazine ring; a pyrrolidinyl group that may have an oxo group as a substituent on the pyrrolidine ring; a lower alkanoylamino group; a cyano group; and a phenoxy group, (6) a phenoxy group, (7) a phenyl lower alkyl group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a halogen atom, a lower alkoxy group that may have a halogen atom as a substituent, and a lower alkyl group, (8) a phenyl lower alkyl group that has a lower alkylenedioxy group as a substituent on the phenyl ring, (10) a lower alkoxycarbonyl-substituted lower alkyl group, (11) a carboxy-substituted lower alkyl group, (12) an amino group that may have a lower alkanoyl group as a substituent, (13) a 1,2,3,4-tetrahydroquinolyl group that may have 1 to 3 groups selected from the group consisting of an oxo group, a lower alkoxy group, and a lower alkylenedioxy group as a substituent(s) on the tetrahydroquinoline ring, (14) a cycloalkyl lower alkyl group, (15) a piperazinyl lower alkanoyl group that may be substituted, on the piperazine ring, by a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring, (16) a pyridyl lower alkyl group, (17) an amino group-substituted lower alkyl group that may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent, (18) a lower alkoxy lower alkyl group, (19) an imidazolyl group, (20) an imidazolyl lower alkyl group, (21) a 1,2,3,4-tetrahydroisoquinolylcarbonyl-substituted lower alkyl group, (22) a piperidinylcarbonyl group that may have a group selected from the group consisting of a lower alkoxycarbonyl group, a phenyl lower alkyl group, and a furyl lower alkyl group as a substituent on the piperidine ring, (23) a thiazolidinyl lower alkanoyl group that may have an oxo group as a substituent on the thiazolidine ring, (24) a piperidinyl group that may be substituted, on the piperidine ring, by a group selected from the group consisting of a lower alkoxycarbonyl group, a phenyl lower alkyl group, a lower alkyl group, a benzoyl group, and a furyl lower alkyl group, (25) a carbonyl lower alkyl group substituted by a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    (26) a carbonyl lower alkyl group substituted by a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    27) a group —CO—B 20 —N(R 36 )R 37 , (26a) a pyrrolidinyl lower alkyl group, (27a) a morpholino lower alkyl group, (28a) a phenyl lower alkenyl group, (29a) an anilinocarbonyl lower alkyl group that may have a lower alkyl group as a substituent on the phenyl ring, (30a) an indolyl group, (31a) a piperazinyl lower alkyl group that may have, as a substituent on the piperazine ring, a group selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring, (32a) an amidino lower alkyl group that may have a lower alkyl group as a substituent, (33a) a fluorenyl group, (34a) a carbazolyl group that may have a lower alkyl group as a substituent on the carbazole ring, (35a) an amidino group that may have a lower alkyl group as a substituent, (36a) a piperazinyl-substituted oxalyl group that may have 1 to 3 groups selected from the group consisting of a phenyl lower alkyl group (that may have 1 to 3 groups selected from the group consisting of a lower alkylenedioxy group and a lower alkoxy group as a substituent(s) on the phenyl ring) and a pyridyl lower alkyl group as a substituent(s) on the piperazine ring, or (37a) a cyano-substituted lower alkyl group,
 
R 34  represents an Oxo group or a phenyl group,
 
d represents an integer from 0 to 3,
 
B 20  represents a lower alkylene group,
 
R 36  and R 37 , together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic group, wherein, on the heterocyclic ring, 1 to 3 phenyl lower alkyl groups that may have a lower alkylenedioxy group on the phenyl ring, may be present as a substituent(s),
 
R 14  and R 15 , together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 10-membered saturated or unsaturated heterocyclic ring; or a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein, on the heterocyclic ring, 1 to 3 substituents may be present which are selected from the group consisting of (28) a phenyl-substituted lower alkyl group, which has 1 to 2 phenyl groups that may be substituted by 1 to 3 groups on the phenyl ring, selected from the group consisting of a lower alkanoyl group, an amino group that may have a lower alkanoyl group as a substituent, a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, a lower alkoxy group that may have a halogen atom as a substituent, a phenyl lower alkoxy group, a hydroxyl group, and a lower alkylenedioxy group, and that may have a pyridyl group on the lower alkyl group, (29) a carbamoyl group, (30) a pyridyl lower alkyl group that may have, as a substituent(s) on the pyridine ring, 1 to 3 groups selected from the group consisting of a hydroxyl group and a lower alkyl group that may have a hydroxyl group as a substituent, (31) a pyrrolyl lower alkyl group that may have 1 to 3 lower alkyl groups as a substituent(s) on the pyrrole ring, (32) a benzoxazolyl lower alkyl group, (33) a benzothiazolyl lower alkyl group, (34) a furyl lower alkyl group, (35) a benzoyl group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a cyano group, an amino group that may have a lower alkylsulfonyl group as a substituent, a halogen atom, a lower alkoxy group, a lower alkyl group that may have a halogen atom as a substituent, a thiazolidinyl lower alkyl group that may have an oxo group as a substituent on the thiazolidine ring, a thiazolidinylidene lower alkyl group that may have an oxo group as a substituent on the thiazolidine ring, and a lower alkylenedioxy group, (36) a pyrimidinyl group, (37) a pyrazinyl group, (38) a pyridyl group, (39) a lower alkoxycarbonyl group, (40) a thiazolidinyl lower alkanoyl group that may be substituted, on the thiazolidine ring, by a group selected from the group consisting of an oxo group and a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    (wherein R a  and R b  each represent a lower alkyl group), (41) a lower alkyl group that may have a group selected from the group consisting of a hydroxyl group and a halogen atom as a substituent, (42) a lower alkanoyl group that may have a halogen atom as a substituent, (43) a phenyl group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a carbamoyl group that may have a group selected from the group consisting of a lower alkoxy lower alkyl group and a lower alkyl group, a lower alkoxycarbonyl group, a carboxy group, a cyano group, a phenyl group, a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, a lower alkoxy group that may have a halogen atom as a substituent, a benzoyl group that may have a halogen atom as a substituent on the phenyl ring, a phenyl lower alkyl group that may have a halogen atom as a substituent on the phenyl ring, and a hydroxyl group, (44) a phenyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring, (45) a naphthyl lower alkyl group, (46) a phenoxy group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a cyano group, a lower alkyl group that may have a halogen atom as a substituent, and a lower alkoxy group that may have a halogen atom as a substituent, (47) a phenoxy lower alkyl group, (48) a phenyl lower alkoxy group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, and a lower alkoxy group that may have a halogen atom as a substituent, (49) a group —(B 12 CO)t-N(R 20 )R 21 , (50) a group —(CO)o-B 13 —N(R 22 )R 23 , (51) a 1,2,3,4-tetrahydronaphthyl-substituted lower alkyl group that may be substituted, on the 1,2,3,4-tetrahydronaphthalene ring, by 1 to 5 lower alkyl groups as a substituent(s), (52) a cycloalkyl group that may have a hydroxyl group as a substituent, (53) a piperidinyl group that may be substituted, on the piperidine ring, by 1 to 3 lower alkyl groups as a substituent(s), (54) a quinolyl lower alkyl group, (55) a 1,2,3,4-tetrazolyl lower alkyl group that may have a group selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group as a substituent on the tetrazole ring, (56) a thiazolyl lower alkyl group that may have a phenyl group as a substituent on the thiazole ring, (57) a benzoyl lower alkyl group that may have 1 to 3 groups selected from the group consisting of a lower alkoxy group and a halogen atom as a substituent(s) on the phenyl ring, (58) a piperidinyl lower alkyl group that may have a lower alkyl group as a substituent on the piperidine ring, (59) an imidazolyl group that may have 1 to 3 phenyl groups as a substituent(s) on the imidazole ring, (60) a benzimidazolyl group that may have 1 to 3 lower alkyl groups as a substituent(s) on the benzimidazole ring, (61) a pyridyl lower alkoxy group, (62) a 1,2,3,4-tetrahydroquinolyl lower alkyl group that may have an oxo group as a substituent on the tetrahydroquinoline ring, (63) a 1,3,4-oxadiazolyl lower alkyl group that may have an oxo group as a substituent on the 1,3,4-oxadizole ring, (64) a cycloalkyl lower alkyl group, (65) a tetrahydropyranyl group, (66) a thienyl lower alkyl group, (67) a pyrimidinylcarbonyl group that may have an oxo group as a substituent on the pyrimidine ring, (68) a hydroxyl group, (69) a carboxy group, (70) a lower alkoxy lower alkyl group, (71) a lower alkoxy lower alkoxy group, (72) a benzoyloxy group, (73) a lower alkoxycarbonyl lower alkoxy group, (74) a carboxy lower alkoxy group, (75) a phenoxy lower alkanoyl group, (76) a 1,2,3,4-tetrahydroquinolylcarbonyl group that may have an oxo group as a substituent on the tetrahydroquinoline ring, (77) a phenylsulfonyl group, (78) an imidazolyl lower alkanoyl group, (79) an imidazolyl lower alkyl group, (80) a pyridylcarbonyl group, (81) an imidazolylcarbonyl group, (82) a lower alkoxycarbonyl lower alkyl group, (83) a carboxy lower alkyl group, (84) a group —(O—B 15 )s-CO—N(R 26 )R 27 , (85) a group —N(R 28 )—CO—B 16 —N(R 29 )R 30 , (86) a group —N(R 31 )—B 17 —CO—N(R 32 )R 33 , (87) a benzoxazolyl group, (88a) a benzothienyl group, (89a) an oxo group, and (90a) a 1,2,3,4-tetrahydroquinolyl group that may have an oxo group as a substituent on the tetrahydroquinoline ring,
 
B 12  represents a lower alkylene group,
 
t represents 0 or 1,
 
R 20  and R 21  may be identical or different and each represent a hydrogen atom; an amino group that may have a lower alkoxycarbonyl group as a substituent; a benzoyl group that may have 1 to 3 lower alkoxy groups as a substituent(s) on the phenyl ring; a lower alkyl group; a lower alkyl group having 1 to 2 phenyl groups that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, a lower alkoxy group that may have a halogen atom as a substituent, and a lower alkylthio group; a phenyl group that may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkoxy group that may have a halogen atom as a substituent and a lower alkyl group that may have a halogen atom as a substituent; a lower alkoxycarbonyl group; a cycloalkyl lower alkyl group; a pyrrolidinyl lower alkyl group that may have 1 to 3 lower alkyl groups that may have a hydroxyl group as a substituent on the pyrrolidine ring; an amino-substituted lower alkyl group that may have a group selected from the group consisting of a phenyl group and a lower alkyl group as a substituent; a 1,2,3,4-tetrahydronaphthyl-substituted lower alkyl group that may have 1 to 5 lower alkyl groups as a substituent(s) on the 1,2,3,4-tetrahydronaphthalene ring; a naphthyl lower alkyl group; a pyridyl lower alkyl group; a quinolyl lower alkyl group; a 1,2,3,4-tetrazolyl lower alkyl group that may have 1 to 3 groups selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group as a substituent(s) on the tetrazole ring; a 1,2,4-triazolyl lower alkyl group; a tetrahydrofuryl lower alkyl group that may have a hydroxyl group as a substituent on the lower alkyl group; a phenoxy lower alkyl group that may have 1 to 3 groups selected from the group consisting of a lower alkyl group and a nitro group as a substituent(s) on the phenyl ring; a phenyl lower alkanoyl group; a lower alkanoyl group that may have a halogen atom as a substituent; an imidazolyl lower alkanoyl group; a lower alkoxycarbonyl lower alkyl group; a pyridyl group; or a carboxy lower alkyl group, or a cycloalkyl group; and R 20  and R 21 , together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic ring (wherein, on the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group consisting of a lower alkyl group, a phenyl group that may have 1 to 3 groups selected from the group consisting of a halogen atom and a lower alkyl group that may have a halogen atom as a substituent(s) on the phenyl ring, and a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring),
 
o represents 0 or 1,
 
B 13  represents a lower alkylene group,
 
R 22  and R 23  may be identical or different and each represent a hydrogen atom, a lower alkyl group, a benzoyl group that may have 1 to 3 lower alkoxy groups as a substituent(s) on the phenyl ring, a phenoxy lower alkyl group that may have a lower alkyl group as a substituent on the phenyl ring, a phenyl lower alkyl group, or a phenyl group, or R 22  and R 23 , together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic ring (wherein, on the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring),
 
B 15  represents a lower alkylene group,
 
s represents 0 or 1,
 
R 26  and R 27  may be identical or different and each represent a hydrogen atom, a lower alkyl group, a phenyl lower alkyl group, or an imidazolyl lower alkyl group, and R 26  and R 27 , together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic ring, (wherein, on the heterocyclic ring, 1 to 3 phenyl lower alkyl groups that may have a lower alkylenedioxy group as a substituent, may be present on the phenyl ring, as a substituent(s)),
 
R 28  represents a hydrogen atom or a lower alkyl group,
 
B 16  represents a lower alkylene group,
 
R 29  and R 30 , together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic group, wherein, on the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group consisting of a lower alkyl group, a phenyl group, and a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring,
 
R 31  represents a hydrogen atom or a lower alkyl group,
 
B 17  represents a lower alkylene group,
 
R 32  and R 33 , together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic group, (wherein, on the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group consisting of a lower alkyl group, a phenyl group, and a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring), provided that the aforementioned compound or a salt thereof satisfies the following requirements (i) to (v):
 
         [0025]    (i) when X 1  represents a group —CH═, then R 3  represents a hydrogen atom; 
         [0026]    (ii) when X 1  represents a group —CH═, l represents 1, T represents —CO—, and R 14  represents a hydrogen atom or an alkyl group that may have a hydroxyl group as a substituent, R 15  represents the group (24); 
         [0027]    (iii) when X 1  represents a group —CH═, l represents 1, and T represents —N(R 17 )—B 3 —CO—, R 14  and R 15 , together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 10-membered saturated or unsaturated heterocyclic ring, wherein, on the heterocyclic ring, 1 to 3 groups of (28) are present as a substituent(s); 
         [0028]    (iv) when X 1  represents a nitrogen atom, and l represents 0, or when X 1  represents a nitrogen atom, l represents 1, and T represents —CO— or —SO 2 , R 15  is not a group (5), (7), (19), or (20); and 
         [0029]    (v) when R 6  represents a cycloalkyl group that may have on the cycloalkyl ring, a substituent selected from the group consisting of an amino-substituted lower alkyl group that may have a lower alkyl group and a lower alkyl group that may have a halogen atom as a substituent, R 4  represents a group -(T) l -N(R 14 )R 15  (wherein T and l are the same as described above, and R 14  and R 15 , together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 10-membered saturated heterocyclic ring; or R 14  and R 15  form a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    Item 55: The use according to item 54, wherein a target of the antitumor agent is a malignant tumor.
 
Item 56: The use according to item 55, wherein the malignant tumor is a solid tumor.
 
Item 57: The use according to item 55, wherein the malignant tumor is a hematological cancer.
 
Item 58: The use according to item 55, wherein the malignant tumor is lymphoma, leukemia, or myeloma.
 
Item 59: The antitumor agent according to any one of items 44 to 47, wherein R 14  and R 15 , together with the nitrogen atom to which they bind, bind to each other, directly or via a nitrogen atom to form a 6-membered saturated heterocyclic group that is substituted, on the heterocyclic ring, by a phenyl-substituted lower alkyl group that may be substituted, on the phenyl ring, by 1 or 2 group(s), as substituent(s), selected from the group consisting of a lower alkanoyl group, an amino group that may have a lower alkanoyl group as a substituent, a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, a lower alkoxy group that may have a halogen atom as a substituent, a phenyl lower alkoxy group, a hydroxyl group, and a lower alkylenedioxy group.
 
Item 60: The antitumor agent according to item 59, wherein the saturated heterocyclic group is a piperazinyl group that is substituted by a phenyl-substituted lower alkyl group that is substituted by a lower alkylenedioxy group on the phenyl ring.
 
Item 61: The antitumor agent according to item 59 or 60, wherein X 1  is a nitrogen atom and Y is an oxygen atom.
 
         [0030]    Specific examples of individual groups shown in the general formula (1) are as follows. 
         [0031]    Examples of the lower alkenylene group include linear or branched alkenylene groups having 2 to 6 carbon atoms and 1 to 3 double bonds such as vinylene, 1-propenylene, 1-methyl-1-propenylene, 2-methyl-1-propenylene, 2-propenylene, 2-butenylene, 1-butenylene, 3-butenylene, 2-pentenylene, 1-pentenylene, 3-pentenylene, 4-pentenylene, 1,3-butadienylene, 1,3-pentadienylene, 2-penten-4-ynylene, 2-hexenylene, 1-hexenylene, 5-hexenylene, 3-hexenylene, 4-hexenylene, 3,3-dimethyl-1-propenylene, 2-ethyl-1-propenylene, 1,3,5-hexatrienylene, 1,3-hexadienylene, and 1,4-hexadienylene groups. 
         [0032]    Examples of the lower alkynylene group include linear or branched alkynylene groups having 2 to 6 carbon atoms and 1 to 3 triple bonds such as ethynylene, 1-propynylene, 1-methyl-1-propynylene, 2-methyl-1-propynylene, 2-propynylene, 2-butynylene, 1-butynylene, 3-butynylene, 2-pentynylene, 1-pentynylene, 3-pentynylene, 4-pentynylene, 2-pentyn-4-ynylene, 2-hexynylene, 1-hexynylene, 5-hexynylene, 3-hexynylene, 4-hexynylene, 3,3-diethyl-1-propynylene, and 2-ethyl-1-propynylene groups. 
         [0033]    Examples of the lower alkoxy group include linear or branched alkoxy groups having 1 to 6 carbon atoms such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxyl, pentyloxy, and hexyloxy groups. 
         [0034]    Examples of the lower alkyl group include linear or branched alkyl groups having 1 to 6 carbon atoms such as methyl, ethyl, propyl, isopropyl, 2,2-dimethylpropyl, 1-ethylpropyl, butyl, isobutyl, tert-butyl, isopentyl, pentyl, and hexyl groups. 
         [0035]    Examples of the lower alkyl group which may have a lower alkoxy group as a substituent include, in addition to the above described lower alkyl groups, linear or branched alkyl groups having 1 to 6 carbon atoms which may have a linear or branched alkoxy group having 1 to 6 carbon atoms as a substituent such as methoxymethyl, 1-ethoxyethyl, 27-methoxyethyl, 2-propoxyethyl, 3-isopropoxypropyl, 4-butoxybutyl, 5-pentyloxypentyl, 6-hexyloxyhexyl, 1,1-dimethyl-2-methoxyethyl, 2-methyl-3-ethoxypropyl, and 3-methoxypropyl groups. 
         [0036]    Examples of the lower alkanoyl group include linear or branched alkanoyl groups having 1 to 6 carbon atoms such as formyl, acetyl, propionyl, butyryl, isobutyryl, pentanoyl, tert-butylcarbonyl, and hexanoyl groups. 
         [0037]    Examples of the phenyl lower alkyl group include phenylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as benzyl, 2-phenylethyl, 1-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 5-phenylpentyl, 6-phenylhexyl, 1,1-dimethyl-2-phenylethyl, and 2-methyl-3-phenylpropyl groups. 
         [0038]    Examples of the lower alkylene group include linear or branched alkylene groups having 1 to 6 carbon atoms such as methylene, ethylene, trimethylene, 2-methyltrimethylene, 2,2-dimethylethylene, 2,2-dimethyltrimethylene, 1-methyltrimethylene, methylmethylene, ethylmethylene, tetramethylene, pentamethylene, and hexamethylene groups. 
         [0039]    Examples of the lower alkenylene group which may have a phenyl group as a substituent include linear or branched alkenylene groups, which have 2 to 6 carbon atoms and 1 to 3 double bonds, and which may have a phenyl group as a substituent such as vinylene, 1-propenylene, 1-methyl-1-propenylene, 2-methyl-1-propenylene, 2-propenylene, 2-butenylene, 1-butenylene, 3-butenylene, 2-pentenylene, 1-pentenylene, 3-pentenylene, 4-pentenylene, 1,3-butadienylene, 1,3-pentadienylene, 2-pentene-4-ynylene, 2-hexenylene, 1-hexenylene, 5-hexenylene, 3-hexenylene, 4-hexenylene, 3,3-dimethyl-1-propenylene, 2-ethyl-1-propenylene, 1,3,5-hexatrienylene, 1,3-hexadienylene, 1,4-hexadienylene, 1-phenylvinylene, 3-phenyl-1-propenylene, 3-phenyl-1-methyl-1-propenylene, 3-phenyl-2-methyl-1-propenylene, 1-phenyl-2-propenylene, 1-phenyl-2-butenylene, 3-phenyl-1-butenylene, 1-phenyl-3-butenylene, 5-phenyl-2-pentenylene, 4-phenyl-1-pentenylene, 2-phenyl-3-pentenylene, 1-phenyl-4-pentenylene, 1-phenyl-1,3-butadienylene, 1-phenyl-1,3-pentadienylene, 1-phenyl-2-penten-4-ynylene, 1-phenyl-2-hexenylene, 3-phenyl-1-hexenylene, 4-phenyl-5-hexenylene, 6-phenyl-3-hexenylene, 5-phenyl-4-hexenylene, 1-phenyl-3,3-dimethyl-1-propenylene, 1-phenyl-2-ethyl-1-propenylene, 6-phenyl-1,3,5-hexatrienylene, 1-phenyl-1,3-hexadienylene, and 2-phenyl-1,4-hexadienylene groups. 
         [0040]    Examples of the lower alkylene group which may be substituted with a group selected from the group consisting of a lower alkoxy group and a phenyl group include, in addition to the above described lower alkylene groups, linear or branched alkylene groups having 1 to 6 carbon atoms which may be substituted with 1 or 2 groups selected from the group consisting of a linear or branched alkoxy group having 1 to 6 carbon atoms and a phenyl group such as methoxymethylene, 2-phenylethylene, 3-ethoxytrimethylene, 1-propoxy-2-methyltrimethylene, 1-phenyl-2,2-dimethylethylene, 3-phenyl-2,2-dimethyltrimethylene, 2-butoxy-1-methyltrimethylene, phenylmethylmethylene, 2-pentyloxyethylmethylene, 4-phenyl-2-hexyloxytetramethylene, 3-phenylpentamethylene, 5-phenylhexamethylene, ethoxymethylene, 1-phenylethylene, 3-phenyltrimethylehe, and 2-phenyl-1-methoxyethylene groups. 
         [0041]    Examples of the 5- to 15-membered monocyclic, bicyclic or tricyclic saturated or unsaturated heterocyclic group which has 1 to 4 nitrogen atoms, oxygen atoms or sulfur atoms include pyrrolidinyl, piperidinyl, piperazinyl, morpholino, pyridyl, 1,2,5,6-tetrahydropyridyl, 1,2,4-triazolyl, 1,2,3-triazolyl, 1,2,5-triazolyl, thiazolidinyl, 1,2,3,4-tetrazolyl, thienyl, quinolyl, 1,4-dihydroquinolyl, benzothiazolyl, pyrazyl, pyrimidyl, pyridazyl, 2H-pyrrolyl, pyrrolyl, 1,3,4-oxadiazolyl, tetrahydropyranyl, tetrahydrofuryl, furazanyl, carbostyryl, 3,4-dihydrocarbostyryl, 1,2,3,4-tetrahydroquinolyl, 1,2,3,4-tetrahydroisoquinolyl, indolyl, isoindolyl, indolinyl, benzoimidazolyl, benzooxazolyl, imidazolidinyl, isoquinolyl, quinazolidinyl, quinoxalinyl, cinnolinyl, phthalazinyl, carbazoyl, acridinyl, chromanyl, isoindolinyl, isochromanyl, pyrazolyl, imidazolyl, pyrazolidinyl, phenothiazinyl, benzofuryl, 2,3-dihydrobenzo[b]furyl, benzothienyl, phenoxathiinyl, phenoxazinyl, 4H-chromenyl, 1H-indazolyl, phenazinyl, xanthenyl, thianthrenyl, 2-imidazolinyl, 2-pyrrolinyl, furyl, oxazolyl, isooxazolyl, isooxazolidinyl, thiazolyl, isothiazolyl, pyranyl, 2-thiazolinyl, 2-pyrazolinyl, quinuclidinyl, 1,4-benzooxadinyl, 3,4-dihydro-2H-1,4-benzooxadinyl, 3,4-dihydro-2H-1,4-benzothiazinyl, 1,4-benzothiazinyl, 1,2,3,4-tetrahydroquinoxalinyl, 1,3-dithia-2,4-dihydronaphthalenyl, phenalthridinyl, 1,4-dithianaphthalenyl, dibenz[b,e]azepine, and 6,11-dihydro-5H-dibenz[b,e]azepine groups. 
         [0042]    Examples of the halogen atom include a fluorine atom, chlorine atom, bromine atom and iodine atom. 
         [0043]    Examples of the lower alkoxy group which may have a halogen atom as a substituent include linear or branched alkoxy groups having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, pentyloxy, hexyloxy, trifluoromethoxy, trichloromethoxy, chloromethoxy, bromomethoxy, fluoromethoxy, iodomethoxy, difluoromethoxy, dibromomethoxy, 2-chloroethoxy, 2,2,2-trifluoroethoxy, 2,2,2-trichloroethoxy, 3-chloropropoxy, 2,3-dichloropropoxy, 4,4,4-trichlorobutoxy, 4-fluorobutoxy, 5-chloropentyloxy, 3-chloro-2-methylpropoxy, 6-bromohexyloxy, and 5,6-dichlorohexyloxy groups. 
         [0044]    Examples of the lower alkyl group which may have a halogen atom as a substituent include, in addition to the above described lower alkyl groups, linear or branched alkyl groups having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents such as trifluoromethyl, trichloromethyl, chloromethyl, bromomethyl, fluoromethyl, iodomethyl, difluoromethyl, dibromomethyl, dichloromethyl, 2-chloroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 3-chloropropyl, 2,3-dichloropropyl, 4,4,4-trichlorobutyl, 4-fluorobutyl, 5-chloropentyl, 3-chloro-2-methylpropyl, 5-bromohexyl, and 5,6-dibromohexyl groups. 
         [0045]    Examples of the lower alkylsulfonyl group include linear or branched alkylsulfonyl groups having 1 to 6 carbon atoms such as methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, tert-butylsulfonyl, pentylsulfonyl, and hexylsulfonyl groups. 
         [0046]    Examples of the phenyl group which may be substituted, on the phenyl ring, with a lower alkyl group which may have a halogen atom include phenyl groups which may be substituted, on the phenyl ring, with 1 to 3 linear or branched alkyl groups having 1 to 56 carbon atoms which may have 1 to 3 halogen atoms such as phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-butylphenyl, 4-pentylphenyl, 4-hexylphenyl, 3,4-dimethylphenyl, 3,4-diethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4,5-trimethylphenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2-(bromomethyl)phenyl, 3-(2-chloroethyl)phenyl, 4-(2,3-dichloropropyl)phenyl, 4-(4-fluorobutyl)phenyl, 3-(5-chloropentyl)phenyl, 4-(5-bromohexyl)phenyl, 4-(5,6-dibromohexyl)phenyl, 3,4-di(trifluoromethyl)phenyl, 3,4-di(4,4,4-trichlorobutyl)phenyl, 2,4-di(3-chloro-2-methylpropyl)phenyl, 2,5-di(3-chloropropyl)phenyl, 2,6-di(2,2,2-trifluoroethyl)phenyl, 3,4,5-tri(trifluoromethyl)phenyl, 4-(2,2,2-trichloroethyl)phenyl, 2-methyl-4-trifluoromethylphenyl, and 3-ethyl-4-trichloromethyl groups. 
         [0047]    Examples of the lower alkylthio group include linear or branched alkylthio groups having 1 to 6 carbon atoms such as methylthio, ethylthio, propylthio, isopropylthio, butylthio, tert-butylthio, pentylthio, and hexylthio groups. 
         [0048]    Examples of the amino group which may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent include amino groups which may have 1 or 2 groups selected from the group consisting of linear or branched alkyl groups having 1 to 6 carbon atoms and linear or branched alkanoyl groups having 1 to 6 carbon atoms as substituents such as amino, methylamino, ethylamino, propylamino, isopropylamino, butylamino, tert-butylamino, pentylamino, hexylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, dipentylamino, dihexylamino, N-methyl-N-ethylamino, N-ethyl-N-propylamino, N-methyl-N-butylamino, N-methyl-N-hexylamino, N-acetylamino, N-formylamino, N-propionylamino, N-butyrylamino, N-isobutyrylamino, N-pentanoylamino, N-tert-butylcarbonylamino, N-hexanoylamino, diacetylamino, N-acetyl-N-methylamino, and N-acetyl-N-ethylamino groups. 
         [0049]    Examples of the naphthyl group which may be substituted on the naphthalene ring with 1 to 3 substituents selected from the group consisting of a lower alkyl group, a halogen atom, and an amino group which may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group include naphthyl groups which may have, on the naphthalene ring, 1 to 3 substituents selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms, a halogen atom, and an amino group which may have 1 or 2 substituents selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms and a linear or branched alkanoyl group having 1 to 6 carbon atoms such as (1- or 2-)naphthyl, 1-methyl-(2-, 3-, 4-, 5-, 6-, 7- or 8-)naphthyl, 2-ethyl-(1-, 3-, 4-, 5-, 6-, 7- or 8-)naphthyl, 3-n-propyl-(1-, 2-, 4-, 5-, 6-, 7- or 8-)naphthyl, 4-n-butyl-(1-, 2-, 3-, 5-, 6-, 7- or 8-)naphthyl, 4-methyl-(1-, 2-, 3-, 5-, 6-, 7- or 8-)naphthyl, 5-n-pentyl-(1-, 2-, 3-, 4-, 6-, 7- or 8-)naphthyl, 6-n-hexyl-(1-, 2-, 3-, 4-, 5-, 7- or 8-)naphthyl, 1,7-dimethyl-(2-, 3-, 4-, 5-, 6- or 8-)naphthyl, 1,2,8-trimethyl-(3-, 4-, 5-, 6- or 7-)naphthyl, 1-dimethylamino-(2-, 3-, 4-, 5-, 6-, 7- or 8-)naphthyl, 2-dimethylamino-(1-, 3-, 4-, 5-, 6-, 7- or 8-)naphthyl, 3-methylamino-(1-, 2-, 4-, 5-, 6-, 7- or 8-)naphthyl, 5-amino-(1-, 2-, 3-, 4-, 6-, 7- or 8-)naphthyl, 5-dimethylamino-(1-, 2-, 3-, 4-, 6-, 7- or 8-)naphthyl, 4-(N-methyl-N-ethylamino)-(1-, 2-, 3-, 5-, 6-, 7- or 8-)naphthyl, 1-methyl-2-dimethylamino-(3-, 4-, 5-, 6-, 7- or 8-)naphthyl, 1-chloro-(2-, 3-, 4-, 5-, 6-, 7- or 8-)naphthyl, and 1-acetylamino-(2-, 3-, 4-, 5-, 6-, 7- or 8-)naphthyl groups. 
         [0050]    Examples of the alkyl group which may have a lower alkoxy group as a substituent include, in addition to the above described lower alkyl groups which may have a lower alkoxy group as a substituent, linear or branched alkyl groups having 1 to 8 carbon atoms which may have a linear or branched alkoxy group having 1 to 6 carbon atoms as a substituent such as heptyl, 1-ethylpentyl, octyl, 7-methoxyheptyl, 1-ethoxyheptyl, 2-propoxyl-1-ethylpentyl, 3-isopropoxyoctyl, 7-butoxyheptyl, 8-pentyloxyoctyl, and 5-hexyloxy-1-ethylpentyl groups. 
         [0051]    Examples of the amino substituted lower alkyl group which may have a lower alkyl group include linear or branched alkyl groups having 1 to 6 carbon atoms substituted with an amino group which may have 1 or 2 linear or branched alkyl groups having 1 to 6 carbon atoms such as aminomethyl, 2-aminoethyl, 1-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl, 1,1-dimethyl-2-aminoethyl, 2-methyl-3-aminopropyl, methylaminomethyl, 1-ethylaminoethyl, 2-propylaminoethyl, 3-isopropylaminopropyl, 4-butylaminobutyl, 5-pentylaminopentyl, 6-hexylaminohexyl, dimethylaminomethyl, 2-diethylaminoethyl, 2-diisopropylaminoethyl, (N-ethyl-N-propylamino)methyl, and 2-(N-methyl-N-hexylamino)ethyl groups. 
         [0052]    Examples of the cycloalkyl group include cycloalkyl groups having 3 to 16 carbon atoms such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl, cyclotridecyl, cycloteradecyl, cyclopentadecyl, and cyclohexadecyl groups. 
         [0053]    Examples of the cycloalkyl group which may be substituted with a group selected from the group consisting of an amino substituted lower alkyl group which may have a lower alkyl group and a lower alkyl group which may have a halogen atom as a substituent on the cycloalkyl ring include, in addition to the above described cycloalkyl groups, cycloalkyl groups having 3 to 16 carbon atoms which may be substituted, on the cycloalkyl ring, with 1 to 3 groups selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms substituted with an amino group which may have 1 or 2 linear or branched alkyl groups having 1 to 6 carbon atoms and a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents such as 4-dimethylaminomethylcyclohexyl, 2-(aminomethyl)cyclopropyl, 3-(2-aminomethyl)cyclobutyl, 2-(1-aminoethyl)cyclopentyl, 3-(3-aminopropyl)cyclohexyl, 3-(4-aminobutyl)cycloheptyl, 4-(5-aminopentyl)cyclooctyl, 4-(6-aminohexyl)cyclohexyl, 2-(1,1-dimethyl-2-aminoethyl)cycloheptyl, 3-(2-methyl-3-aminopropyl)cyclopentyl, 3-(methylaminomethyl)cyclohexyl, 2-(1-ethylaminoethyl)cyclooctyl, 2-(2-propylaminoethyl)cyclohexyl, 3-(3-isopropylaminopropyl)cyclopentyl, 4-(4-butylaminobutyl)cycloheptyl, 2-(5-pentylaminopentyl)cyclohexyl, 2-(6-hexylaminohexyl)cyclopentyl, 3-(dimethylaminomethyl)cyclohexyl, 3-[(N-ethyl-N-propylamino)methyl]cycloheptyl, 4-[2-(N-methyl-N-hexylamino)ethyl]cyclooctyl, 4-dimethylaminomethylcyclononyl, 2-(aminomethyl)cyclodecyl, 3-(2-aminomethyl)cycloundecyl, 2-(1-aminoethyl)cyclododecyl, 3-(3-aminopropyl)cyclotridecyl, 3-(4-aminobutyl)cyclotetradecyl, 4-(5-aminopentyl)cyclopentadecyl, 4-(6-aminohexyl)cyclohexadecyl, 2-(1,1-dimethyl-2-aminoethyl)cyclononyl, 3-(2-methyl-3-aminopropyl)cyclodecyl, 3-(methylaminomethyl)cycloundecyl, 2-(1-ethylaminoethyl)cyclododecyl, 2-(2-propylaminoethyl)cyclotridecyl, 3-(3-isopropylaminopropyl)cyclotetradecyl, 4-(4-butylaminobutyl)cyclopentadecyl, 2-(5-pentylaminopentyl)cyclohexadecyl, 2-(6-hexylaminohexyl)cyclononyl, 3-(dimethylaminomethyl)cyclododecyl, 3-[(N-ethyl-N-propylamino)methyl]cyclodecyl, 4-[2-(N-methyl-N-hexylamino)ethyl]cyclohexadecyl, 2,2-dimethylcyclopropyl, and 2-trifluoromethylcyclopropyl groups. 
         [0054]    Examples of the lower alkenyl group include linear or branched alkenyl groups having 2 to 6 carbon atoms and 1 to 3 double bonds such as vinyl, 1-propenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 2-propenyl, 2-butenyl, 1-butenyl, 3-butenyl, 2-pentenyl, 1-pentenyl, 3-pentenyl, 4-pentenyl, 1,3-butadienyl, 1,3-pentadienyl, 2-penten-4-ynyl, 2-hexenyl, 1-hexenyl, 5-hexenyl, 3-hexenyl, 4-hexenyl, 3,3-dimethyl-1-propenyl, 2-ethyl-1-propenyl, 1,3,5-hexatrienyl, 1,3-hexadienyl, and 1,4-hexadienyl groups. 
         [0055]    Examples of the lower alkenyl group which may have a halogen atom as a substituent include, in addition to the above described lower alkenyl groups, linear or branched alkenyl groups having 2 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents and which have 1 to 3 double bonds such as 3,3,3-trifluoro-1-propenyl, 2-bromovinyl, 3-chloro-1-propenyl, 3-iodo-1-methyl-1-propenyl, 3-fluoro-2-methyl-1-propenyl, 2-butenyl, 4,4,3-trichloro-1-butenyl, 4,4-difluoro-3-butenyl, 5-fluoro-2-pentenyl, 5,5,3-tribromo-1-pentenyl, 5-chloro-3-pentenyl, 5,5,5-trifluoro-4-pentenyl, 4-chloro-1,3-butadienyl, 5-fluoro-1,3-pentadienyl, 5-bromo-2-penten-4-ynyl, 6-fluoro-2-hexenyl, 6,6,5-trifluoro-1-hexenyl, 6-chloro-5-hexenyl, 5-bromo-3-hexenyl, 6-chloro-4-hexenyl, 3,3-dimethyl-2-chloro-1-propenyl, 3-fluoro-2-ethyl-1-propenyl, 6-chloro-1,3,5-hexatrienyl, 6-bromo-1,3-hexadienyl, and 6-fluoro-1,4-hexadienyl groups. 
         [0056]    Examples of the benzoyl group (which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkyl group which may have a halogen atom as a substituent and a halogen atom) include benzoyl groups (which may have, on the phenyl ring, with 1 to 3 substituents selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms and which may have 1 to 3 halogen atoms as substituents and a halogen atom) such as benzoyl, 3,4-difluorobenzoyl, 2-fluorobenzoyl, 3-bromobenzoyl, 4-iodobenzoyl, 4-methylbenzoyl, 2-methylbenzoyl, 3-methylbenzoyl, 2-ethylbenzoyl, 3-ethylbenzoyl, 4-ethylbenzoyl, 4-isopropylbenzoyl, 3-butylbenzoyl, 4-pentylbenzoyl, 4-hexylbenzoyl, 3,4-dimethylbenzoyl, 3,4-diethylbenzoyl, 2,4-dimethylbenzoyl, 2,5-dimethylbenzoyl, 2,6-dimethylbenzoyl, 3,4,5-trimethylbenzoyl, 2-trifluoromethylbenzoyl, 3-trifluoromethylbenzoyl, 4-trifluoromethylbenzoyl, 2-(bromomethyl)benzoyl, 3-(2-chloroethyl)benzoyl, 4-(2,3-dichloropropyl)benzoyl, 4-(4-fluorobutyl)benzoyl, 3-(5-chloropentyl)benzoyl, 4-(5-bromohexyl)benzoyl, 4-(5,6-dibromohexyl)benzoyl, 3,4-di(trifluoromethyl)benzoyl, 3,4-di(4,4,4-trichlorobutyl)benzoyl, 2,4-di(3-chloro-2-methylpropyl)benzoyl, 2,5-di(3-chloropropyl)benzoyl, 2,6-di(2,2,2-trifluoroethyl)benzoyl, 3,4,5-tri(trifluoromethyl)benzoyl, 4-(2,2,2-trichloroethyl)benzoyl, 2-methyl-4-trifluoromethylbenzoyl, 3-ethyl-4-trichloromethylbenzoyl, 2-chloro-4-trifluoromethylbenzoyl, 3-ethyl-4-fluorobenzoyl, 3-fluoro-4-trichloromethylbenzoyl, 2-methyl-3-trifluoromethyl-4-trifluoromethylbenzoyl, 3-fluorobenzoyl, 4-fluorobenzoyl, 2-bromobenzoyl, 4-bromobenzoyl, 2-iodobenzoyl, 3-iodobenzoyl, 2,3-dibromobenzoyl, 2,4-diiodobenzoyl, 2,5-difluorobenzoyl, 2,6-dichlorobenzoyl, 2,4,6-trichlorobenzoyl, 2,4-difluorobenzoyl, 3,5-difluorobenzoyl, 2,6-difluorobenzoyl, 2-chlorobenzoyl, 3-chlorobenzoyl, 4-chlorobenzoyl, 2,3-dichlorobenzoyl, 2,4-dichlorobenzoyl, 2,5-dichlorobenzoyl, 3,4-dichlorobenzoyl, 2,6-dichlorobenzoyl, 3,5-dichlorobenzoyl, 2,4,6-trifluorobenzoyl, and 2,4-difluorobenzoyl groups. 
         [0057]    Examples of the halogen substituted lower alkyl group include linear or branched alkyl groups having 1 to 6 carbon atoms which have 1 to 3 halogen atoms as substituents such as trifluoromethyl, trichloromethyl, chloromethyl, bromomethyl, fluoromethyl, iodomethyl, difluoromethyl, dibromomethyl, 2-chloroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 3-chloropropyl, 2,3-dichloropropyl, 4,4,4-trichlorobutyl, 4-fluorobutyl, 5-chloropentyl, 3-chloro-2-methylpropyl, 5-bromohexyl, and 5,6-dibromohexyl groups. 
         [0058]    Examples of the lower alkylenedioxy group include linear or branched alkylene groups having 1 to 4 carbon atoms such as methylenedioxy, ethylenedioxy, trimethylenedioxy, and tetramethylenedioxy groups. 
         [0059]    Examples of the amino group which may have a substituent selected from the group consisting of a lower alkyl group, a lower alkanoyl group, a benzoyl group and a cycloalkyl group include amino groups which may have 1 or 2 substituents selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkanoyl group having 1 to 6 carbon atoms, a benzoyl group, and a cycloalkyl group having 3 to 16 carbon atoms such as amino, methylamino, ethylamino, propylamino, isopropylamino, butylamino, tert-butylamino, pentylamino, hexylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, dipentylamino, dihexylamino, N-methyl-N-ethylamino, N-ethyl-N-propylamino, N-methyl-N-butylamino, N-methyl-N-hexylamino, N-methyl-N-acetylamino, N-acetylamino, N-formylamino, N-propionylamino, N-butyrylamino, N-isobutyrylamino, N-pentanoylamino, N-tert-butylcarbonylamino, N-hexanoylamino, N-ethyl-N-acetylamino, N-benzoylamino, N-ethyl-N-benzoylamino, N-methyl-N-benzoylamino, N-acetyl-N-benzoylamino, cyclopropylamino, cyclobutylamino, cyclopentylamino, cyclohexylamino, cycloheptylamino, cyclooctylamino, N-methyl-N-cyclohexylamino, N-methyl-N-cyclopentylamino, N-methyl-N-cycloheptylamino, N-cyclohexyl-N-acetylamino, N-cyclopentyl-N-benzoylamino, cyclononylamino, cyclodecylamino, cyclododecylamino, cyclotridecylamino, cyclotetradecylamino, cyclopentadecylamino, N-methyl-N-cyclohexadecylamino, N-methyl-N-cyclononylamino, N-methyl-N-cyclodecylamino, N-cycloundecyl-N-acetylamino, and N-cyclohexadecyl-N-benzoyl groups. 
         [0060]    Examples of the lower alkanoyl group which may have a halogen atom as a substituent include, in addition to the above described lower alkanoyl groups, linear or branched alkanoyl groups having 2 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents such as 2,2,2-trifluoroacetyl, 2,2,2-trichloroacetyl, 2-chloroacetyl, 2-bromoacetyl, 2-fluoroacetyl, 2-iodoacetyl, 2,2-difluoroacetyl, 2,2-dibromoacetyl, 3,3,3-trifluoropropionyl, 3,3,3-trichloropropionyl, 3-chloropropionyl, 2,3-dichloropropionyl, 4,4,4-trichlorobutyryl, 4-fluorobutyryl, 5-chloropentanoyl, 3-chloro-2-methylpropionyl, 6-bromohexanoyl, and 5,6-dibromohexanoyl groups. 
         [0061]    Examples of the lower alkoxycarbonyl group include linear or branched alkoxycarbonyl groups having 1 to 6 carbon atoms such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl, and hexyloxycarbonyl groups. 
         [0062]    Examples of the lower alkanoyloxy group include linear or branched alkanoyloxy groups having 2 to 6 carbon atoms such as acetyloxy, propionyloxy, butyryloxy, isobutyryloxy, pentanoyloxy, tert-butylcarbonyloxy, and hexanoyloxy groups. 
         [0063]    Examples of the 5- or 6-membered saturated or unsaturated heterocyclic group having 1 to 4 nitrogen atoms, oxygen atoms or sulfur atoms include pyrrolidinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino, pyridyl, 1,2,5,6-tetrahydropyridyl, thienyl, pyrazyl, pyrimidyl, pyridazyl, pyrrolyl, 2H-pyrrolyl, imidazolidinyl, pyrazolyl, imidazolyl, pyrazolidinyl, furazanyl, 2-imidazolinyl, imidazolidinyl, 2-pyrrolinyl, furyl, oxazolyl, isooxazolidinyl, isooxazolyl, thiazolyl, isothiazolyl, pyranyl, 2-pyrazolidinyl, 1,2,4-triazolyl, 1,2,3-triazolyl, 1,2,5-triazolyl, thiazolidinyl, 2-thiazolinyl, 1,2,3,4-tetrazolyl, 1,3,4-oxadiazolyl, tetrahydropyranyl, and tetrahydrofuryl groups. 
         [0064]    Examples of the 5- to 7-membered saturated heterocyclic ring formed by binding R 11  and R 12  each other, together with nitrogen atoms bound to them, through or not through a nitrogen atom, a sulfur atom or an oxygen atom, include pyrrolidinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino, and homopiperazinyl groups. 
         [0065]    Examples of the imidazolyl lower alkyl group include imidazolylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1, 2, 4 or 5-)imidazolylmethyl, 2-[(1, 2, 4 or 5-)imidazolyl]ethyl, 1-[(1, 2, 4 or 5-)imidazolyl]ethyl, 3-[(1, 2, 4 or 5-)imidazolyl]propyl, 4-[(1, 2, 4 or 5-)imidazolyl]butyl, 5-[(1, 2, 4 or 5-)imidazolyl]pentyl, 6-[(1, 2, 4 or 5-)imidazolyl]hexyl, 1,1-dimethyl-2-[(1, 2, 4 or 5-)imidazolyl]ethyl, and 2-methyl-3-[(1, 2, 4 or 5-)imidazolyl]propyl groups. 
         [0066]    Examples of the 1,2,4-triazolyl lower alkyl group include 1,2,4-triazolylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1, 3 or 5-)1,2,4-triazolylmethyl, 2-[(1, 3 or 5-)1,2,4-triazolyl]ethyl, 1-[(1, 3 or 5-)1,2,4-triazolyl]ethyl, 3-[(1, 3 or 5-)1,2,4-triazolyl]propyl, 4-[(1, 3 or 5-)1,2,4-triazolyl]butyl, 5-[(1, 3 or 5-)1,2,4-triazolyl]pentyl, 6-[(1, 3 or 5-)1,2,4-triazolyl]hexyl, 1,1-dimethyl-2-[(1, 3 or 5-)1,2,4-triazolyl]ethyl, and 2-methyl-3-[(1, 3 or 5-)1,2,4-triazolyl]propyl groups. 
         [0067]    Examples of the 1,2,3-triazolyl lower alkyl group include 1,2,3-triazolylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1, 4 or 5-)1,2,3-triazolylmethyl, 2-[(1, 4 or 5-)1,2,3-triazolyl]ethyl, 1-[(1, 4 or 5-)1,2,3-triazolyl]ethyl, 3-[(1, 4 or 5-)1,2,3-triazolyl]propyl, 4-[(1, 4 or 5-)1,2,3-triazolyl]butyl, 5-[(1, 4 or 5-)1,2,3-triazolyl]pentyl, 6-[(1, 4 or 5-)1,2,3-triazolyl]hexyl, 1,1-dimethyl-2-[(1, 4 or 5-)1,2,3-triazolyl]ethyl, and 2-methyl-3-[(1, 4 or 5-)1,2,3-triazolyl]propyl groups. 
         [0068]    Examples of the 1,2,5-triazolyl lower alkyl group include 1,2,5-triazolylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 56 carbon atoms such as (1, 3 or 4-)1,2,5-triazolylmethyl, 2-[(1, 3 or 4-)1,2,5-triazolyl]ethyl, 1-[(1, 3 or 4-)1,2,5-triazolyl]ethyl, 3-[(1, 3 or 4-)1,2,5-triazolyl]propyl, 4-[(1, 3 or 4-)1,2,5-triazolyl]butyl, 5-[(1, 3 or 4-)1,2,5-triazolyl]pentyl, 6-[(1, 3 or 4-)1,2,5-triazolyl]hexyl, 1,1-dimethyl-2-[(1, 3 or 4-)1,2,5-triazolyl]ethyl, and 2-methyl-3-[(1, 3 or 4-)1,2,5-triazolyl]propyl groups. 
         [0069]    Examples of the pyrazolyl lower alkyl group include pyrazolylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1, 3, 4 or 5-)pyrazolylmethyll, 2-[(1, 3, 4 or 5-)pyrazolyl]ethyl, 1-[(1, 3, 4 or 5-)pyrazolyl]ethyl, 3-[(1, 3, 4 or 5-)pyrazolyl]propyl, 4-[(1, 3, 4 or 5-)pyrazolyl]butyl, 5-[(1, 3, 4 or 5-)pyrazolyl]pentyl, 6-[(1, 3, 4 or 5-)pyrazolyl]hexyl, 1,1-dimethyl-2-[(1, 3, 4 or 5-)pyrazolyl]ethyl, and 2-methyl-3-[(1, 3, 4 or 5-)pyrazolyl]propyl groups. 
         [0070]    Examples of the pyrimidinyl lower alkyl group which may have an oxo group as a substituent on the pyrimidine ring include pyrimidinylalkyl groups which may have 1 to 3 oxo groups as substituents on the pyrimidine ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2, 4, 5 or 6-)pyrimidinylmethyl, 2-[(2, 4, 5 or 6-)pyrimidinyl]ethyl, 1-[(2, 4, 5 or 6-)pyrimidinyl]ethyl, 3-[(2, 4, 5 or 6-)pyrimidinyl]propyl, 4-[(2, 4, 5 or 6-)pyrimidinyl]butyl, 5-[(2, 4, 5 or 6-)pyrimidinyl]pentyl, 6-[(2, 4, 5 or 6-)pyrimidinyl]hexyl, 1,1-dimethyl-2-[(2, 4, 5 or 6-)pyrimidinyl]ethyl, 2-methyl-3-[(2, 4, 5 or 6-)pyrimidinyl]propyl, [(1, 3, 4 or 5-)2,6-dioxopyrimidinyl]methyl, [(1, 3, 4, 5 or 6-)2-oxopyrimidinyl]methyl, [(1, 2, 4 or 5-)6-oxopyrimidinyl]methyl, [(1, 2, 5 or 6-)4-oxopyrimidinyl]methyl, [(1, 3, 5 or 6-)2,4-dioxopyrimidinyl]methyl, 2-[(4 or 6-)2,5-dioxopyrimidinyl]ethyl, 1-[(1, 3, 4 or 5-)2,6-dioxopyrimidinyl]ethyl, 3-[(1, 3 or 5-)2,4,6-trioxopyrimidinyl]propyl, 4-[(1, 3, 4 or 5-)2,6-dioxopyrimidinyl]butyl, 5-[(4 or 6-)2,5-dioxopyrimidinyl]pentyl, 6-[(1, 3, 5 or 6-)2,4-dioxopyrimidinyl]hexyl, 1,1-dimethyl-[(1, 3, 4 or 5-)2,6-dioxopyrimidinyl]ethyl, and 2-methyl-3-[(1, 3, 4 or 5-)2,6-dioxopyrimidinyl]propyl groups. 
         [0071]    Examples of the 3,5-dioxoisoxazolidin-4-ylidene lower alkyl group include 3,5-dioxoisoxazolidin-4-ylidenealkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as 3,5-dioxoisoxazolidin-4-ylidenemethyl, 3,5-dioxoisoxazolidin-4-ylideneethyl, 3,5-dioxoisoxazolidin-4-ylidenepropyl, 3,5-dioxoisoxazolidin-4-ylideneisopropyl, 3,5-dioxoisoxazolidin-4-ylidenebutyl, 3,5-dioxoisoxazolidin-4-ylidenepentyl, and 3,5-dioxoisoxazolidin-4-ylidenehexyl groups. 
         [0072]    Examples of the 1,2,4-oxadiazolyl lower alkyl group which may have a lower alkyl group as a substituent on the 1,2,4-oxadiazol ring include 1,2,4-oxadiazolylalkyl groups which may have a linear or branched alkyl group having 1 to 6 carbon atoms as a substituent on the 1,2,4-oxadiazol ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (3 or 5-)1,2,4-oxadiazolylmethyl, 2-[(3 or 5-)1,2,4-oxadiazolyl]ethyl, 1-[(3 or 5-)1,2,4-oxadiazolyl]ethyl, 3-[(3 or 5-)1,2,4-oxadiazolyl]propyl, 4-[(3 or 5-)1,2,4-oxadiazolyl]butyl, 5-[(3 or 5-)1,2,4-oxadiazolyl]pentyl, 6-[(3 or 5-)1,2,4-oxadiazolyl]hexyl, 1,1-dimethyl-2-[(3 or 5-)1,2,4-oxadiazolyl]ethyl, 2-methyl-3-[(3 or 5-)1,2,4-oxadiazolyl]propyl, 5-methyl-3-(1,2,4-oxadiazolyl)methyl, 3-ethyl-2-[5-(1,2,4-oxadiazolyl)]ethyl, 1-[3-propyl-5-(1,2,4-oxadiazolyl)]ethyl, 3-[5-butyl-3-(1,2,4-oxadiazolyl)]propyl, 4-[3-pentyl-5-(1,2,4-oxadiazolyl)]butyl, 5-[5-hexyl-3-(1,2,4-oxadiazolyl)]pentyl, 6-[3-methyl-5-(1,2,4-oxadiazolyl)]hexyl, 1,1-dimethyl-2-[5-isopropyl-3-(1,2,4-oxadiazolyl)]ethyl, and 2-methyl-3-[3-isobutyl-5-(1,2,4-oxadiazolyl)]propyl groups. 
         [0073]    Examples of the thiazolydinyl lower alkyl group which may have an oxo group as a substituent on the thiazolydine ring include thiazolydinylalkyl groups which may have 1 to 3 oxo groups as substituents on the thiazolydine ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2, 3, 4 or 5-)thiazolidinylmethyl, 2-[(2, 3, 4 or 5-)thiazolidinyl]ethyl, 1-[(2, 3, 4 or 5-)thiazolidinyl]ethyl, 3-[(2, 3, 4 or 5-)thiazolidinyl]propyl, 4-[(2, 3, 4 or 5-)thiazolidinyl]butyl, 5-[(2, 3, 4 or 5-)thiazolidinyl]pentyl, 6-[(2, 3, 4 or 5-)thiazolidinyl]hexyl, 1,1-dimethyl-2-[(2, 3, 4 or 5-)thiazolidinyl]ethyl, 2-methyl-3-[(2, 3, 4 or 5-)thiazolidinyl]propyl, 2,4-dioxo-5-thiazolidinylmethyl, 2-[2-oxo-(3, 4 or 5-)thiazolidinyl]ethyl, 1-[4-oxo-(2, 3 or 5-)thiazolidinyl]ethyl, 3-[5-oxo-(2, 3 or 4-)thiazolidinyl]propyl, 4-[2,5-dioxo-(3 or 4-)thiazolidinyl]butyl, 5-[2,4,5-trioxo-3-thiazolidinyl]pentyl, 6-[4,5-dioxo-(2 or 3-)thiazolidinyl]hexyl, 1,1-dimethyl-2-[2,4-dioxo-(3 or 5-)thiazolidinyl]ethyl, 2-methyl-3-[2,4-dioxo-(3 or 5-)thiazolidinyl]propyl, and 3-[2,4-dioxo-(3 or 5-)thiazolidinyl]propyl groups. 
         [0074]    Examples of the phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring include, in addition to the above described phenyl lower alkyl groups, phenylalkyl groups which may have a linear or branched alkylenedioxy group having 1 to 4 carbon atoms as a substituent on the phenyl ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as 3,4-methylenedioxybenzyl, 3,4-trimethylenedioxybenzyl, 2-(2,3-ethylenedioxyphenyl)ethyl, 1-(3,4-trimethylenedioxyphenyl)ethyl, 3-(2,3-tetramethylenedioxyphenyl)propyl, 4-(3,4-methylenedioxyphenyl)butyl, 5-(2,3-ethylenedioxyphenyl)pentyl, 6-(3,4-trimethylenedioxyphenyl)hexyl, 1,1-dimethyl-2-(2,3-methylenedioxyphenyl)ethyl, and 2-methyl-3-(3,4-ethylenedioxyphenyl)propyl groups. 
         [0075]    Examples of the lower alkoxycarbonyl lower alkyl group include alkoxycarbonylalkyl groups whose alkoxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as methoxycarbonylmethyl, ethoxycarbonylmethyl, 2-methoxycarbonylethyl, 2-ethoxycarbonylethyl, 1-ethoxycarbonylethyl, 3-methoxycarbonylpropyl, 3-ethoxycarbonylpropyl, 4-ethoxycarbonylbutyl, 5-isopropoxycarbonylpentyl, 6-propoxycarbonylhexyl, 1,1-dimethyl-2-butoxycarbonylethyl, 2-methyl-3-tert-butoxycarbonylpropyl, 2-pentyloxycarbonylethyl, and hexyloxycarbonylmethyl groups. 
         [0076]    Examples of the carboxy lower alkyl group include carboxyalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as carboxymethyl, 2-carboxyethyl, 1-carboxyethyl, 3-carboxypropyl, 4-carboxybutyl, 5-carboxypentyl, 6-carboxyhexyl, 1,1-dimethyl-2-carboxyethyl, and 2-methyl-3-carboxypropyl groups. 
         [0077]    Examples of the morpholino substituted lower alkanoyl group include morpholino substituted alkanoyl groups whose alkanoyl moiety is a linear or branched alkanoyl group having 2 to 6 carbon atoms such as 2-[(2, 3 or 4-)morpholino]acetyl group, 3-[(2, 3 or 4-)morpholino]propionyl, 2-[(2, 3 or 4-)morpholino]propionyl, 4-[(2, 3 or 4-)morpholino]butyryl, 5-[(2, 3 or 4-)morpholino]pentanoyl, 6-[(2, 3 or 4-)morpholino]hexanoyl, 2,2-dimethyl-2-[(2, 3 or 4-)morpholino]propionyl, and 2-methyl-3-[(2, 3 or 4-)morpholino]propionyl groups. 
         [0078]    Examples of the piperazinylcarbonyl lower alkyl group which may be substituted on the piperazine ring with a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring include piperazinylcarbonylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms and which may be substituted on the piperazine ring with 1 to 3 phenylalkyl groups which may have a linear or branched alkylenedioxy group having 1 to 4 carbon atoms as a substituent on the phenyl group and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(1, 2 or 3-)piperazinyl]carbonylmethyl, 2-[(1, 2 or 3-)piperazinyl]carbonylethyl, 1-[(1, 2 or 3-)piperazinyl]carbonylethyl, 3-[(1, 2 or 3-)piperazinyl]carbonylpropyl, 4-[(1, 2 or 3-)piperazinyl]carbonylbutyl, 5-[(1, 2 or 3-)piperazinyl]carbonylpentyl, 6-[(1, 2 or 3-)piperazinyl]carbonylhexyl, 1,1-dimethyl-2-[(1, 2 or 3-)piperazinyl]carbonylethyl, 2-methyl-3-[(1, 2 or 3-)piperazinyl]carbonylpropyl, (4-benzyl-1-piperazinylcarbonyl)methyl, 2-[4-(2-phenylethyl)-1-piperazinylcarbonyl]ethyl, 1-[4-(3-phenylpropyl)-1-piperazinylcarbonyl]ethyl, 3-[4-(4-phenylbutyl)-1-piperazinylcarbonyl]propyl, 4-[4-(5-phenylpentyl)-1-piperazinylcarbonyl]butyl, 5-[4-(6-phenylpropyl)-1-piperazinylcarbonyl]pentyl, 6-(4-benzyl-1-piperazinylcarbonyl)hexyl, 1,1-dimethyl-2-(4-benzyl-1-piperazinylcarbonyl)ethyl, 2-methyl-3-(4-benzyl-1-piperazinylcarbonyl)propyl, [4-(3,4-methylenedioxybenzyl)-1-piperazinylcarbonyl]methyl, 2-{4-[2-(2,3-ethylenedioxyphenyl)ethyl]-1-piperazinylcarbonyl}ethyl, 1-{4-[3-(3,4-trimethylenedioxyphenyl)propyl]-1-piperazinylcarbonyl}ethyl, 3-{4-[4-(2,3-tetramethylenedioxyphenyl)butyl]-1-piperazinylcarbonyl}propyl, 4-{4-[5-(3,4-methylenedioxyphenyl)pentyl]-1-piperazinylcarbonyl}butyl, 5-{4-[3-(2,3-ethylenedioxyphenyl)propyl]-1-piperazinylcarbonyl}pentyl, 6-[4-(3,4-trimethylenedioxybenzyl)-1-piperazinylcarbonyl]hexyl, 1,1-dimethyl-2-[4-(2,3-tetramethylenedioxybenzyl)-1-piperazinylcarbonyl]ethyl, 2-methyl-3-[4-(3,4-methylenedioxybenzyl)-1-piperazinylcarbonyl]propyl, (3,4-dibenzyl-1-piperazinylcarbonyl)methyl, (3,4,5-tribenzyl-1-piperazinylcarbonyl)methyl, [2,4-di(3,4-methylenedioxybenzyl)-1-piperazinylcarbonyl]methyl, [2,4,6-tri(3,4-methylenedioxybenzyl)-1-piperazinylcarbonyl]methyl, and [3-benzyl-4-(3,4-methylenedioxybenzyl)-1-piperazinylcarbonyl]methyl groups. 
         [0079]    Examples of the piperazinyl lower alkanoyl group which may be substituted on the piperazine ring with a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring include piperazinylalkanoyl groups whose alkanoyl moiety is a linear or branched alkanoyl group having 2 to 6 carbon atoms and which may be substituted on the piperazine ring with 1 to 3 phenylalkyl groups which may have a linear or branched alkylenedioxy group having 1 to 4 carbon atoms as a substituent on the phenyl ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms, such as 2-[(1, 2 or 3-)piperazinyl]acetyl, 3-[(1, 2 or 3-)piperazinyl]propionyl, 2-[(1, 2 or 3-)piperazinyl]propionyl, 4-[(1, 2 or 3-)piperazinyl]butyryl, 5-[(1, 2 or 3-)piperazinyl]pentanoyl, 6-[(1, 2 or 3-)piperazinyl]hexanoyl, 2,2-dimethyl-3-[(1, 2 or 3-)piperazinyl]propionyl, 2-methyl-3-[(1, 2 or 3-)piperazinyl]propionyl, 2-(4-benzyl-1-piperazinyl)acetyl, 3-[4-(2-phenylethyl)-1-piperazinyl]propionyl, 2-[4-(3-phenylpropyl)-1-piperazinyl]propionyl, 4-[4-(4-phenylbutyl)-1-piperazinyl]butyryl, 5-[4-(5-phenylpentyl)-1-piperazinyl]pentanoyl, 6-[4-(6-phenylpropyl)-1-piperazinyl]hexanoyl, 6-(4-benzyl-1-piperazinyl)hexanoyl, 2,2-dimethyl-3-(4-benzyl-1-piperazinyl)propionyl, 2-methyl-3-(4-benzyl-1-piperazinyl)propionyl, 2-[4-(3,4-methylenedioxybenzyl)-1-piperazinyl]acetyl, 3-{4-[2-(2,3-ethylenedioxyphenyl)ethyl]-1-piperazinyl}propionyl, 2-{4-[3-(3,4-trimethylenedioxyphenyl)propyl]-1-piperazinyl}propionyl, 4-{4-[4-(2,3-tetramethylenedioxyphenyl)butyl]-1-piperazinyl}butyryl, 5-{4-[5-(3,4-methylenedioxyphenyl)pentyl]-1-piperazinyl}pentanoyl, 5-{4-[3-(2,3-ethylenedioxyphenyl)propyl]-1-piperazinyl}pentanoyl, 6-[4-(3,4-trimethylenedioxybenzyl)-1-piperazinyl]hexanoyl, 2,2-dimethyl-3-[4-(2,3-tetramethylenedioxybenzyl)-1-piperazinyl]propionyl, 2-methyl-3-[4-(3,4-methylenedioxybenzyl)-1-piperazinyl]propionyl, 2-(3,4-dibenzyl-1-piperazinyl)acetyl, 2-(3,4,5-tribenzyl-1-piperazinyl)acetyl, 2-[2,4-di(3,4-methylenedioxybenzyl)-1-piperazinyl]acetyl, 2-[2,4,6-tri(3,4-methylenedioxybenzyl)-1-piperazinyl]acetyl, and 2-[3-benzyl-4-(3,4-methylenedioxybenzyl)-1-piperazinyl]acetyl groups. 
         [0080]    Examples of the morpholinocarbonyl substituted lower alkyl group include morpholinocarbonylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(2, 3 or 4-)morpholino]carbonylmethyl, 2-[(2, 3 or 4-)morpholino]carbonylethyl, 1-[(2, 3 or 4-)morpholino]carbonylethyl, 3-[(2, 3 or 4-)morpholino]carbonylpropyl, 4-[(2, 3 or 4-)morpholino]carbonylbutyl, 5-[(2, 3 or 4-)morpholino]carbonylpentyl, 6-[(2, 3 or 4-)morpholino]carbonylhexyl, 1,1-dimethyl-2-[(2, 3 or 4-)morpholino]carbonylethyl, and 2-methyl-3-[(2, 3 or 4-)morpholino]carbonylpropyl groups. 
         [0081]    Examples of the imidazolyl lower alkanoyl group include imidazolylalkanoyl groups whose alkanoyl moiety is a linear or branched alkanoyl group having 2 to 6 carbon atoms such as 2-[(1, 2, 4 or 5-)imidazolyl]acetyl, 3-[(1, 2, 4 or 5-)imidazolyl]propionyl, 2-[(1, 2, 4 or 5-)imidazolyl]propionyl, 4-[(1, 2, 4 or 5-)imidazolyl]butyryl, 5-[(1, 2, 4 or 5-)imidazolyl]pentanoyl, 6-[(1, 2, 4 or 5-)imidazolyl]hexanoyl, 2,2-dimethyl-3-[(1, 2, 4 or 5-)imidazolyl]propionyl, and 2-methyl-3-[(1, 2, 4 or 5-)imidazolyl]propionyl groups. 
         [0082]    Examples of the cycloalkylcarbonyl group include cycloalkylcarbonyl groups whose cycloalkyl moiety is a cycloalkyl group having 3 to 16 carbon atoms such as cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl, cycloheptylcarbonyl, cyclooctylcarbonyl, cyclononylcarbonyl, cyclodecylcarbonyl, cycloundecylcarbonyl, cyclododecylcarbonyl, cyclotridecylcarbonyl, cyclotetradecylcarbonyl, cyclopentadecylcarbonyl, and cyclohexadecylcarbonyl groups. 
         [0083]    Examples of the amino substituted lower alkanoyl group which may have a lower alkyl group as a substituent include linear or branched alkanoyl groups having 2 to 6 carbon atoms substituted with an amino group which may have 1 or 2 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents such as aminoacetyl, 2-aminopropionyl, 3-aminopropionyl, 4-aminobutyryl, 5-aminopentanoyl, 6-aminohexanoyl, 2,2-dimethyl-3-aminopropionyl, 2-methyl-3-aminopropionyl, methylaminoacetyl, 2-ethylaminopropionyl, 3-propylaminopropionyl, 3-isopropylaminopropionyl, 4-butylaminobutyryl, 5-pentylaminopentanoyl, 6-hexylaminohexanoyl, dimethylaminoacetyl, 3-diisopropylaminopropionyl, (N-ethyl-N-propylamino)acetyl, and 2-(N-methyl-N-hexylamino)acetyl groups. 
         [0084]    Examples of the lower alkylene group which may have a hydroxyl group as a substituent include, in addition to the above described lower alkylene groups, linear or branched alkylene groups having 1 to 6 carbon atoms which may have 1 to 3 hydroxyl groups as substituents such as 1-hydroxymethylene, 2-hydroxyethylene, 1-hydroxyethylene, 2-hydroxytrimethylene, 3-hydroxytrimethylene, 1-hydroxytrimethylene, 3-hydroxy-2-methyltrimethylene, 1-hydroxy-2-methyltrimethylene, 3-hydroxy-2,2-dimethyltrimethylene, 1-hydroxy-2,2-dimethyltrimethylene, 3-hydroxy-1-methyltrimethylene, 2-hydroxy-1-methyltrimethylene, 1-hydroxymethylmethylene, hydroxymethylmethylene, 2-hydroxymethyltrimethylene, 2-hydroxymethyl-2-methyltrimethylene, (2-hydroxyethyl)methylene, (1-hydroxyethyl)methylene, 4-hydroxytetramethylene, 2-hydroxytetramethylene, 3-hydroxytetramethylene, 1-hydroxytetramethylene, 5-hydroxypentamethylene, 4-hydroxypentamethylene, 3-hydroxypentamethylene, 2-hydroxypentamethylene, 1-hydroxypentamethylene, 6-hydroxyhexamethylene, 5-hydroxyhexamethylene, 4-hydroxyhexamethylene, 3-hydroxyhexamethylene, 2-hydroxyhexamethylene, 1-hydroxyhexamethylene, 1,2-dihydroxytrimethylene, 2,2,4-trihydroxytetramethylene, 1,2,6-trihydroxyhexamethylene, and 3,4,5-trihydroxypentamethylene groups. 
         [0085]    Examples of the alkyl group which may have a hydroxyl group as a substituent include, in addition to the above described lower alkyl groups, linear or branched alkyl groups having 1 to 16 carbon atoms which may have 1 to 3 hydroxyl groups as substituents such as heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, 1-methylhexyl, hexadecyl, hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxypentyl, 5-hydroxypentyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, and 2-methyl-3-hydroxypropyl groups. 
         [0086]    Examples of the hydroxyl group substituted alkyl group include linear or branched alkyl groups having 1 to 16 carbon atoms and 1 to 3 hydroxyl groups as substituents such as hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxypentyl, 5-hydroxypentyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, and 2-methyl-3-hydroxypropyl groups. 
         [0087]    Examples of the cycloalkyl group which may have a substituent selected from the group consisting of a hydroxyl group and a lower alkyl group include, in addition to the above described cycloalkyl groups, cycloalkyl groups having 3 to 16 carbon atoms which may have 1 to 3 substituents selected from the group consisting of a hydroxyl group and a linear or branched alkyl group having 1 to 6 carbon atoms such as 2-hydroxycyclopropyl, 3-hydroxycyclobutyl, 3-hydroxycyclopentyl, 2-hydroxycyclohexyl, 4-hydroxycyclohexyl, 3-hydroxycycloheptyl, 4-hydroxycyclooctyl, 5-hydroxycyclononyl, 3-hydroxycyclodecyl, 4-hydroxycycloundecyl, 5-hydroxycyclododecyl, 6-hydroxycyclotridecyl, 7-hydroxycyclotetradecyl, 6-hydroxycyclopentadecyl, 8-hydroxycyclohexadecyl, 2,4-dihydroxycyclohexyl, 2,4,6-trihydroxycyclohexyl, 1-methylcyclopentyl, 2-ethylcyclopropyl, 3-n-propylcyclobutyl, 2-n-butylcyclohexyl, 4-n-pentylcycloheptyl, 4-n-hexylcyclooctyl, 2,3-dimethylcyclohexyl, 2,3,4-trimethylcyclohexyl, and 2-methyl-4-hydroxycyclohexyl groups. 
         [0088]    Examples of the phenoxy lower alkyl group include phenoxyalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as phenoxymethyl, 2-phenoxyethyl, 1-phenoxyethyl, 3-phenoxypropyl, 4-phenoxybutyl, 1,1-dimethyl-2-phenoxyethyl, 5-phenoxypentyl, 6-phenoxyhexyl, 1-phenoxyisopropyl, and 2-methyl-3-phenoxypropyl groups. 
         [0089]    Examples of the amino lower alkoxy group which may have a lower alkyl group as a substituent include linear or branched alkoxy groups having 1 to 6 carbon atoms substituted with an amino group which may have 1 or 2 linear or branched alkyl groups having 1 to 6 carbon atoms such as aminomethoxy, 2-aminoethoxy, 1-aminoethoxy, 3-aminopropoxy, 4-aminobutoxy, 5-aminopentyloxy, 6-aminohexyloxy, 1,1-dimethyl-2-aminoethoxy, 2-methyl-3-aminopropoxy, methylaminomethoxy, 1-ethylaminoethoxy, 2-propylaminoethoxy, 3-isopropylaminopropoxy, 4-butylaminobutoxy, 5-pentylaminopentyloxy, 6-hexylaminohexyloxy, dimethylaminomethoxy, 2-diethylaminoethoxy, 2-diisopropylaminoethoxy, (N-ethyl-N-propylamino)methoxy, and 2-(N-methyl-N-hexylamino)ethoxy groups. 
         [0090]    Examples of the hydroxyl group substituted lower alkyl group include linear or branched alkyl groups having 1 to 6 carbon atoms which have 1 to 3 hydroxyl groups as substituents such as hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxypentyl, 5-hydroxypentyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, and 2-methyl-3-hydroxypropyl groups. 
         [0091]    Examples of the amino group which may have a lower alkylsulfonyl as a substituent include amino groups which may have 1 or 2 linear or branched alkylsulfonyl groups having 1 to 6 carbon atoms as substituents such as amino, methylsulfonylamino, ethylsulfonylamino, propylsulfonylamino, isopropylsulfonylamino, butylsulfonylamino, tert-butylsulfonylamino, pentylsulfonylamino, hexylsulfonylamino, dimethylsulfonylamino, diethylsulfonylamino, dipropylsulfonylamino, dibutylsulfonylamino, dipentylsulfonylamino, dihexylsulfonylamino, N-methylsulfonyl-N-ethylsulfonylamino, N-ethylsulfonyl-N-propylsulfonylamino, N-methylsulfonyl-N-butylsulfonylamino, and N-methylsulfonyl-N-hexylsulfonylamino groups. 
         [0092]    Examples of the lower alkynyl group include linear or branched alkynyl groups having 2 to 6 carbon atoms such as ethynyl, 2-propynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 2-pentynyl, and 2-hexynyl groups. 
         [0093]    Examples of the anilino group which may have a halogen atom as a substituent on the phenyl ring include anilino groups which may have 1 to 3 halogen atoms as substituents on the phenyl ring such as anilino, 2-fluoroanilino, 3-fluoroanilino, 4-fluoroanilino, 2-bromoanilino, 3-bromoanilino, 4-bromoanilino, 2-iodoanilino, 3-iodoanilino, 4-iodoanilino, 2,3-dibromoanilino, 2,4-diiodoanilino, 2,5-difluoroanilino, 2,6-dichloroanilino, 2,4,6-trichloroanilino, 2,6-difluoroanilino, 3,5-difluoroanilino, 2,6-difluoroanilino, 2-chloroanilino, 3-chloroanilino, 4-chloroanilino, 2,3-dichloroanilino, 2,4-dichloroanilino, 2,5-dichloroanilino, 3,4-dichloroanilino, 2,6-dichloroanilino, 3,5-dichloroanilino, 2,4,6-trifluoroanilino, 2,4-difluoroanilino, and 3,4-difluoroanilino groups. 
         [0094]    Examples of the piperazinyl group which may have a lower alkyl group as a substituent on the piperazine ring include piperazinyl groups which may have 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents on the piperazine ring such as (1-, 2- or 3-)piperazinyl, 4-methyl-(1-, 2- or 3-)piperazinyl, 2,3-dimethyl-(1- or 5-)piperazinyl, and 2,3,4-trimethyl-(1-, 5- or 6-)piperazinyl groups. 
         [0095]    Examples of the pyrrolidinyl group which may have an oxo group as a substituent on the pyrrolidine ring include pyrrolidinyl groups which may have 1 or 2 oxo groups as substituents on the pyrrolidine ring such as (1-, 2- or 3-)pyrrolidinyl, 2-oxo-(1-, 3-, 4- or 5-)pyrrolidinyl, 3-oxo-(1-, 2-, 4- or 5-)pyrrolidinyl, 2,3-dioxo-(1-, 4- or 5-)pyrrolidinyl, and 2,5-dioxo-(1-, 3- or 4-)pyrrolidinyl groups. 
         [0096]    Examples of the lower alkanoyl amino group include linear or branched alkanoyl amino groups having 2 to 6 carbon atoms which have 1 to 3 halogen atoms as substituents such as acetyl amino, propionyl amino, butyryl amino, pentanoyl amino, 2-methylpropionyl amino, and hexanoyl amino groups. 
         [0097]    Examples of the phenyl group which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a lower alkyl group; a lower alkoxy group which may have a halogen atom as a substituent; a halogen atom; an amino lower alkoxy group which may have a lower alkyl group as a substituent; a hydroxyl group substituted lower alkyl group; a phenyl lower alkyl group; a lower alkynyl group; an amino group which may have a lower alkylsulfonyl group as a substituent; a lower alkylthio group; a cycloalkyl group; a phenylthio group; an adamantyl group; an anilino group which may have a halogen atom as a substituent on the phenyl ring; a lower alkoxycarbonyl group; a piperazinyl group which may have a lower alkyl group as a substituent on the piperazine ring; a lower alkanoylamino group; a cyano group; a pyrrolidinyl group which may have an oxo group as a substituent on the pyrrolidine ring; and a phenoxy group include phenyl groups which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms; a linear or branched alkoxy group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms; a halogen atom; an aminoalkoxy group whose alkoxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms and which may have 1 or 2 linear or branched alkyl groups having 1 to 6 carbon atom as substituents; a linear or branched alkyl group having 1 to 6 carbon atoms and 1 to 3 hydroxyl groups as substituents; a phenylalkyl group whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms; a linear or branched alkynyl group having 2 to 6 carbon atoms; an amino group which may have 1 or 2 linear or branched alkylsulfonyl groups having 1 to 6 carbon atoms as substituents; a linear or branched alkylthio group having 1 to 6 carbon atoms; a cycloalkyl group having 3 to 16 carbon atoms; a phenylthio group; an adamantyl group; an anilino group which may have 1 to 3 halogen atoms as substituents on the phenyl ring; a linear or branched alkoxycarbonyl group having 1 to 6 carbon atoms; an amino group which may have 1 or 2 linear or branched alkanoyl groups having 2 to 6 carbon atoms; a cyano group; a piperazinyl group which may have 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents on the piperazine ring; a pyrrolidinyl group which may have 1 or 2 oxo groups as substituents on the pyrrolidine ring; and a phenoxy group such as phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 2-isopropylphenyl, 4-isopropylphenyl, 3-butylphenyl, 4-pentylphenyl, 4-hexylphenyl, 3,4-dimethylphenyl, 3,4-diethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4,5-trimethylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 4-isopropoxyphenyl, 3-butoxyphenyl, 4-pentyloxyphenyl, 4-hexyloxyphenyl, 3,4-dimethoxyphenyl, 3,4-diethoxyphenyl, 2,4-dimethoxyphenyl, 2,5-dimethoxyphenyl, 2,6-dimethoxyphenyl, 3,4,5-trimethoxyphenyl, 2-trifluoromethoxyphenyl, 3-trifluoromethoxyphenyl, 4-triflupromethoxyphenyl, 2-(bromomethoxy)phenyl, 3-(2-chloroethoxy)phenyl, 4-(2,3-dichloropropoxy)phenyl, 4-(4-fluorobutoxy)phenyl, 3-(5-chloropentyloxy)phenyl, 4-(5-bromohexyloxy)phenyl, 4-(5,6-dibromohexyloxy)phenyl, 3,4-di(trifluoromethoxy)phenyl, 3,4-di(4,4,4-trichlorobutoxy)phenyl, 2,4-di(3-chloro-2-methoxypropyl)phenyl, 2,5-di(3-chloropropoxy)phenyl, 2,6-di(2,2,2-trifluoroethoxy)phenyl, 3,4,5-tri(trifluoromethoxy)phenyl, 4-(2,2,2-trichloroethoxy)phenyl, 2-methyl-4-trifluoromethoxyphenyl, 3-ethyl-4-trichloromethoxyphenyl, 2-methoxy-4-trifluoromethoxyphenyl, 3-ethoxy-4-trichloromethoxyphenyl, 2-methyl-3-trifluoromethoxy-4-trifluoromethoxyphenyl, 2-phenoxyphenyl, 3-phenoxyphenyl, 4-phenoxyphenyl, 2,3-diphenoxyphenyl, 3,4-diphenoxyphenyl, 2,6-diphenoxyphenyl, 3,4,5-triphenoxyphenyl, 2-methyl-4-phenoxyphenyl, 3-ethyl-4-phenoxyphenyl, 2-methoxy-4-phenoxyphenyl, 3-ethoxy-4-phenoxyphenyl, 2-methyl-3-phenoxy-4-trifluoromethoxyphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 2,5-dichlorophenyl, 3,4-dichlorophenyl, 2,6-dichlorophenyl, 3,5-dichlorophenyl, 2,4,6-trichlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2,5-difluorophenyl, 2,4-difluorophenyl, 3,4-difluorophenyl, 3,5-difluorophenyl, 2,6-difluorophenyl, 2,4,6-trifluorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 2-iodophenyl, 3-iodophenyl, 4-iodophenyl, 2,3-dibromophenyl, 2,4-diiodophenyl, 4-methylthiophenyl, 4-cyclohexylphenyl, 4-chloro-2-anilinophenyl, 2-(4-chloro anilino)-5-ethoxy carbonylphenyl, 4-[2-(N,N-diethylamino)ethoxy]phenyl, 4-(4-methyl-1-piperazinyl)phenyl, 4-(2-oxo-1-pyrrolidinyl)phenyl, 4-methylsulfonylaminophenyl, 4-(2-hydroxyethyl)phenyl, 4-benzylphenyl, 4-ethynylphenyl, 4-phenylthiophenyl, 4-(1-adamantyl)phenyl, 5-acetylamino-2-chlorophenyl, 2-propanoylaminophenyl, 3-cyanophenyl, 2-cyanophenyl, 4-cyanophenyl, 3,4-dicyanophenyl, and 3,4,5-tricyanophenyl groups. 
         [0098]    Examples of the phenyl lower alkyl group which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a halogen atom, a lower alkoxy group which may have a halogen atom as a substituent, and a lower alkyl group include, in addition to the above described phenyl lower alkyl groups, phenylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms and which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a halogen atom, a linear or branched alkoxy group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents, and a linear or branched alkyl group having 1 to 6 carbon atoms such as 4-fluorobenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 2-(2-fluorophenyl)ethyl, 2-(4-fluorophenyl)ethyl, 2-(4-chlorophenyl)ethyl, 3,4-dibromobenzyl, 3,4-diiodobenzyl, 2,4-difluorobenzyl, 2,5-dichlorobenzyl, 2,6-dichlorobenzyl, 3,4,5-trifluorobenzyl, 3-(4-chlorophenyl)propyl, 1-(2-bromophenyl)ethyl, 4-(3-fluorophenyl)butyl, 5-(4-iodophenyl)pentyl, 6-(4-chlorophenyl)hexyl, 1,1-dimethyl-2-(3-fluorophenyl)ethyl, 2-methyl-3-(4-chlorophenyl)propyl, 2-methylbenzyl, 2-(3-methylphenyl)ethyl, 3-(4-methylphenyl)propyl, 1-(2-ethylphenyl)ethyl, 4-(3-ethylphenyl)butyl, 5-(4-ethylphenyl)pentyl, 6-(4-isopropylphenyl)hexyl, 1,1-dimethyl-2-(3-butylphenyl)ethyl, 2-methyl-3-(4-pentylphenyl)propyl, 4-hexylbenzyl, 3,4-dimethylbenzyl, 3,4-diethylbenzyl, 2,4-dimethylbenzyl, 2,5-dimethylbenzyl, 2,6-dimethylbenzyl, 3,4,5-trimethylbenzyl, 2-methoxybenzyl, 2-(2-methoxyphenyl)ethyl, 2-(3-methoxyphenyl)ethyl, 2-(4-methoxyphenyl)ethyl, 4-methoxybenzyl, 1-(2-ethoxyphenyl)ethyl, 3-(3-ethoxyphenyl)propyl, 4-(4-ethoxyphenyl)butyl, 5-(4-isopropoxyphenyl)pentyl, 6-(3-butoxyphenyl)hexyl, 1,1-dimethyl-2-(4-pentyloxyphenyl)ethyl, 2-methyl-3-(4-hexyloxyphenyl)propyl, 3,4-dimethoxybenzyl, 3,4-diethoxybenzyl, 2,4-dimethoxybenzyl, 2,5-dimethoxybenzyl, 2,6-dimethoxybenzyl, 3,4,5-trimethoxybenzyl, 2-trifluoromethoxybenzyl, 3-trifluoromethoxybenzyl, 4-trifluoromethoxybenzyl, 2-[2-(bromomethoxy)phenyl]ethyl, 1-[3′-(2-chloroethoxy)phenyl]ethyl, 3-[4-(2,3-dichloropropoxy)phenyl]propyl, 4-[4-(4-fluorobutoxy)phenyl]butyl, 5-[3-(5-chloropentyloxy)phenyl]pentyl, 6-[4-(5-bromohexyloxy)phenyl]hexyl, 1,1-dimethyl-2-[4-(5,6-dibromohexyloxy)phenyl]ethyl, 3,4-di(trifluoromethoxy)benzyl, 3,4-di(4,4,4-trichlorobutoxy)benzyl, 2,4-di(3-chloro-2-methoxypropyl)benzyl, 2,5-di(3-chloropropoxy)benzyl, 2,6-di(2,2,2-trifluoroethoxy)benzyl, 3,4,5-tri(trifluoromethoxy)benzyl, 4-(2,2,2-trichloroethoxy)benzyl, 2-methyl-4-trifluoromethoxybenzyl, 3-ethyl-4-trichloromethoxybenzyl, 2-methoxy-4-trifluoromethoxybenzyl, 3-ethoxy-4-trichloromethoxybenzyl, 2-methyl-3-trifluoromethoxy-4-trifluoromethoxybenzyl, 2-chloro-3-methylbenzyl, 4-fluoro-2-trifluoromethoxybenzyl, and 3-chloro-2-methyl-4-methoxybenzyl groups. 
         [0099]    Examples of the phenyl lower alkyl group which has a lower alkylenedioxy group as a substituent on the phenyl ring include phenylalkyl groups which have a linear or branched alkylenedioxy group having 1 to 4 carbon atoms as a substituent on the phenyl ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as 3,4-methylenedioxybenzyl, 3,4-trimethylenedioxybenzyl, 2-(2,3-ethylenedioxyphenyl)ethyl, 1-(3,4-trimethylenedioxyphenyl)ethyl, 3-(2,3-tetramethylenedioxyphenyl)propyl, 4-(3,4-methylenedioxyphenyl)butyl, 5-(2,3-ethylenedioxyphenyl)pentyl, 6-(3,4-trimethylenedioxyphenyl)hexyl, 1,1-dimethyl-2-(2,3-methylenedioxyphenyl)ethyl, and 2-methyl-3-(3,4-ethylenedioxyphenyl)propyl groups. 
         [0100]    Examples of the amino group which may have a lower alkanoyl group as a substituent include amino groups which may have a linear or branched alkanoyl group having 1 to 6 carbon atoms as a substituent such as amino, N-acetylamino, N-formylamino, N-propionylamino, N-butyrylamino, N-isobutyrylamino, N-pentanoylamino, N-tert-butylcarbonylamino, and N-hexanoylamino groups. 
         [0101]    Examples of the 1,2,3,4-tetrahydroquinolyl group which may have, on the tetrahydroquinoline ring, 1 to 3 substituents selected from the group consisting of an oxo group, a lower alkoxy group, and a lower alkylenedioxy group include 1,2,3,4-tetrahydroquinolyl groups which may have, on the tetrahydroquinoline ring, 1 to 3 substituents selected from the group consisting of an oxo group, a linear or branched alkoxy group having 1 to 6 carbon atoms, and a linear or branched alkylenedioxy group having 1 to 4 carbon atoms such as (1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl, 2-oxo-(1, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl, 2-oxo-6,7-methylenedioxy-(1, 3, 4, 5 or 8-)1,2,3,4-tetrahydroquinolyl, 4-oxo-(1, 2, 3, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl, 2,4-dioxo-(1, 3, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl, 2,4-dioxo-6,7-methylenedioxy-(1, 3, 5 or 8-)2,3,4-tetrahydroquinolyl, 5,6-ethylenedioxy-(1, 2, 3, 4, 7 or 8-)1,2,3,4-tetrahydroquinolyl, 7,8-trimethylenedioxy-(1, 2, 3, 4, 5 or 6-)1,2,3,4-tetrahydroquinolyl, 6,7-tetramethylenedioxy-(1, 2, 3, 4, 5 or 8-)1,2,3,4-tetrahydroquinolyl, 5-methoxy-2-oxo-(1, 3, 4, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl, and 2-oxo-6,7-ethylenedioxy-(1, 3, 4, 5 or 8-)1,2,3,4-tetrahydroquinolyl groups. 
         [0102]    Examples of the cycloalkyl lower alkyl group include cycloalkylalkyl groups having 3 to 16 carbon atoms whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as cyclopropylmethyl, cyclohexylmethyl, 2-cyclopropylethyl, 1-cyclobutylethyl, 3-cyclopentylpropyl, 4-cyclohexylbutyl, 5-cycloheptylpentyl, 6-cyclooctylhexyl, 1,1-dimethyl-2-cyclononylethyl, 2-methyl-3-cyclodecylpropyl, cycloundecylmethyl, 2-cyclododecylethyl, 1-cyclotridecylethyl, 3-cyclotetradecylpropyl, 4-cyclopentadecylbutyl, and 5-cyclohexadecylpentyl groups. 
         [0103]    Examples of the pyridyl lower alkyl group include pyridylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2, 3 or 4-)pyridylmethyl, 2-[(2, 3 or 4-)pyridyl]ethyl, 1-[(2, 3 or 4-)pyridyl]ethyl, 3-[(2, 3 or 4-)pyridyl]propyl, 4-[(2, 3 or 4-)pyridyl]butyl, 1,1-dimethyl-2-[(2, 3 or 4-)pyridyl]ethyl, 5-[(2, 3 or 4-)pyridyl]pentyl, 6-[(2, 3 or 4-)pyridyl]hexyl, 1-[(2, 3 or 4-)pyridyl]isopropyl, and 2-methyl-3-[(2, 3 or 4-)pyridyl]propyl groups. 
         [0104]    Examples of the amino group substituted lower alkyl group which may have a substituent selected from the group consisting of a lower alkyl group and a lower alkanoyl group include linear or branched alkyl groups having 1 to 6 carbon atoms and an amino group which may have 1 or 2 substituents selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms and a linear or branched alkanoyl group having 1 to 6 carbon atoms such as aminomethyl, 2-aminoethyl, 1-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl, 1,1-dimethyl-2-aminoethyl, 2-methyl-3-aminopropyl, methylaminomethyl, 1-ethylaminoethyl, 2-propylaminoethyl, 3-isopropylaminopropyl, 4-butylaminobutyl, 5-pentylaminopentyl, 6-hexylaminohexyl, dimethylaminomethyl, 2-diisopropylaminoethyl, (N-ethyl-N-propylamino)methyl, 2-(N,N-dimethylamino)ethyl, 2-(N-methyl-N-hexylamino)ethyl, formylaminomethyl, acetylaminomethyl, 1-propionylaminoethyl, 2-acetylaminoethyl, 3-butyrylaminopropyl, 4-pentanoylaminobutyl, 5-hexanoylaminopentyl, 6-acetylaminohexyl, N-methyl-N-acetylaminomethyl, 2-(N-ethyl-N-propanoylamino)ethyl, (N-ethyl-N-butyrylamino)methyl, 2-(N-methyl-N-hexanoylamino)ethyl, and 3-(N,N-dimethylamino)propyl groups. 
         [0105]    Examples of the lower alkoxy lower alkyl group include linear or branched alkyl groups having 1 to 6 carbon atoms which have a linear or branched alkoxy group having 1 to 6 carbon atoms, as a substituent such as methoxymethyl, 1-ethoxyethyl, 2-methoxyethyl, 2-propoxyethyl, 3-isopropoxypropyl, 4-butoxybutyl, 5-pentyloxypentyl, 6-hexyloxyhexyl, 1,1-dimethyl-2-methoxyethyl, 2-methyl-3-ethoxypropyl, and 3-methoxypropyl groups. 
         [0106]    Examples of the 1,2,3,4-tetrahydroisoquinolylcarbonyl substituted lower alkyl group include 1,2,3,4-tetrahydroisoquinolylcarbonyl-alkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroisoquinolylcarbonylmethyl, 2-[(1, 2, 3, 4, 5, 6, 7or 8-)1,2,3,4-tetrahydroisoquinolylcarbonyl]ethyl, 1-[((1, 2, 3, 4, 5, 6, 7 or 8-)1, 2, 3, 4-tetrahydroisoquinolylcarbonyl)ethyl, 3-[(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroisoquinolylcarbonyl]propyl, 4-[(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroisoquinolylcarbonyl]butyl, 1,1-dimethyl-2-[(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroisoquinolylcarbonyl]ethyl, 5-[(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroisoquinolylcarbonyl]pentyl, 6-[(1, 2, 3, 4, 5, 6, 7 or 8-) 1,2,3,4-tetrahydroisoquinolylcarbonyl]hexyl, 1-[(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroisoquinolylcarbonyl]isopropyl, and 2-methyl-3-[(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroisoquinolylcarbonyl]propyl groups. 
         [0107]    Examples of the piperidinylcarbonyl group which may have, on the piperidine ring, a substituent selected from the group consisting of a lower alkoxycarbonyl group, a phenyl lower alkyl group, and a furyl lower alkyl group include piperidinylcarbonyl groups which may have, on the piperidine ring, 1 to 3 substituents selected from the group consisting of an alkoxycarbonyl group whose alkoxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms, a phenylalkyl group whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms, and a furylalkyl group whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1, 2, 3 or 4-)piperidinylcarbonyl, 1-benzyl-(2, 3 or 4-)piperidinylcarbonyl, 1-(2 or 3-)furylmethyl-(2, 3 or 4-)piperidinylcarbonyl, 1-(2-phenylethyl)-(2, 3 or 4-)piperidinylcarbonyl, 1-{2-[(1 or 2-)furyl]ethyl}-(2, 3 or 4-)piperidinylcarbonyl, 1-(1-phenylethyl)-(2, 3 or 4-)piperidinylcarbonyl, 1-{3-[(1 or 2-)furyl]propyl]}-(2, 3 or 4-)piperidinylcarbonyl, 1-(3-phenylpropyl)-(2, 3 or 4-)piperidinylcarbonyl, 1-{1-[(1 or 2-)furyl]ethyl]}-(2, 3 or 4-)piperidinylcarbonyl, 1-(4-phenylbutyl)-(2, 3 or 4-)piperidinylcarbonyl, 1-{4-[(1 or 2-)furyl]butyl]}-(2, 3 or 4-)piperidinylcarbonyl, 1-(5-phenylpentyl)-(2, 3 or 4-)piperidinylcarbonyl, 1-{5-[(1 or 2-)furyl]pentyl]}-(2, 3 or 4-)piperidinylcarbonyl, 1-(6-phenylhexyl)-(2, 3 or 4-)piperidinylcarbonyl, 1-{6-[(1 or 2-)furyl]hexyl]}-(2, 3 or 4-)piperidinylcarbonyl, 1,2-dibenzyl-(3, 4, 5 or 6-)piperidinylcarbonyl, 1,3-di(1 or 2-)furylmethyl-(2, 4, 5 or 6-)piperidinylcarbonyl, 1,3,5-tribenzyl-(2, 4 or 6-)piperidinylcarbonyl, 1,2,6-tri(1 or 2-)furylmethyl-(3, 4 or 5-)piperidinylcarbonyl, 1-benzyl-3-(1 or 2-)furylmethyl-(2, 4, 5 or 6-)piperidinylcarbonyl, 1-{1-[(1 or 2-)furyl]ethyl]}-(2, 3 or 4-)piperidinylcarbonyl, 1-methoxycarbonyl-(2, 3 or 4-)piperidinylcarbonyl, 1-ethoxycarbonyl-(2, 3 or 4-)piperidinylcarbonyl, 1-propoxycarbonyl-(2, 3 or 4-)piperidinylcarbonyl, 1-butoxycarbonyl-(2, 3 or 4-)piperidinylcarbonyl, 1-tert-butoxycarbonyl-(2, 3 or 4-)piperidinylcarbonyl, 1-pentyloxycarbonyl-(2, 3 or 4-)piperidinylcarbonyl, 1-hexyloxycarbonyl-(2, 3 or 4-)piperidinylcarbonyl, 1,2-dimethoxycarbonyl-(3, 4, 5 or 6-)piperidinylcarbonyl, 1,2,6-triethoxycarbonyl-(3, 4 or 5-)piperidinylcarbonyl, 1-(1 or 2-)furylmethyl-3-tert-butoxycarbonyl-(3, 4, 5 or 6-)piperidinylcarbonyl, 1-benzyl-2-methoxycarbonyl-(2, 4, 5 or 6-)piperidinylcarbonyl, and 1-(1 or 2-)furylmethyl-2,4-dimethoxycarbonyl-(3, 5 or 6-)piperidinylcarbonyl groups. 
         [0108]    Examples of the thiazolidinyl lower alkanoyl group which may have an oxo group as a substituent on the thiazolidine ring include thiazolidinylalkanoyl groups which may have 1 to 3 oxo groups as substituents on the thiazolidine ring and whose alkanoyl moiety is a linear or branched alkanoyl group having 2 to 6 carbon atoms such as 2-[(2, 3, 4 or 5-)thiazolidinyl]acetyl, 3-[(2, 3, 4 or 5-)thiazolidinyl]propionyl, 2-[(2, 3, 4 or 5-)thiazolidinyl]propionyl, 4-[(2, 3, 4 or 5-)thiazolidinyl]butyryl, 5-[(2, 3, 4 or 5-)1,2,4-thiazolidinyl]pentanoyl, 6-[(2, 3, 4 or 5-)thiazolidinyl]hexanoyl, 2,2-dimethyl-3-[(2, 3, 4 or 5-)thiazolidinyl]propionyl, 2-methyl-3-[(2, 3, 4 or 5-)thiazolidinyl]propionyl, 2,4-dioxo-(3 or 5-)thiazolidinylacetyl, 3-[2-oxo-(3, 4 or 5-)thiazolidinyl]propionyl, 2-[4-oxo-(2, 3 or 5-)thiazolidinyl]propionyl, 4-[5-oxo-(2, 3 or 4-)thiazolidinyl]butyryl, 5-[2,5-dioxo-(3 or 4-)thiazolidinyl]pentanoyl, 6-[2,4,5-trioxo-3-thiazolidinyl]hexanoyl, 2-[4,5-dioxo-(2 or 3-)thiazolidinyl]acetyl, 2,2-dimethyl-3-[2,4-dioxo-(3 or 5-)thiazolidinyl]propionyl, and 2-methyl-3-[2,4-dioxo-(3 or 5-)thiazolidinyl]propionyl groups. 
         [0109]    Examples of the piperidinyl group which may be substituted on the piperidine ring with a group selected from the group consisting of a lower alkoxycarbonyl group, a phenyl lower alkyl group, a lower alkyl group, a benzoyl group and a furyl lower alkyl group include piperidinyl groups which may be substituted on the piperidine ring with 1 to 3 groups selected from the group consisting of an alkoxycarbonyl group whose alkoxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms, a phenylalkyl group whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkyl group having 1 to 6 carbon atoms, a benzoyl group, and a furylalkyl group whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1, 2, 3 or 4-)piperidinyl, 1-benzyl-(2, 3 or 4-)piperidinyl, 1-(2 or 3-)furylmethyl-(2, 3 or 4-)piperidinyl, 1-(2-phenylethyl)-(2, 3 or 4-)piperidinyl, 1-(2-[(1 or 2-)furyl]ethyl}-(2, 3 or 4-)piperidinyl, 1-(1-phenylethyl)-(2, 3 or 4-)piperidinyl, 1-{3-[(1 or 2-)furyl]propyl]}-(2, 3 or 4-)piperidinyl, 1-(3-phenylpropyl)-(2, 3 or 4-)piperidinyl, 1-{1-[(1 or 2-)furyl]ethyl]}-(2, 3 or 4-)piperidinyl, 1-(4-phenylbutyl)-(2, 3 or 4-)piperidinyl, 1-{4-[(1 or 2-)furyl]butyl]}-(2, 3 or 4-)piperidinyl, 1-(5-phenylpentyl)-(2, 3 or 4-)piperidinyl, 1-{5-[(1 or 2-)furyl]pentyl]}-(2, 3 or 4-)piperidinyl, 1-(6-phenylhexyl)-(2, 3 or 4-)piperidinyl, 1-{6-[(1 or 2-)furyl]hexyl]}-(2, 3 or 4-)piperidinyl, 1,2-dibenzyl-(3, 4, 5 or 6-)piperidinyl, 1,3-di(1 or 2-)furylmethyl-(2, 4, 5 or 6-)piperidinyl, 1,3,5-tribenzyl-(2, 4 or 6-)piperidinyl, 1,2,6-tri(1 or 2-)furylmethyl-(3, 4 or 5-)piperidinyl, 1-benzyl-3-(1 or 2-)furylmethyl-(2, 4, 5 or 6-)piperidinyl, 1-{1-[(1 or 2-)furyl]ethyl]}-(2, 3 or 4-)piperidinyl, 1-benzoyl-(2, 3 or 4-)piperidinyl, 1,2-dibenzoyl-(3, 4, 5 or 6-)piperidinyl, 1,3,5-tribenzoyl-(2, 4 or 6-)piperidinyl, 1-methyl-(2, 3 or 4-)piperidinyl, 1-ethyl-(2, 3 or 4-)piperidinyl, 1-propyl-(2, 3 or 4-)piperidinyl, 1-isopropyl-(2, 3 or 4-)piperidinyl, 1-butyl-(2, 3 or 4-)piperidinyl, 1-isobutyl-(2, 3 or 4-)piperidinyl, 1-tert-butyl-(2, 3 or 4-)piperidinyl, 1-pentyl-(2, 3 or 4-)piperidinyl, 1-hexyl-(2, 3 or 4-)piperidinyl, 1,2-dimethyl-(3, 4, 5 or 6-)piperidinyl, 1,2,6-trimethyl-(3, 4 or 5-)piperidinyl, 1-methyl-3-benzyl-(3, 4, 5 or 6-)piperidinyl, 1-benzoyl-2-methyl-(2, 4, 5 or 6-)piperidinyl, 1-(1 or 2-)furylmethyl-2,4-dimethyl-(3, 5 or 6-)piperidinyl, 1-methoxycarbonyl-(2, 3 or 4-)piperidinyl, 1-ethoxycarbonyl-(2, 3 or 4-)piperidinyl, 1-propoxycarbonyl-(2, 3 or 4-)piperidinyl, 1-butoxycarbonyl-(2, 3 or 4-)piperidinyl, 1-tert-butoxycarbonyl-(2, 3 or 4-)piperidinyl, 1-pentyloxycarbonyl-(2, 3 or 4-)piperidinyl, 1-hexyloxycarbonyl-(2, 3 or 4-)piperidinyl, 1,2-dimethoxycarbonyl-(3, 4, 5 or 6-)piperidinyl, 1,2,6-triethoxycarbonyl-(3, 4 or 5-)piperidinyl, 1-methyl-3-tert-butoxycarbonyl-(3, 4, 5 or 6-)piperidinyl, 1-benzoyl-2-methoxycarbonyl-(2, 4, 5 or 6-)piperidinyl, 1-(1 or 2-)furylmethyl-2,4-dimethoxycarbonyl-(3, 5 or 6-)piperidinyl, and 1-benzyl-2,4-dimethoxycarbonyl-(3, 5 or 6-)piperidinyl groups. 
         [0110]    Examples of the carbonyl lower alkyl group substituted with a group: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    (hereinafter called “A group”) include A group substituted carbonylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as A group substituted carbonylmethyl, 2-A group substituted carbonylethyl, 1-A group substituted carbonylethyl, 3-A group substituted carbonylpropyl, 4-A group substituted carbonylbutyl, 1,1-dimethyl-2-A group substituted carbonylethyl, 5-A group substituted carbonylpentyl, 6-A group substituted carbonylhexyl, 1-A group substituted carbonylisopropyl, and 2-methyl-3-A group substituted carbonylpropyl groups. 
         [0111]    Examples of the carbonyl lower alkyl group substituted with a group: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 34  is an oxo group or a phenyl group, and d is an integer of 0 to 3 (hereinafter called. “B group”), include B group substituted carbonylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as B group substituted carbonylmethyl, 2-B group substituted carbonylethyl, 1-B group substituted carbonylethyl, 3-B group substituted carbonylpropyl, 4-B group substituted carbonylbutyl, 1,1-dimethyl-2-B group substituted carbonylethyl, 5-B group substituted carbonylpentyl, 6-B group substituted carbonylhexyl, 1-B group substituted carbonylisopropyl, and 2-methyl-3-B group substituted carbonylpropyl groups. 
         [0112]    Examples of the pyrrolidinyl lower alkyl group include pyrrolidinylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1-, 2-, or 3-)pyrrolidinylmethyl, 2-[(1-, 2-, or 3-)pyrrolidinyl]ethyl, 1-[(1-, 2-, or 3-)pyrrolidinyl]ethyl, 3-[(1-, 2-, or 3-)pyrrolidinyl]propyl, 4-[(1-, 2-, or 3-)pyrrolidinyl]butyl, 5-[(1-, 2-, or 3-)pyrrolidinyl]pentyl, 6-[(1-, 2-, or 3-)pyrrolidinyl]hexyl, 1,1-dimethyl-2-[(1-, 2-, or 3-)pyrrolidinyl]ethyl, and 2-methyl-3-[(1-, 2-, or 3-)pyrrolidinyl]propyl groups. 
         [0113]    Examples of the morpholino lower alkyl group include morpholinoalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2-, 3- or 4-)morpholinomethyl, 2-[(2-, 3- or 4-)morpholino]ethyl, 1-[(2-, 3- or 4-)morpholino]ethyl, 3-[(2-, 3- or 4-)morpholino]propyl, 4-[(2-, 3- or 4-)morpholino]butyl, 5-[(2-, 3- or 4-)morpholino]pentyl, 6-[(2-, 3- or 4-)morpholino]hexyl, 1,1-dimethyl-2-[(2-, 3- or 4-)morpholino]ethyl, and 2-methyl-3-[(2-, 3- or 4-)morpholino]propyl groups. 
         [0114]    Examples of the phenyl lower alkenyl group include phenylalkenyl groups whose alkenyl moiety is a linear or branched alkenyl group having 2 to 6 carbon atoms and which have 1 to 3 double bonds such as styryl, 3-phenyl-2-propenyl group (trivial name: cinnamyl group), 4-phenyl-2-butenyl, 4-phenyl-3-butenyl, 5-phenyl-4-pentenyl, 5-phenyl-3-pentenyl, 6-phenyl-5-hexenyl, 6-phenyl-4-hexenyl, 6-phenyl-3-hexenyl, 4-phenyl-1,3-butadienyl, and 6-phenyl-1,3,5-hexatrienyl groups. 
         [0115]    Examples of the anilinocarbonyl lower alkyl group which may have a lower alkyl group as a substituent on the phenyl ring include anilinocarbonylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms and which may have 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents on the phenyl ring such as anilinocarbonylmethyl, 2-anilinocarbonylethyl, 1-anilinocarbonylethyl, 3-anilinocarbonylpropyl, 4-anilinocarbonylbutyl, 5-anilinocarbonylpentyl, 6-anilinocarbonylhexyl, 1,1-dimethyl-2-anilinocarbonylethyl, 2-methyl-3-anilinocarbonylpropyl, (4-methylanilinocarbonyl)methyl, 2-(3-methylanilinocarbonyl)ethyl, 3-(4-methylanilinocarbonyl)propyl, 1-(2-ethylanilinocarbonyl)ethyl, 4-(3-ethylanilinocarbonyl)butyl, 5-(4-ethylanilinocarbonyl)pentyl, 6-(4-isopropylanilinocarbonyl)hexyl, 1,1-dimethyl-2-(3-butylanilinocarbonyl)ethyl, 2-methyl-3-(4-pentylanilinocarbonyl)propyl, 4-hexylanilinocarbonylmethyl, 3,4-dimethylanilinocarbonylmethyl, 3,4-diethylanilinocarbonylmethyl, 2,4-dimethylanilinocarbonylmethyl, 2,5-dimethylanilinocarbonylmethyl, 2,6-dimethylanilinocarbonylmethyl, and 3,4,5-trimethylanilinocarbonylmethyl groups. 
         [0116]    Examples of the piperazinyl lower alkyl group which may have, on the piperazine ring, a substituent selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring include piperazinylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms and which may have, on the piperazine ring, 1 to 3 substituents selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms and a phenylalkyl group which may have a linear or branched alkylenedioxy group having 1 to 4 carbon atoms as a substituent on the phenyl ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(1-, 2- or 3-)piperazinyl]methyl, 2-[(1-, 2- or 3-)piperazinyl]ethyl, 1-[(1-, 2- or 3-)piperazinyl]ethyl, 3-[(1-, 2- or 3-)piperazinyl]propyl, 4-[(1-, 2- or 3-)piperazinyl]butyl, 5-[(1-, 2- or 3-)piperazinyl]pentyl, 6-[(1-, 2- or 3-)piperazinyl]hexyl, 1,1-dimethyl-2-[(1-, 2- or 3-)piperazinyl]ethyl, 2-methyl-3-[(1-, 2- or 3-)piperazinyl]propyl, [1-methyl-(2-, 3- or 4-)piperazinyl]methyl, 2-[1-ethyl-(2-, 3- or 4-)piperazinyl]ethyl, 1-[4-propyl-(1-, 2- or 3-)piperazinyl]ethyl, 3-[3-isopropyl-(1-, 2-, 4-, 5- or 6-)piperazinyl]propyl, 4-[2-butyl-(1-, 3-, 4-, 5- or 6-)piperazinyl]butyl, 5-[1-isobutyl-(2-, 3- or 4-)piperazinyl]pentyl, 3-[4-methyl-(1-, 2- or 3-)piperazinyl]propyl, 6-[1-tert-butyl-(2-, 3- or 4-)piperazinyl]hexyl, 1,1-dimethyl-2-[4-pentyl-(1-, 2- or 3-)piperazinyl]ethyl, [1,2-dimethyl-(3-, 4-, 5- or 6-)piperazinyl]methyl, [1,2,6-trimethyl-(3-, 4- or 5-)piperazinyl]methyl, and 2-[4-(3,4-methylenedioxybenzyl)-(1-, 2- or 3-)piperazinyl]ethyl groups. 
         [0117]    Examples of the amidino lower alkyl group which may have a lower alkyl group as a substituent include amidinoalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms and which may have 1 or 2 linear or branched alkyl groups having 1 to 6 carbon atoms such as amidinomethyl, 2-amidinoethyl, 1-amidinoethyl, 3-amidinopropyl, 4-amidinobutyl, 5-amidinopentyl, 6-amidinohexyl, 1,1-dimethyl-2-amidinoethyl, 2-methyl-3-amidinopropyl, N,N-dimethylamidinomethyl, 2-(N,N-dimethylamidino)ethyl, 1-(N-methylamidino)ethyl, 3-(N-ethylamidino)propyl, 4-(N-n-propylamidino)propyl, 5-(N-n-pentylamidino)pentyl, 6-(N-n-hexylamidino)hexyl, and (N-methyl-N-ethylamidino)methyl groups. 
         [0118]    Examples of the carbazolyl group which may have a lower alkyl group as a substituent on the carbazole ring include carbazolyl groups which may have 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents on the carbazole ring such as (1-, 2-, 3- or 4-)carbazolyl, 9-methyl-(1-, 2-, 3- or 4-)carbazolyl, 9-ethyl-(1-, 2-, 3- or 4-)carbazolyl, 1-ethyl-(2-, 3-, 4-, 5-, 6-, 7-, 8- or 9-)carbazolyl, 2-n-propyl-(1-, 3-, 4-, 5-, 6-, 8- or 9-)carbazolyl, 3-n-butyl-(1-, 2-, 4-, 5-, 6-, 7-, 8- or 9-)carbazolyl, 4-n-pentyl-(1-, 2-, 3-, 5-, 6-, 7-, 8- or 9-)carbazolyl, 5-n-hexyl-(1-, 2-, 3-, 4-, 6-, 7-, 8- or 9-)carbazolyl, 6,9-dimethyl-(1-, 2-, 3-, 4-, 5-, 7- or 8-)carbazolyl, and 1,7,8-trityl-(2-, 3-, 4-, 5-, 6-, 7-, 8- or 9-)carbazolyl groups. 
         [0119]    Examples of the amidino group which may have a lower alkyl group as a substituent include amidino groups which may have 1 or 2 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents such as amidino, N,N-dimethylamidino, N-methylamidino, N-ethylamidino, N-n-propylamidino, N-n-butylamidino, N-n-pentylamidino, N-n-hexylamidino, N,N-diethylamidino, and N-methyl-N-ethylamidino groups. 
         [0120]    Examples of the phenyl lower alkyl group (which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkylenedioxy group and a lower alkoxy group), include, in addition to the above described phenyl lower alkyl groups, phenylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms (and which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a linear or branched alkylenedioxy group having 1 to 4 carbon atoms and a linear or branched alkoxy group having 1 to 6 carbon atoms) such as 3,4-methylenedioxybenzyl, 3,4-trimethylenedioxybenzyl, 2-(2,3-ethylenedioxyphenyl)ethyl, 1-(3,4-trimethylenedioxyphenyl)ethyl, 3-(2,3-tetramethylenedioxyphenyl)propyl, 4-(3,4-methylenedioxyphenyl)butyl, 5-(2,3-ethylenedioxyphenyl)pentyl, 6-(3,4-trimethylenedioxyphenyl)hexyl, 1,1-dimethyl-2-(2,3-methylenedioxyphenyl)ethyl, 2-methyl-3-(3,4-ethylenedioxyphenyl)propyl, 2-methoxybenzyl, 2-(2-methoxyphenyl)ethyl, 2-(3-methoxyphenyl)ethyl, 2-(4-methoxyphenyl)ethyl, 4-methoxybenzyl, 1-(2-ethoxyphenyl)ethyl, 3-(3-ethoxyphenyl)propyl, 4-(4-ethoxyphenyl)butyl, 5-(4-isopropoxyphenyl)pentyl, 6-(3-butoxyphenyl)hexyl, 1,1-dimethyl-2-(4-pentyloxyphenyl)ethyl, 2-methyl-3-(4-hexyloxyphenyl)propyl, 3,4-dimethoxybenzyl, 3,4-diethoxybenzyl, 2,4-dimethoxybenzyl, 2,5-dimethoxybenzyl, 2,6-dimethoxybenzyl, and 3,4,5-trimethoxybenzyl groups. 
         [0121]    Examples of the piperazinyl substituted oxalyl group which may have, on the piperazine ring, 1 to 3 substituents selected from the group consisting of a phenyl lower alkyl group (which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkylenedioxy group and a lower alkoxy group) and a pyridyl lower alkyl group include piperazinyl substituted oxalyl groups which may have, on the piperazine ring, 1 to 3 substituents selected from the group consisting of a phenylalkyl group whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms (and which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a linear or branched alkylenedioxy group having 1 to 4 carbon atoms and a linear or branched alkoxy group having 1 to 6 carbon atoms) and a pyridylalkyl group whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as 4-(3,4-methylenedioxybenzyl)-(1-, 2- or 3-)piperazinyloxalyl, 4-(2-, 3- or 4-pyridylmethyl)-(1-, 2- or 3-)piperazinyloxalyl, 4-(3,4-dimethoxybenzyl)-(1-, 2- or 3-)piperazinyloxalyl, 4-(2,3-methylenedioxybenzyl)-(1-, 2- or 3-)piperazinyloxalyl, 4-(3,4-ethylenedioxybenzyl)-(1-, 2- or 3-)piperazinyloxalyl, 4-[2-(2-, 3- or 4-pyridyl)ethyl]-(1-, 2- or 3-)piperazinyloxalyl, 4-[3-(2-, 3- or 4-pyridyl)propyl-(1-, 2- or 3-)piperazinyloxalyl, 2,4-bis(2-, 3- or 4-pyridylmethyl)-(1-, 2- or 3-)piperazinyloxalyl, 2-(3,4-methylenedioxybenzyl)-4-(2-, 3- or 4-pyridylmethyl)-(1-, 2- or 3-)piperazinyloxalyl, and 2,3,4-tri(2-, 3- or 4-pyridylmethyl)-(1-, 2- or 3-)piperazinyloxalyl groups. 
         [0122]    Examples of the cyano substituted lower alkyl group include cyanoalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as cyanomethyl, 2-cyanoethyl, 1-cyanoethyl, 3-cyanopropyl, 4-cyanobutyl, 5-cyanopentyl, 6-cyanohexyl, 1,1-dimethyl-2-cyanoethyl, and 2-methyl-3-cyanopropyl groups. 
         [0123]    Examples of the 5- to 7-membered saturated heterocyclic ring formed by binding R 36  and R 37  each other, together with nitrogen atoms bound to them, through or not through a nitrogen atom, an oxygen atom, or a sulfur atom include pyrrolidinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino, and homopiperazinyl groups. 
         [0124]    Examples of the 5- to 10-membered saturated or unsaturated heterocyclic ring formed by binding R 14  and R 15  each other, together with nitrogen atoms bound to them, through or not through a nitrogen atom, an oxygen atom, or a sulfur atom include 1,2,3,4,5,6-hexahydropyrimidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino, homopiperazinyl, homopiperidinyl, thiazolidinyl, 1,2,5,6-tetrahydropyridyl, pyrrolyl, pyrazolyl, imidazolyl, 2-pyrrolinyl, 2-imidazolinyl, imidazolidinyl, 2-pyrazolinyl, pyrazolidinyl, 1,2-dihydropyridyl, 1,2-dihydroquinolyl, 1,2,3,4-tetrahydroquinolyl, 1,2,3,4-tetrahydroisoquinolyl, 1,2-dihydroisoquinolyl, indolyl, isoindolyl, indolinyl, isoindolinyl, 3,4-dihydro-2H-1,4-benzooxazinyl, 3,4-dihydro-2H-1,4-benzothiazolidinyl, 1,4-benzothiazinyl, 1,2,3,4-tetrahydroquinoxalinyl, 1,2,3,4-tetrahydrocinnolinyl, 1,2,3,4-tetrahydrophthalazinyl, 1,2,3,4-tetrahydroquinazolinyl, 1,2-dihydroquinoxalinyl, 3,4-dihydroquinoxalinyl, 1,4-dihydroquinoxalinyl, 1,2-dihydrocinnolinyl, 1,2-dihydrophthalazinyl, 3,4-dihydrophthalazinyl, 1,2-dihydroquinazolinyl, 3,4-dihydroquinazolinyl, indazolyl, indazolinyl, 6-azabicyclo[3,2,1]octyl, 3-aza-spiro[5,5]undecyl, and thiazolidinyl groups. Preferably, R 14  and R 15 , together with the nitrogen atom to which they bind, bind to each other, directly or via a nitrogen atom to form a 6-membered saturated heterocyclic group. Most preferably, they include piperidinyl and piperazinyl groups. 
         [0125]    Examples of the phenyl lower alkoxy group include phenylalkoxy groups whose alkoxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms such as benzyloxy, 2-phenylethoxy, 1-phenylethoxy, 3-phenylpropoxy, 4-phenylbutoxy, 5-phenylpentyloxy, 6-phenylhexyloxy, 1,1-dimethyl-2-phenylethoxy, and 2-methyl-3-phenylpropoxy groups. 
         [0126]    Examples of the phenyl substituted lower alkyl group which has 1 or 2 phenyl groups which may be substituted on the phenyl ring with 1 to 3 substituents selected from the group consisting of a lower alkanoyl group, an amino group which may have a lower alkanoyl group as a substituent, a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, a phenyl lower alkoxy group, a hydroxyl group, and a lower alkylenedioxy groups; and which may have a pyridyl group on the lower alkyl group include in addition to the above described phenyl lower alkyl groups, phenyl substituted alkyl groups which have 1 or 2 phenyls which may be substituted on the phenyl ring with 1 to 3 substituents selected from the group consisting of a linear or branched alkanoyl group having 1 to 6 carbon atoms, an amino group which may have 1 or 2 linear or branched alkanoyl groups having 1 to 6 carbon atoms as substituents, a linear or branched alkoxycarbonyl group having 1 to 6 carbon atoms, a cyano group, a nitro group, a phenyl group, a halogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents, a linear or branched alkoxy group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents, a phenylalkoxy groups whose alkoxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms, a hydroxy group, and a linear or branched alkylenedioxy group having 1 to 4 carbon atoms; which may have a pyridyl group on the alkyl group, and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms, such as 1-phenyl-1-(2, 3 or 4-)pyridyl methyl, 1,1-diphenylmethyl, 1,1-di(4-fluorophenyl)methyl, 1-phenyl-1-(4-methoxyphenyl)methyl, 3,4-methylenedioxybenzyl, 3,4-ethylenedioxybenzyl, 3,4-trimethylenedioxybenzyl, 2,5-difluorobenzyl, 2,4-difluorobenzyl, 3,4-difluorobenzyl, 3,5-difluorobenzyl, 2,6-difluorobenzyl, 3-trifluoromethylbenzyl, 2-trifluoromethylbenzyl, 4-trifluoromethylbenzyl, 3,4-dimethoxybenzyl, 3,5-dimethoxybenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 2-methylbenzyl, 3-methylbenzyl, 4-methylbenzyl, 3,4-dimethylbenzyl, 2,3-dimethylbenzyl, 2-methoxybenzyl, 3-methoxybenzyl, 4-cyanobenzyl, 2-cyanobenzyl, 3-cyanobenzyl, 4-methoxybenzyl, 2,3-dichlorobenzyl, 2,4-dichlorobenzyl, 2,5-dichlorobenzyl, 3,4-dichlorobenzyl, 2,6-dichlorobenzyl, 4-fluorobenzyl, 3-fluorobenzyl, 2-fluorobenzyl, 4-nitrobenzyl, 3-nitrobenzyl, 2-nitrobenzyl, 3-trifluoromethoxybenzyl, 4-trifluoromethoxybenzyl, 2-trifluoromethoxybenzyl, 4-methoxycarbonylbenzyl, 3-methoxycarbonylbenzyl, 4-tert-butylbenzyl, 4-ethylbenzyl, 4-isopropylbenzyl, 4-methoxy-3-chlorobenzyl, 2-(4-methoxyphenyl)ethyl, 2-(4-fluorophenyl)ethyl, 2-(4-chlorophenyl)ethyl, 2-(3-methoxyphenyl)ethyl, 2-(4-methylphenyl)ethyl, 4-phenylbenzyl, 3,3-diphenylpropyl, 3-methyl-4-nitrobenzyl, 4-(4-methoxyphenyl)butyl, 2-(4-methylphenyl)ethyl, 4-tert-butoxycarbonylbenzyl, 3-chloro-6-methoxybenzyl, 4-acetylaminobenzyl, 4-nitro-3-methylbenzyl, 4-hydroxybenzyl, 3-hydroxybenzyl, 2-hydroxybenzyl, 4-tert-butyrylbenzyl, 4-benzyloxybenzyl, 4-pivaloylbenzyl, 2-(4-acetylphenyl)ethyl, 1-(3-propionylphenyl)ethyl, 3-(2-butyrylphenyl)propyl, 4-(4-pentanoylphenyl)butyl, 5-(3-hexanoylphenyl)pentyl, 6-(2,4-diacetylphenyl)hexyl, 1,1-dimethyl-2-(2,4,6-triacetylphenyl)ethyl, 2-methyl-3-(3,4-diacetylphenyl)propyl, 2-(4-aminophenyl)ethyl, 1-(3-propionylaminophenyl)ethyl, 3-(2-butyrylaminophenyl)propyl, 4-(4-pentanoylamino)phenylbutyl, 5-(hexanoylaminophenyl)pentyl, 6-(N-acetyl-N-propionylaminophenyl)hexyl, 1,1-dimethyl-2-(3,4-diaminophenyl)ethyl, 2-methyl-3-(3,4,5-triacetylaminophenyl)propyl, 2-(2-ethoxycarbonylphenyl)ethyl, 1-(3-propoxycarbonylphenyl)ethyl, 3-(4-pentyloxycarbonylphenyl)propyl, 4-(3-hexyloxycarbonylphenyl)butyl, 5-(3,4-dimethoxycarbonylphenyl)pentyl, 6-(3,4,5-triethoxycarbonylphenyl)hexyl, 1,1-dimethyl-2-(4-butoxycarbonylphenyl)ethyl, 2-methyl-3-(4-methoxycarbonylphenyl)propyl, 2-(2-cyanophenyl)ethyl, 1-(3-cyanophenyl)ethyl, 3-(4-cyanophenyl)propyl, 4-(2-cyanophenyl)butyl, 5-(3-cyanophenyl)pentyl, 6-(4-cyanophenyl)hexyl, 1,1-dimethyl-2-(2,4-dicyanophenyl)ethyl, 2-methyl-3-(2,4,6-tricyanophenyl)propyl, 2-(2-nitrophenyl)ethyl, 1-(3-nitrophenyl)ethyl, 3-(4-nitrophenyl)propyl, 4-(2-nitrophenyl)butyl, 5-(3-nitrophenyl)pentyl, 6-(4-nitrophenyl)hexyl, 1,1-dimethyl-2-(2,4-dinitrophenyl)ethyl, 2-methyl-3-(2,4,6-trinitrophenyl)propyl, 2-(2-phenylphenyl)ethyl, 1-(3-phenylphenyl)ethyl, 3-(4-phenylphenyl)propyl, 4-(2-phenylphenyl)butyl, 5-(3-phenylphenyl)pentyl, 6-(4-phenylphenyl)hexyl, 1,1-dimethyl-2-(2,4-diphenylphenyl)ethyl, 2-methyl-3-(2,4,6-triphenylphenyl)propyl, 2-(2-fluorophenyl)ethyl, 1-(3-bromophenyl)ethyl, 3-(4-iodophenyl)propyl, 4-(2-bromophenyl)butyl, 5-(3-chlorophenyl)pentyl, 6-(4-bromophenyl)hexyl, 1,1-dimethyl-2-(2,4-dichlorophenyl)ethyl, 2-methyl-3-(2,4,6-trifluorophenyl)propyl, 2-(2-ethylphenyl)ethyl; 1-(3-propylphenyl)ethyl, 3-(4-butylphenyl)propyl, 4-(2-pentylphenyl)butyl, 5-(3-hexylphenyl)pentyl, 6-(4-trifluoromethylphenyl)hexyl, 1,1-dimethyl-2-(2,4-dimethylphenyl)ethyl, 2-methyl-3-[2,4,6-tri(trifluoromethyl)phenyl]propyl, 2-(2-ethoxyphenyl)ethyl, 1-(3-propoxyphenyl)ethyl, 3-(4-butoxyphenyl)propyl, 4-(2-pentyloxyphenyl)butyl, 5-(3-hexyloxyphenyl)pentyl, 6-(4-trifluoromethoxyphenyl)hexyl, 1,1-dimethyl-2-(2,4-dimethoxyphenyl)ethyl, 2-methyl-3-[2,4,6-tri(trifluoromethoxy)phenyl]propyl, 2-(2-benzyloxyphenyl)ethyl, 1-[3-(2-phenylethoxy)phenyl]ethyl, 3-[4-(3-phenylpropoxy)phenyl]propyl, 4-[2-(4-phenylbutoxy)phenyl]butyl, 5-[3-(5-phenylpentyloxy)phenyl]pentyl, 6-[4-(6-phenylhexyloxy)phenyl]hexyl, 1,1-dimethyl-2-(2,4-dibenzyloxyphenyl)ethyl, 2-methyl-3-(2,4,6-tribenzyloxyphenyl)propyl, 2-(2-hydroxyphenyl)ethyl, 1-(3-hydroxyphenyl)ethyl, 3-(4-hydroxyphenyl)propyl, 4-(2-hydroxyphenyl)butyl, 5-(3-hydroxyphenyl)pentyl, 6-(4-hydroxyphenyl)hexyl, 1,1-dimethyl-2-(2,4-dihydroxyphenyl)ethyl, 2-methyl-3-(2,4,6-trihydroxyphenyl)propyl, 2-(3,4-methylenedioxyphenyl)ethyl, 1-(2,3-ethylenedioxyphenyl)ethyl, 3-(3,4-trimethylenedioxyphenyl)propyl, 4-(3,4-tetramethylenedioxyphenyl)butyl, 5-(3,4-methylenedioxyphenyl)pentyl, 6-(3,4-ethylenedioxyphenyl)hexyl, 1,1-dimethyl-2-(3,4-methylenedioxy)ethyl, and 2-methyl-3-(3,4-methylenedioxyphenyl)propyl groups. Preferably, they include phenyl substituted lower alkyl groups which may be substituted on the phenyl ring with group(s), as substituent(s), selected from the group consisting of a lower alkanoyl group, an amino group which may have a lower alkanoyl group as a substituent, a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, a phenyl lower alkoxy group, a hydroxyl group, and a lower alkylenedioxy groups. 
         [0127]    Examples of the pyridyl lower alkyl group which may have, on the pyridine ring, 1 to 3 substituents selected from the group consisting of a hydroxyl group and a lower alkyl group which may have a hydroxyl group as a substituent include, in addition to the above described pyridyl lower alkyl groups, pyridylalkyl groups which may have, on the pyridine ring, 1 to 3 substituents selected from the group consisting of a hydroxy group and a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 hydroxy groups as substituents, and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [2-methyl-(3, 4, 5 or 6-)pyridyl]methyl, [2-methyl-3-hydroxy-5-hydroxy methyl-(4 or 6-)pyridyl]methyl, 2-[3-ethyl-(2, 4, 5 or 6-)pyridyl]ethyl, 1-[4-propyl-(2, 3, 5 or 6-)pyridyl]ethyl, 3-[2-butyl-(3, 4, 5 or 6-)pyridyl]propyl, 4-[3-pentyl-(2, 4, 5 or 6-)pyridyl]butyl, 1,1-dimethyl-2-[4-hexyl-(2, 3, 5 or 6-)pyridyl]ethyl, 5-[2,3-dimethyl-(4, 5 or 6-)pyridyl]pentyl, 6-[2,4,6-trimethyl-(3 or 5-)pyridyl]hexyl, 1-[2-hydroxy-(2, 3, 5 or 6-)pyridyl]isopropyl, 2-methyl-3-[3-hydroxy-(2, 4, 5 or 6-)pyridyl]propyl, [2-hydroxy-(3, 4, 5 or 6-)pyridyl]methyl, 2-[3-hydroxy-(2, 4, 5 or 6-)pyridyl]ethyl, 1-[4-hydroxy-(2, 3, 5 or 6-)pyridyl]ethyl, 3-[2-hydroxy-(3, 4, 5 or 6-)pyridyl]propyl, 4-[3-hydroxy-(2, 4, 5 or 6-)pyridyl]butyl, 1,1-dimethyl-2-[4-hydroxy-(2, 3, 5 or 6-)pyridyl]ethyl, 5-[2,3-dihydroxy-(4, 5 or 6-)pyridyl]pentyl, 6-[2,4,6-trihydroxy-(3 or 5-)pyridyl]hexyl, [2-hydroxymethyl-(3, 4, 5 or 6-)pyridyl]methyl, 2-[3-(2-hydroxyethyl)-(2, 4, 5 or 6-)pyridyl]ethyl, 1-[4-(3-hydroxypropyl)-(2, 3, 5 or 6-)pyridyl]ethyl, 3-[2-(4-hydroxybutyl)-(3, 4, 5 or 6-)pyridyl]propyl, 4-[3-(5-hydroxypentyl)-(2, 4, 5 or 6-)pyridyl]butyl, 1,1-dimethyl-2-[4-(6-hydroxyhexyl)-(2, 3, 5 or 6-)pyridyl]ethyl, 5-[2,3-di(hydroxymethyl)-(4, 5 or 6-)pyridyl]pentyl, 6-[2,4,6-tri(hydroxymethyl)-(3 or 5-)pyridyl]hexyl, 1-[2-hydroxymethyl-(2, 3, 5 or 6-)pyridyl]isopropyl, 2-methyl-3-[3-(2,3-dihydroxypropyl)-(2, 4, 5 or 6-)pyridyl]propyl, [2-methyl-3-(2,2,4-trihydroxybutyl)-(4, 5 or 6-)pyridyl]methyl, and [2-methyl-5-hydroxymethyl-(3, 4 or 6-)pyridyl]methyl groups. 
         [0128]    Examples of the pyrrolyl lower alkyl group which may have 1 to 3 lower alkyl groups as substituents on the pyrrole ring include pyrrolylalkyl groups which may have 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms on the pyrrole ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(1, 2 or 3-)pyrrolyl]methyl, 2-[(1, 2 or 3-)pyrrolyl]ethyl, 1-[(1, 2 or 3-)pyrrolyl]ethyl, 3-[(1, 2 or 3-)pyrrolyl]propyl, 4-[(1, 2 or 3-)pyrrolyl]butyl, 5-[(1, 2 or 3-)pyrrolyl]pentyl, 6-[(1, 2 or 3-)pyrrolyl]hexyl, 1,1-dimethyl-2-[(1, 2 or 3-)pyrrolyl]ethyl, 2-methyl-3-[(1, 2 or 3-)pyrrolyl]propyl, [1-methyl-(2 or 3-)pyrrolyl]methyl, 2-[2-ethyl-(1, 3, 4 or 5-)pyrrolyl]ethyl, 1-[3-propyl-(1, 2, 4 or 5-)pyrrolyl]ethyl, 3-[1-butyl-(2, 3 or 4-)pyrrolyl]propyl, 4-[2-pentyl-(1, 3, 4 or 5-)pyrrolyl]butyl, 5-[3-hexyl-(1, 2, 4 or 5-)pyrrolyl]pentyl, 6-[1,2-dimethyl-(3, 4 or 5-)pyrrolyl]hexyl, 1,1-dimethyl-2-[1,2,3-trimethyl-(4 or 5-)pyrrolyl]ethyl, and 2-methyl-3-[1-ethyl-2-methyl-(3, 4 or 5-)pyrrolyl]propyl groups. 
         [0129]    Examples of the benzoxazolyl lower alkyl group include benzoxazolylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(2, 4, 5, 6 or 7-)benzooxazolyl]methyl, 2-[(2, 4, 5, 6 or 7-)benzooxazolyl]ethyl, 1-[(2, 4, 5, 6 or 7-)benzooxazolyl]ethyl, 3-[(2, 4, 5, 6 or 7-)benzooxazolyl]propyl, 4-[(2, 4, 5, 6 or 7-)benzooxazolyl]butyl, 5-[(2, 4, 5, 6 or 7-)benzooxazolyl]pentyl, 6-[(2, 4, 5, 6 or 7-)benzooxazolyl]hexyl, 1,1-dimethyl-2-[(2, 4, 5, 6 or 7-)benzooxazolyl]ethyl, and 2-methyl-3-[(2, 4, 5, 6 or 7-)benzooxazolyl]propyl groups. 
         [0130]    Examples of the benzothiazolyl lower alkyl group include benzothiazolylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(2, 4, 5, 6 or 7-)benzothiazolyl]methyl, 2-[(2, 4, 5, 6 or 7-)benzothiazolyl]ethyl, 1-[(2, 4, 5, 6 or 7-)benzothiazolyl]ethyl, 3-[(2, 4, 5, 6 or 7-)benzothiazolyl]propyl, 4-[(2, 4, 5, 6 or 7-)benzothiazolyl]butyl, 5-[(2, 4, 5, 6 or 7-)benzothiazolyl]pentyl, 6-[(2, 4, 5, 6 or 7-)benzothiazolyl]hexyl, 1,1-dimethyl-2-[(2, 4, 5, 6 or 7-)benzothiazolyl]ethyl, and 2-methyl-3-[(2, 4, 5, 6 or 7-)benzothiazolyl]propyl groups. 
         [0131]    Examples of the furyl lower alkyl group include furylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(2 or 3-)furyl]methyl, 2-[(2 or 3-)furyl]ethyl, 1-[(2 or 3-)furyl]ethyl, 3-[(2 or 3-)furyl]propyl, 4-[(2 or 3-)furyl]butyl, 5-[(2 or 3-)furyl]pentyl, 6-[(2 or 3-)furyl]hexyl, 1,1-dimethyl-2-[(2 or 3-)furyl]ethyl, and 2-methyl-3-[(2 or 3-)furyl]propyl groups. 
         [0132]    Examples of the thiazolidinyl lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring include thiazolidinylalkyl groups which may have 1 to 3 oxo groups as substituents on the thiazolidine ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2, 3, 4 or 5-)thiazolidinylmethyl, 2-[(2, 3, 4 or 5-)thiazolidinyl]ethyl, 1-[(2, 3, 4 or 5-)thiazolidinyl]ethyl, 3-[(2, 3, 4 or 5-)thiazolidinyl]propyl, 4-[(2, 3, 4 or 5-)thiazolidinyl]butyl, 5-[(2, 3, 4 or 5-)thiazolidinyl]pentyl, 6-[(2, 3, 4 or 5-)thiazolidinyl]hexyl, 1,1-dimethyl-2-[(2, 3, 4 or 5-)thiazolidinyl]ethyl, 2-methyl-3-[(2, 3, 4 or 5-)thiazolidinyl]propyl, [2,4-dioxo-(3 or 5-)thiazolidinyl]methyl, 2-[2-oxo-(3, 4 or 5-)thiazolidinyl]ethyl, 1-[4-oxo-(2, 3 or 5-)thiazolidinyl]ethyl, 3-[2-oxo-(3, 4 or 5-)thiazolidinyl]propyl, 4-[5-oxo-(2, 3 or 4-)thiazolidinyl]butyl, 5-[2,5-dioxo-(3 or 4-)thiazolidinyl]pentyl, 6-[2,4,5-trioxo-3-thiazolidinyl]hexyl, 1-[4,5-dioxo-(2 or 3-)thiazolidinyl]ethyl, 2-[4,5-dioxo-(2- or 3-)thiazolidinyl]ethyl, 1,1-dimethyl-2-[2,4-dioxo-(3 or 5-)thiazolidinyl]ethyl, and 2-methyl-3-[2,4-dioxo-(3 or 5-)thiazolidinyl]propyl groups. 
         [0133]    Examples of the thiazolidinylidene lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring include thiazolidinylidenealkyl groups which may have 1 to 3 oxo groups as substituents on the thiazolidine ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2, 4 or 5-)thiazolidinylidenemethyl, (2, 4 or 5-)thiazolidinylideneethyl, (2, 4 or 5-)thiazolidinylidenepropyl, (2, 4 or 5-)thiazolidinylideneisopropyl, (2, 4 or 5-)thiazolidinylidenebutyl, (2, 4 or 5-)thiazolidinylidenepentyl, (2, 4 or 5-)thiazolidinylidenehexyl, 4,5-dioxo-2-thiazolidinylidenemethyl, 2,5-dioxo-4-thiazolidinylidenemethyl, 2,4-dioxo-5-thiazolidinylidenemethyl, 4-oxo-(2 or 5-)thiazolidinylideneethyl, 5-oxo-(2 or 4-)thiazolidinylidenepropyl, and 2-oxo-(4 or 5-)thiazolidinylidenebutyl groups. 
         [0134]    Examples of the benzoyl group which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a cyano group, an amino group which may have a lower alkylsulfonyl group as a substituent, a halogen atom, a lower alkoxy group, a lower alkyl group which may have a halogen atom as a substituent, a thiazolidinyl lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, a thiazolidinylidene lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, and a lower alkylenedioxy group include benzoyl groups which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a cyano group; an amino group which may have 1 or 2 linear or branched alkylsulfonyl groups having 1 to 6 carbon atoms as substituents; a halogen atom; a linear or branched alkoxy group having 1 to 6 carbon atoms; a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents; a thiazolidinylalkyl group which may have 1 to 3 oxo groups as substituents on the thiazolidine ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms; a thiazolidinylidenealkyl group which may have 1 to 3 oxo groups as substituents on the thiazolidine ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms; and a linear or branched alkylenedioxy group having 1 to 4 carbon atoms such as benzoyl, 4-cyanobenzoyl, 3,4-methylenedioxybenzoyl, 2-aminobenzoyl, 3-aminobenzoyl, 4-aminobenzoyl, 3,4-diaminobenzoyl, 2,4,6-triaminobenzoyl, 4-methoxybenzoyl, 4-trifluoromethylbenzoyl, 4-chlorobenzoyl, 3,4-difluorobenzoyl, 2-fluorobenzoyl, 3-bromobenzoyl, 4-iodobenzoyl, 3,4-dimethoxybenzoyl, 4-fluorobenzoyl, 3-cyanobenzoyl, 2-cyanobenzoyl, 2,3-dicyanobenzoyl, 3,4,5-tricyanobenzoyl, 4-methylbenzoyl, 4-(2,4-dioxothiazolidinylmethyl)benzoyl, 4-(2,4-dioxothiazolidinylidenemethyl)benzoyl, 2-methylbenzoyl, 3-methylbenzoyl, 2-ethylbenzoyl, 3-ethylbenzoyl, 4-ethylbenzoyl, 4-isopropylbenzoyl, 3-butylbenzoyl, 4-pentylbenzoyl, 4-hexylbenzoyl, 3,4-dimethylbenzoyl, 3,4-diethylbenzoyl, 2,4-dimethylbenzoyl, 2,5-dimethylbenzoyl, 2,6-dimethylbenzoyl, 3,4,5-trimethylbenzoyl, 2-methoxybenzoyl, 3-methoxybenzoyl, 2-ethoxybenzoyl, 3-ethoxybenzoyl, 4-ethoxybenzoyl, 4-isopropoxybenzoyl, 3-butoxybenzoyl, 4-pentyloxybenzoyl, 4-hexyloxybenzoyl, 3,4-diethoxybenzoyl, 2,4-dimethoxybenzoyl, 2,5-dimethoxybenzoyl, 2,6-dimethoxybenzoyl, 3,4,5-trimethoxybenzoyl, 2-trifluoromethylbenzoyl, 3-trifluoromethylbenzoyl, 4-trifluoromethylbenzoyl, 2-(bromomethyl)benzoyl, 3-(2-chloroethyl)benzoyl, 4-(2,3-dichloropropyl)benzoyl, 4-(4-fluorobutyl)benzoyl, 3-(5-chloropentyl)benzoyl, 4-(5-bromohexyl)benzoyl, 4-(5,6-dibromohexyl)benzoyl, 3,4-di(trifluoromethyl)benzoyl, 3,4-di(4,4,4-trichlorobutyl)benzoyl, 2,4-di(3-chloro-2-methylpropyl)benzoyl, 2,5-di(3-chloropropyl)benzoyl, 2,6-di(2,2,2-trifluoroethyl)benzoyl, 3,4,5-tri(trifluoromethyl)benzoyl, 4-(2,2,2-trichloroethyl)benzoyl, 2-methyl-4-trifluoromethylbenzoyl, 3-ethyl-4-trichloromethylbenzoyl, 2-methoxy-4-trifluoromethylbenzoyl, 3-ethyl-4-fluorobenzoyl, 3-ethoxy-4-trichloromethylbenzoyl, 2-methyl-3-trifluoromethyl-4-trifluoromethylbenzoyl, 3-fluorobenzoyl, 4-fluorobenzoyl, 2-bromobenzoyl, 4-bromobenzoyl, 2-iodobenzoyl, 3-iodobenzoyl, 2,3-dibromobenzoyl, 2,4-diiodobenzoyl, 2,5-difluorobenzoyl, 2,6-dichlorobenzoyl, 2,4,6-trichlorobenzoyl, 2,4-difluorobenzoyl, 3,4-difluorobenzoyl, 3,5-difluorobenzoyl, 2,6-difluorobenzoyl, 2-chlorobenzoyl, 3-chlorobenzoyl, 4-chlorobenzoyl, 2,3-dichlorobenzoyl, 2,4-dichlorobenzoyl, 2,5-dichlorobenzoyl, 3,4-dichlorobenzoyl, 2,6-dichlorobenzoyl, 3,5-dichlorobenzoyl, 2,4,6-trifluorobenzoyl, 2,4-difluorobenzoyl, 3,4-difluorobenzoyl, 3,4-methylenedioxybenzoyl, 3,4-trimethylenedioxybenzoyl, 2,3-ethylenedioxybenzoyl, 3,4-trimethylenedioxybenzoyl, 2,3-tetramethylenedioxybenzoyl, 2,3-methylenedioxybenzoyl, 3,4-ethylenedioxybenzoyl, and 2-methanesulfonylaminobenzoyl groups. 
         [0135]    Examples of the thiazolidinyl lower alkanoyl group which may be substituted on the thiazolidine ring with a group selected from the group consisting of an oxo group and a group of the formula: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R a  and R b  each represent a lower alkyl group, include thiazolidinylalkanoyl groups which may be substituted on the thiazolidine ring with 1 to 3 substituents selected from the group consisting of an oxo group and a group of the formula: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R a  and R b  each represent a linear or branched alkyl group having 1 to 6 carbon atoms, and whose alkanoyl moiety is a linear or branched alkanoyl group having 2 to 6 carbon atoms such as 2-[(2, 3, 4 or 5-)thiazolidinyl]acetyl, 3-[(2, 3, 4 or 5-)thiazolidinyl]propionyl, 2-[(2, 3, 4 or 5-)thiazolidinyl]propionyl, 4-[(2, 3, 4 or 5-)thiazolidinyl]butyryl, 5-[(2, 3, 4 or 5-)thiazolidinyl]pentanoyl, 6-[(2, 3, 4 or 5-)thiazolidinyl]hexanoyl, 2,2-dimethyl-3-[(2, 3, 4 or 5-)thiazolidinyl]propionyl, 2-methyl-3-[(2, 3, 4 or 5-)thiazolidinyl]propionyl, [2,4-dioxo-(3 or 5-)thiazolidinyl]acetyl, 3-[2-oxo-(3, 4 or 5-)thiazolidinyl]propionyl, 2-[4-oxo-(2, 3 or 5-)thiazolidinyl]propionyl, 4-[5-oxo-(2, 3 or 4-)thiazolidinyl]butyryl, 5-[2,5-dioxo-(3 or 4-)thiazolidinyl]pentanoyl, 6-[2,4,5-trioxo-3-thiazolidinyl]hexanoyl, 2-[4,5-dioxo-(2 or 3-)thiazolidinyl]acetyl, 2,2-dimethyl-3-[2,4-dioxo-(3 or 5-)thiazolidinyl]propionyl, 2-methyl-3-[2,4-dioxo-(3 or 5-)thiazolidinyl]propionyl, 2-[4-oxo-2-isopropylidenehydrazono-(3 or 5-)thiazolidinyl]acetyl, 2-[2-oxo-5-isopropylidenehydrazono-(3 or 4-)thiazolidinyl]acetyl, 2-[2,4-di(isopropylidenehydrazono)-(3 or 5-)thiazolidinyl]acetyl, 3-[2-methylidenehydrazono-(3, 4 or 5-)thiazolidinyl]propionyl, 2-[4-ethylidenehydrazono-(2, 3 or 5-)thiazolidinyl]propionyl, 4-[5-propylidenehydrazono-(2, 3 or 4-)thiazolidinyl]butyryl, 5-[2,5-di(isopropylidenehydrazono)-(3 or 4-)thiazolidinyl]pentanoyl, 6-[2,4,5-tri(isopropylidenehydrazono)-3-thiazolidinyl]hexanoyl, 2-[4,5-di(isopropylidenehydrazono)-(2 or 3-)thiazolidinyl]acetyl, 2,2-dimethyl-3-[4-butylidenehydrazono(2, 3 or 5-)thiazolidinyl]propionyl, 2-methyl-3-[5-pentylidene-(2, 3 or 4-)thiazolidinyl]propionyl, and 2-(hexylidenehydrazono)-(3, 4 or 5-)thiazolidinylacetyl groups. 
         [0136]    Examples of the lower alkyl group which may have a substituent selected from the group consisting of a hydroxyl group and a halogen atom include, in addition to the above described lower alkyl groups, linear or branched alkyl groups having 1 to 6 carbon atoms which may have 1 to 3 substituents selected from the group consisting of a hydroxy group and a halogen atom such as hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxypentyl, 5-hydroxypentyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, 2-methyl-3-hydroxypropyl, trifluoromethyl, trichloromethyl, chloromethyl, bromomethyl, fluoromethyl, iodomethyl, difluoromethyl, dibromomethyl, 2-chloroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 3-chloropropyl, 2,3-dichloropropyl, 4,4,4-trichlorobutyl, 4-fluorobutyl, 5-chloropentyl, 3-chloro-2-methylpropyl, 5-bromohexyl, 5,6-dibromohexyl, 2-hydroxy-3-fluoropropyl, and 2,2-dichloro-3-hydroxybutyl groups. 
         [0137]    Examples of the carbamoyl group which may have a group selected from the group consisting of a lower alkoxy lower alkyl group and a lower alkyl group include carbamoyl groups which may have 1 or 2 groups selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms and which has a linear or branched alkoxy group having 1 to 6 carbon atoms and a linear or branched alkyl group having 1 to 6 carbon atoms such as carbamoyl, N-(2-methoxyethyl)carbamoyl, methylcarbamoyl, ethylcarbamoyl, propylcarbamoyl, isopropylcarbamoyl, butylcarbamoyl, tert-butylcarbamoyl, pentylcarbamoyl, hexylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl, dipropylcarbamoyl, dibutylcarbamoyl, dipentylcarbamoyl, dihexylcarbamoyl, N-methyl-N-ethylcarbamoyl, N-ethyl-N-propylcarbamoyl, N-methyl-N-butylcarbamoyl, N-methyl-N-hexylcarbamoyl, N-(methoxymethyl)carbamoyl, N-(3-propoxypropyl)carbamoyl, N-(4-butoxybutyl)carbamoyl, N-(4-ethoxybutyl)carbamoyl, N-(5-pentyloxypentyl)carbamoyl, N-(5-methoxypentyl)carbamoyl, N-(6-hexyloxyhexyl)carbamoyl, di(2-methoxyethyl)carbamoyl, N-(2-methoxyethyl)-N-methylcarbamoyl, and N-(2-methoxyethyl)-N-ethylcarbamoyl groups. 
         [0138]    Examples of the phenyl group which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a carbamoyl group which may have a group selected from the group consisting of a lower alkoxy lower alkyl group and a lower alkyl group, a lower alkoxycarbonyl group, a carboxy group, a cyano group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, a benzoyl group which may have a halogen atom as a substituent on the phenyl ring, a phenyl lower alkyl group which may have a halogen atom as a substituent on, the phenyl ring, and a hydroxyl group include phenyl groups which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a carbamoyl group which may have 1 or 2 groups selected from the group consisting of an alkoxyalkyl group whose alkoxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms and a linear or branched alkyl group having 1 to 6 carbon atoms; a linear or branched alkoxycarbonyl group having 1 to 6 carbon atoms; a carboxy group; a cyano group; a phenyl group; a halogen atom; a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents; a linear or branched alkoxy group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents; a benzoyl group which may have 1 to 3 halogen atoms as substituents on the phenyl ring; a phenylalkyl group which may have 1 to 3 halogen atoms as substituents on the phenyl ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms, and a hydroxyl group such as phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-butylphenyl, 4-pentylphenyl, 4-hexylphenyl, 3,4-dimethylphenyl, 3,4-diethylphenyl, 2,4-dimethylphenyl, 2,3-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4,5-trimethylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 4-isopropoxyphenyl, 3-butoxyphenyl, 4-pentyloxyphenyl, 4-hexyloxyphenyl, 3,4-dimethoxyphenyl, 3,4-diethoxyphenyl, 2,4-dimethoxyphenyl, 2,5-dimethoxyphenyl, 2,6-dimethoxyphenyl, 3,4,5-trimethoxyphenyl, 2-trifluoromethoxyphenyl, 3-trifluoromethoxyphenyl, 4-trifluoromethoxyphenyl, 2-(bromomethoxy)phenyl, 3-(2-chloroethoxy)phenyl, 4-(2,3-dichloropropoxy)phenyl, 4-(4-fluorobutoxy)phenyl, 3-(5-chloropentyloxy)phenyl, 4-(5-bromohexyloxy)phenyl, 4-(5,6-dibromohexyloxy)phenyl, 3,4-di(trifluoromethoxy)phenyl, 3,4-di(4,4,4-trichlorobutoxy)phenyl, 2,4-di(3-chloro-2-methoxypropyl)phenyl, 2,5-di(3-chloropropoxy)phenyl, 2,6-di(2,2,2-trifluoroethoxy)phenyl, 3,4,5-tri(trifluoromethoxy)phenyl, 4-(2,2,2-trichloroethoxy)phenyl, 2-methyl-4-trifluoromethoxyphenyl, 3-ethyl-4-trichloromethoxyphenyl, 2-methoxy-4-trifluoromethoxyphenyl, 3-ethoxy-4-trichloromethoxyphenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluorbmethylphenyl, 2-(bromomethyl)phenyl, 3-(2-chloroethyl)phenyl, 4-(2,3-dichloropropyl)phenyl, 4-(4-fluorobutyl)phenyl, 3-(5-chloropentyl)phenyl, 4-(5-bromohexyl)phenyl, 4-(5,6-dibromohexyl)phenyl, 3,4-di(trifluoromethyl)phenyl, 3,4-di(4,4,4-trichlorobutyl)phenyl, 2,4-di(3-chloro-2-methylpropyl)phenyl, 2,5-di(3-chloropropyl)phenyl, 2,6-di(2,2,2-trifluoroethyl)phenyl, 3,4,5-tri(trifluoromethyl)phenyl, 4-(2,2,2-trichloroethyl)phenyl, 2-methyl-4-trifluoromethylphenyl, 3-ethyl-4-trichloromethylphenyl, 2-methoxycarbonylphenyl, 3-methoxycarbonylphenyl, 4-methoxycarbonylphenyl, 2-ethoxycarbonylphenyl, 3-ethoxycarbonylphenyl, 4-ethoxycarbonylphenyl, 4-isopropoxycarbonylphenyl, 3-butoxycarbonylphenyl, 4-tert-butoxycarbonylphenyl, 4-pentyloxycarbonylphenyl, 4-hexyloxycarbonylphenyl, 3,4-dimethoxycarbonylphenyl, 3,4-diethoxycarbonylphenyl, 2,4-dimethoxycarbonylphenyl, 2,5-diethoxycarbonylphenyl, 2,6-dimethoxycarbonylphenyl, 3,4,5-triethoxycarbonylphenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, 3,4-dicyanophenyl, 3,5-dicyanophenyl, 2,4-dicyanophenyl, 2,5-dicyanophenyl, 2,6-dicyanophenyl, 3,4,5-tricyanophenyl, 2-phenylphenyl, 3-phenylphenyl, 4-phenylphenyl, 3,4-diphenylphenyl, 3,5-diphenylphenyl, 2,4-diphenylphenyl, 2,5-diphenylphehyl, 2,6-diphenylphenyl, 3,4,5-triphenylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 2,5-dichlorophenyl, 3,4-dichlorophenyl, 2,6-dichlorophenyl, 3,5-dichlorophenyl, 2,4,6-trichlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2,5-difluorophenyl, 2,4-difluorophenyl, 3,4-difluorophenyl, 3,5-difluorophenyl, 2,6-difluorophenyl, 2,4,6-trifluorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 2-iodophenyl, 3-iodophenyl, 4-iodophenyl, 2,3-dibromophenyl, 2,4-diiodophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 4-hydroxyphenyl, 3,4-dihydroxyphenyl, 3,5-dihydroxyphenyl, 2,4-dihydroxyphenyl, 2,5-dihydroxyphenyl, 2,6-dihydroxyphenyl, 3,4,5-trihydroxyphenyl, 3-benzylphenyl, 2-(2-phenylethyl)phenyl, 4-(1-phenylethyl)phenyl, 2-(3-phenylpropyl)phenyl, 3-(4-phenylbutyl)phenyl, 4-(5-phenylpentyl)phenyl, 2-(6-phenylhexyl)phenyl, 4-(1,1-dimethyl-2-phenylethyl)phenyl, 3-(2-methyl-3-phenylpropyl)phenyl, 2-(4-fluorobenzyl)phenyl, 2-methyl-5-chlorophenyl, 2-methoxy-5-chlorophenyl, 4-(4-fluorobenzoyl)phenyl, 4-(4-fluorobenzyl)phenyl, 3-(2-chlorobenzyl)phenyl, 4-(3-chlorobenzyl)phenyl, 2-(4-chlorobenzyl)phenyl, 3-[2-(4-fluorophenyl)ethyl]phenyl, 4-[2-(4-chlorophenyl)ethyl]phenyl, 2-(3,4-dibromobenzyl)phenyl, 3-(3,4-diiodobenzyl)phenyl, 4-(2,4-difluorobenzyl)phenyl, 2-(2,5-dichlorobenzyl)phenyl, 3-(2,6-dichlorobenzyl)phenyl, 4-(3,4,5-trifluorobenzyl)phenyl, 2-[3-(4-chlorophenyl)propyl]phenyl, 3-[1-(2-bromophenyl)ethyl]phenyl, 4-[4-(3-fluorophenyl)butyl]phenyl, 2-[5-(4-iodophenyl)pentyl]phenyl, 3-[6-(4-chlorophenyl)hexyl]phenyl, 2-[1,1-dimethyl-2-(3-fluorophenyl)ethyl]phenyl, 4-[2-methyl-3-(4-chlorophenyl)propyl]phenyl, 2,4-dibenzylphenyl, 2,4,6-tribenzylphenyl, 2-chloro-4-cyanophenyl, 3-hydroxy-4-phenylphenyl, 3-ethoxycarbonyl-2-benzoylphenyl, 2-benzyl-4-methyl-6-methoxyphenyl, 4-[(2-methoxyethyl)carbamoyl]phenyl, 3-(N-ethyl-N-isopropylcarbamoyl)phenyl, 4-dimethylcarbamoylphenyl, 2-carboxyphenyl, 3-carboxyphenyl, and 4-carboxyphenyl groups. 
         [0139]    Examples of the phenyl group which has a lower alkylenedioxy group as a substituent on the phenyl ring include phenyl groups which has a linear or branched alkylenedioxy group having 1 to 4 carbon atom as a substituent on the phenyl ring such as 3,4-methylenedioxyphenyl, 3,4-trimethylenedioxyphenyl, 2,3-ethylenedioxyphenyl, 2,3-tetramethylenedioxyphenyl, 2,3-methylenedioxyphenyl, 3,4-ethylenedioxyphenyl, and 2,3-trimethylenedioxyphenyl groups. 
         [0140]    Examples of the naphthyl lower alkyl group include naphthylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1 or 2-)naphthylmethyl, 2-[(1 or 2-)naphthyl]ethyl, 1-[(1 or 2-)naphthyl]ethyl, 3-[(1 or 2-)naphthyl]propyl, 4-[(1 or 2-)naphthyl]butyl, 5-[(1 or 2-)naphthyl]pentyl, 6-[(1 or 2-)naphthyl]hexyl, 1,1-dimethyl-2-[(1 or 2-)naphthyl]ethyl, and 2-methyl-3-[(1 or 2-)naphthyl]propyl groups. 
         [0141]    Examples of the phenoxy group which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a cyano group, a lower alkyl group which may have a halogen atom as a substituent, and a lower alkoxy group which may have a halogen atom as a substituent include phenoxy groups which may be substituted on the phenyl group with 1 to 3 groups selected from the group consisting of a cyano group, a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents, and a linear or branched alkoxy group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents such as phenoxy, 2-methylphenoxy, 3-methylphenyl, 4-methylphenoxy, 2-ethylphenoxy, 3-ethylphenoxy, 4-ethylphenoxy, 4-isopropylphenoxy, 3-butylphenoxy, 4-pentylphenoxy, 4-hexylphenoxy, 3,4-dimethylphenoxy, 3,4-diethylphenoxy, 2,4-dimethylphenoxy, 2,5-dimethylphenoxy, 2,6-dimethylphenoxy, 3,4,5-trimethylphenoxy, 2-methoxyphenoxy, 3-methoxyphenoxy, 4-methoxyphenoxy, 2-ethoxyphenoxy, 3-ethoxyphenoxy, 4-ethoxyphenoxy, 4-isopropoxyphenoxy, 3-butoxyphenoxy, 4-pentyloxyphenoxy, 4-hexyloxyphenoxy, 3,4-dimethoxyphenoxy, 3,4-diethoxyphenoxy, 2,4-dimethoxyphenoxy, 2,5-dimethoxyphenoxy, 2,6-dimethoxyphenoxy, 3,4,5-trimethoxyphenoxy, 2-trifluoromethoxyphenoxy, 3-trifluoromethoxyphenoxy, 4-trifluoromethoxyphenoxy, 2-(bromomethoxy)phenoxy, 3-(2-chloroethoxy)phenoxy, 4-(2,3-dichloropropoxy)phenoxy, 4-(4-fluorobutoxy)phenoxy, 3-(5-chloropentyloxy)phenoxy, 4-(5-bromohexyloxy)phenoxy, 4-(5,6-dibromohexyloxy)phenoxy, 3,4-di(trifluoromethoxy)phenoxy, 3,4-di(4,4,4-trichlorobutoxy)phenoxy, 2,4-di(3-chloro-2-methoxypropyl)phenoxy, 2,5-di(3-chloropropoxy)phenoxy, 2,6-di(2,2,2-trifluoroethoxy)phenoxy, 3,4,5-tri(trifluoromethoxy)phenoxy, 4-(2,2,2-trichloroethoxy)phenoxy, 2-methyl-4-trifluoromethoxyphenoxy, 3-ethyl-4-trichloromethoxyphenoxy, 2-methoxy-4-trifluoromethoxyphenoxy, 3-ethoxy-4-trichloromethoxyphenoxy, 2-trifluoromethylphenoxy, 3-trifluoromethylphenoxy, 4-trifluoromethylphenoxy, 2-(bromomethyl)phenoxy, 3-(2-chloroethyl)phenoxy, 4-(2,3-dichloropropyl)phenoxy, 4-(4-fluorobutyl)phenoxy, 3-(5-chloropentyl)phenoxy, 4-(5-bromohexyl)phenoxy, 4-(5,6-dibromohexyl)phenoxy, 3,4-di(trifluoromethyl)phenoxy, 3,4-di(4,4,4-trichlorobutyl)phenoxy, 2,4-di(3-chloro-2-methylpropyl)phenoxy, 2,5-di(3-chloropropyl)phenoxy, 2,6-di(2,2,2-trifluoroethyl)phenoxy, 3,4,5-tri(trifluoromethyl)phenoxy, 4-(2,2,2-trichloroethyl)phenoxy, 2-methyl-4-trifluoromethylphenoxy, 3-ethyl-4-trichloromethylphenoxy, 2-cyanophenoxy, 3-cyanophenoxy, 4-cyanophenoxy, 3,4-dicyanophenoxy, 3,5-dicyanophenoxy, 2,3-dicyanophenoxy, 2,4-dicyanophenoxy, 2,5-dicyanophenoxy, 2,6-dicyanophenoxy, 3,4,5-tricyanophenoxy, 2-cyano-4-methylphenoxy, 3-cyano-4-methoxyphenoxy, 3-cyano-5-trifluoromethylphenoxy, and 4-cyano-3-trifluoromethoxyphenoxy groups. 
         [0142]    Examples of the phenyl lower alkoxy group which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, and a lower alkoxy group which may have a halogen atom as a substituent include, in addition to the above described phenyl lower alkoxy groups, phenylalkoxy groups which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a halogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents, and a linear or branched alkoxy group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents, and whose alkoxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms such as 2,5-difluorobenzyloxy, 2,4-difluorobenzyloxy, 3,4-difluorobenzyloxy, 3,5-difluorobenzyloxy, 2,6-difluorobenzyloxy, 3-trifluoromethylbenzyloxy, 2-trifluoromethylbenzyloxy, 4-trifluoromethylbenzyloxy, 3,4-dimethoxybenzyloxy, 3,5-dimethoxybenzyloxy, 2-chlorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 2-methylbenzyloxy, 3-methylbenzyloxy, 4-methylbenzyloxy, 3,4-dimethylbenzyloxy, 2,3-dimethylbenzyloxy, 2-methoxybenzyloxy, 3-methoxybenzyloxy, 4-methoxybenzyloxy, 2,3-dichlorobenzyloxy, 2,4-dichlorobenzyloxy, 2,5-dichlorobenzyloxy, 3,4-dichlorobenzyloxy, 2,6-dichlorobenzyloxy, 4-fluorobenzyloxy, 3-fluorobenzyloxy, 2-fluorobenzyloxy, 3-trifluoromethoxybenzyloxy, 4-trifluoromethoxybenzyloxy, 2-trifluoromethoxybenzyloxy, 4-tert-butylbenzyloxy, 4-ethylbenzyloxy, 4-isopropylbenzyloxy, 4-methoxy-3-chlorobenzyloxy, 2-(4-methoxyphenyl)ethoxy, 2-(4-fluorophenyl)ethoxy, 2-(4-chlorophenyl)ethoxy, 2-(3-methoxyphenyl)ethoxy, 2-(4-methylphenyl)ethoxy, 3-methyl-4-chlorobenzyloxy, 4-(4-methoxyphenyl)butoxy, 2-(4-methylphenyl)ethoxy, 4-tert-butitocybenzyloxy, 3-chloro-6-methoxybenzyloxy, 4-methoxy-3-methylbenzyloxy, 2-(2-fluorophenyl)ethoxy, 1-(3-bromophenyl)ethoxy, 3-(4-iodophenyl)propoxy, 4-(2-bromophenyl)butoxy, 5-(3-chlorophenyl)pentyloxy, 6-(4-bromophenyl)hexyloxy, 1,1-dimethyl-2-(2,4-dichlorophenyl)ethoxy, 2-methyl-3-(2,4,6-trifluorophenyl)propoxy, 2-(2-ethylphenyl)ethoxy, 1-(3-propylphenyl)ethoxy, 3-(4-butylphenyl)propoxy, 4-(2-pentylphenyl)butoxy, 5-(3-hexylphenyl)pentyloxy, 6-(4-trifluoromethylphenyl)hexyloxy, 1,1-dimethyl-2-(2,4-dimethylphenyl)ethoxy, 2-methyl-3-[2,4,6-tri(trifluoromethyl)phenyl]propoxy, 2-(2-ethoxyphenyl)ethoxy, 1-(3-propoxyphenyl)ethoxy, 3-(4-butoxyphenyl)propoxy, 4-(2-pentyloxyphenyl)butoxy, 5-(3-hexyloxyphenyl)pentyloxy, 6-(4-trifluoromethoxyphenyl)hexyloxy, 1,1-dimethyl-2-(2,4-dimethoxyphenyl)ethoxy, and 2-methyl-3-[2,4,6-tri(trifluoromethoxy)phenyl]propoxy groups. 
         [0143]    Examples of the 1,2,3,4-tetrahydronaphthyl substituted lower alkyl group which may have 1 to 5 lower alkyl groups as substituents on the 1,2,3,4-tetrahydronaphthalene ring include 1,2,3,4-tetrahydronaphthyl substituted alkyl groups which may have 1 to 5 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents on the 1,2,3,4-tetrahydronaphthalene ring, and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1, 2, 5 or 6-)1,2,3,4-tetrahydronaphthylmethyl, 2-[(1, 2, 5 or 6-)1,2,3,4-tetrahydronaphthyl]ethyl, 1-[(1, 2, 5 or 6-)1,2,3,4-tetrahydronaphthyl]ethyl, 3-[(1, 2, 5 or 6-)1,2,3,4-tetrahydronaphthyl]propyl, 4-[(1, 2, 5 or 6-)1,2,3,4-tetrahydronaphthyl]butyl, 5-[(1, 2, 5 or 6-)1,2,3,4-tetrahydronaphthyl]pentyl, 6-[(1, 2, 5 or 6-)1,2,3,4-tetrahydronaphthyl]hexyl, 1,1-dimethyl-2-[(1, 2, 5 or 6-)1,2,3,4-tetrahydronaphthyl]ethyl, 2-methyl-3-[(1, 2, 5 or 6-)1,2,3,4-tetrahydronaphthyl]propyl, 1,1,4,4-tetramethyl(2, 3, 5 or 6-)1,2,3,4-tetrahydronaphthylmethyl, 1,1,4,4,5-pentamethyl(2, 3, 6, 7 or 8-)1,2,3,4-tetrahydronaphthylmethyl, 1,4,4-trimethyl(2, 3, 5, 6, 7 or 8-)1,2,3,4-tetrahydronaphthylmethyl, 5,6-dimethyl(2, 3, 7 or 8-)1,2,3,4-tetrahydronaphthylmethyl, 2-[1-methyl-(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydronaphthyl]ethyl, 1-[2-ethyl-(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydronaphthyl]ethyl, 3-[3-propyl-(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydronaphthyl]propyl, 4-[(4-butyl-(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydronaphthyl]butyl, 5-[5-pentyl-(1, 2, 3, 4, 6, 7 or 8-)1,2,3,4-tetrahydronaphthyl]pentyl, 6-[6-hexyl-(1, 2, 3, 4, 5, 7 or 8-)1,2,3,4-tetrahydronaphthyl]hexyl, 1,1-dimethyl-2-[1,7-dimethyl-(1, 2, 3, 4, 5, 6 or 8-)1,2,3,4-tetrahydronaphthyl]ethyl, and 2-methyl-3-[1,1,4-trimethyl-(2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydronaphthyl]propyl groups. 
         [0144]    Examples of the piperidinyl group which may have 1 to 3 lower alkyl groups as substituents on the piperidine ring include piperidinyl group which may have 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents on the piperidine ring such as (1, 2, 3 or 4-)piperidinyl, 1-methyl-(2, 3 or 4-)piperidinyl, 1-ethyl-(2, 3 or 4-)piperidinyl, 1-propyl-(2, 3 or 4-)piperidinyl, 1-isopropyl-(2, 3 or 4-)piperidinyl, 1-butyl-(2, 3 or 4-)piperidinyl, 1-isobutyl-(2, 3 or 4-)piperidinyl, 1-tert-butyl-(2, 3 or 4-)piperidinyl, 1-pentyl-(2, 3 or 4-)piperidinyl, 1-hexyl-(2, 3 or 4-)piperidinyl, 1,2-dimethyl-(3, 4, 5 or 6-)piperidinyl, and 1,2,6-trimethyl-(3, 4 or 5-)piperidinyl groups. 
         [0145]    Examples of the quinolyl lower alkyl group include quinolylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2, 3, 4, 5, 6, 7 or 8-)quinolylmethyl, 2-[(2, 3, 4, 5, 6, 7 or 8-)quinolyl]ethyl, 1-[(2, 3, 4, 5, 6, 7 or 8-)quinolyl]ethyl, 3-[(2, 3, 4, 5, 6, 7 or 8-)quinolyl]propyl, 4-[(2, 3, 4, 5, 6, 7 or 8-)quinolyl]butyl, 5-[(2, 3, 4, 5, 6, 7 or 8-)pentyl, and 6-[(2, 3, 4, 5, 6, 7 or 8-)hexyl groups. 
         [0146]    Examples of the 1,2,3,4-tetrazolyl lower alkyl group which may have, on the tetrazole ring, a substituent selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group include 1,2,3,4-tetrazolylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms and which may have, on the tetrazole ring, a substituent selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms and a phenyl alkyl group whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms, such as [(1 or 5-)1,2,3,4-tetrazolyl]methyl, 2-[(1 or 5-)1,2,3,4-tetrazolyl]ethyl, 1-[(1 or 5-)1,2,3,4-tetrazolyl]ethyl, 3-[(1 or 5-)1,2,3,4-tetrazolyl]propyl, 4-[(1 or 5-)1,2,3,4-tetrazolyl]butyl, 5-[(1 or 5-)1,2,3,4-tetrazolyl]pentyl, 6-[(1 or 5-)1,2,3,4-tetrazolyl]hexyl, 5-[1-methyl-5-(1,2,3,4-tetrazolyl)]pentyl, 6-[1-methyl-5-(1,2,3,4-tetrazolyl)]hexyl, 5-methyl-1-(1,2,3,4-tetrazolyl)methyl, 2-[5-ethyl-1-(1,2,3,4-tetrazolyl]hexyl, 1,1-dimethyl-2-[(1 or 5-)1,2,3,4-tetrazolyl)]ethyl, 2-methyl-3-[(1 or 5-)1,2,3,4-tetrazolyl]propyl, [1-methyl-5-(1,2,3,4-tetrazolyl)]methyl, [1-ethyl-5-(1,2,3,4-tetrazolyl)]methyl, 2-[1-propyl-5-(1,2,3,4-tetrazolyl)]ethyl, 1-[1-butyl-5-(1,2,3,4-tetrazolyl)]ethyl, 3-[1-pentyl-5-(1,2,3,4-tetrazolyl)]propyl, 3-[5-propyl-1-(1,2,3,4-tetrazolyl)]propyl, 4-[5-butyl-1-(1,2,3,4-tetrazolyl)]butyl, 5-[5-pentyl-1-(1,2,3,4-tetrazolyl)]pentyl, 6-[5-hexyl-1-(1,2,3,4-tetrazolyl)]hexyl, [1-ethyl-5-(1,2,3,4-tetrazolyl)]methyl, [1-benzyl-5-(1,2,3,4-tetrazolyl)]methyl, 1-[(2-phenylethyl)-5-(1,2,3,4-tetrazolyl)]methyl, 2-[1-(3-phenylpropyl)-5-(1,2,3,4-tetrazolyl)]ethyl, 1-[1-(4-phenylbutyl)-5-(1,2,3,4-tetrazolyl)]ethyl, 3-[1-(5-phenylpentyl)-5-(1,2,3,4-tetrazolyl)]propyl, 4-[1-(6-phenylhexyl)-5-(1,2,3,4-tetrazolyl)]butyl, 5-[1-(1,1-dimethyl-2-phenylethyl)-5-(1,2,3,4-tetrazolyl)]methyl, 6-[1-(2-methyl-3-phenylpropyl)-5-(1,2,3,4-tetrazolyl)]hexyl, 5-benzyl-1-(1,2,3,4-tetrazolyl)methyl, 2-[5-(1-phenylethyl)-1-(1,2,3,4-tetrazolyl)]ethyl, 3-[5-(3-phenylpropyl)-1-(1,2,3,4-tetrazolyl)]propyl, 4-[5-(4-phenylbutyl)-1-(1,2,3,4-tetrazolyl)]butyl, 5-[5-(5-phenylpentyl)-1-(1,2,3,4-tetrazolyl)]pentyl, and 6-[5-(6-phenylhexyl)-1-(1,2,3,4-tetrazolyl)]hexyl groups. 
         [0147]    Examples of the thiazolyl lower alkyl group which may have a phenyl group as a substituent on the thiazole ring include thiazolylalkyl groups which may have 1 or 2 phenyl groups as substituents on the thiazole ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(2, 4 or 5-)thiazolyl]methyl, 2-[(2, 4 or 5-)thiazolyl]ethyl, 1-[(2, 4 or 5-)thiazolyl]ethyl, 3-[(2, 4 or 5-)thiazolyl]propyl, 4-[(2, 4 or 5-)thiazolyl]butyl, 5-[(2, 4 or 5-)thiazolyl]pentyl, 6-[(2, 4 or 5-)thiazolyl]hexyl, 1,1-dimethyl-2-[(2, 4 or 5-)thiazolyl]ethyl, 2-methyl-3-[(2, 4 or 5-)thiazolyl]propyl, [2-phenyl-(4 or 5-)thiazolyl]methyl, 2-[4-phenyl-(2 or 5-)thiazolyl]ethyl, 1-[5-phenyl-(2 or 4-)thiazolyl]ethyl, 3-[2-phenyl-(2 or 5-)thiazolyl]propyl, 4-(2,4-diphenyl-5-thiazolyl)butyl, 5-(2,5-diphenyl-4-thiazolyl)pentyl, 6-(4,5-diphenyl-2-thiazolyl)hexyl, 1,1-dimethyl-2-[2-phenyl-(4 or 5-)thiazolyl]ethyl, 2-methyl-3-[4-phenyl-(2 or 5-)thiazolyl]propyl, [4-phenyl-(2 or 5-)thiazolyl]methyl, [5-phenyl-(2 or 4-)thiazolyl]methyl, (2,4-diphenyl-5-thiazolyl)methyl, (2,5-diphenyl-4-thiazolyl)methyl, and (4,5-diphenyl-2-thiazolyl)methyl groups. 
         [0148]    Examples of the benzoyl lower alkyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkoxy group and a halogen atom include benzoylalkyl groups which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a linear or branched alkoxy group having 1 to 6 carbon atoms and a halogen atom and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as benzoylmethyl, 2-benzoylethyl, 1-benzoylethyl, 3-benzoylpropyl, 4-benzoylbutyl, 5-benzoylpentyl, 6-benzoylhexyl, 1,1-dimethyl-2-benzoylethyl, 2-methyl-3-benzoylpropyl, 4-fluorobenzoylmethyl, 2-chlorobenzoylmethyl, 3-chlorobenzoylmethyl, 4-chlorobenzoylmethyl, 2-(4-fluorobenzoyl)ethyl, 2-(4-chlorobenzoyl)ethyl, 3,4-dibromobenzoylmethyl, 3,4-diiodobenzoylmethyl, 2,4-difluorobenzoylmethyl, 2,5-dichlorobenzoylmethyl, 2,6-dichlorobenzoylmethyl, 3,4,5-trifluorobenzoylmethyl, 3-(4-chlorobenzoyl)propyl, 1-(2-bromobenzoyl)ethyl, 4-(3-fluorobenzoyl)butyl, 5-(4-iodobenzoyl)pentyl, 6-(4-chlorobenzoyl)hexyl, 1,1-dimethyl-2-(3-fluorobenzoyl)ethyl, 2-methyl-3-(4-chlorobenzoyl)propyl, 2-methoxybenzoylmethyl, 2-(3-methoxybenzoyl)ethyl, 2-(4-methoxybenzoyl)ethyl, 4-methoxybenzoylmethyl, 1-(2-ethoxybenzoyl)ethyl, 3-(3-ethoxybenzoyl)propyl, 4-(4-ethoxybenzoyl)butyl, 5-(4-isopropoxybenzoyl)pentyl, 6-(3-butoxybenzoyl)hexyl, 1,1-dimethyl-2-(4-pentyloxybenzoyl)ethyl, 2-methyl-3-(4-hexyloxybenzoyl)propyl, 3,4-dimethoxybenzoylmethyl, 3,4-diethoxybenzoylmethyl, 2,4-dimethoxybenzoylmethyl, 2,5-dimethoxybenzoylmethyl, 2,6-dimethoxybenzoylmethyl, 3,4,5-trimethoxybenzoylmethyl, 2-chloro-4-methoxybenzoylmethyl, and 3-fluoro-5-ethoxybenzoylmethyl groups. 
         [0149]    Examples of the piperidinyl lower alkyl group which may have a lower alkyl group as a substituent on the piperidine ring include piperidinylalkyl groups which may have 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents on the piperidine ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(1, 2, 3 or 4-)piperidinyl]methyl, 2-[(1, 2, 3 or 4-)piperidinyl]ethyl, 1-[(1, 2, 3 or 4-)piperidinyl]ethyl, 3-[(1, 2, 3 or 4-)piperidinyl]propyl, 4-[(1, 2, 3 or 4-)piperidinyl]butyl, 5-[(1, 2, 3 or 4-)piperidinyl]pentyl, 6-[(1, 2, 3 or 4-)piperidinyl]hexyl, 1,1-dimethyl-2-[(1, 2, 3 or 4-)piperidinyl]ethyl, 2-methyl-3-[(1, 2, 3 or 4-)piperidinyl]propyl, [1-methyl-(2, 3 or 4-)piperidinyl]methyl, 2-[1-ethyl-(2, 3 or 4-)piperidinyl]ethyl, 1-[4-propyl-(1, 2 or 3-)piperidinyl]ethyl, 3-[3-isopropyl-(1, 2, 4, 5 or 6-)piperidinyl]propyl, 4-[2-butyl-(1, 3, 4, 5 or 6-)piperidinyl]butyl, 5-[1-isobutyl-(2, 3 or 4-)piperidinyl]pentyl, 6-[1-tert-butyl-(2, 3 or 4-)piperidinyl]hexyl, 1,1-dimethyl-2-[4-pentyl-(1, 2 or 3-)piperidinyl]ethyl, 2-methyl-3-[1-hexyl-(2, 3 or 4-)piperidinyl]propyl, [1,2-dimethyl-(3, 4, 5 or 6-)piperidinyl]methyl, and [1,2,6-trimethyl-(3, 4 or 5-)piperidinyl]methyl groups. 
         [0150]    Examples of the imidazolyl group which may have 1 to 3 phenyl groups as substituents on the imidazole ring include imidazolyl groups which may have 1 to 3 phenyl groups as substituents on the imidazole ring such as 1, 2, 4 or 5-)imidazolyl, 1-phenyl-(2, 4 or 5-)imidazolyl, 2-phenyl-(1, 4 or 5-)imidazolyl, 4-phenyl-(1, 2 or 5-)imidazolyl, 5-phenyl-(1, 2 or 4-)imidazolyl, 1,2-diphenyl-(4 or 5-)imidazolyl, 2,4-diphenyl-(1 or 5-)imidazolyl, 4,5-diphenyl-(1 or 2-)imidazolyl, 2,5-diphenyl-(1 or 4-)imidazolyl, and 2,4,5-triphenyl-1-imidazolyl groups. 
         [0151]    Examples of the benzimidazolyl group which may have 1 to 3 lower alkyl groups as substituents on the benzimidazole ring include benzimidazolyl group which may have 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents on the benzimidazole ring such as (1, 2, 4, 5, 6 or 7-)benzimidazolyl, 1-methyl-(2, 4, 5, 6 or 7-)benzimidazolyl, 2-ethyl-(1, 4, 5, 6 or 7-)benzimidazolyl, 4-propyl-(1, 2, 5, 6 or 7-)benzimidazolyl, 5-butyl-(1, 2, 4, 6 or 7-)benzimidazolyl, 6-pentyl-(1, 2, 4, 5 or 7-)benzimidazolyl, 7-hexyl-(1, 2, 4, 5 or 6-)benzimidazolyl, 1-ethyl-(2, 4, 5, 6 or 7-)benzimidazolyl]hexyl, 1-butyl-(2, 4, 5, 6 or 7-)benzimidazolyl, 1-isopropyl-(1, 2, 4, 5, 6 or 7-)benzimidazolyl, 1,2-dimethyl-(4, 5, 6 or 7-)benzimidazolyl, 1-methyl-4-ethyl-(2, 5, 6 or 7-)benzimidazolyl, 1-propyl-5-methyl-(2, 4, 6 or 7-)benzimidazolyl, and 1,2,5-trimethyl-(2, 4, 5, 6 or 7-)benzimidazolyl groups. 
         [0152]    Examples of the pyridyl lower alkoxy group include pyridylalkoxy groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2, 3 or 4-)pyridylmethoxy, 2-[(2, 3 or 4-)pyridyl]ethoxy, 1-[(2, 3 or 4-)pyridyl]ethoxy, 3-[(2, 3 or 4-)pyridyl]propoxy, 4-[(2, 3 or 4-)pyridyl]butoxy, 1-1-dimethyl-2-[(2, 3 or 4-)pyridyl]ethoxy, 5-[(2, 3 or 4-)pyridyl]pentyloxy, 6-[(2, 3 or 4-)pyridyl]hexyloxy, 1-[(2, 3 or 4-)pyridyl]isopropoxy, and 2-methyl-3-[(2, 3 or 4-)pyridyl]propoxy groups. 
         [0153]    Examples of the 1,2,3,4-tetrahydroquinolyl lower alkyl group which may have an oxo group as a substituent on the tetrahydroquinoline ring include 1,2,3,4-tetrahydroquinolylalkyl groups which may have 1 or 2 oxo groups as substituents on the tetrahydroquinoline ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolylmethyl, 2-[(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]ethyl, 1-[(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]ethyl, 3-[(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]propyl, 4-[(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]butyl, 5-[(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]pentyl, 6-[(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]hexyl, 1,1-dimethyl-2-[(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]ethyl, 2-methyl-3-[(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]propyl, [2-oxo-(1, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]methyl, [4-oxo-(1, 2, 3, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]methyl, [2,4-dioxo-(1, 3, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]methyl, 2-[2-oxo-(1, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]ethyl, 3-(4-oxo-(1, 2, 3, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]propyl, 4-[2,4-dioxo-(1, 3, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]butyl, 5-[2-oxo-(1, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]pentyl, and 6-[4-oxo-(1, 2, 3, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]hexyl groups. 
         [0154]    Examples of the 1,3,4-oxadiazolyl lower alkyl group which may have an oxo group as a substituent on the 1,3,4-oxadiazole ring include 1,3,4-oxadiazolylalkyl groups which may have an oxo group as a substituent on the 1,3,4-oxadiazole ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2 or 5-)1,3,4-oxadiazolylmethyl, 2-[(2 or 5-)1,3,4-oxadiazolyl]ethyl, 1-[(2 or 5-)1,3,4-oxadiazolyl]ethyl, 3-[(2 or 5-)1,3,4-oxadiazolyl]propyl, 4-[(2 or 5-)1,3,4-oxadiazolyl]butyl, 5-[(2 or 5-)1,3,4-oxadiazolyl]pentyl, 6-[(2 or 5-)1,3,4-oxadiazolyl]hexyl, 1,1-dimethyl-2-[(2 or 5-)1,3,4-oxadiazolyl]ethyl, 2-methyl-3-[(2 or 5-)1,3,4-oxadiazolyl]propyl, 2-oxo-[(3 or 5-)1,3,4-oxadiazolyl]methyl, 5-oxo-[(2 or 3-)1,3,4-oxadiazolyl]methyl, 2-[2-oxo-(3 or 5-)(1,3,4-oxadiazolyl)]ethyl, 1-[5-oxo-(2 or 3-)1,3,4-oxadiazolyl]ethyl, 3-[(2 or 5-)1,3,4-oxadiazolyl]propyl, 4-[2-oxo(3 or 5-)1,3,4-oxadiazolyl]butyl, 5-[5-oxo(2 or 3-)1,3,4-oxadiazolyl]pentyl, 6-[2-oxo(3 or 5-)1,3,4-oxadiazolyl]hexyl, 1,1-dimethyl-2-[5-oxo(2 or 3-)1,3,4-oxadiazolyl]ethyl, and 2-methyl-3-[2-oxo(3 or 5-)1,3,4-oxadiazolyl]propyl groups. 
         [0155]    Examples of the thienyl lower alkyl group include thienylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2 or 3-)thienylmethyl, 2-[(2 or 3-)thienyl]ethyl, 1-[(2 or 3-)thienyl]ethyl, 3-[(2 or 3-)thienyl]propyl, 4-[(2 or 3-)thienyl]butyl, 5-[(2 or 3-)thienyl]pentyl, 6-[(2 or 3-)thienyl]hexyl, 1,1-dimethyl-2-[(2 or 3-)thienyl]ethyl, and 2-methyl-3-[(2 or 3-)thienyl]propyl groups. 
         [0156]    Examples of the pyrimidinylcarbonyl group which may have an oxo group as a substituent on the pyrimidine ring include pyrimidinylcarbonyl groups which may have 1 to 3 oxo groups as substituents on the pyrimidine ring such as (2, 3, 4 or 6-)pyrimidinylcarbonyl, 2,6-dioxo-(1, 3, 4 or 5-)pyrimidinylcarbonyl, 2-oxo-(1, 3, 4, 5 or 6-)pyrimidinylcarbonyl, 6-oxo-(1, 2, 3, 4 or 5-)pyrimidinylcarbonyl, 4-oxo-(1, 2, 3, 5 or 6-)pyrimidinylcarbonyl, 2,4-dioxo-(1, 3, 4 or 6-)pyrimidinylcarbonyl, and 2,4,6-trioxo-(1, 3 or 5-)pyrimidinylcarbonyl groups. 
         [0157]    Examples of the lower alkoxy lower alkoxy group include linear or branched alkoxy groups having 1 to 6 carbon atoms which may have a linear or branched alkoxy group having 1 to 6 carbon atoms as a substituent such as methoxymethoxy, 1-ethoxyethoxy, 2-methoxyethoxy, 2-propoxyethoxy, 3-isopropoxypropoxy, 4-butbxybutoxy, 5-pentyloxypentyloxy, 6-hexyloxyhexyloxy, 1,1-dimethyl-2-methoxyethoxy, 2-methyl-3-ethoxypropoxy, and 3-methoxypropoxy groups. 
         [0158]    Examples of the lower alkoxycarbonyl lower alkoxy group include alkoxycarbonylalkoxy groups whose two alkoxy moieties are linear or branched alkoxy groups having 1 to 6 carbon atoms such as methoxycarbonylmethoxy, ethoxycarbonylmethoxy, 2-methoxycarbonylethoxy, 2-ethoxycarbonylethoxy, 1-ethoxycarbonylethoxy, 3-methoxycarbonylpropoxy, 3-ethoxycarbonylpropoxy, 4-ethoxycarbonylbutoxy, 5-isopropoxycarbonylpentyloxy, 6-propoxycarbonylhexyloxy, 1,1-dimethyl-2-butoxycarbonylethoxy, 2-methyl-3-tert-butoxycarbonylpropoxy, 2-pentyloxycarbonylethoxy, and hexyloxycarbonylmethoxy groups. 
         [0159]    Examples of the carboxy lower alkoxy group include carboxyalkoxy groups whose alkoxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms such as carboxymethoxy, 2-carboxyethoxy, 1-carboxyethoxy, 3-carboxypropoxy, 4-carboxybutoxy, 5-carboxypentyloxy, 6-carboxyhexyloxy, 1,1-dimethyl-2-carboxyethoxy, and 2-methyl-3-carboxypropoxy groups. 
         [0160]    Examples of the phenoxy lower alkanoyl group include phenoxyalkanoyl groups whose alkanoyl moiety is a linear or branched alkanoyl group having 2 to 6 carbon atoms such as 2-phenoxyacetyl, 3-phenoxypropionyl, 2-phenoxypropionyl, 4-phenoxybutyryl, 5-phenoxypentanoyl, 6-phenoxyhexanoyl, 2,2-dimethyl-2-phenoxypropionyl, and 2-methyl-3-phenoxypropionyl groups. 
         [0161]    Examples of the 1,2,3,4-tetrahydroquinolylcarbonyl group which may have an oxo group as a substituent on the tetrahydroquinoline ring include 1,2,3,4-tettahydroquinolylcarbonyl groups which may have 1 or 2 oxo groups as substituents on the tetrahydroquinoline ring such as [(1, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]carbonyl, [2-oxo-(1, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]carbonyl, [4-oxo-(1, 2, 3, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]carbonyl, and [2,4-dioxo-(1, 3, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]carbonyl groups. 
         [0162]    Examples of the 1,2,3,4-tetrahydroquinolyl group which may have an oxo group as a substituent on the tetrahydroquinoline ring include 1,2,3,4-tetrahydroquinolyl groups which may have 1 or 2 oxo groups as substituents on the tetrahydroquinoline ring such as (1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl, 2-oxo-(1, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl, 4-oxo-(1, 2, 3, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl, and 2,4-dioxo-(1, 3, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl groups. 
         [0163]    Examples of the amino group which may have a lower alkoxycarbonyl group as a substituent include amino groups which may have a linear or branched alkoxycarbonyl group having 1 to 6 carbon atoms such as amino, methoxycarbonylamino, ethoxycarbonylamino, propoxycarbonylamino, isopropoxycarbonylamino, butoxycarbonylamino, tert-butoxycarbonylamino, pentyloxycarbonylamino, and hexyloxycarbonylamino groups. 
         [0164]    Examples of the benzoyl group which may have 1 to 3 lower alkoxy groups as substituents on the phenyl ring include benzoyl groups which may have 1 to 3 linear or branched alkoxy groups having 1 to 6 carbon atoms as substituents on the phenyl ring such as benzoyl, 2-methoxybenzoyl, 3-methoxybenzoyl, 4-methoxybenzoyl, 2-ethoxybenzoyl, 3-ethoxybenzoyl, 4-ethoxybenzoyl, 4-isopropoxybenzoyl, 3-butoxybenzoyl, 4-pentyloxybenzoyl, 4-hexyloxybenzoyl, 3,4-dimethoxybenzoyl, 3,4-diethoxybenzoyl, 2,4-dimethoxybenzoyl, 2,5-dimethoxybenzoyl, 2,6-dimethoxybenzoyl, and 3,4,5-trimethoxybenzoyl groups. 
         [0165]    Examples of the lower alkyl group which have 1 or 2 phenyls which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, and a lower alkylthio group include, in addition to the above described phenyl lower alkyl groups, linear or branched alkyl groups which have 1 to 6 carbon atoms and 1 to 2 phenyls which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a linear or branched alkoxycarbonyl group having 1 to 6 carbon atoms, a cyano group, a nitro group, a phenyl group, a halogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents, a linear or branched alkoxy group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents, and a linear or branched alkylthio group having 1 to 6 carbon atoms such as 1,1-diphenylmethyl, 1,1-di(4-fluorophenyl)methyl, 1-phenyl-1-(4-methoxyphenyl)methyl, 3,3-diphenylpropyl, 2,5-difluorobenzyl, 2,4-difluorobenzyl, 3,4-difluorobenzyl, 3,5-difluorobenzyl, 2,6-difluorobenzyl, 3-trifluoromethylbenzyl, 2-trifluoromethylbenzyl, 4-trifluoromethylbenzyl, 3,4-dimethoxybenzyl, 3,5-dimethoxybenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 2-methylbenzyl, 37-methylbenzyl, 4-methylbenzyl, 3,4-dimethylbenzyl, 2,3-dimethylbenzyl, 2-methoxybenzyl, 3-methoxybenzyl, 4-cyanobenzyl, 2-cyanobenzyl, 3-cyanobenzyl, 4-methoxybenzyl, 2,3-dichlorobenzyl, 2,4-dichlorobenzyl, 2,5-dichlorobenzyl, 3,4-dichlorobenzyl, 2,6-dichlorobenzyl, 4-fluorobenzyl, 3-fluorobenzyl, 2-fluorobenzyl, 4-nitrobenzyl, 3-nitrobenzyl, 2-nitrobenzyl, 3-trifluoromethoxybenzyl, 4-trifluoromethoxybenzyl, 2-trifluoromethoxybenzyl, 4-methoxycarbonylbenzyl, 3-methoxycarbonylbenzyl, 4-tert-butylbenzyl, 4-ethylbenzyl, 4-isopropylbenzyl, 4-methoxy-3-chlorobenzyl, 2-(4-methoxyphenyl)ethyl, 2-(4-fluorophenyl)ethyl, 2-(4-chlorophenyl)ethyl, 2-(3-methoxyphenyl)ethyl, 2-(4-methylphenyl)ethyl, 4-phenylbenzyl, 3,3-diphenylpropyl, 3-methyl-4-nitrobenzyl, 4-(4-methoxyphenyl)butyl, 2-(4-methylphenyl)ethyl, 4-tert-butitocycarbonylbenzyl, 3-chloro-6-methoxybenzyl, 4-nitro-3-methylbenzyl, 4-tert-butyrylbenzyl, 2-(2-ethoxycarbonylphenyl)ethyl, 1-(3-propoxycarbonylphenyl)ethyl, 3-(4-pentyloxycarbonylphenyl)propyl, 4-(3-hexyloxycarbonylphenyl)butyl, 5-(3,4-dimethoxycarbonylphenyl)pentyl, 6-(3,4,5-diethoxycarbonylphenyl)hexyl, 1,1-dimethyl-2-(4-butoxycarbonylphenyl)ethyl, 2-methyl-3-(4-methoxycarbonylphenyl)propyl, 2-(2-cyanophenyl)ethyl, 1-(3-cyanophenyl)ethyl, 3-(4-cyanophenyl)propyl, 4-(2-cyanophenyl)butyl, 5-(3-cyanophenyl)pentyl, 6-(4-cyanophenyl)hexyl, 1,1-dimethyl-2-(2,4-dicyanophenyl)ethyl, 2-methyl-3-(2,4,6-tricyanophenyl)propyl, 2-(2-nitrophenyl)ethyl, 1-(3-nitrophenyl)ethyl, 3-(4-nitrophenyl)propyl, 4-(2-nitrophenyl)butyl, 5-(3-nitrophenyl)pentyl, 6-(4-nitrophenyl)hexyl, 1,1-dimethyl-2-(2,4-dinitrophenyl)ethyl, 2-methyl-3-(2,4,6-trinitrophenyl)propyl, 2-(2-phenylphenyl)ethyl, 1-(3-phenylphenyl)ethyl, 3-(4-phenylphenyl)propyl, 4-(2-phenylphenyl)butyl, 5-(3-phenylphenyl)pentyl, 6-(4-phenylphenyl)hexyl, 1,1-dimethyl-2-(2,4-diphenylphenyl)ethyl, 2-methyl-3-(2,4,6-triphenylphenyl)propyl, 2-(2-fluorophenyl)ethyl, 1-(3-bromophenyl)ethyl, 3-(4-iodoruphenyl)propyl, 4-(2-bromophenyl)butyl, 5-(3-chlorophenyl)pentyl, 6-(4-bromoruphenyl)hexyl, 1,1-dimethyl-2-(2,4-dichlorophenyl)ethyl, 2-methyl-3-(2,4,6-trifluorophenyl)propyl, 2-(2-ethylphenyl)ethyl, 1-(3-propylphenyl)ethyl, 3-(4-butylphenyl)propyl, 4-(2-pentylphenyl)butyl, 5-(3-hexylphenyl)pentyl, 6-(4-trifluoromethylphenyl)hexyl, 1,1-dimethyl-2-(2,4-dimethylphenyl)ethyl, 2-methyl-3-[2,4,6-tri(trifluoromethyl)phenyl]propyl, 2-(2-ethoxyphenyl)ethyl, 1-(3-propoxyphenyl)ethyl, 3-(4-butoxyphenyl)propyl, 4-(2-pentyloxyphenyl)butyl, 5-(3-hexyloxyphenyl)pentyl, 6-(4-trifluoromethoxyphenyl)hexyl, 1,1-dimethyl-2-(2,4-dimethoxyphenyl)ethyl, 2-methyl-3-[2,4,6-tri(trifluoromethoxy)phenyl]propyl, 2-methylthiobenzyl, 3-methylthiobenzyl, 4-methylthiobenzyl, 3,4-dimethylthiobenzyl, 2,3-dimethylthiobenzyl, 2-(2-ethylthiophenyl)ethyl, 2-(4-methylthiophenyl)ethyl, 1-(3-propylthiophenyl)ethyl, 3-(4-butylthiophenyl)propyl, 4-(2-pentylthiophenyl)butyl, 5-(3-hexylthiophenyl)pentyl, 6-(4-methylthiophenyl)hexyl, 1,1-dimethyl-2-(2,4-dimethylthiophenyl)ethyl, 2-methyl-3-[2,4,6-trimethylthiophenyl]propyl, 2-methyl-4-cyanobenzyl, 3-ethoxy-4-ethoxycarbonylbenzyl, 4-phenyl-3-nitrobenzyl, 3-fluoro-4-methoxybenzyl, 4-trifluoromethyl-3-cyanobenzyl, and 3-trifluoromethoxy-3-fluorobenzyl groups. 
         [0166]    Examples of the phenyl group which may have, on the phenyl ring, 1 to 3 groups selected from the group consisting of a lower alkoxy group which may have a halogen atom as a substituent and a lower alkyl group which may have a halogen atom as a substituent include phenyl groups which may have, on the phenyl ring, 1 to 3 groups selected from the group consisting of a linear or branched alkoxy group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents and a linear or branched alkyl group having 1 to 6 carbon atoms and which may have 1 to 3 halogen atoms as substituents such as phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-butylphenyl, 4-pentylphenyl, 4-hexylphenyl, 3,4-dimethylphenyl, 3,4-diethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4,5-trimethylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxylphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 4-isopropoxyphenyl, 3-butoxyphenyl, 4-pentyloxyphenyl, 4-hexyloxyphenyl, 3,4-dimethoxyphenyl, 3,4-diethoxyphenyl, 2,4-dimethoxyphenyl, 2,5-dimethoxyphenyl, 2,6-dimethoxyphenyl, 3,4,5-trimethoxyphenyl, 2-trifluoromethoxyphenyl, 3-trifluoromethoxyphenyl, 4-trifluoromethoxyphenyl, 2-(bromoethoxy)phenyl, 3-(2-chloroethoxy)phenyl, 4-(2,3-dichloropropoxy)phenyl, 4-(4-fluorobutoxy)phenyl, 3-(5-chloropentyloxy)phenyl, 4-(5-bromohexyloxy)phenyl, 4-(5,6-dibromohexyloxy)phenyl, 3,4-di(trifluoromethoxy)phenyl, 3,4-di(4,4,4-trichlorobutoxy)phenyl, 2,4-di(3-chloro-2-methoxypropyl)phenyl, 2,5-di(3-chloropropoxy)phenyl, 2,6-di(2,2,2-trifluoroethoxy)phenyl, 3,4,5-tri(trifluoromethoxy)phenyl, 4-(2,2,2-trichloroethoxy)phenyl, 2-methyl-4-trifluoromethoxyphenyl, 3-ethyl-4-trichloromethoxyphenyl, 2-methoxy-4-trifluoromethoxyphenyl, 3-ethoxy-4-trichloromethoxyphenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2-(bromomethyl)phenyl, 3-(2-chloroethyl)phenyl, 4-(2,3-dichloropropyl)phenyl, 4-(4-fluorobutyl)phenyl, 3-(5-chloropentyl)phenyl, 4-(5-bromohexyl)phenyl, 4-(5,6-dibromohexyl)phenyl, 3,4-di(trifluoromethyl)phenyl, 3,4-di(4,4,4-trichlorobutyl)phenyl, 2,4-di(3-chloro-2-methylpropyl)phenyl, 2,5-di(3-chloropropyl)phenyl, 2,6-di(2,2,2-trifluoroethyl)phenyl, 3,4,5-tri(trifluoromethyl)phenyl, 4-(2,2,2-trichloroethyl)phenyl, 2-methyl-4-trifluoromethylphenyl, and 3-ethyl-4-trichloromethylphenyl groups. 
         [0167]    Examples of the pyrrolidinyl lower alkyl group which may have, on the pyrrolidine ring, 1 to 3 lower alkyl groups which may have a hydroxyl group as a substituent include pyrrolidinylalkyl groups which may have, on the pyrrolidine ring, 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms which may have 1 to 3 hydroxyl groups as substituents and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(1, 2 or 3-)pyrrolidinyl]methyl, 2-[(1, 2 or 3-)pyrrolidinyl]ethyl, 1-[(1, 2 or 3-)pyrrolidinyl]ethyl, 3-[(1, 2 or 3-)pyrrolidinyl]propyl, 4-[(1, 2 or 3-)pyrrolidinyl]butyl, 5-[(1, 2 or 3-)pyrrolidinyl]pentyl, 6-[(1, 2 or 3-)pyrrolidinyl]hexyl, 1,1-dimethyl-2-[(1, 2 or 3-)pyrrolidinyl]ethyl, 2-methyl-3-[(1, 2 or 3-)pyrrolidinyl]propyl, [1-methyl-(2 or 3-)pyrrolidinyl]methyl, 2-[2-ethyl-(1, 3, 4 or 5-)pyrrolidinyl]ethyl, 1-[3-propyl-(1, 2, 4 or 5-)pyrrolidinyl-ethyl, 3-[1-butyl-(2 or 3-)pyrrolidinyl]propyl, 4-[2-pentyl-(1, 3, 4 or 5-)pyrrolidinyl]butyl, 5-[3-hexyl-(1, 2, 4 or 5-)pyrrolidinyl]pentyl, 6-[1,2-dimethyl-(3, 4 or 5-)pyrrolidinyl]hexyl, 1,1-dimethyl-2-[1,2,3-trimethyl-(4 or 5-)pyrrolidinyl]ethyl, 2-methyl-3-[1-ethyl-2-methyl-(3, 4 or 5-)pyrrolidinyl]propyl, [1-(2-hydroxyethyl)-(2 or 3-)pyrrolidinyl]methyl, [2-hydroxymethyl-(1, 3, 4 or 5-)pyrrolidinyl]methyl, 2-[2-hydroxymethyl-(1, 3, 4 or 5-)pyrrolidinyl]ethyl, 1-[3-(3-hydroxypropyl)-(1, 2, 4 or 5-)pyrrolidinyl]ethyl, 3-[1-(4-hydroxybutyl)-(2 or 3-)pyrrolidinyl]propyl, 4-[2-(5-hydroxypentyl)-(1, 3, 4 or 5-)pyrrolidinyl]butyl, 5-[3-(6-hydroxyhexyl)-(1, 2, 4 or 5-)pyrrolidinyl]pentyl, 6-[1,2-dihydroxymethyl-(3, 4 or 5-)pyrrolidinyl]hexyl, 1,1-dimethyl-2-[1,2,3-trihydroxymethyl-(4 or 5-)pyrrolidinyl]ethyl, 2-methyl-3-[2-(1,2-hydroxyethyl)-(1, 3, 4 or 5-)pyrrolidinyl]propyl, and [2-(2,3,4-trihydroxybutyl)-(1, 3, 4 or 5-)pyrrolidinyl]methyl groups. 
         [0168]    Examples of the amino substituted lower alkyl group which may have a substituent selected from the group consisting of a phenyl group and a lower alkyl group include linear or branched alkyl groups having 1 to 6 carbon atoms substituted with an amino group which may have 1 or 2 substituents selected from the group consisting of a phenyl group and a linear or branched alkyl group having 1 to 6 carbon atoms such as aminomethyl, 2-aminomethyl, 1-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl, 1,1-dimethyl-2-aminoethyl, N,N-diethyl-2-aminoethyl, 2-methyl-3-aminopropyl, methylaminomethyl, 1-ethylaminoethyl, 2-propylaminoethyl, 3-isopropylaminopropyl, 4-butylaminobutyl, 5-pentylaminopentyl, 6-hexylaminohexyl, dimethylaminomethyl, 2-diisopropylaminoethyl, (N-ethyl-N-propylamino)methyl, 2-(N-methyl-N-hexylamino)ethyl, phenylaminomethyl, 1-phenylaminoethyl, 2-phenylaminoethyl, 3-phenylaminopropyl, 4-phenylaminobutyl, 5-phenylaminopentyl, 6-phenylaminohexyl, N-methyl-N-phenylaminomethyl, 2-(N-ethyl-N-phenylamino)ethyl, (N-ethyl-N-phenylamino)methyl, and 2-(N-methyl-N-phenylamino)ethyl groups. 
         [0169]    Examples of the tetrahydrofuryl lower alkyl group which may have a hydroxyl group as a substituent on the lower alkyl group include tetrahydrofurylalkyl groups which may have a hydroxyl group as a substituent on the lower alkyl group and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(2 or 3-)tetrahydrofuryl]methyl, 2-[(2 or 3-)tetrahydrofuryl]ethyl, 1-[(2 or 3-)tetrahydrofuryl]ethyl, 3-[(2 or 3-)tetrahydrofuryl]propyl, 4-[(2 or 3-)tetrahydrofuryl]butyl, 5-[(2 or 3-)tetrahydrofuryl]pentyl, 6-[(2 or 3-)tetrahydrofuryl]hexyl, 1,1-dimethyl-2-[(2 or 3-)tetrahydrofuryl]ethyl, 2-methyl-3-[(2 or 3-)tetrahydrofuryl]propyl, 1-hydroxy-1-[(2 or 3-)tetrahydrofuryl]methyl, 2-hydroxy-2-[(2 or 3-)tetrahydrofuryl]ethyl, 2-hydroxy-1-[(2 or 3-)tetrahydrofuryl]ethyl, 3-hydroxy-3-[(2 or 3-)tetrahydrotetrahydrofuryl]propyl, 4-hydroxy-4-[(2 or 3-)tetrahydrofuryl]butyl, 5-hydroxy-5-[(2 or 3-)tetrahydrofuryl]pentyl, 6-hydroxy-6-[(2 or 3-)tetrahydrofuryl]hexyl, 2-hydroxy-1,1-dimethyl-2-[(2 or 3-)tetrahydrofuryl]ethyl, and 3-hydroxy-2-methyl-3-[(2 or 3-)tetrahydrofuryl]propyl groups. 
         [0170]    Examples of the phenoxy lower alkyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkyl group and a nitro group include, in addition to the above described phenoxy lower alkyl groups, phenoxyalkyl groups which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms and a nitro group and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as 2-methylphenoxymethyl, 3-methylphenoxymethyl, 4-methylphenoxymethyl, 3,4-dimethylphenoxymethyl, 2,3-dimethylphenoxymethyl, 3,4,5-trimethylphenoxymethyl, 2-(2-ethylphenoxy)ethyl, 2-(3-methylphenoxy)ethyl, 2-(4-methylphenoxy)ethyl, 1-(3-propylphenoxy)ethyl, 3-(4-butylphenoxy)propyl, 4-(2-pentylphenoxy)butyl, 5-(3-hexylphenoxy)pentyl, 6-(4-methylphenoxy)hexyl, 1,1-dimethyl-2-(2,4-dimethylphenoxy)ethyl, 2-methyl-3-(2,4,6-trimethylphenoxy)propyl, 2-(4-nitro-3-methylphenoxy)ethyl, 4-nitrophenoxymethyl, 3-nitrophenoxymethyl, 2-nitrophenoxymethyl, 2-(2-nitrophenoxy)ethyl, 2-(4-nitrophenoxy)ethyl, 1-(3-nitrophenoxy)ethyl, 3-(4-nitrophenoxy)propyl, 4-(2-nitrophenoxy)butyl, 5-(3-nitrophenoxy)pentyl, 6-(4-nitrophenoxy)hexyl, 1,1-dimethyl-2-(2,4-dinitrophenoxy)ethyl, and 2-methyl-3-(2,4,6-trinitrophenoxy)propyl groups. 
         [0171]    Examples of the phenyl lower alkanoyl group include phenylalkanoyl groups whose alkanoyl moiety is a linear or branched alkanoyl group having 2 to 6 carbon atoms such as 2-phenylacetyl, 3-phenylpropionyl, 2-phenylpropionyl, 4-phenylbutyryl, 5-phenylpentanoyl, 6-phenylhexanoyl, 2,2-dimethyl-3-phenylpropionyl, and 2-methyl-3-phenylpropionyl groups. 
         [0172]    Examples of the phenyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkyl group which may have a halogen atom include phenyl groups which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a halogen atom and a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms such as phenyl, 3,4-difluorophenyl, 2-fluorophenyl, 3-bromophenyl, 4-iodophenyl, 4-methylphenyl, 2-methylphenyl, 3-methylphenyl, 2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-butylphenyl, 4-pentylphenyl, 4-hexylphenyl, 3,4-dimethylphenyl, 3,4-diethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4,5-trimethylphenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2-(bromomethyl)phenyl, 3-(2-chloroethyl)phenyl, 4-(2,3-dichloropropyl)phenyl, 4-(4-fluorobutyl)phenyl, 3-(5-chloropentyl)phenyl, 4-(5-bromohexyl)phenyl, 4-(5,6-dibromohexyl)phenyl, 3,4-di(trifluoromethyl)phenyl, 3,4-di(4,4,4-trichlorobutyl)phenyl, 2,4-di(3-chloro-2-methylpropyl)phenyl, 2,5-di(3-chloropropyl)phenyl, 2,6-di(2,2,2-trifluoroethyl)phenyl, 3,4,5-tri(trifluoromethyl)phenyl, 4-(2,2,2-trichloroethyl)phenyl, 2-methyl-4-trifluoromethylphenyl, 3-ethyl-4-trichloromethylphenyl, 2-chloro-4-trifluoromethylphenyl, 3-ethyl-4-fluorophenyl, 3-fluoro-4-trichloromethylphenyl, 2-methyl-3-trifluoromethyl-4-trifluoromethylphenyl, 3-fluorophenyl, 4-fluorophenyl, 2-bromophenyl, 4-bromophenyl, 2-iodophenyl, 3-iodophenyl, 2,3-dibromophenyl, 2,4-diiodophenyl, 2,5-difluorophenyl, 2,6-dichlorophenyl, 2,4,6-trichlorophenyl, 2,4-difluorophenyl, 3,5-difluorophenyl, 2,6-difluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 2,5-dichlorophenyl, 3,4-dichlorophenyl, 2,6-dichlorophenyl, 3,5-dichlorophenyl, 2,4,6-trifluorophenyl, and 2,4-difluorophenyl groups. 
         [0173]    Examples of the 5- to 7-membered saturated heterocyclic group formed by mutually binding R 20  and R 21 , R 22  and R 23 , R 26  and R 27 , R 29  and R 30  or R 32  and R 33  together with the nitrogen atoms bound to them, through or not through a nitrogen atom, an oxygen atom or a sulfur atom, include pyrrolidinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino, and homopiperazinyl groups. 
         [0174]    Examples of the phenoxy lower alkyl group which may have, on the phenyl ring, a lower alkyl group as a substituent include, in addition to the above described phenoxy lower alkyl groups, phenoxyalkyl groups which may have, on the phenyl ring, 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as 2-methylphenoxymethyl, 3-methylphenoxymethyl, 4-methylphenoxymethyl, 3,4-dimethylphenoxymethyl, 2,3-dimethylphenoxymethyl, 3,4,5-trimethylphenoxymethyl, 2-(2-ethylphenoxy)ethyl, 2-(4-methylphenoxy)ethyl, 1-(3-propylphenoxy)ethyl, 3-(4-butylphenoxy)propyl, 4-(2-pentylphenoxy)butyl, 5-(3-hexylphenoxy)pentyl, 6-(4-methylphenoxy)hexyl, 1,1-dimethyl-2-(2,4-dimethylphenoxy)ethyl, and 2-methyl-3-(2,4,6-trimethylphenoxy)propyl groups. 
         [0175]    A compound represented by the general formula (I) or a salt thereof is more preferred, wherein 
         [0000]    X 1  represents a nitrogen atom or a group —CH═,
 
R 1  represents a group -Z-R 6  
 
Z represents a group —N(R 8 )—B—, a group —B—N(R 8 )—, a group —B 0 —O— or a group —N(R 9a )—CO—N—(R 9b )—,
 
R 8  represents a hydrogen atom, a lower alkyl group that may have a lower alkoxy group as a substituent, a lower alkanoyl group, a lower alkylsulfonyl group or a phenyl lower alkyl group,
 
B represents a group —CO— or a lower alkylene group,
 
B 0  represents a lower alkylene group,
 
R 9a  represents a hydrogen atom or a lower alkyl group,
 
R 9b  represents a hydrogen atom or a lower alkyl group,
 
R 6  represents a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R 7  represents a halogen atom or a lower alkyl group that may have a halogen atom as a substituent,
 
m represents an integer of 1 or 2 (when m represents 2, two R 7 s may be identical or different) and
 
R 2  represents a hydrogen atom, a halogen atom, or a lower alkyl group,
 
Y represents a group —O—, or a group —N(R 5 )—,
 
R 5  represents a hydrogen atom, or a lower alkyl group,
 
A represents a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    p represents 1 or 2,
 
R 3  represents a hydrogen atom, a lower alkoxy group, a halogen atom, or a lower alkyl group that may have a halogen atom as a substituent,
 
R 9  represents a group -(T) l -N(R 14 )R 15 ,
 
T represents a group —N(R 17 )—B 3 —CO—, a group —B 4 —CO—, or a group —CO—,
 
R 17  represents a hydrogen atom, or a lower alkyl group,
 
B 3  represents a lower alkylene group,
 
B 4  represents a lower alkenylene group or a lower alkylene group that may have a hydroxyl group as a substituent,
 
l represents 0 or 1′,
 
R 14  represents a hydrogen atom or an alkyl group that may have a hydroxyl group as a substituent,
 
R 15  represents (36a) a piperazinyl-substituted oxalyl group that may have 1 to 3 groups selected from the group consisting of a phenyl lower alkyl group (that may have 1 to 3 groups selected from the group consisting of a lower alkylenedioxy group and a lower alkoxy group as a substituent(s) on the phenyl ring) and a pyridyl lower alkyl group as a substituent(s) on the piperazine ring,
 
R 14  and R 15 , together with the nitrogen atom to which they bind, form a heterocyclic group which is piperidinyl or piperazinyl group,
 
wherein the heterocyclic ring may be substituted by a group selected from the group consisting of (28) a phenyl-substituted lower alkyl group that may be substituted by a group, on the phenyl ring, selected from the group consisting of a lower alkanoyl group, an amino group that may have a lower alkanoyl group as a substituent, a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group that may have a halogen atom as a substituent, a lower alkoxy group that may have a halogen atom as a substituent, a phenyl lower alkoxy group, a hydroxyl group, and a lower alkylenedioxy group (49) a group —(B 12 CO)t-N(R 20 )R 21 , or (84) a group —(O—B 15 )s-CO—N(R 26 )R 27 ,
 
B 12  represents a lower alkylene group,
 
t represents 0 or 1,
 
R 20  and R 21 , together with the nitrogen atom to which they bind, form a saturated heterocyclic group which is piperidinyl or piperazinyl group that, on the heterocyclic ring, may be substituted by a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring,
 
B 15  represents a lower alkylene group,
 
s represents 0 or 1,
 
R 26  and R 27  may be identical or different and each represent a hydrogen atom, a lower alkyl group, a phenyl lower alkyl group, or an imidazolyl lower alkyl group, and R 26  and R 27 , together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic ring, (wherein the heterocyclic ring may be substituted by 1 to 3 phenyl lower alkyl groups that may have a lower alkylenedioxy group on the phenyl ring).
 
         [0176]    For example, a compound represented by the general formula (1) or a salt thereof is further more preferred, wherein 
         [0000]    X 1  represents a nitrogen atom,
 
R 1  represents a group -Z-R 6 ,
 
Z represents a group —N(R 8 )—B—,
 
R 8  represents a hydrogen atom, or a lower alkyl group that may have a lower alkoxy group as a substituent,
 
B represents a group —CO—,
 
R 6  represents a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R 7  represents a halogen atom or a lower alkyl group that may have a halogen atom as a substituent,
 
m represents an integer of 1 or 2 (when m represents 2, two R 7 s may be identical or different) and
 
R 2  represents a hydrogen atom,
 
Y represents a group —O—, or a group —N(R 5 )—,
 
R 5  represents a hydrogen atom, or a lower alkyl group,
 
A represents a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    p represents 1 or 2,
 
R 3  represents a hydrogen atom, a lower alkoxy group, a halogen atom, or a lower alkyl group that may have a halogen atom as a substituent,
 
R 4  represents a group -(T) l -N(R 14 )R 15 ,
 
T represents a group —N(R 17 )—B 3 —CO—, a group —B 4 —CO—, or a group —CO—,
 
R 17  represents a hydrogen atom, or a lower alkyl group,
 
B 3  represents a lower alkylene group,
 
B 4  represents a lower alkylene group that may have a hydroxyl group as a substituent,
 
l represents 0 or 1,
 
R 14  and R 15 , together with the nitrogen atom to which they bind, form a heterocyclic group which is piperidinyl or piperazinyl group that, on the heterocyclic ring, may be substituted by (28) a phenyl-substituted lower alkyl group that may be substituted by a lower alkylenedioxy group on the phenyl ring.
 
         [0177]    Another more preferred example is a compound represented by the general formula (1) or a salt thereof, wherein 
         [0000]    X 1  represents a nitrogen atom,
 
R 1  represents a group -Z-R 6  
 
Z represents a group N(R 8 )—B—,
 
R 8  represents a hydrogen atom, or a lower alkyl group that may have a lower alkoxy group as a substituent,
 
B represents a group —CO—,
 
R 6  represents a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R 7  represents a halogen atom or a lower alkyl group that may have a halogen atom as a substituent,
 
m represents an integer of 1 or 2 (when m represents 2, two R 7 s may be identical or different) and
 
R 2  represents a hydrogen atom,
 
Y represents a group —O—, or a group —N(R 5 )—,
 
R 5  represents a hydrogen atom, or a lower alkyl group,
 
A represents a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    represents 1 or 2,
 
R 3  represents a hydrogen atom, a lower alkoxy group, a halogen atom, or a lower alkyl group that may have a halogen atom as a substituent,
 
R 4  represents a group -(T) l -N(R 14 )R 15 ,
 
R 17  represents a hydrogen atom, or a lower alkyl group,
 
B 3  represents a lower alkylene group,
 
B 4  represents a lower alkylene group that may have a hydroxyl group as a substituent,
 
l represents 0,
 
R 14  and R 15 , together with the nitrogen atom to which they bind, form a heterocyclic group which is piperidinyl or piperazinyl group
 
wherein, on the heterocyclic ring, one substituent may be present which is selected from the group consisting of (49) a group —(B 12 CO)t-N(R 20 )R 21 , and (84) a group —(O—B 15 )s-CO—N(R 26 )R 27 ,
 
B 12  represents a lower alkylene group,
 
t represents 0 or 1,
 
R 20  and R 21 , together with the nitrogen atom to which they bind, form a saturated heterocyclic group which is piperazine or piperidine
 
wherein, on the heterocyclic ring, one substituent may be present which is a phenyl lower alkyl group that may have a lower alkylenedioxy group as a substituent on the phenyl ring,
 
B 15  represents a lower alkylene group,
 
s represents 0 or 1,
 
R 26  and R 27 , together with the nitrogen atom to which they bind, bind to each other, directly or via an oxygen atom or nitrogen atom to form a 6-membered saturated heterocyclic ring, (wherein the heterocyclic ring may be substituted by 1 to 3 phenyl lower alkyl groups that may have a lower alkylenedioxy group as a substituent on the phenyl ring).
 
         [0178]    Methods for producing compounds according to the present invention will be described below. 
         [0179]    A compound according to the present invention represented by the general formula (1), in which various groups may be used as Y, is produced, for example, in accordance with reaction formulas 1 to 4 below. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein, R 1 , R 2 , X 1  and A are the same as described above, Y 1  represents a group —O—, a group —S— or a group —NH—, and X 2  represents a halogen atom. 
         [0180]    The reaction between the compound (2) and the compound (3) is generally carried out in the presence or absence of an appropriate solvent and in the presence or absence of a basic compound. 
         [0181]    Examples of the inert solvent to be used include aromatic hydrocarbons such as benzene, toluene, and xylene, ethers such as diethyl ether, tetrahydrofuran, dioxane, monoglyme, and diglyme, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, and carbon tetrachloride, lower alcohols such as methanol, ethanol, isopropanol, butanol, tert-butanol, and ethylene glycol, fatty acids such as acetic acid, esters such as ethyl acetate and methyl acetate, ketones such as acetone and methyl ethyl ketone, acetonitrile, pyridine, dimethylsulfoxide, N,N-dimethylformamide, N-methylpyrrolidone, and hexamethylphosphoric acid triamide, and a mixture thereof. 
         [0182]    Examples of the basic compound include carbonates such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, and cesium carbonate, metal hydroxides such as sodium hydroxide, potassium hydroxide, and calcium hydroxide, sodium hydride, potassium hydride, potassium, sodium, sodium amide, metal alcoholates such as sodium methylate, sodium ethylate, and sodium n-butoxide, and organic bases such as pyridine, imidazole, N-ethyldiisopropylamine, dimethylaminopyridine, triethylamine, trimethylamine, dimethylaniline, N-methylmorpholine, 1,5-diazabicyclo[4.3.0]nonene-5 (DBN), 1,8-diazabicyclo[5.4.0]undecene-7 (DBU), and 1,4-diazabicyclo[2.2.2]octane (DABCO), and a mixture thereof. 
         [0183]    When the reaction is carried out in the presence of a basic compound, the basic compound is used typically in an equimolar amount to that of the compound (2) and preferably 1 to 10 times that of the compound (2) on a molar basis. 
         [0184]    The compound (3) is used typically in at least equimolar amount to that of the compound (2) and preferably 1 to 10 times that of the compound (2) on a molar basis. 
         [0185]    The reaction is carried out typically at −30 to 200° C., and preferably at about −30 to 150° C., and generally completed in about 5 minutes to 80 hours. 
         [0186]    To this reaction system, an alkali metal halide such as sodium iodide or potassium iodide may be added, and a phase-transfer catalyst may be added. 
         [0187]    Examples of the phase-transfer catalyst include quaternary ammonium salts substituted with a group selected from the group consisting of a linear or branched alkyl group having 1 to 18 carbon atoms, a phenyl alkyl group whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms and a phenyl group, such as tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium fluoride, tetrabutylammonium iodide, tetrabutylammonium hydroxide, tetrabutylammonium hydrogensulfite, tributylmethylammonium chloride, tributylbenzylammonium chloride, tetrapentylammonium chloride, tetrapentylammonium bromide, tetrahexylammonium chloride, benzyldimethyloctylammonium chloride, methyltrihexylammonium chloride, benzyldimethyloctadecanylammonium chloride, methyltridecanylammonium chloride, benzyltripropylammonium chloride, benzyltriethylammonium chloride, phenyltriethylammonium chloride, tetraethylammonium chloride, tetramethylammonium chloride; phosphonium salts substituted with a linear or branched alkyl group having 1 to 18 carbon atoms such as tetrabutylphosphonium chloride; and pyridinium salts substituted with a linear or branched alkyl group having 1 to 18 carbon atoms such as 1-dodecanylpyridinium chloride. These phase-transfer catalysts are used singly or in a combination of two types or more. 
         [0188]    Typically the phase-transfer catalyst is used in an equimolar amount of 0.1 to 1 times that of the compound (2) and preferably 0.1 to 0.5 times that of the compound (2) on a molar basis. 
         [0189]    A compound (1a) wherein Y 1  represents a group —NH—, may be produced also by reacting a compound (2) with a compound (3) in the presence of an acid in place of a basic compound. Examples of the acid used herein include mineral acids such as hydrochloric acid, sulfuric acid, and hydrobromic acid, and organic acids such as acetic acid, trifluoroacetic acid, and p-toluenesulfonic-acid. These acids are used singly or in a mixture of two types or more. 
         [0190]    A compound (1) wherein Y represents a group —N(R 5 )— group, and R 5  represents a group other than a hydrogen atom, may be produced from a compound (1) wherein Y represents a group —NH— in accordance with reaction formula 2. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , A and X 2  are the same as described above, R 5a  represents a lower alkyl group, phenyl lower alkyl group or cycloalkyl group, R 5b  represents a hydrogen atom, lower alkyl group, phenyl group or phenyl lower alkyl group, R 5c  represents a lower alkanoyl group or benzoyl group, R B  represents a hydrogen atom or lower alkyl group, and R 5b  and R B  may bind to each other together with carbon atoms bound to these groups to form a cycloalkyl ring, provided that the carbon number of the alkyl moiety in the group —CHR B R 5b  of the compound (1d) is 1 to 6. 
         [0191]    The reaction of the compound (1b) and the compound (4) is carried out under the same conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0192]    The reaction of the compound (1b) and the compound (5) is carried out, for example, in the presence of a reducing agent and in the presence or absence of an appropriate solvent. Hereinafter, this method is called “method A”. 
         [0193]    Examples of the solvent used herein include water, lower alcohols such as, methanol, ethanol, isopropanol, butanol, tert-butanol, and ethylene glycol, acetonitrile, fatty acids such as formic acid, and acetic acid, ethers such as diethyl ether, tetrahydrofuran, dioxane, monoglyme, and diglyme, aromatic hydrocarbons such as benzene, toluene, and xylene, and halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, and carbon tetrachloride, and a mixture thereof. 
         [0194]    Examples of the reducing agent include fatty acids and alkali metal salts thereof such as formic acid, sodium formate, and sodium acetate, hydride reducing agents such as sodium borohydride, sodium cyanoborohydride, sodium triacetyloxyborohydride, and aluminum lithium hydride, or a mixture of these hydride reducing agents, and catalytic hydrogen reducing agents such as palladium black, palladium-carbon, platinum oxide, platinum black, and Raney nickel. 
         [0195]    In using a fatty acid or an alkali metal salt thereof such as formic acid, sodium formate, or sodium acetate as a reducing agent, the appropriate reaction temperature is typically from room temperature to about 200° C., and preferably about 50 to about 150° C. The reaction is completed generally in about 10 minutes to 10 hours. It is preferable to use a fatty acid or an alkali metal salt thereof in a large excess amount with respect to the compound (1b). 
         [0196]    In using a hydride reducing agent, the appropriate reaction temperature is typically −80 to 100° C., and preferably −80 to 70° C. The reaction is completed generally in about 30 minutes to 60 hours. The hydride reducing agent is used typically in an equimolar amount 1 to 20 times that of the compound (1b), and preferably 1 to 6 times that of the compound (1b) on a molar basis. Especially in using aluminum lithium hydride as a hydride reducing agent, it is preferable to employ an ether such as diethyl ether, tetrahydrofuran, dioxane, monoglyme, or diglyme, or an aromatic hydrocarbon such as benzene, toluene, or xylene, as a solvent. To the reaction system, an amine such as trimethylamine, triethylamine, and N-ethyldiisopropylamine, or molecular sieves such as Molecular Sieves 3A (MS-3A) or Molecular Sieves 4A (MS-4A) may be added. 
         [0197]    In using a catalytic hydrogen reducing agent, the reaction is preferably carried out in a hydrogen atmosphere typically at a normal pressure to about 20 atm, and preferably at a normal pressure to about 10 atm, or in the presence of a hydrogen donor such as formic acid, ammonium formate, cyclohexene, or hydrazine hydrate, at a temperature of typically −30 to 100° C., and preferably 0 to 60° C. The reaction is generally completed in about 1 to 12 hours. The catalytic hydrogen reducing agent is used typically in an amount of about 0.1% to 40% by weight, and preferably about 1 to 20% by weight based on the compound (1b). 
         [0198]    In the reaction of the compound (1b) and the compound (5), the compound (5) is used typically in at least an equimolar amount to that of the compound (1b), and preferably in an equal amount to a large excess amount on a molar basis. 
         [0199]    The reaction is carried out using a compound (5), whose R B  and R 5b  (bound to a carbon atom) are mutually bound to form a cycloalkyl ring together with the carbon atom in the presence of a hydride reducing agent, as a starting material. In this case, in place of the compound (5), cycloalkyloxytrialkylsilane such as [(1-ethoxycyclopropyl)oxy]trimethylsilane may be used as the starting material to produce the above described compound (5) in the reaction system. 
         [0200]    The compound (1d) may be also produced by reacting the compound (1b) with the compound (5) under the same conditions as in the reaction between the compound (1f) with hydroxylamine of the later described reaction formula 3, and then reducing the resulting compound represented by the general formula: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , R B  and R 5b  are the same as described above. 
         [0201]    The same reaction conditions as in the method A may be applied to this reducing reaction. 
         [0202]    The reaction of the compound (1b) and the compound (6) is carried out by a method for reacting the compound (1b) with the carboxylic acid of the compound (6) in accordance with a general reaction for producing an amide bond. This reaction may be performed by any known reaction for producing an amide bond. Specific examples of the method include: (a) a mixed acid anhydride method, specifically, a method of reacting an alkylhalocarboxylic acid with the carboxylic acid (6) to prepare a mixed acid anhydride, and then reacting the amine (1b) with the mixed acid anhydride; (b) an active ester method, specifically, a method of preparing, from the carboxylic acid (6), an active ester such as a phenyl ester, p-nitrophenyl ester, N-hydroxysuccinimide ester, or 1-hydroxybenzotriazole ester, or an active amide with benzoxazoline-2-thione, and then reacting the active ester or amide with the amine (1b); (c) a carbodiimide method, specifically, a method of condensating the carboxylic acid (6) with the amine (1b) in the presence of an activator such as dicyclohexylcarbodiimide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (WSC), or carbonyldiimidazole; (d) other methods, for example, a method of preparing a carboxylic anhydride from the carboxylic acid (6) by the action of a dehydrator such as acetic anhydride, and then reacting the carboxylic anhydride with the amine (1b), a method of reacting an ester of the carboxylic acid (6) with a lower alcohol with the amine (1b) at a high pressure and a high temperature, and a method of reacting an acid halide of the carboxylic acid (6), that is, carboxylic acid halide, with the amine (1b). 
         [0203]    The mixed acid anhydride used in the mixed anhydride method (a) described above, which is obtained by a general Schotten-Baumann reaction, is used as it is without isolation in the reaction with the amine (2) to produce the compound of the present invention represented by the general formula (1e). 
         [0204]    The Schotten-Baumann reaction described above is carried out in the presence of a basic compound. 
         [0205]    Examples of the basic compound to be used include compounds commonly used in the Schotten-Baumann reaction, for example, organic bases such as triethylamine, trimethylamine, pyridine, dimethylaniline, N-ethyldiisopropylamine, dimethylaminopyridine, N-methylmorpholine, 1,5-diazabicyclo[4.3.0]nonene-5 (DBN), 1,8-diazabicyclo[5.4.0]undecene-7 (DBU), and 1,4-diazabicyclo[2.2.2]octane (DABCO), and inorganic bases including carbonates such as sodium carbonate, potassium carbonate, sodium bicarbonate, and potassium bicarbonate, metal hydroxides such as sodium hydroxide, potassium hydroxide, and calcium hydroxide, potassium hydride, sodium hydride, potassium, sodium, sodium amide, and metal alcoholates such as sodium methylate and sodium ethylate. These basic compounds are used singly or in a combination of two types or more. The reaction is carried out at typically about −20 to 100° C., and preferably about 0 to 50° C. The reaction time is about 5 minutes to 10 hours, and preferably about 5 minutes to 2 hours. 
         [0206]    The resulting mixed acid anhydride is reacted with the amine (1b) typically at about −20 to 150° C. and preferably about 10 to 50° C. The reaction time is about 5 minutes to 10 hours and preferably about 5 minutes to 5 hours. 
         [0207]    The mixed acid anhydride method is generally carried out in a solvent. Any solvent may be used as long as it is conventionally used in the mixed acid anhydride method. Specific examples of the solvent include halogenated hydrocarbons such as chloroform, dichloromethane, dichloroethane, and carbon tetrachloride, aromatic hydrocarbons such as benzene, toluene and xylene, ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, and dimethoxyethane, esters such as methyl acetate, ethyl acetate, and isopropyl acetate, and aprotic polar solvents such as N,N-dimethylformamide, dimethylsulfoxide, and hexamethylphosphoric acid triamide, and a mixture thereof. 
         [0208]    Examples of the alkylhalocarboxylic acid used in the mixed acid anhydride method include methyl chloroformate, methyl bromoformate, ethyl chloroformate, ethyl bromoformate, and isobutyl chloroformate. 
         [0209]    In the mixed acid anhydride method, the carboxylic acid (6), alkylhalocarboxylic acid, and the amine (1b) may be preferably used in equimolar amounts to each other. However, each of alkyl halocarboxylic acid and the carboxylic acid (6) may be used 1 to 1.5 times that of the amine (1b) on a molar basis, respectively. 
         [0210]    In the method (c) of performing a condensation reaction in the presence of an activator, the reaction is carried out in an appropriate solvent in the presence or absence of a basic compound. Any of the solvents and basic compounds used in the reaction in the methods (d) of reacting the amine (1b) with a carboxylic acid halide described below may be used for this reaction. It is appropriate to use the activator typically in at least an equimolar amount to that of the compound (1b), and preferably 1 to 5 times that of the compound (1b) on a molar basis. When WSC is used as an activator, the reaction may be carried out advantageously if 1-hydroxybenzotriazole and/or an acid such as hydrochloric acid is added to the reaction system. This reaction is carried out typically at about −20 to 180° C. and preferably at about 0 to 150° C., and completed typically in about 5 minutes to 90 hours. 
         [0211]    When a method (d) of reacting the amine (1b) with a carboxylic acid halide is employed, the reaction is carried out in an appropriate solvent in the presence of a basic compound. Any basic compound may be used as long as it is widely known in the art. Any basic compound may be used as long as it is used in, for example, the Shotten-Baumann reaction. Examples of the solvent include, in addition to the solvents used in the mixed acid anhydride method, alcohols such as methanol, ethanol, isopropanol, propanol, butanol, 3-methoxy-1-butanol, ethyl cellosolve, and methyl cellosolve, acetonitrile, pyridine, acetone, and water. The ratio of the amine (1b) to the carboxylic acid halide is not particularly limited and may be appropriately selected in a wide range. Typically, the latter one may be used in an amount at least about equimolar to that of the former one, and preferably about 1 to 5 times that of the former one on a molar basis. This reaction is carried out typically at about −20 to 180° C. and preferably at about 0 to 150° C., and completed typically in 5 minutes to 50 hours. 
         [0212]    Further, the reaction for producing an amide bond shown in reaction formula 2 may be carried out also by reacting the carboxylic acid (6) and the amine (1b) in the presence of a condensation agent of a phosphorus compound such as triphenylphosphine, diphenylphosphinyl chloride, phenyl-N-phenylphosphoramide chloridate, diethyl chlorophosphate, diethyl cyanophosphate, diphenylphosphoric acid azide, or bis(2-oxo-3-oxazolidinyl)phosphinic chloride. The condensation agent is used singly or in a mixture of two types or more. 
         [0213]    The reaction is carried out, in the presence of the solvent and the basic compound which are used in the method for reacting the amine (1b) with the carboxylic acid halide described above, typically at about −20 to 150° C., and preferably at about 0 to 100° C., and completed typically in 5 minutes to about 30 hours. The condensation agent and the carboxylic acid (6) each may be used approximately in at least an equimolar amount to that of the amine (1b), and preferably about 1 to 2 times that of the amine (1b) on a molar basis. 
         [0214]    The compound (1), wherein Y represents a group —CH(OH)— or a group —C(═N—OH), is produced from a compound wherein Y represents a group —CO—, in accordance with reaction formula 3. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0215]    wherein R 1 , R 2 , X 1  and A are the same as described above. 
         [0216]    The compound (1g) is produced by reducing the compound (1f). 
         [0217]    In the reducing reaction described above, a reducing method employing a hydride reducing agent is favorably used. Examples of the reducing agent to be used include aluminum lithium hydride, sodium borohydride, borane, diborane, and lithium borohydride-trimethoxyborane. These reducing agents are used singly or in a mixture of two types or more. The reducing agent is used typically in at least an equimolar amount to that of the compound (1f), and preferably 1 to 15 times that of the compound (1f) on a molar basis. This reducing reaction is typically carried out in an appropriate solvent, for example, water, a lower alcohol such as methanol, ethanol, or isopropanol, an ether such as tetrahydrofuran, diethyl ether, diisopropyl ether, or diglyme, or a halogenated hydrocarbon such as dichloromethane, chloroform, or carbon tetrachloride, or a mixture thereof, at about −60 to 150° C. preferably about −30 to 100° C. and generally for about 10 minutes to 40 hours. In the case where aluminum lithium hydride or borane is used as the reducing agent, it is preferable to use an anhydrous solvent such as tetrahydrofuran, diethyl ether, diisopropyl ether, or diglyme. 
         [0218]    The compound (1 h) is produced by reacting the compound (1f) and hydroxylamine in an appropriate inert solvent in the presence or absence of a basic compound. 
         [0219]    Examples of the basic compound used herein include inorganic basic compounds such as sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, and potassium carbonate, fatty acid alkali metal salts such as sodium acetate, organic bases such as piperidine, piperidinium acetate, triethylamine, trimethylamine, pyridine, dimethylaniline, N-ethyldiisopropylamine, dimethylaminopyridine, N-methylmorpholine, 1,5-diazabicyclo[4.3.0]nonene-5 (DBN), 1,8-diazabicyclo[5.4.0]undecene-7 (DBU), and 1,4-diazabicyclo[2.2.2]octane (DABCO). These basic compounds may be used singly or in a mixture of two types or more. 
         [0220]    Any inert solvent may be used as long as it does not negatively affect the reaction. Examples of the inert solvent include water, aromatic hydrocarbons such as benzene, toluene, and xylene, ethers such as diethyl ether, tetrahydrofuran, dioxane, monoglyme, and diglyme, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, and carbon tetrachloride, lower alcohols such as methanol, ethanol, isopropanol, butanol, tert-butanol, and ethylene glycol, fatty acids such as acetic acid, esters such as ethyl acetate and methyl acetate, ketones such as acetone and methyl ethyl ketone, acetonitrile, pyridine, dimethyl sulfoxide, N,N-dimethylformamide, and hexamethyl phosphate triamide, and a mixture thereof. 
         [0221]    Hydroxylamine is used typically in at least an equimolar amount to that of the compound (1f), and preferably 1 to 5 times that of the compound (1f) on a molar basis. The reaction temperature is typically at room temperature to 200° C. and preferably about 50 to 150° C. The reaction is generally completed in about 5 minutes to 30 hours. 
         [0222]    The compound (1), wherein Y represents a group —S(O)n- (n=1 or 2), is produced from a compound wherein Y represents a group —S—, in accordance with reaction formula 4. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0223]    wherein R 1 , R 2 , X 1  and A are the same as described above, A 16  represents a group -A or a group -A 10 -T 2 -COOR 59a , T 2  represents a group —N(R 17 )—B 3 —, a group —B 19 —N(R 18 )—, a group —B 4 —, a group -Q-B 5 —, a group —B 6 —N—(R 19 )—B 7 —, a group —CO—B 10 —, a group —CH(OH)—B 11 —, a group —B 23a —CO— group, or a direct bond, wherein R 17 , B 3 , B 19 , R 18 , B 4 , B 5 , B 6 , R 19 , B 7 , B 10  and B 11  are the same as described above, A 10  represents 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 3  and p are the same as described above, provided that a is bound to a group —S or a group —S(O)j, and b is bound to group -T 2 , R 59a  is a hydrogen atom or a lower alkyl group, and j is 1 or 2. 
         [0224]    The reaction for converting the compound (1zzzz) into the compound (1aaaaa) is carried out in an appropriate solvent in the presence of an oxidizing agent. 
         [0225]    Examples of the solvent include water, fatty acids such as formic acid, acetic acid, and trifluoroacetic acid, alcohols such as methanol and ethanol, and halogenated hydrocarbons such as chloroform and dichloromethane, and a mixture thereof. 
         [0226]    Examples of the oxidizing agent include peracids such as performic acid, peracetic acid, pertrifluoroacetic acid, perbenzoic acid, m-chloroperbenzoic acid, and o-carboxyperbenzoic acid, hydrogen peroxide, sodium metaperidodate, dichromic acid, dichromates such as sodium dichromate and potassium dichromate, permanganic acid, permanganates such as sodium permanganate and potassium permanganate, and lead salts such as lead tetraacetate. These oxidizing agents are used singly or in a mixture of two types or more. 
         [0227]    The oxidizing agent is appropriately used typically in at least an equimolar amount to that of the compound (1zzzz), and preferably 1 to 2 times that of the compound (1zzzz) on a molar basis. In the oxidizing reaction which converts a sulfur atom into a sulfonyl group (j=2), the oxidizing agent is preferably used typically in an amount at least two times that of the compound (1zzzz) and preferably 2 to 4 times that of the compound (1zzzz) on a molar basis. 
         [0228]    The reaction is carried out at typically −10 to 150° C., and preferably about −10 to 100° C. and generally completed in about 1 to 100 hours. 
         [0229]    The compound of the present invention represented by the general formula (1) wherein various groups may be used as A, is produced, for example, in accordance with the following reaction formulas 5 to 36. 
         [0230]    The compound (1), wherein A represents: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0231]    wherein R 4  represents an imidazolyl lower alkyl group, a 1,2,4-triazolyl lower alkyl group, a 1,2,3-triazolyl lower alkyl group, a 1,2,5-triazolyl lower alkyl group, a pyrazolyl lower alkyl group, a pyrimidinyl lower alkyl group which may have an oxo group as a substituent on the pyrimidine ring, a 1,2,4-oxadiazolyl lower alkyl group which may have an lower alkyl group as a substituent on the 1,2,4-oxadiazole ring, a thiazolidinyl lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, or a group -(T) l -NR 14 R 15 , (T is a lower alkylene group and l is 1) is produced by reacting the compound (7) with the compound (8) as shown in reaction formula 5. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2  Y 1  and X 1  are the same as described above, A 1  represents 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 3  and p are the same as described above, R 37a  represents a group —B 21 —X 2 , B 21  represents a lower alkylene group, and X 2  is the same as described above, and A 2  represents 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 3  and p are the same as described above, R 38  represents a group —B 21 —R 4a , B 21  is the same as described above, R 4a  represents an imidazolyl group, a 1,2,4-triazolyl group, a 1,2,3-triazolyl group, a 1,2,5-triazolyl group, a pyrazolyl group, a pyrimidynyl group which has an oxo group as a substituent on the pyrimidine ring, a 1,2,4-oxadiazolyl group which may have a lower alkyl group as a substituent on the 1,2,4-oxadiazole ring, a thiazolidinyl group which may have an oxo group as a substituent on the thiazolidine ring, or an —NR 14 R 15  group, and R 14  and R 15  are the same as described above: 
         [0232]    The reaction of the compound (7) with the compound (8) is carried out under the same conditions as in the reaction between the compound (2) and the compound (3) in accordance with reaction formula 1. 
         [0233]    The compound (1), wherein A represents 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 4  is an imidazolyl lower alkyl group, a 1,2,4-triazolyl lower alkyl group, a 1,2,3-triazolyl lower alkyl group, a 1,2,5-triazolyl lower alkyl group, a pyrazolyl lower alkyl group, a pyrimidinyl lower alkyl group which has an oxo group as a substituent on the pyrimidine ring, a 1,2,4-oxadiazolyl lower alkyl group which may have a lower alkyl group as a substituent on the 1,2,4-oxadiazole ring, a thiazolidinyl lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, or a group -(T) l -NR 14 R 15  (T is a lower alkylene group and l is 1)
 
is also produced by reacting the compound (8) with the compound (9) in accordance with reaction formula 6.
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1  and Y 1 , and R 4a  are the same as described above, A 3  represents 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 3  and p are the same as described above, R 39  represents a —(B 21 ) f COR A  group, B 21  is the same as described above, R A  represents a hydrogen atom or a lower alkyl group, and f represents 0 or 1, and A 4  represents 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 3  and p are the same as described above, R 40  represents a group —(B 21 ) f CHR A R 4a , and B 21 , R A , f and R 4a  are the same as described above, provided that the alkyl moiety of the group —(B 21 ) f CHR A R 4a  has not more than 6 carbon atoms. 
         [0234]    The reaction of the compound (9) with the compound (8) is carried out under the same conditions as in the reaction between the compound (1b) and the compound (5) of reaction formula 2. 
         [0235]    The compound (1), wherein A represents 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 4  represents a 3,5-dioxoisooxazolidinyl lower alkylidene group which may have an oxo group as a substituent on the 3,5-dioxoisooxazolidine ring, is produced by reacting the compound (11) with the compound (10) in accordance with reaction formula 7. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1  and Y are the same as described above, and
 
A 5  represents
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 3  and p are the same as described above, R 41  represents a group —B 22  (CO 2 R 43 )(CO 2 R 44 ), B 22  represents a lower alkylidene group, and R 43  and R 44  each represent a lower alkyl group, and
 
A 6  represents
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 3  and p are the same as described above, and R 42  is a group represented by 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein B 22  is the same as described above. 
         [0236]    The reaction of the compound (10) with the compound (11) is carried out under the same condition as in the reaction for converting the compound (1f) into the compound (1 h) in accordance with reaction formula 3. 
         [0237]    The compound (1), wherein A represents 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 4  represents 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    is produced from the compound (13), as shown in reaction formula 8. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y and R 13  are the same as described above,
 
A 7  represents
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 3  and p are the same as described above, and
 
R 45  represents a halogen atom,
 
A 8  represents
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 3  and p are the same as described above, and
 
R 46  represents
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 13  is the same as described above,
 
A 9  represents:
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 3  and p are the same as described above, and
 
R 47  represents a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 13  is the same as described above, and
 
A 8a  represents
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 3  and p are the same as described above, and
 
R 46  represents a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 13  is the same as described above. 
         [0238]    The reaction of the compound (13) with the compound (12) is carried out in an appropriate inert solvent in the presence of a basic compound. 
         [0239]    Examples of the basic compound used herein include such as metal sodium, metal potassium, metal magnesium, sodium hydride, sodium amide, metal alcoholates such as sodium methylate, sodium ethylate, and potassium tert-butoxide, and alkyl and aryl lithiums or lithium amides such as methyl lithium, n-butyl lithium, phenyl lithium, and lithium diisopropylamide. These basic compounds are used singly or in a mixture of two types or more. 
         [0240]    The basic compound is appropriately used typically in at least an equimolar amount to that of the compound (13), and preferably 1 to 5 times that of the compound (13) on a molar basis. 
         [0241]    Examples of the inert solvent to be used include aromatic hydrocarbons such as benzene, toluene, and xylene, ethers such as diethyl ether, tetrahydrofuran, dioxane, monoglyme, and diglyme, aliphatic hydrocarbons such as n-hexane, heptane, and cyclohexane, halogenated hydrocarbons such as chloroform, dichloromethane, dichloroethane, and carbon tetrachloride, dimethylsulfoxide, and N,N-dimethylformamide, and a mixture thereof. 
         [0242]    The reaction is carried out typically at about −90 to 150° C. and preferably at about −90 to 120° C., and completed generally in about 10 minutes to 10 hours. 
         [0243]    The compound (12) is appropriately used typically in at least an equimolar amount to that of the compound (13) and preferably 1 to 5 times that of the compound (13) on a molar basis. 
         [0244]    The reaction for converting the compound (1l) into the compound (1m) is carried out in an appropriate inert solvent and in the presence of an acid. 
         [0245]    Examples of the acid used herein include mineral acids such as hydrochloric acid, sulfuric acid, and hydrobromic acid, and organic acids such as sulfonic acids including p-toluenesulfonic acid. These acids are used singly or in a mixture of two types or more. 
         [0246]    The acid is preferably used typically in at least an equimolar amount to that of the compound (1l) and preferably in an equal amount to a large excess amount with respect to the compound (1l) on a molar basis. 
         [0247]    Any solvent may be used in this reaction as long as it is used in the reaction between the compound (13) and the compound (12). 
         [0248]    This reaction is carried out typically at room temperature to 200° C., preferably at room temperature to about 150° C., and completed generally in about 1 to 20 hours. 
         [0249]    The reaction for converting the compound (1l) into the compound (1l′) is carried out in an appropriate solvent and in the presence of an acid and a catalyst. 
         [0250]    Examples of the solvent used herein include water, lower alcohols such as methanol, ethanol, and isopropanol, ketones such as acetone and methyl ethyl ketone, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, and carbon tetrachloride, ethers such as diethyl ether, dimethoxyethane, tetrahydrofuran, diisopropyl ether, diglyme, and 1,4-dioxane, aromatic hydrocarbons such as benzene, toluene, and xylene, acetonitrile, dimethyl sulfoxide, N,N-dimethylacetamide, N,N-dimethylformamide, and N-methylpyrrolidone, and a mixture thereof. 
         [0251]    Examples of the acid used herein include inorganic acids such as hydrochloric acid, sulfuric acid, and hydrobromic acid, and organic acids such as boron trifluoride diethyl etherate, formic acid, acetic acid, trifluoroacetic acid, and p-toluenesulfonic acid. 
         [0252]    Examples of the catalyst include alkylsilane compounds such as triethylsilane. 
         [0253]    The acid and the catalyst described above each are used typically in an amount about 0.01 to 5 times that of the compound (1l), and preferably about 0.01 to 1 times to that of the compound (1l) on a molar basis. 
         [0254]    The reaction is carried out at about room temperature to 200° C., and preferably about room temperature to 150° C., and completed generally in about 1 to 10 hours. 
         [0255]    The reaction which converts the compound (1l) into the compound (1l′) may be carried out in an appropriate solvent and in the presence of a catalytic hydrogen reducing agent. 
         [0256]    Examples of the solvent to be used include water, fatty acids such as acetic acid, alcohols such as methanol, ethanol, and isopropanol, aliphatic hydrocarbons such as n-hexane, alicyclic hydrocarbons such as cyclohexane, ethers such as diethyl ether, dimethoxyethane, tetrahydrofuran, monoglyme, diglyme, and 1,4-dioxane, esters such as methyl acetate, ethyl acetate, and butyl acetate, and aprotic polar solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, and a mixture thereof. 
         [0257]    Examples of the catalytic hydrogen reducing agent include palladium, palladium-black, palladium-carbon, palladium hydroxide-carbon, rhodium-alumina, platinum, platinum oxide, copper chromite, Raney nickel, and palladium acetate. 
         [0258]    The catalytic hydrogen reducing agent is used typically in an amount of 0.01 to 1 times that of the compound (1l) on a weight basis. 
         [0259]    The reaction favorably proceeds typically at about −20 to 100° C. and preferably at about 0 to 80° C., and completed generally in about 0.5 to 20 hours. The hydrogen pressure is typically at 1 to 10 atm. 
         [0260]    It is preferable to add a mineral acid such as hydrochloric acid to this reaction system. 
         [0261]    The compound (1), wherein A represents 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 4  represents 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 13  represents a group other than a hydrogen atom,
 
is produced from a compound wherein R 13  is a hydrogen atom, in accordance with the following reaction formula 9.
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y, A 10 , R A , R 13a  and X 2  are the same as described above, provided that a and b of A 10  are bound to Y and a piperidinyl group, respectively,
 
R 13b  represents a lower alkyl group which may have a halogen atom as a substituent, a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, an imidazolyl lower alkyl group, a lower alkoxycarbonyl lower alkyl group, a carboxy lower alkyl group, a piperazinylcarbonyl lower alkyl group which may be substituted, on the piperazine ring, with a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, or a morpholinocarbonyl substituted lower alkyl group,
 
R 13c  represents a lower alkanoyl group which may have a halogen atom as a substituent, a lower alkoxy carbonyl group, a benzoyl group, a morpholino substituted lower alkanoyl group, a piperazinyl lower alkanoyl group which may be substituted, on the piperazine ring, with a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring; or an imidazolyl lower alkanoyl group, and
 
R 13d  represents a hydrogen atom, a lower alkyl group which may have a halogen atom as a substituent, a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, a phenyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, an imidazolyl group, an imidazolyl lower alkyl group, a lower alkoxycarbonyl lower alkyl group, a carboxy lower alkyl group, a piperazinylcarbonyl lower alkyl group which may be substituted, on the piperazine ring, with a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, or a morpholinocarbonyl substituted lower alkyl group, provided that the alkyl moiety of the side chain (group —CHR A R 13d ) of the compound (1q) has not more than 6 carbon atoms.
 
         [0262]    The reaction of the compound (1n-1) with the compound (13′) is carried out under the same conditions as in the reaction between the compound (1b) and the compound (4) in accordance with reaction formula 2. 
         [0263]    The reaction between the compound (1n-1) and the compound (14) is carried out under the same conditions as in the reaction between the compound (1b) and the compound (6) in accordance with reaction formula 2. 
         [0264]    The reaction between the compound (1n-1) and the compound (15) is carried out under the same conditions as in the reaction between the compound (1b) and the compound (5) of reaction formula 2. 
         [0265]    Also, the reaction between the compound (1n-2) and the compound (13′) is carried out under the same conditions as in the reaction between the compound (1b) and the compound (4) in accordance with reaction formula 2, the reaction between the compound (1n-2) and the compound (14) is carried out under the same conditions as in the reaction between the compound (1b) and the compound (6) in accordance with reaction formula 2, and the reaction between the compound (1n-2) and the compound (15) is carried out under the same conditions as in the reaction between the compound (1b) and the compound (5) in accordance with reaction formula 2. 
         [0266]    In reaction formula 9, the hydrolysis of the compounds (1o-1) and (1o-2) wherein R 13b  represents a lower alkoxycarbonyl lower alkyl group may produce the corresponding compounds (1o-1) and (1o-2) wherein R 13b  represents a carboxy lower alkyl group. 
         [0267]    In reaction formula 9, the hydrolysis of compounds (1p-1) and (1p-2), wherein R 13c  represents a lower alkoxycarbonyl group, may produce the corresponding compounds (1p-1) and (1p-2), wherein R 13c  is a hydrogen atom. 
         [0268]    The hydrolysis reaction (hereinafter, this hydrolysis reaction will be called “hydrolysis B”) may be carried out in the presence or absence of an appropriate solvent and in the presence of an acidic or basic compound. 
         [0269]    Examples of the solvent to be used herein include water, lower alcohols such as methanol, ethanol, isopropanol, and tert-butanol, ketones such as acetone and methyl ethyl ketone, ethers such as diethyl ether, dioxane, tetrahydrofuran, monoglyme, and diglyme, fatty acids such as acetic acid and formic acid, esters such as methyl acetate and ethyl acetate, halogenated hydrocarbons such as chloroform, dichloromethane, dichloroethane, and carbon tetrachloride, dimethylsulfoxide, N,N-dimethylformamide, and hexamethylphosphoric acid triamide, and a mixture thereof. 
         [0270]    Examples of the acid include mineral acids such as hydrochloric acid, sulfuric acid, and hydrobromic acid, organic acids such as formic acid, acetic acid, trifluoroacetic acid, sulfonic acids including p-toluenesulfonic acid, and Lewis acids such as boron tribromide and boron trichloride. These acids are used singly or in a mixture of two types or more. 
         [0271]    Examples of the basic compound include carbonates such as sodium carbonate, potassium carbonate, sodium bicarbonate, and potassium bicarbonate, and metal hydroxides such as sodium hydroxide, potassium hydroxide, calcium hydroxide, and lithium hydroxide. These basic compounds are used singly or in a mixture of two types or more. 
         [0272]    The hydrolysis reaction favorably proceeds typically at about 0 to about 200° C. and preferably at about 0 to 150° C., and is completed generally in about 10 minutes to 50 hours. 
         [0273]    The compound (1) wherein A represents 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 4  represents 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 13  represents an imidazolyl lower alkyl group, is produced as shown in reaction formula 10 below. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y, A 10 , R 13a , B 2 , and X 2  are the same as described above, provided that a and b of A 10  are bound to Y and a piperidinyl group, respectively. 
         [0274]    The reaction of the compound (1r-1) and the compound (16) and the reaction of the compound (1r-2) and the compound (16) are carried out under the same conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0275]    The compound (1) wherein A represents 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 4  represents 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 13  represents a morpholino substituted lower alkanoyl group, a piperazinyl lower alkanoyl group which may be substituted on the piperazine ring with a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, or an imidazolyl lower alkanoyl group, may be produced from the corresponding compound, wherein R 13  represents a lower alkanoyl group which may have a halogen atom as a substituent, as shown in reaction formula 11 below. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y, R 13a , B 21  and X 2  are the same as described above, and R 47′  is a morpholino group, a piperazinyl group which may be substituted, on the piperazine ring, with a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, or an imidazolyl group, provided that a and b of A 10  are bound to Y and a piperidinyl group, respectively. 
         [0276]    The reaction of the compound (1t-1) and the compound (17) and the reaction of the compound (1t-2) and the compound (17) are carried out under the same conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0277]    The compound (1) wherein A represents 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 4  represents 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 13  represents a piperazinylcarbonyl lower alkyl group which is substituted, on the piperazine ring, with a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, or a morpholinocarbonyl substituted lower alkyl group,
 
is produced from the corresponding compound wherein R 13  is a carboxy group, as shown in reaction formula 12 below.
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y, A 10 , R 13a  and B 21  are the same as described above, R 48  is a piperazinyl group which may be substituted, on the piperazine ring, with a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, or a morpholino group, provided that a and b of A 10  are bound to Y and a piperidinyl group, respectively. 
         [0278]    The reaction of the compound (1v-1) and the compound (18) and the reaction of the compound (1v-2) and the compound (18) are carried out under the same conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula above. 
         [0279]    The compound (1) wherein A represents 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 4  represents a group -(T) l -NR 14 R 15 , is produced as shown in reaction formulas 13 and 14 below. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y, A 10 , X 2 , l, R 14  and R 15  are the same as described above, T 1  is a lower alk ylene group, a group —COB 8 —, a group —SO 2 — or a group —CH(OH)—B 9 —, and B 8  and B 9  are the same as described above, provided that, in the compounds (35) and (1pp), a and b of A 10  are bound to Y and -(T l ) l , respectively. 
         [0280]    The reaction of the compound (35) and the compound (36) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0281]    The compound (35) wherein l is 0 may also be produced by reacting the corresponding compound (35) with the compound (36) in an appropriate solvent in the presence of a basic compound and a catalyst. 
         [0282]    Any solvent and basic compound may be used as long as they are used in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0283]    Examples of the catalyst include various metal complexes as well as various combinations of a metal complex with a ligand. Examples of the metal complex include palladium acetate (II), tetrakis(triphenylphosphine)palladium(0), and tris(dibenzylideneacetone)dipalladium(0). Examples of the ligand include R-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (R-BINAP), S-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (S-BINAP), RAC-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (RAC-BINAP), t-butylphosphine, and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene. 
         [0284]    The catalyst is appropriately used typically in at least an equimolar amount to the compound (35) and preferably 1 to 5 times that of the compound (35) on a molar basis. 
         [0285]    This reaction is carried out typically at about 0 to 200° C. and preferably at about 0 to 150° C., and completed generally in about 1 to 60 hours. This reaction will be hereinafter called “reaction C”. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, A 10 , T 2 , R 14  and R 15  are the same as described above, provided that, in the compounds (37) and (1qq), a and b of A 10  are bound to Y and T 2 , respectively, and R 95  represents a group R 1  or a halogen atom. The R 1  used herein is the same as described above. 
         [0286]    The reaction of the compound (37) and the compound (36) is carried out in the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0287]    The compound (1) wherein A represents 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 4  represents a group -(T) l -NR 14 R 15 , and l represents 0,
 
may also be produced by the method shown in reaction formula 15.
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y, R A , X 2 , T, l and A 10  are the same as described above,
 
R 49  is the same group as R 15  defined in (15), (22), (23), (27) and (36a),
 
R 49a  is R 15  defined in (2) to (5), (7), (8), (10), (11), (13), (14), (16) to (21), (24), (25), (26), (26a), (27a), (28a), (29a), (30a), (31a), (32a), (33a), (34a), (35a), or (37a), a phenoxycarbonyl group and a lower alkylsulfonyl group,
 
R 49b  represents a hydrogen atom, an alkyl group which may have a hydroxyl group as a substituent, a phenoxy lower alkyl group, a phenyl lower alkyl group which may have, on the phenyl ring, with 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkoxy group which may have a halogen atom as a substituent, and a lower alkyl group, a phenyl group which may have, on the phenyl ring, with 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkoxy group which may have a halogen atom as a substituent, and a lower alkyl group, a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, a phenyl group which may have a lower alkylenedioxy group on the phenyl ring, a lower alkoxycarbonyl substituted lower alkyl group, a carboxy substituted lower alkyl group, a cycloalkyl lower alkyl group, a cycloalkyl group, a pyridyl lower alkyl group, a pyridyl group, an amino group substituted lower alkyl group which may have a substituent selected from the group consisting of a lower alkyl group and a lower alkanoyl group, a lower alkoxy lower alkyl group, an imidazolyl group, an imidazolyl lower alkyl group, a 1,2,3,4-tetrahydroisoquinolylcarbonyl substituted lower alkyl group, an A group-substituted carbonyl lower alkyl group, a pyrrolidinyl group, a pyrrolidinyl lower alkyl group, a morpholino group, a morpholino lower alkyl group, an anilinocarbonyl lower alkyl group which may have a lower alkyl group as a substituent on the phenyl ring, a piperazinyl group which may have, on the piperazine ring, a substituent selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, a piperazinyl lower alkyl group which may have, on the piperazine ring, a substituent selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, an amidino group which may have a lower alkyl group as a substituent, an amidino lower alkyl group which may have a lower alkyl group as a substituent, a B group substituted carbonyl lower alkyl group, or a cyano substituted lower alkyl group,
 
R 14a  represents a hydrogen atom or a lower alkyl group which may have a hydroxyl group as a substituent, and R 34 , d, R 36 , R 37  and B 20  are the same as described above, provided that, in the compounds (1rr), (1ss), (1ss′) and (1ss″), a and b of A 10  are bound to Y and N, respectively, and, in the compound (1ss″), the CHR A R 49b  moiety of the side chain (—Y-A 1 oN(R 14a )(CHR A R 49b ) has not more than 6 carbon atoms.
 
         [0288]    The reaction of the compound (1rr) and the compound (38a) is carried out under the same conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 above. 
         [0289]    The reaction of the compound (1rr) with the compound (38) is carried out under the same conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0290]    The reaction of the compound (1rr) with the compound (38b) is carried out under the condition similar to that of the reaction of the compound (1b) and the compound (5) shown in reaction formula 2 above. 
         [0291]    The compound (1) wherein A represents 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 4  represents a group -(T) l -NR 14 R 15 , l represents 1, and T represents a group —CH(OH)—B 9 —, may also be produced by the method shown in reaction formula 16 below. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , A 10 , Y, B 8 , B 9 , R 14  and R 15  are the same as described above, provided that, in the compounds (1tt) and (1uu), a and b of A 10  are bound to Y and B 8  or B 9 , respectively. 
         [0292]    The reaction which converts the compound (1tt) into the compound (1uu) is carried out under the same condition as in the reaction which converts the compound (1f) into the compound (1g) shown in reaction formula 3 above. 
         [0293]    The compound (1) wherein A represents 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 4  represents a group -(T) l -NR 14 R 15 , l represents 1, and T represents a group —CH(OH)—B 11 , —CO—, may also be produced by the method shown in reaction formula 17 below. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , A 10 , Y, B 10 , B 11 , R 14  and R 15  are the same as described above, provided that, in the compounds (1vv) and (1ww), a and b of A 10  are bound to Y and a group —COB 10  or —CH(OH)B 11 —, respectively. 
         [0294]    The reaction which converts the compound (1vv) into the compound (1ww) is carried out under the same conditions as in the reaction which converts the compound (1f) into the compound (1g) shown in reaction formula 3 above. 
         [0295]    The compound (1) wherein A represents 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 4  is a group -(T) 1 NR 14 R 15 , and R 14  and R 15  are bound with each other to form a 5- to 10-membered saturated or unsaturated heterocyclic group which has various substituents thereon,
 
may be produced as shown in reaction formulas 18 to 20, 22, 24 to 31, and 34 to 36 below.
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , R B , X 1 , Y, T, l, A 10  and X 2  are the same as described above, provided that a and b of A 10  are bound to a group Y and a group (T)l, respectively;
 
R 14b  and R 15a  represent the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one secondary amine thereon;
 
R 14c  and R 15b  represent the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above respectively, except that each of the heterocyclic groups has at least one tertiary amine substituted with R 50  thereon;
 
R 14d  and R 15c  represent the same 5- to 10-membered saturated or unsaturated heterocyclic group defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one tertiary amine substituted with R 51  thereon;
 
R 14e  and R 15d  represent the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one tertiary amine substituted with a R 52 (R B )CH— group thereon; R 14f  and R 15e  represent the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one tertiary amine thereon substituted with a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 50  is the same substituent for the heterocyclic ring, which is formed by binding R 14  and R 15  to each other, as (28), (30), (31), (32), (33), (34), (36), (37), (38), (41), (43), (44), (45), (47), (49) (provided that t is 1), (50) (provided that o is 0), (51), (52), (53), (54), (55), (56), (57), (58), (59), (60), (62), (63), (64), (65), (66), (70), (77), (79), (82), (83), (87), (88a), or (90a) described above;
 
R 51  is the same substituent for the heterocyclic group, which is formed by binding R 14  and R 15  to each other, as (35), (39), (40), (42), (50) (provided that o is 1), (67), (75), (76), (77), (78), (80), (81) or (84) (provided that s is 0) described above;
 
R 52  is a hydrogen atom, a lower alkyl group which has 1 or 2 phenyls which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkanoyl group, an amino group which may have a lower alkanoyl group as a substituent, a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, a phenyl lower alkoxy group, a hydroxyl group, and a lower alkylenedioxy group, (the lower alkyl group optionally having a pyridyl group on the lower alkyl group), a phenyl group which may have, on the phenyl ring 1 to 3 substituents selected from the group consisting of a lower alkanoyl group, an amino group which have a lower alkanoyl group as a substituent, a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, a phenyl lower alkoxy group, a hydroxy group, and a lower alkylenedioxy group, a pyridyl lower alkyl group which may have, on the pyridine ring, 1 to 3 substituents selected from the group consisting of a hydroxyl group and a lower alkyl group which may have a hydroxyl group as a substituent, a pyridyl group which may have, on the pyridine ring, 1 to 3 substituents selected from the group consisting of a hydroxyl group and a lower alkyl group which may have a hydroxyl group as a substituent, a pyrrolyl lower alkyl group which may have 1 to 3 lower alkyl groups as substituents on the pyrrole ring, a pyrrolyl group which may have 1 to 3 lower alkyl groups as substituents on the pyrrole ring, a benzoxazolyl lower alkyl group, a benzoxazolyl group, a benzothiazolyl lower alkyl group, a benzothiazolyl group, a furyl lower alkyl group, a furyl group, a lower alkyl group which may have a substituent selected from the group consisting of a hydroxyl group and a halogen atom, a naphthyl lower alkyl group, a naphthyl group, a phenoxy lower alkyl group, a group —B 12 CO—NR 20 R 21 ; a group —B 13 NR 22 R 23  group, a group 1,2,3,4-tetrahydronaphthyl substituted lower alkyl group which may have 1 to 5 lower alkyl groups as substituents on the 1,2,3,4-tetrahydronaphthalene ring, a 1,2,3,4-tetrahydronaphthyl group which may have 1 to 5 lower alkyl groups as substituents on the 1,2,3,4-tetrahydronaphthalene ring, a quinolyl lower alkyl group, a quinolyl group, a 1,2,3,4-tetrazolyl lower alkyl group which may have, on the tetrazole ring, a substituent selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group, a 1,2,3,4-tetrazolyl group which may have, on the tetrazole ring, a substituent selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group, a thiazolyl lower alkyl group which may have a phenyl group as a substituent on the thiazole ring, a thiazolyl group which may have a phenyl group as a substituent on the thiazole ring, a benzoyl lower alkyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkoxy group and a halogen atom, a piperidinyl lower alkyl group which may have a lower alkyl group as a substituent on the piperidine ring, a benzoyl lower alkyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkoxy group and a halogen atom, a piperidinyl group which may have a lower alkyl group on the piperidine ring, a 1,2,3,4-tetrahydroquinolyl lower alkyl group which may have an oxo group as a substituent on the tetrahydroquinoline ring, a 1,2,3,4-tetrahydroquinolyl group which may have an oxo group as a substituent on the tetrahydroquinoline ring, a 1,3,4-oxadiazolyl lower alkyl group which may have an oxo group as a substituent on the 1,3,4-oxadiazole ring, a 1,3,4-oxadiazolyl group which may have an oxo group as a substituent on the 1,3,4-oxadiazole ring, a cycloalkyl lower alkyl group, a cycloalkyl group, a thienyl lower alkyl group, a thienyl group, a lower alkoxy lower alkyl group, a carboxy lower alkyl group, a lower alkoxycarbonyl lower alkyl group, an imidazolyl lower alkyl group, or an imidazolyl group; and R B  and R 52 , together with carbon atoms to which they bind, may form a cycloalkyl group or a tetrahydro-4H-pyranyl group;
 
provided that the alkyl moiety of the R 52 (R B )CH— group in the compound (1aaa) has not more than six carbon atoms.
 
         [0296]    The reaction of the compound (35′) and the compound (39) is carried out under the same conditions as in the reaction of the compound (1b) with the compound (4) shown in reaction formula 2 above. 
         [0297]    The reaction of the compound (35′) and the compound (40) is carried out under the same conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0298]    The reaction of the compound (35′) and the compound (41) is carried out under the same conditions as in the reaction of the compound (1b) and the compound (5) shown in reaction formula 2 above. 
         [0299]    The reaction is carried out using a compound (41), whose R B  and R 52  (bound to a carbon atom) are mutually bound to form a cycloalkyl ring or a tetrahydro-4H-pyran ring together with the carbon atom in the presence of a hydride reducing agent, as a starting material. In this case, in place of the compound (41), cycloalkyloxytrialkylsilane such as [(1-ethoxycyclopropyl)oxy]trimethylsilane may be used as the starting material (to produce the above described compound (41) in the reaction system). 
         [0300]    The reaction of the compound (35′) and the compound (42) is carried out under the same conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0301]    The compound (35′) may also be produced from the compound (1yy), (1zz) or (1aaa) under the same reaction conditions as in the reaction which converts the compound (1iii′) into the compound (1hhh′) shown in reaction formula 24 below. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y, T, l, A 10  and X 2  are the same as described above, provided that a and b of A 10  are bound to Y and (T)l, respectively;
 
R 14g  and R 15f  are the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one tertiary amine substituted with a lower alkoxycarbonyl group thereon; and
 
R 14h  and R 15g  are the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one secondary amine thereon.
 
         [0302]    The reaction which converts the compound (1ccc) into the compound (1ddd) may be carried out under the same reaction conditions as in hydrolysis B as described in reaction formula 9 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y, T, l and A 10  are the same as described above, provided that a and b of A 10  are bound to a group Y and a group (T)l, respectively, R 74a  represents a nitro group or a group —R 1 , and; R 14i  and R 15i  are the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one lower alkoxycarbonyl lower alkoxy group, lower alkoxycarbonyl group, lower alkoxycarbonyl lower alkyl group, or a group —(B 12 CO)t-N(R 20a )R 51′  thereon;
 
R 14j  and R 15i  are the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one carboxy lower alkoxy group, carboxy group, carboxy lower alkyl group, or a group —(B 12 CO)t-N(R 20a )R 52′  group thereon;
 
B 12  and t are the same as described above;
 
R 20a  represents a hydrogen atom, a cycloalkyl group, an amino group which may have a lower alkoxycarbonyl group as a substituent, a benzoyl group which may have 1 to 3 alkoxy groups as substituents on the phenyl ring, a lower alkyl group,
 
a lower alkyl group which may have, on the phenyl ring, substituents selected from the group consisting of an lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, and a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, and a lower alkylthio group, a phenyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkoxy group which may have a halogen atom as a substituent and a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxycarbonyl group, a cycloalkyl lower alkyl group, a pyrrolidinyl lower alkyl group which may have, on the pyrrolidine ring, 1 to 3 lower alkyl groups which may have a hydroxyl group as a substituent, an amino substituted lower alkyl group which may have a substituent selected from the group consisting of a phenyl group and a lower alkyl group,
 
a 1,2,3,4-tetrahydronaphthyl substituted lower alkyl group which may have 1 to 5 lower alkyl groups as substituents on the 1,2,3,4-tetrahydronaphthalene ring, a naphthyl lower alkyl group, a pyridyl lower alkyl group, a quinolyl lower alkyl group, a 1,2,3,4-tetrazolyl lower alkyl group which may have, on the tetrazole ring, 1 to 3 substituents selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group, a 1,2,4-triazolyl lower alkyl group, a tetrahydrofuryl lower alkyl group which may have a hydroxyl group as a substituent on the lower alkyl group, a phenoxy lower alkyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkyl group and a nitro group, a phenyl lower alkanoyl group, a lower alkanoyl group which may have a halogen atom as a substituent, an imidazolyl lower alkanoyl group, a lower alkoxycarbonyl lower alkyl group, a pyridyl group, or a carboxy lower alkyl group;
 
R 51′  is a lower alkdxycarbonyl group or a lower alkoxycarbonyl lower alkyl group;
 
R 52  is a hydrogen atom or a carboxy lower alkyl group; and
 
R 53  is a lower alkyl group.
 
         [0303]    The reaction which converts the compound (1eee) into the compound (1fff) may be carried out under the same reaction conditions as described in hydrolysis B as described in reaction formula 9 above. 
         [0304]    The reaction of the compound (1fff) and the compound (43) may be carried out under any conditions of a typical esterification reaction. For example, the reaction is carried out in the presence of a mineral acid such as hydrochloric acid or sulfuric acid, and a halogenating agent such as thionylchloride, phosphorus oxychloride, phosphorus pentachloride, or phosphorus trichloride. The compound (43) is used in a large excess amount of that of the compound (1fff). The reaction favorably proceeds typically at about 0 to 150° C. and preferably at about 50 to 100° C., and is completed generally in about 1 to 10 hours. 
         [0305]    The esterification reaction may be carried out using a condensation agent such as carbodiimide in the presence of a basic compound such as dimethylaminopyridine. Typical reaction conditions for producing an amide bond, which are used in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2, may also be used. 
         [0306]    The reaction of the compound (1fff) and compound (43) is carried out in the presence of the same basic compound and the solvent as those used in the reaction of the compound (2) and the compound (3) of reaction formula 1. The reaction is carried out typically at about 0 to 100° C. and preferably at about 0 to 70° C., and completed generally in about 1 to 30 hours. 
         [0307]    The compound (1eee) may also be produced using a halogenated lower alkyl such as methyl iodide in place of the compound (43) under the same conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y, A 10 , R 13a , B 21  and R 53  are the same as described above, and R 54  is a lower alkyl group, provided that a and b of A 10  are bound to a group Y and a piperidinyl group, respectively. 
         [0308]    The reaction which converts the compound (1ggg-1) into the compound (1v-1) and the reaction which converts the compound (1ggg-2) into the compound (1v-2) is carried out under the same reaction conditions as in hydrolysis B as described in reaction formula 9. 
         [0309]    The reaction of the compound (1v-1) and the compound (43) and the reaction of the compound (1v-2) and the compound (43) are carried out under the same reaction conditions as in the reaction of the compound (1fff) and the compound (43) shown in reaction formula above. 
         [0310]    The compound (1ggg-1) may also be produced using a halogenated lower alkyl such as methyl iodide in place of the compound (43) under the same conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0311]    Similarly, the compound (1ggg-2) may also be produced using a halogenated lower alkyl such as methyl iodide in place of the compound (43) under the same conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y, T, l and A 10  are the same as described above, provided that a and b of A 10  are bound to a group Y and a group (T)l, respectively; R 14k  and R 15j  are the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one group —B 21 CONHNH 2  (wherein B 21  is the same as described above) thereon; and
 
R 14l  and R 15k  are the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    thereon. 
         [0312]    The reaction which converts the compound (1hhh) into compound (1iii) is carried out under the same conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y, A 10 , B 21  and X 2  are the same as described above, provided that a and b of A 10  are bound to a group Y and a group (T)l, respectively, R 55  is a lower alkanoyl group, and R 55a  is a lower alkyl group. 
         [0313]    The reaction of the compound (44) and the compound (45) is carried out under the same conditions as in the reaction which converts the compound (1f) into the compound (1 h) shown in reaction formula 3 above. 
         [0314]    The reaction of the compound (44a) and the compound (46) is carried out under the same conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0315]    The reaction which converts the compound (47) into the compound (1rrr) is carried out under the same conditions as in the reaction which converts the compound (1f) into the compound (1 h) shown in reaction formula 3 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y, T, l, A 10  and X 2  are the same as described above, provided that a and b of A 10  are bound to a group Y and a group (T)l, respectively; R 14m  and R 15l  are the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one hydroxyl group or hydroxyl group substituted lower alkyl group thereon;
 
R 14n  and R 15m  are the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one group —OR 56  thereon;
 
R 56  represents a phenyl group which have, on the phenyl ring, with 1 to 3 substituents selected from the group consisting of a cyano group, a lower alkyl group which may have a halogen atom as a substituent, and a lower alkoxy group which may have a halogen atom as a substituent, a phenyl lower alkyl group which may have, on the phenyl ring, with 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, and a lower alkoxy group which may have a halogen atom as a substituent, a pyridyl lower alkyl group, a lower alkyl group, a lower alkoxy lower alkyl group, a benzoyl group, a lower alkoxycarbonyl lower alkyl, a carboxy lower alkyl group; or a group —B 15 —CO—NR 26 R 27  group (wherein B 15 , R 26  and R 27  are the same as described above),
 
provided that, the R 56  of the compound (48), which reacts with the heterocyclic group substituted with at least one hydroxyl group substituted lower alkyl group of the compound (1hhh′), is an unsubstituted phenyl group or a lower alkyl group.
 
         [0316]    The reaction of the compound (1hhh′) and the compound (48) is carried out under the same conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0317]    The reaction which converts the compound (1iiil) into the compound (1hhh′) is carried out under the same conditions as in hydrolysis B as described in reaction formula 9 above. 
         [0318]    The compound (1iii′) may be converted into the compound (1hhh′) by a reduction reaction. This reduction reaction is, for example, carried out in an appropriate solvent in the presence of a catalytic hydrogen reducing agent. 
         [0319]    Examples of the solvent include water, fatty acids such as acetic acid, alcohols such as methanol, ethanol, and isopropanol, aliphatic hydrocarbons such as hexane and cyclohexane, ethers such as dioxane, tetrahydrofuran, diethyl ether, monoglyme, and diglyme, esters such as ethyl acetate and methyl acetate, aprotic polar solvents such as N,N-dimethylformamide, and a mixture thereof. 
         [0320]    Examples of the catalytic hydrogen reducing agent include palladium, palladium black, palladium-carbon, platinum, platinum oxide, copper chromite, and Raney nickel. These reducing agents may be used singly or as a mixture of two types or more. 
         [0321]    The catalytic hydrogen reducing agent is preferably used generally in an amount of 0.02 to 1 times that of the compound (1iii′) on a weight basis. 
         [0322]    The reaction temperature is typically set at about −20 to 100° C. and preferably at about 0 to about 80° C. The reaction is preferably carried out at a hydrogen pressure of typically 1-10 atm, and completed generally in about 0.5 to 20 hours. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y, T, l, A 10 , R A  and X 2  are the same as described above, provided that a and b of A 10  are bound to a group Y and a group (T)l, respectively; R 14o  and R 15n  are the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one group —(B 12 CO)tNHR 20a  thereon;
 
R 14p  and R 15o  are the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one group —(B 12 CO)tN(R 20a )R 21b  thereon; and
 
R 14q  and R 15p  are the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one group —(B 12 CO)tN(R 20a )R 21c  thereon;
 
R 14r  and R 15q  represent the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one group —(B 12 CO)tN(R 20a )(CHR A R 21d ) thereon,
 
wherein B 12 , t and R 20a  are the same as described above;
 
R 21b  represents a lower alkyl group, a cycloalkyl group, a lower alkyl group which may have 1 or 2 phenyls which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent and a lower alkylthio group, a phenyl group which may have, on the phenyl ring, 1 to 3 groups selected from the group consisting of a lower alkoxy group which may have a halogen atom as a substituent and a lower alkyl group which may have a halogen atom as a substituent, a cycloalkyl lower alkyl group, a pyrrolidinyl lower alkyl group which may have, on the pyrrolidine ring, 1 to 3 lower alkyl groups which may have a hydroxyl group as a substituent, an amino substituted lower alkyl group which may have a substituent selected from the group consisting of a phenyl group and a lower alkyl group, a 1,2,3,4-tetrahydronaphthyl substituted lower alkyl group which may have 1 to 5 lower alkyl groups as substituents on the 1,2,3,4-tetrahydronaphthalene ring, a naphthyl lower alkyl group, a pyridyl lower alkyl group, a quinolyl lower alkyl group, a 1,2,3,4-tetrazolyl lower alkyl group which may have, on the tetrazole ring, 1 to 3 substituents selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group, a 1,2,4-triazolyl lower alkyl group, a tetrahydrofuryl lower alkyl group which may have a hydroxyl group as a substituent on the lower alkyl group, a phenoxy lower alkyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkyl group and a nitro group, a lower alkoxycarbonyl lower alkyl group, a pyridyl group, or a carboxy lower alkyl group;
 
R 21c  represents a benzoyl group which may have 1 to 3 lower alkoxy groups as substituents on the phenyl ring, a lower alkoxycarbonyl group, a phenyl lower alkanoyl group, a lower alkanoyl group which may have a halogen atom as a substituent or an imidazolyl lower alkanoyl group; and
 
R 21d  represents a hydrogen atom, a lower alkyl group, a lower alkyl group which have 1 or 2 phenyl groups which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent and a lower alkylthio group, a phenyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may be substituted with a halogen atom, a lower alkoxy group which may be substituted with a halogen atom and a lower alkylthio group, a cycloalkyl lower alkyl group, a cycloalkyl group, a pyrrolidinyl lower alkyl group which may have, on the pyrrolidine ring, 1 to 3 lower alkyl groups which may have a hydroxyl group as a substituent, a pyrrolidinyl group which may have, on the pyrrolidine ring, 1 to 3 lower alkyl groups which may have a hydroxyl group as a substituent, an amino substituted lower alkyl group which may have a group selected from the group consisting of a phenyl group and a lower alkyl group, a 1,2,3,4-tetrahydronaphthyl substituted lower alkyl group which may have 1 to 5 lower alkyl groups as substituents on the 1,2,3,4-tetrahydronaphthalene ring, a 1,2,3,4-tetrahydronaphthyl group which may have 1 to 5 lower alkyl groups as substituents on the 1,2,3,4-tetrahydronaphthalene ring, a naphthyl lower alkyl group, a naphthyl group, a pyridyl lower alkyl group, a pyridyl group, a quinolyl lower alkyl group, a quinolyl group, a 1,2,3,4-tetrazolyl lower alkyl group which may have, on the tetrazole ring, 1 to 3 substituents selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group, a 1,2,3,4-tetrazolyl group which may have, on the tetrazole ring, 1 to 3 substituents selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group, a 1,2,4-triazolyl lower alkyl group, a 1,2,4-triazolyl group, a tetrahydrofuryl lower alkyl group which may have a hydroxyl group as a substituent on the lower alkyl group, a tetrahydrofuryl group which may have a hydroxyl group as a substituent on the lower alkyl group, a phenoxy lower alkyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkyl group and a nitro group, a lower alkoxycarbonyl lower alkyl group or a carboxy lower alkyl group;
 
provided that the alkyl moiety of CHR A R 21d  in the side chain (—(B 21 CO)tN(R 20a )(CHR A R 21d )) has not more than 6 carbon atoms.
 
         [0323]    The reaction of the compound (1uuu) with the compound (49) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 above. 
         [0324]    The reaction of the compound (1uuu) and the compound (51) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (5) shown in reaction formula 2 above. 
         [0325]    The reaction of the compound (1uuu) and the compound (50) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y, T, l, and A 10  are the same as described above, provided that a and b of A 10  are bound to Y and (T)l, respectively;
 
R 14s  and R 15r  represent the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one group —(CO)oB 13 X 2  thereon;
 
R 14t  and R 15s  represent the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one group —(CO)o B 13 R 84  thereon; and
 
R 84  is a group —NR 22 R 23  or an imidazolyl group (wherein B 13 , o, X 2 , R 22  and R 23  are the same as described above).
 
         [0326]    The reaction of the compound (1yyy) and the compound (52) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y, T, l, and A 10  are the same as described above, provided that a and b of A 10  are bound to a group Y and group (T)l, respectively;
 
R 14s′  and R 15r′  represent the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one group —N(R 28 )—CO—B 16 X 2  thereon; and
 
R 14u  and R 15t  represent the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one group —N(R 28 )—CO—B 16 NR 29 R 30  thereon;
 
(wherein R 28 , B 16 , X 2 , R 29  and R 30  represent the same as described above).
 
         [0327]    The reaction of the compound (1aaaa) and the compound (53) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 74a , R 2 , X 1 , Y, T, l, and A 10  are the same as described above, provided that a and b of A 10  are bound to a group Y and a group (T)l, respectively;
 
R 14v  and R 15u  represent the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one group —B 12 COOH thereon; and
 
R 14w  and R 15v  represent the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one group —B 12 CONR 20 R 21  thereon;
 
(wherein B 12 , R 20  and R 21  are the same as described above).
 
         [0328]    The reaction of the compound (1cccc) and the compound (54) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y, T, l, and A 10  are the same as described above, provided that a and b of A 10  are bound to a group Y and a group (T) l , respectively;
 
R 14x  and R 15w  represent the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one group —O—B 15 COOH; and
 
R 14y  and R 15x  represent the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one group —O—B 15 CONR 26 R 27  thereon;
 
(wherein B 15 , R 26  and R 27  are the same as described above).
 
         [0329]    The reaction of the compound (1eeee) and the compound (55) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y, T, l, and A 10  are the same as described above, provided that a and b of A 10  are bound to a group Y and (T)l, respectively;
 
R 14z  and R 15y  represent the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one group —N(R 31 )—B 17 —COOH thereon; and
 
R 14aa  and R 15z  represent the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one group —N(R 31 )—B 17 CONR 32 R 33  thereon;
 
(wherein R 31 , B 17 , and R 32 , R 33  are the same as described above).
 
         [0330]    The reaction of the compound (1gggg) and the compound (56) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) of reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y, T, l, and A 10  are the same as described above, provided that a and b of A 10  are bound to a group Y and a group (T)l, respectively;
 
R 14bb  and R 15aa  represent the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one group —COOH thereon; and
 
R 14cc  and R 15bb  represent the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one group —CONR 26 R 27  thereon;
 
wherein R 26  and R 27  are the same as described above.
 
         [0331]    The reaction of the compound (1iiii) and the compound (57) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y, T, l, R 14a  and A 10  are the same as described above, provided that a and b of A 10  are bound to a group Y and a group (T) l , respectively;
 
h represents 0 or 1; and R 57  represents a lower alkoxycarbonyl group.
 
         [0332]    The reaction which converts the compound (1kkkk) into the compound (1llll) may be carried out under the same reaction conditions as in hydrolysis B described in reaction formula 9 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , R 3 , R 4 , Y, R 11  and R 12  are the same as described above, R 58  represents a lower alkyl group, and g represents 0 or 1. 
         [0333]    The reaction which converts the compound (1mmmm) into the compound (1nnnn) may be carried out under the same reaction conditions as in hydrolysis B as described in reaction formula 9 above. 
         [0334]    The reaction of the compound (1nnnn) with the compound (58) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y, T, l, A 10  and X 2  are the same as described above, provided that a and b of A 10  are bound to a group Y and a group (T)l, respectively;
 
R 14hh  and R 15gg  represent the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one group —(CO)o-B 13 NH(R 22a ) thereon;
 
R 14ii  and R 15hh  represent the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above respectively, except that each of the heterocyclic groups has at least one group —(CO)o-B 13 N(R 22a ) thereon;
 
R 14ii  and R 15hh  represent the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one group —(CO)o-B 13 N(R 22a )R 23b  thereon;
 
R 14kk  and R 15jj  represent the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic ring has at least one —(CO)o-B 13 N(R 22a )(CHR A R 23c ) group thereon,
 
(wherein R A , B 13  and o are the same as described above);
 
R 22a  is a hydrogen atom, a lower alkyl group, a benzoyl group which may have 1 to 3 lower alkoxy groups as substituents on the phenyl ring, a phenoxy lower alkyl group which may have a lower alkyl group as a substituent on the phenyl ring, a phenyl lower alkyl group or a phenyl group;
 
R 23a  represents a lower alkyl group, a phenoxy lower alkyl group which may have a lower alkyl group as a substituent on the phehyl ring, a phenyl lower alkyl group or a phenyl group;
 
R 23b  represents a benzoyl group which may have 1 to 3 lower alkoxy groups as substituents on the phenyl ring; and
 
R 23c  represents a hydrogen atom, a lower alkyl group, a phenoxy lower alkyl group which may have a lower alkyl group as a substituent on the phenyl ring, a phenyl lower alkyl group or a phenyl group; provided that the alkyl moiety of the —CHR A R 23c  group in the side chain (—(CO)o-B 13 —N(R 22a )(CHR A R 23c )) of the compound (1ssss) has not more than 6 carbon atoms.
 
         [0335]    The reaction of the compound (1pppp) and the compound (59) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 above. 
         [0336]    The reaction of the compound (1pppp) and the compound (61) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (5) shown in reaction formula 2 above. 
         [0337]    The reaction of the compound (1pppp) and the compound (60) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y, T, l, A 10  and X 2  are the same as described above, provided that a and b of A 10  are bound to a group Y and a group (T)l, respectively;
 
R 14ll  and R 15kk  represent the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one group —(O—B 15 )s-CONH(R 26a ) thereon;
 
R 14mm  and R 15ll  represent the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one group —(O—B 15 )s-CON(R 26a )(R 27a ) thereon;
 
         [0338]    R 14nn  and R 15mm  represent the same 5- to 10-membered saturated or unsaturated heterocyclic group as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic rings has at least one group —(O—B 15 )s-CON(R 26a )(CHR A R 27b ) 
         [0000]    (wherein B 15 , s and R A  are the same as described above);
 
R 26a  represents a hydrogen atom, a lower alkyl group, a phenyl lower alkyl group or an imidazolyl lower alkyl group;
 
R 27a  represents a lower alkyl group, a phenyl lower alkyl group or an imidazolyl lower alkyl group; and
 
R 27b  represents a hydrogen atom, a lower alkyl group, a phenyl lower alkyl group, a phenyl group, an imidazolyl group or an imidazolyl lower alkyl group;
 
provided that the alkyl moiety of the —CHR A R 27b  group in the side chain (—(O—B 15 )s-CO(R 26a )(CHR A R 27b )) of the compound (1vvvv) has not more than 6 carbon atoms.
 
         [0339]    The reaction of the compound (1tttt) and the compound (62) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 above. 
         [0340]    The reaction of the compound (1tttt) and the compound (63) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (5) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y, T, l, A 10 , R 14v , R 15u , R 14k  and R 14j  are the same as described above, provided that a and b of A 10  are bound to a group Y and a group (T)l, respectively;
 
R 59  represents a lower alkyl group; and
 
R 14oo  and R 15nn  represent the same 5- to 10-membered saturated or unsaturated heterocyclic groups as defined in R 14  and R 15  above, respectively, except that each of the heterocyclic groups has at least one group —B 21 CONHNHCOOR 59 ,
 
(wherein B 21  is the same as described above).
 
         [0341]    The reaction of the compound (1cccc′) and the compound (102) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0342]    The reaction which converts the compound (1yyyy) into the compound (1hhh) may be carried out under the same reaction conditions as in hydrolysis B as described in reaction formula 9 above. 
         [0343]    The compound of the present invention of the general formula (1) in which various groups are taken as R 1  is produced, for example, as shown by reaction formulas 37 to 46 below. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, A 16 , R 6 , R 8 , B 21 , R A  and X 2  are the same as described above, provided that the B 21 CHR A  moiety of the (R 6 —B 21 CHR A —) group of the compound (1y) has hot more than 6 carbon atoms. 
         [0344]    The reaction of the compound (19) and the compound (20) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 above. 
         [0345]    The reaction of the compound (19) and the compound (21) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (5) of reaction formula 2 above. 
         [0346]    The reaction of the compound (19) and the compound (22) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) of reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, A, R 6 , B, R A  and X 2  are the same as described above, R 8a  represents a lower alkyl group which may have a lower-alkoxy group as a substituent, a lower alkylsulfonyl group or a phenyl lower alkyl group, R 8b  represents a hydrogen atom, a phenyl group, phenyl lower alkyl group or a lower alkyl group which may have a lower alkoxy group as a substituent, and R 8c  represents a lower alkanoyl group, provided that the alkyl moiety of the —CHR A R 8b  group of the compound (1cc) has not more than 6 carbon atoms. 
         [0347]    The reaction of the compound (1aa) and the compound (23) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 above. 
         [0348]    The reaction of the compound (1aa) and the compound (24) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (5) shown in reaction formula 2 above. 
         [0349]    The reaction of the compound (1aa) and the compound (25) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, A, B 21 , f, R A  and R 6  are the same as described above, provided that the (B 21 )fCHR A  moiety of the side chain (—(B 21 )fCHR A NH R6) of the compound (1ee) has not more than 6 carbon atoms. 
         [0350]    The reaction of the compound (26) and the compound (27) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (5) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 88  represents a group —Y-A or a halogen atom, and R 2 , X 1 , Y, A, and R 6  are the same as described above. 
         [0351]    The reaction of the compound (28) and the compound (27) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, A, R 6 , R 8a , R 8b , R 8c , R A  and X 2  are the same as described above, provided that the alkyl moiety of the group —CHR A R 8b  of the compound (1hh) has not more than 6 carbon atoms. 
         [0352]    The reaction of the compound (1ff′) and the compound (23) is carried out under the same reaction conditions similar as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 above. 
         [0353]    The reaction of the compound (1ff′) and the compound (24) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (5) shown in reaction formula 2 above. 
         [0354]    The reaction of the compound (1ff′) and the compound (25) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, A, R 6  and X 2  are the same as described above. 
         [0355]    The reaction which converts the compound (30) into the compound (1jj) is carried out under the same reaction conditions as in the reaction which converts the compound (1f) into the compound (1 h) shown in reaction formula 3 above. 
         [0356]    The reaction which converts the compound (1jj) into the compound (1kk) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (5) shown in reaction formula 2 above. 
         [0357]    The reaction of the compound (30) and the compound (32) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, A, X 2  and R 6  are the same as described above, B 23  represents a lower alkylene group or a lower alkenylene group, and the B 23 —HC═CH— moiety in the side chain (R 6 B 23 —HC═CH—) of the compound (1 mm) has 1 to 3 double bonds and has not more than 6 carbon atoms. 
         [0358]    The reaction of the compound (33) and the compound (34) is carried out in an appropriate inert solvent and in the presence of a condensation agent. 
         [0359]    Examples of the inert solvent to be used in the above described reaction include aromatic hydrocarbons such as benzene, toluene, and xylene, ethers such as diethyl ether, tetrahydrofuran, dioxane, monoglyme, and diglyme, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, and carbon tetrachloride, lower alcohols such as methanol, ethanol, isopropanol, butanol, tert-butanol, and ethylene glycol, fatty acids such as α-dimethylaminoacetic acid and acetic acid, esters such as ethyl acetate and methyl acetate, ketones such as acetone and methyl ethyl ketone, acetonitrile, 1-methyl-2-pyrrolidone, pyridine, dimethyl sulfoxide, dimethylformamide, and hexamethylphosphoric acid triamide, and a mixture thereof. 
         [0360]    Examples of the condensation agent include palladium complexes such as bis(benzonitrile)dichloropalladium(II). 
         [0361]    The condensation agent is favorably used typically in an amount 0.01 to 1 times and preferably 0.01 to 0.5 times that of the compound (33) on a molar basis. 
         [0362]    The above described reaction favorably proceeds typically at 0 to 200° C. and preferably at about room temperature to about 150° C. and is generally completed in about 10 minutes to 20 hours. 
         [0363]    The above described reaction proceeds advantageously by adding an alkali metal salt of a fatty acid such as sodium acetate to the reaction system. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, A and R 6  are the same as described above. 
         [0364]    The reaction which converts the compound (inn) into the compound (1oo) is carried out under the same reaction conditions as in the reaction which converts the compound (1f) into the compound (1g) shown in reaction formula 3 above. 
         [0000]    [Reaction formula 45] 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein A 17  represents a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , R 3 , p, X 1 , Y, A, Bo and R 6  are the same as described above. 
         [0365]    The reaction of the compound (64) and the compound (65) is carried out in an appropriate solvent in the presence of a condensation agent. 
         [0366]    Any solvent may be used as long as it is used in the reaction of a carboxylic acid halide with an amine (1b) of the reactions between the compound (1b) and the compound (6) (an amide bond generation reaction) shown in reaction formula 2. 
         [0367]    Examples of the condensation agent include a mixture of an azocarboxylate (such as diethyl azodicarboxylate) and a phosphorus compound (such as triphenylphosphine). 
         [0368]    The condensation agent is favorably used typically in at least an equimolar amount to the compound (64) and preferably 1 to 2 times that of the compound (64) on a molar basis. 
         [0369]    The compound (65) is favorably used typically in an amount of at least an equimolar to the compound (64) and preferably 1 to 2 times that of the compound (64) on a molar basis. 
         [0370]    The above described reaction favorably proceeds typically at 0 to 200° C., preferably at about 0 to 150° C. and is generally completed in about 1 to 10 hours. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, A, and R 6  are the same as described above. 
         [0371]    The reaction of the compound (30) and the compound (66) is carried out in the presence or absence of a basic compound and preferably in the absence of the basic compound and in the presence or absence of an appropriate solvent. 
         [0372]    Any inert solvent and basic compound may be used as long as they are used in the reaction of a carboxylic acid halide and an amine (1b) of the reactions between the compound (1b) and the compound (6) (an amide bond generation reaction) shown in reaction formula 2. 
         [0373]    The compound (66) may be used typically in an amount of about 1 to 5 times and preferably about 1 to 3 times that of the compound (30) on a molar basis. 
         [0374]    The above described reaction is carried out typically at 0 to 200° C. and preferably at about room temperature to 150° C. and is generally completed in about minutes to 50 hours. 
         [0375]    A boron compound such as a boron trifluoride-diethyl ether complex may be added to the reaction system of the above described reaction. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, T 2 , A 10 , R 14 , R 15 , B 21 , R A , X 2 , R 6  and R 59  are the same as described above, provided that a and b of A 10  are bound to a group Y and a group T 2 , respectively. 
         [0376]    The reaction which converts the compound (68) into the compound (71) may be carried out under the same reaction conditions as in hydrolysis B as described in reaction formula 9 above. 
         [0377]    The reaction of the compound (71) and the compound (100) is carried out under the same reaction conditions as in the reaction of the compound (1fff) and the compound (43) shown in reaction formula 20 above. 
         [0378]    The compound (68) may also be produced using a halogenated lower alkyl group such as methyl iodide in place of the compound (100) in the same as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0379]    The reaction which converts the compound (68) into the compound (69) may be carried out, for example, (1) by reducing the compound (68) with a catalytic hydride reducing agent in an appropriate solvent, or (2) by reducing the compound (68) with a reducing agent such as a mixture of a metal or a metal salt with an acid, or a mixture of a metal or a metal salt with an alkali metal hydroxide, a sulfide, an ammonium salt or the like, in an appropriate inert solvent. 
         [0380]    Examples of the solvent for use in the method (1) include water, acetic acid, alcohols such as methanol, ethanol, and isopropanol, hydrocarbons such as n-hexane and cyclohexane, ethers such as dioxane, tetrahydrofuran, diethyl ether, and diethylene glycol dimethyl ether, esters such as ethyl acetate and methyl acetate, and aprotic polar solvents such as N,N-dimethylformamide, and a mixture thereof. Examples of the catalytic hydride reducing agent include palladium, palladium black, palladium-carbon, platinum-carbon, platinum, platinum oxide, copper chromite, and Raney nickel. These reducing agents may be used singly or in a mixture of two types or more. The reducing agent may be used generally in an amount 0.02 to 1 times that of the compound (68) on a weight basis. The reaction temperature is set typically at about −20 to 150° C. and preferably at about 0 to 100° C., and the hydrogen pressure is set typically at 1 to 10 atm. Generally, the above described reaction is completed in about 0.5 to 100 hours. An acid such as hydrochloric acid may be added to the reaction system. 
         [0381]    The reducing agent for use in the method (2) is a mixture of iron, zinc, tin or stannous chloride with a mineral acid such as hydrochloric acid or sulfuric acid; or a mixture of iron, ferrous sulfate, zinc or tin with an alkali metal hydroxide such as sodium hydroxide, a sulfate such as ammonium sulfate or an ammonium salt such as ammonium hydroxide or ammonium chloride. Examples of the inert solvent include water, acetic acid, alcohols such as methanol and ethanol, and ethers such as dioxane, and a mixture thereof. The reducing reaction conditions may be chosen appropriately depending on the reducing agent to be used. For example, when stannous chloride or hydrochloric acid is used as the reducing agent, the reaction is favorably carried out advantageously at about 0 to 150° C., for about 0.5 to 10 hours. The reducing agent is used in an amount at least an equimolar to the compound (68) and typically 1 to 5 times that of the compound (68) on a molar basis. 
         [0382]    The reaction of the compound (69) and the compound (20) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 above. 
         [0383]    The reaction of the compound (69) and the compound (22) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0384]    The reaction of the compound (69) and the compound (21) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (5) shown in reaction formula 2 above. 
         [0385]    The reaction which converts the compound (69) into the compound (37a), the reaction which converts the compound (70a) into the compound (37d), the reaction which converts the compound (70b) into the compound (37c) and the reaction which converts the compound (70c) into the compound (37b) is carried out under the same reaction conditions as in hydrolysis B as described in reaction formula 9. 
         [0386]    The reaction of the compound (71) and the compound (36) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2. 
         [0387]    The reaction of the compound (69) and the compound (32) is carried out under the same reaction conditions as in the reaction of the compound (30) and the compound (32) shown in reaction formula 42 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, A 10 , B 3 , R 14 , R 15 , R A , R 74a  and X 2  are the same as described above; 
         [0388]    R c  represents a group —CONR 14 R 15  or a group —COOR 59b , R 59b  represents a lower alkyl group or a phenyl lower alkyl group; 
         [0000]    R 17a  represents a lower alkyl group, a cycloalkyl group, a lower alkyl sulfonyl group or a lower alkenyl group;
 
R 17b  represents a hydrogen atom or a lower alkyl group; and
 
R 17c  represents a cycloalkylcarbonyl group, a lower alkanoyl group which may have a halogen atom as a substituent or an amino substituted lower alkanoyl group which may have a lower alkyl group as a substituent (wherein a of A 10  is bound to a group Y and b is bound to a group —NHB 3 —Rc, a group —N(R 17a )B 3 —Rc, a group —N(CH(R A )(R 17b ))B 3 —Rc or a group —N(R 17c )B 3 —Rc.
 
         [0389]    The reaction of the compound (72a) and the compound (73) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 above is The reaction of the compound (72a) and the compound (75) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0390]    The reaction of the compound (72a) and the compound (74) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (5) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, A 10 , B 3 , R 14  and R 15  are the same as described above, R 17d  represents a lower alkanoyl group which has a halogen atom as a substituent, R 60  represents an amino group which may be substituted with a lower alkyl group, and R 61  represents an amino substituted lower alkanoyl group which may be substituted with a lower alkyl group, wherein a of A 10  is bound to a group Y and b is bound to a group —N(R 17d )B 3 —CONR 14 R 15  or a group —NR 61 B 3 —CONR 14 R 15 . 
         [0391]    The reaction of the compound (72e) and the compound (76) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, R 6 , B 21 , R A  and X 2  are the same as described above, and A 11  represents 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 3  and p are the same as described above, provided that the alkyl moiety in the side chain (—NHCH(R A )(B 21 R 6 ) group) of the compound (78b) has not more than 6 carbon atoms. 
         [0392]    The reaction which converts the compound (77a) into the compound (77b) is carried out under the same reaction conditions as in the reaction which converts the compound (68) into the compound (69) shown in reaction formula 47 above. 
         [0393]    The reaction of the compound (77b) and the compound (20) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 above. 
         [0394]    The reaction of the compound (77b) and the compound (22) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0395]    The reaction of the compound (77b) and the compound (21) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (5) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y and A 11  are the same as described above, and i represents an integer of 2 to 4. 
         [0396]    The reaction of the compound (77c) and the compound (79) is generally called Friedel-Crafts reaction and carried out in an appropriate solvent in the presence of a Lewis acid. 
         [0397]    Any Lewis acid may be used herein as long as it is typically used in the Friedel-Crafts reaction. Examples of the Lewis acid include aluminum chloride, zinc chloride, iron chloride, tin chloride, boron tribromide, and concentrated sulfuric acid. These Lewis acids are used singly or in a mixture of two types or more. The Lewis acid is used typically in an amount 2 to 6 times that of the compound (77c) on a molar basis. 
         [0398]    Examples of the solvent to be used herein include aromatic hydrocarbons such as carbon disulfide, nitrobenzene, and chlorobenzene, and halogenated hydrocarbons such as dichloromethane, dichloroethane, carbon tetrachloride, and tetrachloroethane, and a mixture thereof. 
         [0399]    The compound (7 g) is used typically in at least an equimolar amount to the compound (77c) and preferably 1 to 5 times that of the compound (77c) on a molar basis. 
         [0400]    The above described reaction favorably proceeds typically at 0 to 120° C. and preferably at about 0 to 70° C., and is generally completed in about 0.5 to 24 hours. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, R 6 , X 2 , B 21  and R A  are the same as described above. A 12  represents a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 3  and p are the same as defined above, and R 62  represents a lower alkanoyl group or a hydroxyl group substituted lower alkyl group, provided that the alkyl moiety in the side chain (—NHCH(R A )(B 21 R 6 ) group) of the compound (81b) has not more than 6 carbon atoms. 
         [0401]    The reaction which converts the compound (80a) into the compound (80b) is carried out under the same reaction conditions as in the reaction which converts the compound (68) into the compound (69) shown in reaction formula 47 above. 
         [0402]    The reaction of the compound (80b) and the compound (20) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 above. 
         [0403]    The reaction of the compound (80b) and the compound (22) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0404]    The reaction of the compound (80b) and the compound (21) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (5) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , and Y are the same as above,
 
A 13  represents a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 3  and p are the same as described above, and
 
R 63a  represents a lower alkanoyl group or a lower alkyl group, and
 
A 14  represents a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 63b  represents a lower alkanoyl group which is substituted with a halogen atom at the α-position or a lower alkyl group which is substituted with a halogen atom at the 2 position. 
         [0405]    The reaction which converts the compound (80b′) into the compound (35a) is carried out in the presence of a halogenating agent in an appropriate solvent. 
         [0406]    Examples of the halogenating agent include halogen molecules such as bromine and chlorine, iodine chloride, sulfuryl chloride, copper compounds such as cupric bromide, and N-halogenated succinic acid imides such as N-bromosuccinic acid imide and N-chlorosuccinic acid imide. 
         [0407]    Examples of the solvent to be used herein include halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, and carbon tetrachloride, fatty acids such as acetic acid and propionic acid, and carbon disulfide. 
         [0408]    The halogenating agent is favorably used typically in an amount 1 to 10 times and preferably 1 to 5 times that of the compound (80b′) on a molar basis. 
         [0409]    The above described reaction is carried out typically at 0° C. to the boiling point of the solvent and preferably at about 0 to 100° C., and completed typically for about 5 minutes to 30 hours. 
         [0410]    When an N-halogenated succinic acid imide is used as a halogenating agent, a peroxide such as benzoyl peroxide may be added to the reaction system as a radical reaction initiator. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, A 10 , T 2 , R 59 , R 8a , R 8b , R 8c , X 2  and R A  are the same as described above, and
 
R 64  represents a phenyl lower alkoxycarbonyl group, provided that each of the alkyl moieties in the side chain (—N(CHR A R 8b )(R 64 ) group) of the compound (84b) and the side chain (—NH(CHR A R 8b ) group) of the compound (84e) has not more than 6 carbon atoms and a and b of A 10  are bound to a group Y and a group T 2 , respectively.
 
         [0411]    The reaction of the compound (83) and the compound (23) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 above. 
         [0412]    The reaction of the compound (69) and the compound (82), and the reaction of the compound (83) and the compound (25) are carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0413]    The reaction of the compound (83) and the compound (24) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (5) shown in reaction formula 2 above. 
         [0414]    The reactions which convert the compound (84a) into the compound (84d), the compound (84b) into the compound (84e), and the compound (84c) into the compound (84f) are carried out under the same reaction conditions as in the reaction in which the compound (1iii′) is reduced to convert into the compound (1hhh′) as described in reaction formula 24 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, A 10 , B 21 , R 74a  and X 2  are the same as described above, provided that a and b of A 10  are bound to a group Y and a group B 21 , respectively. 
         [0415]    The reaction which converts the compound (85) into the compound (7′) is carried out by reacting compound (85) with a halogenating agent in the presence or absence of an appropriate solvent. 
         [0416]    Examples of the halogenating agent include mineral acids such as hydrochloric acid and hydrobromic acid, N,N-diethyl-1,2,2-trichlorovinyl azide, phosphorus pentachloride, phosphorus pentabromide, phosphorus oxychloride, sulfonyl halide compounds such as thionyl chloride, mesyl chloride, and tosyl chloride, and a mixture of carbon tetra bromide with triphenylphosphine. The sulfonyl halide compound may be used together with a basic compound. 
         [0417]    Any basic compound may be used as long as it is used in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0418]    Examples of the solvent to be used include ethers such as dioxane, tetrahydrofuran, and diethyl ether, halogenated hydrocarbons such as chloroform, methylene chloride, and carbon tetrachloride, and dimethylformamide, and a mixture thereof. 
         [0419]    When a sulfonyl halide compound serving as a halogenating agent is used together with a basic compound, the sulfonyl halide compound is favorably used typically in at least an equimolar amount to the compound (85) and preferably 1 to 2 times that of the compound (85) on a molar basis. The basic compound is used typically in a catalytic amount of the compound (85) and preferably in a catalytic amount to an equimolar amount to the compound (85). When a halogenating agent other than sulfonyl halide compound is used, the halogenating agent is used in at least an equimolar amount to the compound (85) and typically used in a large excess amount. 
         [0420]    The above described reaction favorably proceeds typically at room temperature to 200° C. and preferably at room temperature to 150° C., and is generally completed in about 1 to 80 hours. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 74a , R 2 , X 1 , Y, A 10  and B 2 , are the same as described above, and R 65  represents a tri-lower alkyl silyl group, provided that a and b of A 10  are bound to a group Y and a group B 21 , respectively. 
         [0421]    Examples of the tri-lower alkyl silyl group to be used herein include trialkylsilyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as tert-butyldimethylsilyl, trimethylsilyl, and diethylmethylsilyl groups. 
         [0422]    The reaction which converts the compound (86) into the compound (85) may be carried out under the same reaction conditions as in hydrolysis B as described in reaction formula 9 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 74a , R 2 , X 1 , Y, A 10 , B 21 , R 65  and X 2  are the same as described above, and R 66  represents a hydrogen atom, a lower alkyl group or a lower alkoxycarbonyl group, provided that a and b of A 10  are bound to a group Y and a group B 21 , respectively, and each of the alkyl moieties in the side chain (—Y-A 10 -B 21 CH 2 OH) of the compound (85a) and the side chain (—Y-A 10 -B 21 CH 2 OR 65 ) of the compound (86a) has not more than 6 carbon atoms. 
         [0423]    The reaction which converts the compound (69a) into the compound (85a) is carried out under the same reaction conditions as in the reaction which converts the compound (1f) into the compound (1g) shown in reaction formula 3 above. 
         [0424]    The reaction of the compound (85a) and the compound (101) is carried out under the same reaction conditions as in the reaction which converts the compound (2) into the compound (3) shown in reaction formula 1 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, A 10 , B 21 , R 6 , R A , f, R 43 , R 44  and X 2  are the same as described above, and B 21  represents a lower alkylene group, provided that a and b of A 10  are bound to a group Y and a group B 21′ , respectively, and each of the (B 21′ )f-CH═C moiety in the side chain (—Y-A 10 -(B 21′ )f-CH═C(COOR 43 )(COOR 44 )) of the compound (90c) and the alkyl moiety in the side chain (—NHCH(R A )B 21 R 6 )) of the compound (90b) have not more than 6 carbon atoms, respectively. 
         [0425]    The reaction of the compound (87) and the compound (88) is carried out under the same reaction conditions as in the reaction of the compound (1f) and a hydroxylamine shown in reaction formula 3 above. 
         [0426]    The reaction which converts the compound (89a) into the compound (89b) is carried out under the same reaction conditions as in the reaction which converts the compound (68) into the compound (69) shown in reaction formula 47 above. 
         [0427]    The reaction of the compound (89b) and the compound (20) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 above. 
         [0428]    The reaction of the compound (89b) and the compound (22) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6)shown in reaction formula 2 above. 
         [0429]    The reaction of the compound (89b) and the compound (21) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (5) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, A 10 , B 21′ , R 65 , R 6 , B 21 , R A  and X 2  are the same as defined above, provided that a and b of A 10  are bound to a group Y and a group B 21′ , respectively, and the alkyl moiety in the side chain (—NHCH(R A )(B 21 R 6 )) of the compound (91b) has not more than 6 carbon atoms. 
         [0430]    The reaction which converts the compound (86a′) into the compound (86b) is carried out under the same reaction conditions as in the reaction which converts the compound (68) into the compound (69) shown in reaction formula 47 above. 
         [0431]    The reaction of the compound (86b) and the compound (20) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 above. 
         [0432]    The reaction of the compound (86b) and the compound (22) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0433]    The reaction of the compound (86b) and the compound (21) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (5) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, A 10 , B 21 , B 21′ , R 6 , R A  and X 2  are the same as described above, provided that a and b of A 10  are bound to a group Y and a group B 21′ , respectively, and the alkyl moiety in the side chain (—NHCH(R A )(B 21 R 6 )) of the compound (44c) has not more than 6 carbon atoms. 
         [0434]    The reaction which converts the compound (92a) into the compound (92b) is carried out under the same reaction conditions as in the reaction which converts the compound (68) into the compound (69) shown in reaction formula 47 above. 
         [0435]    The reaction of the compound (92b) and the compound (20) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 above. 
         [0436]    The reaction of the compound (92b) and the compound (22) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0437]    The reaction of the compound (92b) and the compound (21) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (5) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , and X 2  are the same as described above, R 67  represents a group -A 10 B 21 CN, a group -A 10 -R 59d  a group -A 10 -T 2 -COOR 59a  or a group -A, R 59d  represents a lower alkyl group, A 10 , B 21 , T 2  and R 59a  are the same as described above, and R 68  represents a nitro group or a halogen atom. 
         [0438]    The reaction of the compound (93) and the compound (94) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , R 67  and X 1  are the same as described above. 
         [0439]    The reaction which converts the compound (95a) into the compound (95b) is carried out under the same reaction conditions as in the reaction which converts the compound (68) into the compound (69) shown in reaction formula 47 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, A 7 , R 6 , B 21 , R A  and X 2  are the same as described above, provided that the alkyl moiety in the side chain (—NHCH(R A )(B 21 R 6 )) of the compound (13b) has not more than 6 carbon atoms. 
         [0440]    The reaction of the compound (96) and the compound (20) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2. 
         [0441]    The reaction of the compound (96) and the compound (22) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0442]    The reaction of the compound (96) and the compound (21) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (5) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, B 21 , f, i, R 6 , B 21 , A 10 , R A  and X 2  are the same as described above, and R A′  represents a hydrogen atom or a lower alkyl group, provided that the alkyl moiety in the side chain
 
(—NHCH(R A )(B 21 R 6 )) in compound (98b) has not more than 6 carbon atoms, and a and b of A 10  are bound to a group Y and a group (B 21 )f, respectively.
 
         [0443]    The reaction which converts the compound (97a) into the compound (97b) is carried out under the same reaction conditions as in the reaction which converts the compound (68) into the compound (69) shown in reaction formula 47 above. 
         [0444]    The reaction of the compound (97b) and the compound (20) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 above. 
         [0445]    The reaction of the compound (97b) and the compound (22) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0446]    The reaction of the compound (97b) and the compound (21) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (5) shown in reaction formula 2. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , F 2 , X 1 , Y, A 10 , B 21 , f, R A′  and A 3  are the same as described above, provided that a and b of A 10  are bound to a group Y and a group (B 21 )f, respectively. 
         [0447]    The reaction which converts the compound (98d) into the compound (9′) may be carried out under the same reaction conditions as in hydrolysis B described in reaction formula 9 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y, A 3 , R 59 , A 10 , B 21  and f are the same as described above, T 3  represents a direct bond or group B 7 , and B 7  represents the same as described above, provided that a and b of A 10  are bound to a group Y and a group (B 21 )f, respectively. 
         [0448]    The reaction of the compound (9′) and the compound (99) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (5) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 3 , X 1 , Y, A 10 , R 14a , R 49a , R 49 , R 49b , T, l, R A  and X 2  are the same as described above, provided that the CHR A  moiety in the side chain (—N(R 14a )(CHR A R 49b )) of the compound (104c) has not more than 6, a of A 10  is bound to a group Y, and b of A 10  is bound to a group —NR 14a H, a group NR 14a R 49a  a group —NR 14a R 49 , or a group —NR 14a (CHR A R 49b ). 
         [0449]    The reaction of the compound (103) and the compound (38a) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 above. 
         [0450]    The reaction of the compound (103) and the compound (38) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0451]    The reaction of the compound (103) and the compound (38b) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (5) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y and A are the same as described above. 
         [0452]    The reaction which converts the compound (105) into the compound (19a) is carried out under the same reaction conditions as in the reaction which converts the compound (68) into the compound (69) shown in reaction formula 47 above. The compound (19a) can be subjected to the following reaction without isolation. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y and A 10  are the same as described above, R 69a  represents a thiazolidinyl group which may have an oxo group as a substituent on the thiazolidine ring, R 69  represents a thiazolidinylidene lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, and R 70  represents a thiazolidinyl lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, provided that a of A 10  is bound to a group Y and b of A 10  is bound to a group —R 69  or a group —R 70 . 
         [0453]    The reaction of the compound (106a) and the compound (160) is carried out under the same reaction conditions as in the reaction of the compound (87) and the compound (88) shown in reaction formula 58 above. 
         [0454]    The reaction which converts the compound (106) into the compound (19b) is carried out under the same reaction conditions as in the reaction which converts the compound (68) into the compound (69) shown in reaction formula 47 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , X 2 , A, Y 1 , A 10  T 2 , R 59  and R 59a  are the same as described above, R 71  represents a group —R 1  (wherein R 1  is the same as described above), a nitro group or a lower alkoxycarbonyl group, X 3  represents a halogen atom, and R 72  represents a lower alkyl group which may have a hydroxyl group as a substituent, a nitro group, an amino group which may have a lower alkanoyl group, a carboxy lower alkyl group, a —(B 21 )fC(═O)R A  group (wherein B 21 , f and R A  are the same as described above), a lower alkanoyl group, a lower alkoxy group or a hydrogen atom; provided that a of A 10  is bound to a group Y 1  and b of A 10  is bound to a group -T 2  or a group —R 72 . 
         [0455]    The reaction of the compound (94a) and the compound (107), and the reaction of the compound (94a) and the compound (107a) each are carried out in an appropriate solvent and in the presence of a catalyst. 
         [0456]    Any solvent may be used herein as long as it is used in the reaction of the compound (2) and the compound (3) shown in reaction formula 1. 
         [0457]    As the catalyst to be used herein, various metal complexes as well as various combinations of a metal complex and a ligand may be used. Examples of the metal complexes include, palladium acetate (II), tetrakis(triphenylphosphine)palladium(0), and tris(dibenzylideneacetone)dipalladium(0). Examples of the ligand include. R-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (R-BINAP), S-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (S-BINAP), RAC-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (RAC-BINAP), t-butylphosphine, and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene. 
         [0458]    Such a catalyst is favorably used typically in at least an equimolar amount to the compound (94a) and preferably 1 to 5 times that of the compound (94a) on a molar basis. 
         [0459]    The above described reaction is carried out typically at about 0 to 200° C. and preferably at about 0 to 150° C., and generally completed in about 30 minutes to 10 hours. 
         [0460]    When molecular sieves such as Molecular Sieves 3A (MS3A) or Molecular Sieves 4A (MS4A) or a phosphorus compound such as triphenylphosphine or tri(2-furyl)phosphine are added in the reaction system, the reaction proceeds advantageously. 
         [0461]    The reaction of the compound (94a) and the compound (108), compound (3) or compound (110) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0462]    The compound (109c) wherein R 71  represents a lower alkoxycarbonyl group, may be converted into the corresponding compound (109c) wherein R 7  represents a carboxy group, by hydrolyzing it under the same reaction conditions as in hydrolysis B described in reaction formula 9 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , X 2 , Y 1 , A 10  and T 2  are the same as described above, and R c  represents a hydrogen atom, a lower alkyl or a phenyl lower alkyl group, provided that a and b of A 10  are bound to a group Y, and a group -T 2 , respectively. 
         [0463]    The reaction of the compound (2) and the compound (108′) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , R 5a , R 5b , R A , R 5c  and X 2  are the same as described above, and R 73a  represents a group -A 10 -T 2 -COOR 59  (wherein A 10 , T 2  and R 59  are the same as described above) or a group -A (wherein A is the same as described above), provided that a of A 10  is bound to a group —NH—, group —NR 5a —, group —N(CHR A R 5b )— or a group —NR 5c —, and b of A 10  is bound to a group -T 2 , and the alkyl moiety in the side chain (—N(R 73a )(CHR A R 5b )) of the compound (68d) has not more than 6 carbon atoms. 
         [0464]    The reaction of the compound (111) and the compound (4) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 above. 
         [0465]    The reaction of the compound (111) and the compound (6) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0466]    The reaction of the compound (111) and the compound (5) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (5) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, A 10 , X 2 , R 17 , B 3 , R 74a  and R c  are the same as described above, provided that a of A 10  is bound to a group —Y and b of A 10  is bound to a group —NHR 17  or a group —NR 17 B 3 R c . 
         [0467]    The reaction of the compound (112) and the compound (113) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, A 10 , T 1 , l, R 14  and R 15  are the same as described above, provided that a and b of A 10  are bound to a group —Y and a group -(T 1 )l, respectively. 
         [0468]    The reaction of the compound (114) and the compound (36) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (5) shown in reaction formula 2 above. 
         [0469]    The compound (109e) in which l is 0 may also be produced by reacting the corresponding compound (114) and the compound (36) in an appropriate solvent in the presence of a basic compound and a catalyst. 
         [0470]    The above described reaction is carried out under the same reaction conditions as in reaction C described in reaction formula 13 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, R 8 , B 21 , R 6 , A 10 , T 2 , R 59 , R A  and X 2  are the same as described above, provided that the CHR A B 21  moiety in the side chain (—N(R 8 )(CH(R A ) B 21 R 6 )) of the compound (84i) has not more than 6 carbon atoms, and a and b of A 10  are bound to a group —Y and a group -T 2 , respectively. 
         [0471]    The reaction of the compound (84g) and the compound (20) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 above. 
         [0472]    The reaction of the compound (84g) and the compound (22) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0473]    The reaction of the compound (84g) and the compound (21) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (5) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, R 8a , R 8b , R 8c , B, R 6 , A 10 , T 2 , R 59 , R A  and X 2  are the same as described above, provided that the CHR A  moiety in the side chain (—NB(R 6 )(CH(R A )R 8b )) of the compound (116b) has not more than 6 carbon atoms, and a and b of A 10  are bound to a group —Y and a group -T 2 , respectively. 
         [0474]    The reaction of the compound (115) and the compound (23) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 above. 
         [0475]    The reaction of the compound (115) and the compound (25) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0476]    The reaction of the compound (115) and the compound (24) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (5) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 ; X 1 , Y, A 3 , R 14  and R 15  are the same as described above, and A 15  represents a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 73  represents a group —(B 21 )fCH(R A )(NR 14 R 15 ), and B 21 , f and R A  are the same as described above, provided that the (B 21 )fCH(R A ) moiety has not more than 6 carbon atoms. 
         [0477]    The reaction of the compound (117) and the compound (36) is carried out the same reaction conditions as in the reaction of the compound (1b) and the compound (5) shown in reaction formula 2. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein, R 2 , X 1 , Y, A 10 , T 2 , R 6 , R 9a  and R 59  are the same as described above, provided that a and b of A 10  are bound to a group —Y and a -T 2  group, respectively. 
         [0478]    The reaction of the compound (69′) and the compound (66) is carried out under the same reaction conditions as in the reaction of the compound (30) and the compound (66) shown in reaction formula 46 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 95 , R 2 , X 1 , Y, A10, T 2 , and R 59b  are the same as described above, provided that a and b of A 10  are bound to a group —Y and a group -T 2 , respectively. 
         [0479]    The reaction which converts the compound (120a) into the compound (120b) may be carried out under the same reaction conditions as in hydrolysis B described for reaction formula 9 above. 
         [0480]    The reaction of the compound (120b) and the compound (100′) is carried out under the same reaction conditions as in the reaction of the compound (1fff) and the compound (43) in reaction formula 20 above. 
         [0481]    The compound (120a) may also be produced using a lower alkyl halide such as methyl iodide in place of the compound (100′) under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y, A 10 , B 5 , R 59a  and j are the same as described above, provided that a and b of A 10  are bound to a group —Y and a group —S, respectively. 
         [0482]    The reaction which converts the compound (120c) into the compound (120d) is carried out under the same reaction conditions as in the reaction which converts the compound (1zzzz) into the compound (1aaaaa) in reaction formula 4 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, A 10 , T, l, R 6 , X 2 , R A , B 21  and R 14a  are the same as described above, and R 49c  represents a lower alkoxycarbonyl group, provided that a and b of A 10  are bound to a group —Y and a group -(T) l , respectively. 
         [0483]    The reaction of the compound (103) and the compound (38c) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0484]    The reaction which converts the compound (104d) into the compound (104e) is carried out under the same reaction conditions as in the reaction which converts the compound (68) into the compound (69) shown in reaction formula 47 above. 
         [0485]    The reaction of the compound (104e) and the compound (20) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 above. 
         [0486]    The reaction of the compound (104e) and the compound (22) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0487]    The reaction of the compound (104e) and the compound (21) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (5) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, A 3 , A 10 , B 21 , f, R A  and i are the same as described above, provided that a and b of A 10  are bound to a group —Y and a group —(B 21 )f, respectively, and the moiety (B 21 )fC(R A ) in the side chain of the compound (123a) has not more than 6 carbon atoms in total. 
         [0488]    The reaction of the compound (121) and the compound (122) may be carried out in an appropriate solvent in the presence of an acid. 
         [0489]    Any solvent may be used herein as long as it is used in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0490]    Examples of the acid include mineral acids such as hydrochloric acid, sulfuric acid, and hydrobromic acid, and organic acids such as acetic acid, trifluoroacetic acid, and sulfonic acids including p-toluenesulfonic acid. These acids may be used singly or in a mixture of two type&#39;s or more. The acid is favorably used typically in an amount at least 0.01 to 5 times and preferably 0.01 to 2 times that of the compound (121) on a molar basis. The compound (122) is favorably used typically in at least an equimolar amount to the compound (121) and preferably 1 to 10 times that of the compound (121) on a molar basis. 
         [0491]    The above described reaction is carried out typically at 0 to 200° C. and preferably at about 0 to 150° C. and generally completed in about 30 minutes to 10 hours. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y and A 10  are the same as described above, and R 72a  represents a lower alkoxy group, provided that a of A 10  is bound to a group —Y and b of A 10  is bound to a group —R 72  or a hydroxyl group. 
         [0492]    The reaction which converts the compound (109f) into the compound (124) may be carried out in an appropriate solvent in the presence of an acid. 
         [0493]    As the solvent, in addition to water, any solvent may be used herein as long as it is used in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0494]    Examples of the acid include mineral acids such as hydrobromic acid, hydrochloric acid, and concentrated sulfuric acid, fatty acids such as formic acid and acetic acid, organic acids such as p-toluenesulfonic acid, Lewis acids such as aluminum chloride, zinc chloride, iron chloride, tin chloride, boron trifluoride, and boron tribromide, iodides such as sodium iodide and potassium iodide, a mixture of a Lewis acid and an iodide as described above. The acid is favorably used typically in an amount 0.1 to 5 times and preferably 0.5 to 3 times that of the compound (109f) on a molar basis. 
         [0495]    The above described reaction is carried out typically at 0 to 150° C. and preferably at about 0 to 100° C. and generally completed in about 0.5 to 15 hours. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, A 10 , B 5 , X 2 , R 14  and R 15  are the same as described above, and Q1 represents an oxygen atom or a sulfur atom, provided that a and b of A 10  are bound to a group —Y and a group -Q 1 , respectively. 
         [0496]    The reaction of the compound (124a) and the compound (125) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, A 10 , R 14a , R 74a , T and l are the same as described above, and R 74b  represents a lower alkanoyl group or a lower alkoxycarbonyl group, provided that a and b of A 10  are bound to a group —Y and a group -(T)l, respectively. 
         [0497]    The reaction which converts the compound (109g) into the compound (109h) may be carried out under the same reaction conditions as in hydrolysis B described in reaction formula 9 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, A 10 , T 2 , X 2 , R 59a , B 23  and R 6  are the same as described above, provided that a and b of A 10  are bound to —Y group and a group -T 2 , respectively. 
         [0498]    The reaction of the compound (126) and the compound (34) is carried out under the same reaction conditions as in the reaction of the compound (33) and the compound (34) in reaction formula 43 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, R 74  and A 10  are the same as described above, R 74c  represents an amino group or a group —R 1  (wherein R 1  is the same as described above), R 75  represents a lower alkanoyl group, R 76  represents a lower alkoxycarbonyl group, R 77  and R 78  are both lower alkoxy groups, and R 79  represents a hydrogen atom or a lower alkyl group, provided that a of A 10  is bound to a group —Y, and b of A 10  is bound to a group —R 75 , a group —C(R 79 )═CHR 76  or a group —CH(R 79 )CH 2 R 76 , and each of the C(R 79 )═CH moiety and the CH(R 79 )CH 2  moiety has not more than 6 carbon atoms. 
         [0499]    The reaction of the compound (128) and the compound (129) is carried out in an appropriate solvent in the presence of a basic compound. 
         [0500]    Any conventional solvent may be used as long as it does not affect the reaction. Examples of such a solvent include ethers such as diethyl ether, dioxane, tetrahydrofuran, monoglyme, and diglyme, aromatic hydrocarbons such as benzene, toluene, and xylene, aliphatic hydrocarbons such as n-hexane, heptane, and cyclohexane, amines such as pyridine and N,N-dimethylaniline, aprotic polar solvents such as acetonitrile, N,N-dimethylformamide, dimethyl sulfoxide, and hexamethylphosphoric acid triamide, and alcohols such as methanol, ethanol, and isopropanol, and a mixture thereof. 
         [0501]    Examples of the basic compound include metal sodium, metal potassium, sodium hydride, sodium amide, metal hydroxides such as sodium hydroxide, potassium hydroxide, and calcium hydroxide, carbonates such as sodium carbonate, potassium carbonate, and sodium bicarbonate, metal alcoholates such as sodium methylate, sodium ethylate, and potassium tert-butoxide, alkyl and aryl lithiums or lithium amides such as methyl lithium, n-butyryl lithium, phenyl lithium, and lithium diisopropylamide, and organic bases such as pyridine, piperidine, quinoline, trimethylamine, diisopropylethylamine, and N,N-dimethylaniline. These basic compounds are used singly or in a mixture of two types or more. The basic compound is favorably used typically in an amount 0.1 to 10 times and preferably 0.5 to 5 times that of the compound (128) on a molar basis. 
         [0502]    The compound (129) is favorably used typically in at least an equimolar amount to the compound (128) and preferably 1 to 5 times that of the compound (128) on a molar basis. 
         [0503]    The above described reaction is carried out typically at −80 to 150° C. and preferably at about −80 to 120° C. and generally completed in, about 0.5 to 40 hours. 
         [0504]    When an organic base is used as the basic compound, the reaction advantageously proceeds by adding a lithium salt such as lithium chloride to the reaction system. 
         [0505]    The reaction which converts the compound (130) into the compound (131) is carried out under the same reaction conditions as in the reaction which converts the compound (68) into the compound (69) shown in reaction formula 47 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, R 66  and A 17  are the same as described above. 
         [0506]    The reaction which converts the compound (28′) into the compound (64a) is carried out under the same reaction conditions as in the reaction which converts the compound (1f) into the compound (1g) shown in reaction formula 3 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y and A are the same as described above. 
         [0507]    The reaction which converts the compound (64b) into the compound (26a) is carried out in an appropriate solvent in the presence of an oxidizing agent. 
         [0508]    Examples of the solvent include water, fatty acids such as formic acid, acetic acid, trifluoroacetic acid, and propionic acid, esters such as ethyl acetate and methyl acetate, alcohols such as methanol, ethanol, and isopropanol, ethers such as dioxane, tetrahydrofuran, and diethyl ether, ketones such as acetone and methyl ethyl ketone, aromatic hydrocarbons such as benzene, toluene, chlorobenzene, and xylene, and halogenated hydrocarbons such as chloroform and dichloromethane, hexamethylphosphoric acid triamide, N,N-dimethylformamide, dimethyl sulfoxide, and pyridine, and a mixture thereof. 
         [0509]    Examples of the oxidizing agent include peracids such as performic acid, peracetic acid, pertrifluoroacetic acid, perbenzoic acid, m-chloroperbenzoic acid, and o-carboxyperbenzoic acid, hydrogen peroxide, sodium metaperidodate, dichromic acid, dichromates such as sodium dichromate and potassium dichromate, manganese dioxide, permanganic acid, permanganates such as sodium permanganate and potassium permanganate, lead salts such as lead tetraacetate, silver oxide, and a Dess-Martin reagent (Dess-Martin periodinane). These oxidizing agents are used singly or in a mixture of two or more. The oxidizing agent is used typically in at least an equimolar amount to the compound (64b) and preferably 1 to 3 times that of the compound (64b) on a molar basis. 
         [0510]    The above described reaction is carried out typically at −10 to 100° C. and preferably at about 0 to 50° C. and completed in about 30 minutes to 24 hours. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, A 10 , B 19 , R 18 , X 2 , R 14 , R 74a  and R 15  are the same as described above, provided that a and b of A 10  are bound to a group —Y and a group —B 19 , respectively. 
         [0511]    The reactions between compound (133) and the compound (134), and compound (135) and the compound (36) each are carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein A 10 , B 3 , R 17a , R 17b , R A , R 17 , Y 1 , R c  and X 2  are the same as described above, and R 80  represents group —Y 1 H or group —OR 81 , R 81  represents a protective group of the hydroxyl group, provided that the CHR A  moiety in the side chain
 
(—N(B 3 R c )(CHR A R 17b )) of the compound (108c) has not more than 6 carbon atoms, a of A 10  is bound to a group —R 80 , and b is bound to a group —NHB 3 R c , a group —N(R 17a ) B 3 R c , a group —N(CHR A R 17b )B 3 R c  or a group —N(R 17 ) B 3 R c .
 
         [0512]    Examples of the protective group of the hydroxyl group include a phenyl lower alkyl group, a lower alkoxy lower alkyl group, tetrahydropyranyl group, tri lower alkylsilyl group, a lower alkanoyl group, and a lower alkyl group described above. 
         [0513]    The reaction of the compound (108a) and the compound (73) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 above. 
         [0514]    The reaction of the compound (108a) and the compound (75′) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0515]    The reaction of the compound (108a) and the compound (74) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (5) shown in reaction formula 2 above. 
         [0516]    The reaction is carried out using a compound (74), whose R A  and R 17b  (bound to a carbon atom) are mutually bound to form a cycloalkyl ring together with the carbon atom in the presence of a hydride reducing agent, as a starting material. In this case, in place of the compound (74), cycloalkyloxytrialkylsilane such as [(1-ethoxycyclopropyl)oxy]trimethylsilane may be used as the starting material (to produce the above described compound (74) in the reaction system). 
         [0000]    
       
                 
         
             
             
         
       
     
         [0517]    wherein R 80 , A 10 , R 17 , B 3 , R c , X 2  and R 59b  are the same as described above, provided that a of A 10  is bound to a group —R 80  and b is bound to a group —NHR 17 , a group —N(R 17 )B 3 R c  or a group —N(R 17 )CH 2 CH 2 COOR 59 . 
         [0518]    The reaction of the compound (108e) and the compound (113) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 above. 
         [0519]    The reaction of the compound (108e) and the compound (137) is carried out in an appropriate solvent in the presence of an acid. 
         [0520]    Any solvent may be used as long as it is used in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0521]    Examples of the acid include mineral acids such as hydrochloric acid, sulfuric acid, and hydrobromic acid, organic acids such as acetic acid, trifluoroacetic acid, and sulfonic acids including p-toluenesulfonic acid, and Lewis acids such as aluminum chloride, zinc chloride, iron chloride, tin chloride, boron tribromide, and a boron trifluoride/diethyl ether complex. These acids may be used singly or in a mixture of two types or more. The acid is favorably used typically in an amount at least 0.01 to 5 times and preferably 0.1 to 2 times that of the compound (108e) on a molar basis. The compound (137) is favorably used typically in at least an equimolar amount to the compound (108e) and preferably 1 to 10 times that of the compound (108e) on a molar basis. 
         [0522]    The above described reaction is carried out typically at 0 to 200° C. and preferably at about 0 to 150° C. and generally completed in about 30 minutes to 80 hours. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 81  is the same as described above, R 73b  represents a group A 10 -T 2 -COOR 59a  or a group -A, and A 10 , T 2 , R 59a  and A are the same as described above, provided that a of A 10  is bound to a group —OR 81  group or a hydroxyl group, and b of A 10  is bound to a group -T 2 . 
         [0523]    When R 81  of the starting compound (138) represents a phenyl lower alkyl group, the reaction which converts the compound (138) into the compound (139) may be carried out under the same reaction conditions as in the reduction reaction (1) (method using a catalytic hydrogen reducing agent), which is one of the reactions which convert the compound (68) into the compound (69) shown in reaction formula 47 above. 
         [0524]    The starting compound (138), in which R 81  represents a tetrahydropyranyl group or a tri-lower alkylsilyl group is converted into the compound (139), may be carried out under the same reaction conditions as in hydrolysis reaction B described in reaction formula 9 above. In the reaction which converts the compound (138) into the compound (139), hydrolysis is favorably carried out by use of an acid. The acid is favorably used typically in an amount 1 to 10 times and preferably 1 to 2 times that of the compound (138) on a molar basis. 
         [0525]    The compound (138) in which R 81  represents a tri-lower alkylsilyl group, may be treated with a fluorine compound such as tetra-n-butyl ammonium fluoride, hydrogen fluoride or cesium fluoride. 
         [0526]    The starting compound (138) in which R 81  represents a lower alkoxy lower alkyl group or a lower alkyl group, may be treated in an appropriate solvent in the presence of an acid. Examples of the solvent include water, lower alcohols such as methanol, ethanol, and isopropanol, ethers such as dioxane, tetrahydrofuran, and diethyl ether, halogenated hydrocarbons such as dichloromethane, chloroform, and carbon tetrachloride, and polar solvents such as acetonitrile, and a mixture thereof. Examples of the acid include mineral acids such as hydrochloric acid, sulfuric acid, and hydrobromic acid, fatty acids such as formic acid and acetic acid, sulfonic acids such as p-toluenesulfonic acid, Lewis acids such as boron trifluoride, aluminum chloride, and boron tribromide, iodides such as sodium iodide and potassium iodide, and a mixture of an iodide with a Lewis acid as described above. The above described reaction is carried out typically at 0 to 200° C. and preferably at about room temperature to 150° C. and generally completed in about 0.5- to 25 hours. 
         [0527]    Furthermore, the hydrolysis may be carried out using a basic compound under the same reaction conditions as in hydrolysis reaction B described in reaction formula 9 above. In this case, an amine such as triethylamine may be used other than the basic compounds used in hydrolysis reaction B, as the basic compound. 
         [0528]    The material compound (138), in which R 81  represents a lower alkanoyl group, is converted into the compound (139) under the same reaction conditions as in hydrolysis reaction B described in reaction formula 9 above. 
         [0529]    The compound (138) in which R 73a  represents a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    , a dehydration reaction takes place under the hydrolysis conditions above, with the result that the compound (138), in which the corresponding R 73a  represents a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    , may be obtained in some cases. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 80 , A 10 , T 2 , R 14  and R 15  are the same as described above, provided that a and b of A 10  are to a group —R 80  and a group -T 2 , respectively. 
         [0530]    The reaction of the compound (140) and the compound (36) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein Y 1 , A 7 , R 13  and A 9  are the same as described above. 
         [0531]    The reaction of the compound (141) and the compound (12) is carried out under the same reaction conditions as in the reaction of the compound (13) and the compound (12) shown in reaction formula 8 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 80 , A 10 , B 21  and f are the same as described above, provided that the alkyl moiety in the side chain (—(B 21 )f-CH 2 NH 2 ) of the compound (144) has not more than 6 carbon atoms. 
         [0532]    The reaction which converts the compound (143) into the compound (144) is carried out under the same reaction conditions as in the reaction using a hydride reducing agent, which is one of the reactions of the compound (1b) and the compound (5) shown in reaction formula 2. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 80 , A 10 , B 19 , X 2 , R 18 , R 14  and R 15  are the same as described above, provided that a of A 10  is bound to a group —R 80  and b is bound to a group —B 19 . 
         [0533]    The reaction of the compound (145) and the compound (134) is carried out under the same reaction conditions as in the reaction of the compound (133) and the compound (134) shown in reaction formula 90 above. 
         [0534]    The reaction of the compound (146) and the compound (36) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein, A 10 , B 19 , R 14 , R 15 , R 80 , and X 2  are the same as described above, and R 18a  represents a lower alkyl group, provided that a and b of A 10  are bound to a group —R 80  and a group —B 19 , respectively. 
         [0535]    The reaction of the compound (108j) and the compound (147) is carried out under the same-reaction conditions as in the reaction of the compound (1b) and the compound (4 shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , X 2 , X 3  and R 6  are the same as described above, R 82  represents a lower alkyl group, and R 83  represents a lower alkoxy group. 
         [0536]    The reaction of the compound (148) and the compound (149) is carried out in an appropriate solvent in the presence of a catalyst. 
         [0537]    Any solvent may be used herein as long as it is used in the reaction of the compound (2) and the compound (3) shown in reaction formula 1. 
         [0538]    Examples of the catalyst include magnesium. The catalyst is favorably used typically in at least an equimolar amount to the compound (148) and preferably 1 to 5 times that of the compound (148) on a molar basis. 
         [0539]    The above described reaction is carried out typically at 0 to 200° C. and preferably at about 0 to 150° C. and generally completed in about 30 minutes to 10 hours. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein A 18  represents a group -A or 
         [0540]    a group -A 10 -T 2 -COOR 59b , and A, A 10 , T 2 , R 59b  and X 3  are the same as described above. 
         [0541]    The reaction which converts the compound (150) into the compound (107′) is carried out under the same reaction conditions as in the reaction which converts the compound (85) into the compound (7′) shown in reaction formula 55 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , A 10 , T 2  and R 6  are the same as described above, provided that a of A 10  is bound to a —CO group, a —CH(OH) group or —CH 2  group, and b of A 10  is bound to a group -T 2 . 
         [0542]    The reaction which converts the compound (109a′) into the compound (151) is carried out under the same reaction conditions as in the reaction using a hydride reducing agent which is one of the reactions of the compound (1b) and the compound (5) shown in reaction formula 2 above. 
         [0543]    The reaction which converts the compound (151) into the compound (152) is carried out under the same reaction conditions as in the reaction which converts the compound (68) into the compound (69) shown in reaction formula 47 above. 
         [0544]    The reaction of the compound (152) and the compound (22) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0545]    The reaction which converts the compound (153) into the compound (154) may be carried out under the same react-ion conditions as in hydrolysis B reaction described in reaction formula 9 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y, A 10 , B 6 , B 7  or R 59  are the same as described above, and R 19a  represents a lower alkanoyl group, provided that a and b of A 10  are bound to a group —Y and a group —B 6 , respectively. 
         [0546]    The reaction of the compound (155) and the compound (156) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 80 , A 10 , X 2 , R 14  and R 15  are the same as described above. 
         [0547]    The reaction of the compound (158) and the compound (36) is carried out under the same reaction conditions as the reaction of the compound (114) and the compound (36) shown in reaction formula 74 in which l is 0. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , Y, A 10 , R 14a , h, T, l, R B , X 1  and X 2  are the same as described above, R 85a  represents a benzoyl group, R 85b  represents a lower alkoxy carbonyl group, a phenyl lower alkyl group, a lower alkyl group or furyl lower alkyl group, and R 85c  represents a hydrogen atom, a lower alkyl group, a phenyl group, phenyl lower alkyl group, a furyl group or a furyl lower alkyl group, provided that the a group —CH(R B )R 85c  of the compound (1bbbbb) has not more than 6 carbon atoms. 
         [0548]    The reaction of the compound (1yyyy′) and the compound (160′) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0549]    The reaction of the compound (1yyyy′) and the compound (161) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 abbve. 
         [0550]    The reaction of the compound (1yyyy′) and the compound (162) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (5) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , B 0 , Y, X 1 , A 17 , R 8 , X 2 , X 3  and R 6  are the same as described above, R 86  represents a lower alkylsulfonyl group, and R 87  represents an oxygen atom or a group —N(R 8 )—. 
         [0551]    The reaction of the compound (165) and the compound (163) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0552]    The reaction which converts the compound (165) into the compound (167) is carried out under the same reaction conditions as in the reaction which converts the compound (85) into the compound (7′) of the above described formula 55. 
         [0553]    The reaction of the compound (166) or the compound (167) and the compound (164) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 80  and A 10  are the same as described above, R 15  represents the same group as that of (5) in R 15  described above. 
         [0554]    The reaction of the compound (168) and the compound (170) is carried out under the same reaction conditions as in the reaction of the compound (30) and the compound (66) shown in reaction formula 46 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 80 , A 10 , T, l, R 14bb , R 15aa , R 14cc , R 15bb , R 26  and R 27  are the same as described above. 
         [0555]    The reaction of the compound (171) and the compound (57) is carried out under the same reaction conditions as in the reaction of the compound (1iiii) and the compound (57) shown in reaction formula 31 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y, A 10 , R 15′  and X 2  are the same as described above, and R 89  represents a lower alkyl group. 
         [0556]    The reaction of the compound (173) and the compound (170) is carried out under the same reaction conditions as in the reaction of the compound (30) and the compound (66) shown in reaction formula 46 above. 
         [0557]    The reaction of the compound (1ddddd) and the compound (173) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y, X 2 , B 3 , R 14  and R 15  are the same as described above, and A 19  represents a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    A 20  represents a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 3 , p, R 17 , B 3 , R 14  and R 15  are the same as described above. 
         [0558]    The reaction of the compound (174) and the compound (175) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , and Y are the same as described above, A 21  represents a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    and A 22  represents a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 3 , p, R 17 , B 3 , R 14  and R 15  are the same as described above. 
         [0559]    The reaction which converts the compound (1ggggg) into the compound (1hhhhh) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (5) shown in reaction formula 2 in which a hydride reducing agent is used. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 ; R 2 , X 1  and Y are the same as described above,
 
A 23  represents a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    and A 24  represents a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 3  and p are the same as described above. 
         [0560]    The reaction which converts the compound (1iiiii) into the compound (1jjjjj) is carried out under the same reaction conditions as in the reaction which converts the compound (68) into the compound (69) shown in reaction formula 47. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1  and Y are the same as described above,
 
A 25  represents a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    and A 26  represents a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein B 4a  represents a lower alkenylene group, B 4b  represents a lower alkylene group, and R 3 , p, R 14  and R 15  are the same as described above. 
         [0561]    The reaction which converts the compound (1kkkkk) into the compound (1lllll) is carried out the same as in the reaction of the method (1) of the reactions which convert the compound (68) into the compound (69) shown in reaction formula 47 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, and R 59b  are the same as described above, and A 28  represents a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    and A 27  represents a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 3 , p and R 59b  are the same as described above. 
         [0562]    The reaction which converts the compound (1mmmmm) into the compound (1nnnnn) is carried out under the same reaction conditions as in hydrolysis B described in reaction formula 9 above. 
         [0563]    The reaction of the compound (1nnnnn) and the compound (100′) is carried out under the same reaction conditions as in the reaction of the compound (1fff) and the compound (43) shown in reaction formula 20 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , X 2  and Y are the same as described above,
 
A 29  represents a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    and A 30  represents 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 90  represents a lower alkyl group which may have a hydroxyl group as a substituent, and R 3 , p and R 59b  are the same as described above. 
         [0564]    The reaction of the compound (1ooooo) and the compound (176) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , X 2  and Y are the same as described above,
 
A 31  represents a group
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein A 32  represents a group 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 3 , p, R 59b  and R 89  are the same as described above. 
         [0565]    The reaction of the compound (1qqqqq) and the compound (173) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y, A 10 , T, l, R 90  and X 2  are the same as described above.
 
R 15″  represents the group (2), (3), (4), (5), (6), (7), (8), (10), (11), (12), (13), (14), (15), (16), (17), (18), (19), (20), (21), (22), (23), (24), (25), (26), (27), (26a), (27a), (28a), (29a), (30a), (31a), (32a), (33a), (34a), (35a), (36a), or (37a), which is defined in R 15  described above.
 
         [0566]    The reaction of the compound (1sssss) and the compound (176) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y, A 10 , T and l are the same as described above,
 
R 14AA  and R 15BB  each represent the same 5- to 10-membered saturated or unsaturated heterocyclic group as defined in R 14  and R 15  described above except that the heterocyclic ring has at least one group —(B 12 CO)t-N(R 20 )—CO—B 16 X 2  thereon,
 
R 14CC  and R 15DD  each represent the same 5- to 10-membered saturated or unsaturated heterocyclic group as defined in R 14  and R 15  described above except that the heterocyclic ring has at least one group —(B 12 CO)t-N(R 20′ )—CO—B 16 R 91  thereon, wherein B 12 , t, B 16  and X 2  are the same as described above,
 
R 91  represents an imidazolyl group, and
 
R 20′  represents a hydrogen atom, a cycloalkyl group, an amino group which may have a lower alkoxycarbonyl group as a substituent, a benzoyl group which may have 1 to 3 lower alkoxy groups as substituents on the phenyl ring, a lower alkyl group, a lower alkyl group which have 1 or 2 phenyls which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent and a lower alkylthio group which may have a halogen atom as a substituent, a phenyl group which may be substituted, on the phenyl ring, with 1 to 3 groups selected from the group consisting of a lower alkoxy group which may have a halogen atom as a substituent and a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxycarbonyl group, a cycloalkyl lower alkyl group, a pyrrolidinyl lower alkyl group which may have, on the pyrrolidine ring, 1 to 3 lower alkyl groups which may have a hydroxyl group as a substituent, an amino substituted lower alkyl group which may have a substituent selected from the group consisting of a phenyl group and a lower alkyl group, a 1,2,3,4-tetrahydronaphthyl substituted lower alkyl group which may have 1 to 5 lower alkyl groups as substituents on the 1,2,3,4-tetrahydronaphthalene ring, a naphthyl lower alkyl group, a pyridyl lower alkyl group, a quinolyl lower alkyl group, a 1,2,3,4-tetrazolyl lower alkyl group which may have, on the tetrazole ring, 1 to 3 substituents selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group, a 1,2,4-triazolyl lower alkyl group, a tetrahydrofuryl lower alkyl group which may have a hydroxyl group as a substituent on the lower alkyl group, a phenoxy lower alkyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkyl group and a nitro group, a phenyl lower alkanoyl group, a lower alkanoyl group which may have a halogen atom as a substituent, an imidazolyl lower alkanoyl group, a lower alkoxycarbonyl lower alkyl group, a pyridyl group or a carboxy lower alkyl group.
 
         [0567]    The reaction of the compound (1uuuuu) and the compound (177) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein X 1 , X 2 , R 2 , Y, A and R 6  are the same as described above, and R 91  represents a hydrogen atom or a lower alkyl group. 
         [0568]    The reaction of the compound (33) and the compound (178) is carried out in an appropriate solvent in the presence of a basic compound and a catalyst. 
         [0569]    As the solvent, an inert solvent selected from a wide range may be used. Examples of the inert solvent include water, aromatic hydrocarbons such as benzene, toluene, and xylene, ethers such as diethyl ether, tetrahydrofuran, dioxane, 2-methoxyethanol, monoglyme, and diglyme, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, and carbon tetrachloride, lower alcohols such as methanol, ethanol, isopropanol, butanol, tert-butanol, and ethylene glycol, fatty acids such as acetic acid, esters such as ethyl acetate and methyl acetate, ketones such as acetone and methyl ethyl ketone, acetonitrile, pyridine, N-methylpyrrolidone, dimethyl sulfoxide, N,N-dimethylformamide, and hexamethylphosphoric acid triamide, and a mixture thereof. 
         [0570]    Examples of the basic compound include carbonates such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, and cesium carbonate, metal hydroxides such as sodium hydroxide, potassium hydroxide, and calcium hydroxide, potassium phosphate, sodium phosphate, sodium hydride, potassium hydride, potassium, sodium, sodium amide, metal alcoholates such as sodium methylate, sodium ethylate, sodium n-butoxide, sodium tert-butoxide, and potassium tert-butoxide, alkylsilylamide alkali metal salts such as potassium bis(trimethylsilyl)amide, and organic bases such as pyridine, imidazole, N-ethyldiisopropylamine, dimethylaminopyridine, triethylamine, trimethylamine, dimethylaniline, N-methylmorpholine, 1,5-diazabicyclo[4.3.0]nonene-5 (DBN), 1,8-diazabicyclo[5.4.0]undecene-7 (DBU), and 1,4-diazabicyclo[2.2.2]octane (DABCO), and a mixture thereof. 
         [0571]    Examples of the catalyst may include palladium compounds such as palladium acetate, bis(tributyltin)/bis(dibenzylideneacetone)palladium, copper iodide/2,2′-bipyridyl, bis(dibenzylideneacetone)palladium, copper iodide/bis(triphenylphosphine)palladium dichloride, tris(dibenzylideneacetone)dipalladium, R-tris(dibenzylideneacetone)-dipalladium, S-tris(dibenzylideneacetone)dipalladium, palladium(II) acetate, [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), and tetrakis(triphenylphosphine)palladium, compounds such as R-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (R-BINAP), S-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (S-BINAP), RAC-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl-(RAC-BINAP), and 2,2-bis(diphenylimidazolidinylidene), xanthene compounds such as 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, and borates such as tri-tert-butylphosphine tetrafluoroborate, and a mixture thereof. 
         [0572]    The basic compound is favorably used in an amount at least 0.5 times and preferably 0.5 to 40 times that of the compound (33) on a molar basis. The catalyst is favorably used in a typical catalyst amount based on the compound (33). 
         [0573]    The compound (178) is favorably used in an amount at least in 0.5 times and preferably 0.5 to 3 times that of the compound (33) on a molar basis. 
         [0574]    The above described reaction is carried out typically at room temperature to 200° C., preferably at room temperature to about 150° C., and completed in about 0.5 to 20 hours. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein B o , X 1 , R 2 , Y, A 17 , R 6  and X 2  are the same as described above, R 92  represents a group R 6 -Z 4 - or a group R 6 — and Z 4  represents a lower alkylene group. 
         [0575]    The reaction of the compound (64) and the compound (179) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , X 1 , Y, A and R 6  are the same as described above. 
         [0576]    The method for converting the compound (30) into the compound (1bbbbbb) is carried out by subjecting the compound (30) to diazotization to obtain a diazonium salt and reacting the diazonium salt with the compound (180). 
         [0577]    The diazotization reaction 1) is carried out in an appropriate solvent in the presence of an acid and a diazotizing agent. Examples of the solvent to be used herein include water and acetonitrile. Examples of the acid include hydrochloric acid, hydrobromic acid, sulfuric acid, tetrafluoroboric acid, and hexafluorophosophoric acid. Examples of the diazotizing-agent include metal nitrites such as sodium nitrite and potassium nitrite, lower alkyl nitrites such as t-butyl nitrite and isoamyl nitrite. 
         [0578]    The acid is favorably used typically in an amount about 1 to 10 times that of the compound (30) and preferably about 1 to 5 times that of the compound (30) on a molar basis. The diazotizing agent is used typically in at least about equimolar amount to the compound (30) and preferably 1 to 3 times that of the compound (30) on a molar basis. 
         [0579]    The above described reaction is carried out typically at about 0 to 70° C. and preferably at about 0° C. to room temperature, and completed in about a few minutes to 5 hours. 
         [0580]    The reaction of the diazonium salt obtained in the diazotination reaction and the compound (180) is carried out in the same solvent as in the diazotization reaction 1) and in the presence of a basic compound. 
         [0581]    Any basic compound may be used herein as long as it is used in the reaction of the compound (2) and the compound (3) shown in reaction formula 1. 
         [0582]    The basic compound is favorably used in at least an equimolar amount to the compound (30) and preferably 1 to 5 times that of the compound (30) on a molar basis. 
         [0583]    The compound (180) is favorably used in at least an equimolar amount to the compound (30) and preferably 1 to 5 times that of the compound (30) on a molar basis. 
         [0584]    The above described reaction is carried out typically at about 0 to 70° C., preferably at about 0° C. to room temperature, and completed in about a few minutes to 5 hours. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein X 1 , R 8d , Y, A, R 2  and R 6  are the same as described above. 
         [0585]    The reaction of the compound (30a) and the compound (181) may be carried out in an appropriate solvent in the presence of a basic compound and a catalyst. 
         [0586]    Examples of the solvent used herein include water, aromatic hydrocarbons such as benzene, toluene, and xylene, ethers such as diethyl ether, tetrahydrofuran, dioxane, 2-methoxyethanol, monoglyme, and diglyme, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, and carbon tetrachloride, lower alcohols such as methanol, ethanol, isopropanol, butanol, tert-butanol, and ethylene glycol, fatty acids such as acetic acid, esters such as ethyl acetate and methyl acetate, ketones such as acetone and methylethyl ketone, acetonitrile, pyridine, dimethylsulfoxide, N,N-dimethylformamide, and hexamethylphosphoric acid triamide, and a mixture thereof. 
         [0587]    Examples of the basic compound include carbonates such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, and cesium carbonate, metal hydroxides such as sodium hydroxide, potassium hydroxide, and calcium hydroxide, sodium hydride, potassium hydride, potassium, sodium, sodium amide, metal alcoholates such as sodium methylate, sodium ethylate, sodium n-butoxide, sodium tert-butoxide, and potassium tert-butoxide, organic bases such as pyridine, imidazole, N-ethyldiisopropylamine, dimethylaminopyridine, triethylamine, trimethylamine, dimethylaniline, N-methylmorpholine, 1,5-diazabicyclo[4.3.0]nonene-5 (DBN), 1,8-diazabicyclo[5.4.0]undecene-7 (DBU), and 1,4-diazabicyclo[2.2.2]octane (DABCO), and a mixture thereof. 
         [0588]    Examples of the catalyst include palladium compounds such as tetrakis(triphenylphosphine)palladium(0) and dichlorobis(triphenylphosphine)palladium(II), and copper compounds such as copper (II) acetate. 
         [0589]    The basic compound is favorably used in at least an equimolar amount to the compound (30a) and preferably 1 to 5 times that of the compound (30a) on a molar basis. 
         [0590]    The catalyst is favorably used in an amount 0.001 to 1 times and preferably 0.01 to 0.5 times that of the compound (30a) on a molar basis. 
         [0591]    The compound (181) is favorably used in at least an equimolar amount to the compound (30a) and preferably 1 to 5 times that of the compound (30a) on a molar basis. 
         [0592]    The above described reaction is carried out typically at −30 to 200° C. and preferably at 0 to 150° C. and generally completed in 0.5 to about 30 hours. A molecular sieve such as Molecular Sieves 3A (MS-3A), Molecular Sieves 4A (MS-4A) may be added to the reaction. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 6 , Z 1 , X 1 , R 2 , Y 4  and A are the same as described above. 
         [0593]    The reaction which converts the compound (1dddddd) into the compound (1eeeeee) is carried out in an appropriate solvent in the presence of a catalytic hydrogen reducing agent. 
         [0594]    Examples of the solvent include water, fatty acids such as acetic acid, alcohols such as methanol, ethanol, and isopropanol, aliphatic hydrocarbons such as n-hexane, alicyclic hydrocarbons such as cyclohexane, ethers such as diethyl ether, dimethoxyethane, tetrahydrofuran, monoglyme, diglyme, and 1,4-dioxane, esters such as methyl acetate, ethyl acetate, and butyl acetate, and aprotic polar solvents such as N,N-dimethylformamide, N,N-dimethylacetoamide, and N-methylpyrrolidone, and a mixture thereof. 
         [0595]    Examples of the catalytic hydrogen reducing agent include palladium, palladium-black, palladium-carbon, palladium hydroxide-carbon, rhodium-alumina, platinum, platinum oxide, copper chromite, Raney nickel, and palladium acetate. 
         [0596]    The above described catalytic hydrogen reducing agent is used typically in an amount 0.01 to 1 times that of the compound (1dddddd) on a molar basis. 
         [0597]    The above reaction favorably proceeds typically at about −20 to 150° C., and preferably at 0 to 100° C. and generally completed in 0.5 to 20 hours. The hydrogen pressure may be applied typically at 1 to 10 atm. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y, A 10 , T and l are the same as described above; R 14II  and R 15JJ  each represent the same 5- to 10-membered saturated or unsaturated heterocyclic group as defined in R 14  and R 15  above, except that they have at least one phenyl group which has a lower alkoxycarbonyl group on the heterocyclic ring; R 14EE  and R 15FF  each represent the same 5- to 10-membered saturated or unsaturated heterocyclic group as defined in R 14  and R 15  above, except that they have at least one phenyl group which has a carboxy group on the heterocyclic ring;
 
R 14GG  and R 15HH  each represent the same 5- to 10-membered saturated or unsaturated heterocyclic group as defined in R 14  and R 15  above, except that they have, on the heterocyclic ring, at least one phenyl group which may have a carbamoyl group which may have a group selected from the group consisting of a lower alkoxy lower alkyl group and a lower alkyl group; and
 
R 93  and R 94  each represent a hydrogen atom, a lower alkyl group or a lower alkoxy lower alkyl group.
 
         [0598]    The reaction which converts the compound (1hhhhhh) into the compound (1ffffff) may be carried out the under the same reaction conditions as in the hydrolysis B described in reaction formula 9 above. 
         [0599]    The reaction of the compound (1ffffff) and the compound (182) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein X 1 , R 2 , Y, A, X 2 , k, X 3 , R 6 , B 20a  and d′ are the same as described above. 
         [0600]    The reaction of the compound (30) and the compound (183) is carried out under the same reaction conditions as in the reaction of the compound (30) and the compound (66) shown in reaction formula 46 above. 
         [0601]    The reaction which converts the compound (184) into the compound (1jjjjjj) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0602]    The reaction of the compound (1jjjjjj) and the compound (185) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0603]    When the compound (185) wherein d′ represents 0, the reaction which converts the compound (1jjjjjj) into the compound (1kkkkkk) may be carried out in an appropriate solvent in the presence of a halogenated copper such as copper iodide, an alkylglycine such as N,N-dimethylglycine, or an alkali metal phosphate such as potassium phosphate. 
         [0604]    Any solvent may be used herein as long as it is used in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0605]    A halogenated copper or an alkylglycine is used in a typical catalyst amount. The alkali metal phosphate is favorably used typically in at least an equimolar amount to the compound (1jjjjjj) and preferably 1 to 5 times that of the compound (1jjjjjj) on a molar basis. The compound (185) is used in an amount typically 0.5 to 5 times and preferably 0.5 to 3 times that of the compound (1jjjjjj) on a molar basis. The above described reaction is carried out typically at room temperature to 200° C. preferably at about room temperature to 150° C. and generally completed in about 1 to 30 hours. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein X 2 , R 2 , X 1 , Y, A and R 6  are the same as described above. 
         [0606]    The reaction of the compound (33) and the compound (186) is carried out under the same reaction conditions as in the reaction of the compound (33) and the compound (178) shown in reaction formula 118 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein X 1 , X 2 , R 2 , Y, A, B 21a , R 6 , and c are the same as described above. 
         [0607]    The reaction of the compound (33) and the compound (187) is carried out under the same reaction conditions as in the reaction of the compound (33) and the compound (178) shown in reaction formula 118 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 9a , R 2 , R 6 , X 1 , Y, A 16 , X 2  and R 9b  are the same as described above. 
         [0608]    The reaction of the compound (188) and the compound (189) is carried out under the same reaction conditions as in the reaction in which an amine is reacted with a carboxylic acid halide among the methods (d) in which the compound (1b) is reacted with the compound (6) shown in reaction formula 2. 
         [0609]    The reaction of the compound (190) and the compound (191) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y and A 16  are the same as described above. Xa represents a halogen atom. 
         [0610]    The reaction which converts the compound (1oooooo) into the compound (1pppppp) is carried out in an appropriate solvent in the presence of a catalytic hydrogen reducing agent and a hydrogen donor such as formic acid, ammonium formate, cyclohexene, or hydrazine hydrate. 
         [0611]    Any solvent and catalytic hydrogen reducing agent may be used as long as they are used in the reaction which converts the compound (1dddddd) into the compound (1eeeeee) shown in reaction formula 122 above. 
         [0612]    The catalytic hydrogen reducing agent is typically used in an amount of 0.01 to 40 wt % and preferably 0.01 to 20 wt % of the compound (1oooooo). 
         [0613]    The hydrogen donor is used typically in at least an equimolar amount to the compound (1oooooo) and preferably 1 to 10 times that of the compound (1oooooo) on a molar basis. 
         [0614]    The above described reaction is carried out under a hydrogen atmosphere typically at about normal pressure to 20 atm and preferably at normal pressure to 10 atm, and at a temperature of about −30 to 150° C. and preferably at about 0 to 100° C. The reaction is generally completed in about 1 to 12 hours. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein A 10 , X 2 , k, X 3 , R 80  and R B  are the same as described above; R 94a  represents a group defined as a substituent present on a heterocyclic group formed by binding R 14  and R 15  to each other, and include a substituent represented by (35), (40), (42), (67), (75), (76), (78), (80) or (81) in which o is 1, or (84) in which s is 0. 
         [0615]    R 94b  represents a group defined as a substituent present on a heterocyclic ring formed by binding R 14  and R 15  to each other, and include a substituent represented by (28), (30) to (34), (36) to (39), (41), (43) to (45), (47), (52) to (60), (62) to (66), (70), (77), (79), (82), (83), (87), (88a) or (90a), a substituent represented by (49) in which t is 1, or a substituent represented by (50) in which o is 0; and R 94c  represents a group defined as a substituent present on a heterocyclic ring formed by binding R 14  and R 15  to each other and include a substituent represented by (28), (30) to (34), (39), (41), (45), (47), (54) to (58), (62) to (64), (66), (70), (79), (82) or (83), a substituent represented by (49) in which t is 1, or a substituent represented by (50) in which o is 0; a phenyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkanoyl group, an amino group which may have a lower alkanoyl group as a substituent, a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, a phenyl lower alkoxy group, a hydroxy group and a lower alkylenedioxy group, a pyridyl group which may have, on the pyridine ring, 1 to 3 substituents selected from the group consisting of a hydroxy group and a lower alkyl group which may have a hydroxyl group as a substituent, a pyrrolyl group which may have 1 to 3 lower alkyl groups as substituents on a pyrrolyl group, a benzoxazolyl group, a benzothiazolyl group, a furyl group, a lower alkyl group which may have a substituent selected from the group consisting of a hydroxy group and a halogen atom, a naphthyl group, a 1,2,3,4-tetrahydronaphthyl group which may have 1 to 5 lower alkyl groups as substituents on the 1,2,3,4-tetrahydronaphthalene ring, a quinolyl group, a 1,2,3,4-tetrazolyl group which may have, on the tetrazole ring, a substituent selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group; a thiazolyl group which may have a phenyl group as a substituent on the thiazole ring; a benzoyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkoxy group and a halogen atom, a piperidinyl group which may have a lower alkyl group as a substituent on the piperidine ring, a 1,2,3,4-tetrahydroquinolyl group which may have an oxo group as a substituent on the tetrahydroquinoline ring, a 1,3,4-oxadiazolyl group which may have an oxo group as a substituent on the 1,3,4 oxadiazole ring, a cycloalkyl group, a thienyl group, or an imidazolyl group. 
         [0616]    The reaction of the compound (192) and the compound (183) is carried out under the same reaction conditions as in the reaction of the compound (30) and the compound (183) shown in reaction formula 124 above. 
         [0617]    The reaction which converts the compound (193) into the compound (1qqqqqq) is carried out under the same reaction conditions as in the reaction which converts the compound (184) into the compound (1jjjjjj) shown in reaction formula 124 above. 
         [0618]    The reaction of the compound (1qqqqqq) and the compound (195) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 above. 
         [0619]    The compound (195), in which R 94b  is a group represented by (36) to (38), (43), (44), (53), (59), (60), (87), (88a) or (90a), is reacted with the compound (1qqqqqq) in an appropriate solvent in the presence of a copper halide such as copper iodide, an alkylglycine such as N,N-dimethylglycine, and an alkyl metal phosphate such as potassium phosphate. 
         [0620]    Any solvent may be used herein as long as it is used in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. The copper halide and alkyliglycine are used in a normal catalyst amount. The alkali metal phosphate is favorably used typically in at least an equimolar amount to the compound (1qqqqqq) and preferably 1 to 5 times that of the compound (1qqqqqq) on a molar basis. The compound (195) is favorably used typically in an amount 0.5 to 5 times and preferably 0.5 to 3 times that of the compound (1qqqqqq) on a molar basis. The above described reaction is carried out typically at room temperature to 200° C. and preferably about room temperature to 150° C. and completed in about 1 to 30 hours. 
         [0621]    The reaction of the compound (1qqqqqq) and the compound (194) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0622]    The reaction of the compound (1qqqqqq) and the compound (196) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (5) of the above described formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein X 1 , Y, A, R 2 , R 6 , B 22a , e and X 2  are the same as described above, and R 10a′  represents a lower alkyl group. 
         [0623]    The reaction of the compound (1uuuuuu) and the compound (197) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) of reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein X 1 , Y, A, R 2 , R 6  and X 2  are the same as described above. R 10b′  represents a lower alkyl group. 
         [0624]    The reaction of the compound (1wwwwww) and the compound (197a) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (4) shown in reaction formula 2 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , X 1 , Y, X 2 , R 14a  and R 59b  are the same as described above, and R 96  represents a piperazinyl group which may have, on the piperazine ring, 1 to 3 substituents selected from the group consisting of a phenyl lower alkyl group (which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkylenedioxy group and a lower alkoxy group) and a pyridyl lower alkyl group. 
         [0625]    The reaction of the compound (198) and the compound (199) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0626]    The reaction which converts the compound (200) into the compound (201) may be carried out under the same reaction conditions as in hydrolysis B described in reaction formula 9 above. 
         [0627]    The reaction of the compound (201) and the compound (100′) is carried out under the same reaction conditions as in the reaction of the compound (120b) and the compound (100′) shown in reaction formula 79 above. 
         [0628]    The reaction of the compound (201) and the compound (202) is carried out under the same reaction conditions as in the reaction of the compound (1b) and the compound (6) shown in reaction formula 2 above. 
         [0629]    The compound (200) may also be produced by the method shown in the following reaction formula 133: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 74a , R 2 , X 1 , Y. A 10 , R 59b  and X 2  are the same as described above, and R 14a′  represents a lower alkyl group which may have a hydroxyl group as a substituent. 
         [0630]    The reaction of the compound (200a) and the compound (203) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. 
         [0631]    The compound (3) may also be produced by the method of the following reaction formula 134: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 80 , A 10 , B 23a , R 14  and R 15  are the same as described above. 
         [0632]    The reaction which converts the compound (108l) into the compound (108m) is carried out under the same reaction conditions as in the reaction which converts the compound (1f) into the compound (1g) shown in reaction formula 3 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X 1 , Y, A 10 , B 23a , R 14  and R 15  are the same as described above. 
         [0633]    The reaction which converts the compound (1zzzzzz) into the compound (1AAAAAA) is carried out under the same reaction conditions as in the reaction which converts the compound (64b) into the compound (26a) shown in reaction formula 89 above. 
         [0634]    A reaction mixture containing each of the target compounds obtained by reaction formulas shown above is cooled, and thereafter, a crude reaction product can be isolated from the reaction mixture cooled by an isolation operation such as filtration, concentration, or extraction, and purified by a conventional purification operation such as column chromatography or re-crystallization. 
         [0635]    The compound of the present invention represented by the general formula (1) includes a stereoisomer, an optical isomer, a solvate (hydrate and ethanolate, etc.) 
         [0636]    Of the compounds of the present invention, a compound having a basic group may be easily reacted with a conventional pharmacologically acceptable acid to form a salt. Examples of such an acid include mineral acids such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, and phosphoric acid, and organic acids such as methanesulfonic acid, p-toluenesulfonic acid, acetic acid, citric acid, tartaric acid, maleic acid, fumaric acid, malonic acid, and lactic acid. 
         [0637]    Of the compounds of the present invention, a compound having an acidic group may be easily reacted with a conventional pharmacologically acceptable basic compound to form a salt. Examples of such a basic compound include sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, and potassium bicarbonate. 
         [0638]    Next, a medical formulation containing a compound according to the present invention as an active ingredient will be described. 
         [0639]    The medical formulation is obtained by formulating a compound according to the present invention in the form of pharmaceutical preparation, and more specifically, prepared using a diluent or an excipient such as a filler, expander, binder, moistener, disintegrator, surfactant, or lubricant. 
         [0640]    The form of such a medicinal formulation may be chosen from various forms depending upon the therapeutic purpose, and typical forms include tablets, pills, powders, liquids, suspensions, emulsions, granules, capsules, suppositories, and injections (liquids, suspensions). 
         [0641]    The carrier to be used in forming tablets may be chosen widely from conventionally known ones. Examples of the carrier include excipients such as lactose, saccharose, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, and crystalline cellulose, binders such as water, ethanol, propanol, simple syrup, a glucose solution, a starch solution, a gelatin solution, carboxymethylcellulose, shellac, methylcellulose, potassium phosphate, and polyvinylpyrrolidone, disintegrators such as dried starch, sodium arginate, agar powder, laminaran powder, sodium bicarbonate, calcium carbonate, polyoxyethylene sorbitan fatty acid ester, sodium lauryl sulfate, stearic acid monoglyceride, starch, and lactose, anti-disintegrators such as saccharose, stearine, cacao butter, and hydrogenated oil, absorbefacients such as quartenary ammonium base and sodium lauryl sulfate, wetting agents such as glycerol and starch, adsorbents such as starch, lactose, kaolin, bentonite, and colloidal silicate, and lubricants such as purified talc, stearate, boric acid powder, and polyethylene glycol. 
         [0642]    Further, tablets may be coated in a conventional manner as needed. Examples of coated tablets include sugar-coated tablets, gelatin-coated tablets, enteric-coated tablets, film-coated tablets, or double or multi-layered tablets. 
         [0643]    The carriers to be used in forming pills may be chosen widely from the conventionally known ones. Examples of the carrier include excipients such as glucose, lactose, starch, cacao butter, hydrogenated vegetable oil, kaolin, and talc, binders such as gum arabic powder, tragacanth powder, gelatin, and ethanol, and disintegrators such as laminaran and agar. 
         [0644]    The carriers to be used in forming suppositories may be chosen widely from the conventionally known ones. Examples of the carrier include polyethylene glycol, cacao butter, higher alcohols, esters of higher alcohols, gelatin, and semi-synthetic glycerides. 
         [0645]    When liquid, emulsion and suspension are prepared as injection preparations, they are preferably sterilized and controlled to be isotonic with the blood. Diluents to be used in forming these liquid, emulsion and suspension preparations may be chosen widely from the conventionally known ones. Examples of the diluents include water, ethanol, propylene glycol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, and polyoxyethylene sorbitan fatty acid ester. In this case, the medical formulations may contain sodium chloride, glucose or glycerol in a sufficient amount to prepare isotonic solutions. Also, conventional solubilizers, buffers, analgesics, and the like, and, as necessary, coloring agents, preservatives, spices, flavors, sweets and the like, or other pharmaceuticals may be contained. 
         [0646]    Although the amount of a compound according to the present invention contained in a medical formulation is not particularly limited and may be appropriately selected from a wide range of compounds. It is preferable that a compound according to the present invention is contained in an amount of 1 to 70 wt % in a medical formulation. 
         [0647]    The method for administrating a medical formulation according to the present invention is not particularly limited. The medical formulation can be administered by a method determined depending upon the form of medical formulation, patient&#39;s age, sex, severity of the disease and other conditions. For example, tablets, pills, liquids, suspensions, emulsions, granules and capsules are administered orally. The injection formulations are administered singly or by mixing with a conventional fluid replacement such as a glucose solution or amino acid solution, intravenously or, as necessary, singly administered intramuscularly, intradermally, subcutaneously or intraperitoneally. Suppositories are administered into the rectum. 
         [0648]    The dosage for the above mentioned medical formulation may be chosen appropriately depending upon the usage, patient&#39;s age, sex and severity of the disease and other conditions. Typically, 0.001 to 100 mg per kg (body weight) per day, preferably 0.001 to 50 mg per kg (body weight) per day, is administered once or in several times a day. 
         [0649]    Since the above described dosage varies depending upon various conditions, the dosage may be smaller than the lower limit of the range described above or larger than the upper limit of the range described above. 
         [0650]    The medicinal drug has an excellent antitumor effect and thus useful as a tumor therapeutic drug. 
         [0651]    As a tumor upon which antitumor effect is exerted, for example, a malignant tumor and the like may be mentioned. 
         [0652]    As such a malignant tumor, for example, a solid tumor (cancer, sarcoma and the like), blood cancers (lymphoma, leukemia, myeloma and the like) may be mentioned. 
         [0653]    Specific examples of the malignant tumor include brain tumors of an infant such as astroglioma, malignant medulloblastoma, germ cell tumor, craniopharyngioma, and ependymoma; brain tumors of an adult such as glioma, meningioma, pituitary gland adenoma, and neurilemma; head cervix cancers such as cancer of maxillary sinus, pharyngeal cancer (nasopharyngeal carcinoma, mesopharyngeal carcinoma, hypopharyngeal carcinoma), laryngeal cancer, oral cavity cancer, labial cancer, tongue cancer, and parotoid cancer; 
         [0000]    chest cancers and tumors, such as cellule lung cancer, non-small-cell lung cancer, chest adenoma, and mesotheliomas;
 
digestive organ cancers and tumors such as esophagus cancer, liver cancer, primary hepatic cancer, gallbladder cancer, bile duct cancer, stomach cancer, large bowel cancer, colonic cancer, rectal cancer, anal cancer, pancreatic cancer, and pancreas internal secretion tumor; urinary organ cancers and tumors such as penile cancer, renal pelvic/ureteral cancer, renal cell cancer, testicular tumor, prostatic cancer, bladder cancer, Wilms tumor, and urothelial cancer; gynecologic cancers and tumors such as vulvar cancer, cancer of the uterine cervix, corpus uteri cancer, endometrial cancer, uterine sarcoma, chorioma, vaginal cancer, breast cancer, ovary cancer, ovary germ cell tumor;
 
a soft part sarcoma of an infant and adult; tumors of bones such as osteosarcoma and Ewing tumor; cancers and tumors of the endocrine tissue such as adrenocortical cancer, thyroid cancer;
 
malignancy lymphoma and leukemia such as malignant lymphoma, non-Hodgkin&#39;s lymphoma, Hodgkin&#39;s disease, multiple myeloma, plasmacytic tumor, acute myelogenous leukemia, acute lymphatic leukemia, adult T cell leukemia lymphoma, chronic myelogenous leukemia, and chronic lymphatic leukemia; cancers and tumors of skin such as chronic myeloproliferative disorders, malignant melanoma, prickle cell cancer, basal cell cancer, and mycosis fungoides; and metastatic foci of tumors and cancers mentioned above. Of them, the medicinal drug of the present invention have an effect upon liver cancer, chronic myelogenous leukemia, acute myelogenous leukemia, lymphoma, and multiple myeloma.
 
         [0654]    The medical drug of the present invention has less side effects and excellent safety and is thus more excellent tumor therapeutic agent. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0655]    The present invention will be explained more specifically by way of Reference Examples, Examples, Preparation Examples and Pharmacological Tests. 
       Reference Example 1 
     Production of 1-(t-butoxycarbonyl)-4-(4-hydroxyphenyl)-1,2,5,6-tetrahydropyridine 
     Step 1 
     Production of 1-(t-butoxycarbonyl)-4-[(4-methoxymethoxy)phenyl]-4-hydroxypiperidine 
       [0656]    A solution of 1-bromo-4-methoxymethoxybenzene (5.43 g, 25.0 mmol) in tetrahydrofuran (THF) (100 mL) was stirred at −85° C., and a 2.46 M n-butyllithium hexane solution (10.2 mL, 25.0 mmol) was added dropwise to the stirred solution over 10 minutes. The resulting solution was stirred at the same temperature for 40 minutes. To the reaction solution was added dropwise for 10 minutes a solution of 1-(t-butoxycarbonyl)-4-piperidone (5.20 g, 26.0 mmol) in THF (30 mL). The temperature of the resulting solution was raised to 25° C. over 4 hours, and then the solution was stirred at that temperature for 2 hours. An aqueous solution of saturated ammonium chloride was then added to this solution. The reaction solution was extracted with ethyl acetate and dried over anhydrous magnesium sulfate, after which the solvent was evaporated. The residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=2:3, in ratio by volume; hereinafter the same), to thereby yield 7.63 g of the title compound. 
         [0657]    Appearance: Colorless oil 
         [0658]      1 H NMR (CDCl 3 ) δ 1.49 (9H, s), 1.73 (2H, d, J=12.0 Hz), 1.97 (2H, brs), 3.24 (2H, brs), 3.48 (3H, s), 4.00 (2H, brs), 5.17 (2H, s), 7.03 (2H, d, J=9.0 Hz), 7.39 (2H, d, J=9.0 Hz). 
       Step 2 
     Production of 1-(t-butoxycarbonyl)-4-(4-hydroxyphenyl)-1,2,5,6-tetrahydropyridine 
       [0659]    To a solution of 1-(t-butoxycarbonyl)-4-[(4-methoxymethoxy)phenyl]-4-hydroxypiperidine (5.32 g, 15.8 mmol) in toluene (100 mL) was added p-toluenesulfonic acid monohydrate (0.56 g, 2.95 mmol), and the resulting solution was refluxed for 21 hours. The reaction solution was cooled to room temperature, and evaporated under reduced pressure. To this crude product were added ethanol (60 mL) and 2 M hydrochloric acid (40 mL, 80 mmol), and the resulting solution was stirred for 2 hours at 60° C. The reaction solution was again cooled to room temperature, and evaporated under reduced pressure. To the residue were added methanol (100 mL), triethylamine (9.0 mL, 64.6 mmol) and di-t-butyl dicarbonate (5.20 g, 23.8 mmol), and the resulting solution was stirred for 24 hours at room temperature. The solvent was evaporated under reduced pressure, after which to the residue was added 100 mL of ethyl acetate. Insoluble matter was removed by filtration, after which the filtrate was evaporated under reduced pressure. To the residue were added 1,4-dioxane (50 mL) and a 1 M aqueous solution of sodium hydroxide (50 mL, 50 mmol) and stirred for 14 hours at 60° C. To the resulting reaction solution was added at room temperature 2 M hydrochloric acid (25 mL, 50 mmol) to neutralize, and then extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate, and evaporated to thereby yield 4.10 g of the title compound. 
         [0660]    Appearance: Brown amorphous 
         [0661]      1 H NMR (CDCl 3 ) δ 1.49 (9H, s), 2.47 (2H, brs), 3.62 (2H, t, J=5.5 Hz), 4.05 (2H, brs), 5.91 (1H, brs), 6.81 (2H, d, J=9.0 Hz), 7.25 (2H, d, J=9.0 Hz). 
       Reference Example 2 
     Production of methyl 5-(4-benzylpiperazin-1-yl)-2-methoxymethoxybenzoate 
       [0662]    To a solution of methyl 5-chloro-2-methoxymethoxybenzoate (1.45 g, 6.29 mmol) and 1-benzylpiperazine (1.66 g, 9.43 mmol) in toluene (50 mL) were added palladium acetate (28 mg, 0.126 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (157 mg, 0.252 mmol) and cesium carbonate (3.07 g, 9.43 mmol), and the resulting solution was refluxed for 3 hours. Water was added to the resulting solution, and extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=1:2), to thereby yield 400 mg of the title compound. 
         [0663]    Appearance: Yellow oil 
         [0664]      1 H NMR (CDCl 3 ) δ 2.59-2.62 (4H, m), 3.12-3.16 (4H, m), 3.51 (3H, s), 3.57 (2H, s), 3.88 (3H, s), 5.16 (2H, s), 7.01 (1H, dd, J=9.1 Hz, 3.1 Hz), 7.10 (1H, d, J=9.1 Hz), 7.28-7.35 (6H, m). 
         [0665]    The following compounds were produced in the same manner as in Reference Example 2. 
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 1 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 101   
                 R 102   
                 R 103   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 3 
                 —CH 2 OCH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 1.27 (3H, t, J = 7.0 Hz), 1.43- 1.48 (2H, m), 1.83 (2H, brd, J = 13.0 Hz), 1.90 (1H, m), 2.28 (2H, d, J = 7.0 Hz), 2.66 (2H, dt, J = 2.5 Hz, 12.0 Hz), 3.47 (3H, s), 3.50 (2H, brd, J = 12.0 Hz), 4.15 (2H, q, J = 7.0 Hz), 5.10 (2H, s), 6.89 (2H, d, J = 9.0 Hz), 6.95 (2H, d, J = 9.0 Hz). 
               
               
                   
               
               
                 4 
                 —CH 2 OCH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 1.27 (3H, t, J = 7.0 Hz), 1.57- 1.75 (2H, m), 1.82 (1H, m), 2.00 (1H, m), 2.68-2.75 (2H, m), 2.93 (1H, dd, J = 10.0 Hz, 12.0 Hz), 3.34 (1H, d, J = 12.0 Hz), 3.48 (3H, s), 3.56 (1H, brd, J = 10.0 Hz), 4.16 (2H, q, J = 7.0 Hz), 5.11 (2H, s), 6.91 (2H, d, J = 9.0 Hz), 6.96 (2H, d, J = 9.0 Hz). 
               
               
                   
               
               
                 5 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 1.27 (3H, t, J = 7.0 Hz), 1.91 (2H, dq, J = 3.0 Hz, 13.5 Hz), 2.02 (2H, dd, J = 13.5 Hz, 3.0 Hz), 2.38 (1H, m), 2.69 (2H, dt, J = 3.0 Hz, 12.0 Hz), 3.48 (2H, dt, J = 12.0 Hz, 3.0 Hz), 3.37 (3H, s), 4.16 (2H, q, J = 7.0 Hz), 6.83 (2H, d, J = 9.0 Hz), 6.91 (2H, d, J = 9.0 Hz). 
               
               
                   
               
               
                 6 
                 —CH 2 OCH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 1.27 (3H, t, J = 7.1 Hz), 1.82- 1.99 (4H, m), 2.22 (3H, s), 2.33- 2.42 (1H, m), 2.64-2.73 (2H, m), 3.50-3.52 (5H, m), 4.15 (2H, q, J = 7.1 Hz), 5.12 (2H, s), 6.70 (1H, dd, J = 8.9 Hz, 3.1 Hz), 6.78 (1H, d, J = 3.0 Hz), 6.95 (1H, d, J = 8.7 Hz). 
               
               
                   
               
               
                 7 
                 —CH 2 OCH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —OCH 3   
                 1.27 (3H, t, J = 7.1 Hz), 1.37- 1.47 (2H, m), 1.81-1.94 (3H, m), 2.29 (2H, d, J = 6.9 Hz), 2.64- 2.73 (2H, m), 3.51 (3H, s), 3.54 (2H, brs), 3.85 (3H, s), 4.15 (2H, q, J = 7.1 Hz), 5.13 (2H, s), 6.44 (1H, dd, J = 8.7 Hz, 2.6 Hz), 6.56 (1H, d, J = 2.6 Hz), 7.02 (1H, d, J = 8.7 Hz). 
               
               
                   
               
               
                 8 
                 —CH 2 OCH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 1.27 (3H, t, J = 7.1 Hz), 1.37- 1.49 (2H, m), 1.80-2.04 (3H, m), 2.22 (3H, s), 2.27 (2H, d, J = 6.9 Hz), 2.60-2.68 (2H, m), 3.48 (3H, s), 3.52 (2H, brs), 4.14 (2H, q, J = 7.1 Hz), 5.11 (2H, s), 6.69-6.79 (2H, m), 6.94 (1H, d, J = 8.7 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
               
               
               
             
           
               
                 TABLE 2 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
               
               
                 Example 
                   
                   
               
               
                 No. 
                 R 104   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
             
          
           
               
                 9 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.48 (9H, s), 1.76-l.89 (4H, m), 2.78 (3H, brs), 2.81 (2H, brt, J = 12.0 Hz), 3.71 (2H, brd, J = 12.0 Hz), 4.15 (1H, brs), 6.96 (2H, d, J = 9.0 Hz), 6.98 (4H, s), 8.17 (2H, d, J =9.0 Hz). 
               
               
                   
               
               
                 10 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.49 (9H, s), 3.13 (4H, t, J = 5.0 Hz), 3.60 (4H, t, J = 5.0 Hz), 6.96-7.00 (6H, m), 8.18 (2H, d, J = 9.0 Hz). 
               
               
                   
               
               
                 11 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.79 (2H, m), 2.03 (2H, m), 2.96 (2H, m), 3.41 (3H, s), 3.51 (2H, m), 3.73 (1H, m), 4.74 (2H, s), 6.95-6.98 (6H, m), 8.17 (2H, d, J = 9.0 Hz). 
               
               
                   
               
               
                 12 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.28 (3H, t, J = 7.0 Hz), 1.90 (2H, dq, J = 4.0 Hz, 13.0 Hz), 2.05 (2H, dd, J = 13.0 Hz, 4.0 Hz), 2.45 (1H, m), 2.82 (2H, dt, J = 2.5 Hz, 12.0 Hz), 3.62 (2H, brd, J = 12.5 Hz), 4.17 (2H, q, J = 7.0 Hz), 6.95-6.98 (6H, m), 8.17 (2H, d, J = 9.0 Hz). 
               
               
                   
               
               
                 13 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.31 (3H, t, J = 7.0 Hz), 1.83 (2H, m), 2.05 (2H, m), 2.96 (1H, m), 3.07 (1H, m), 3.46 (1H, m), 3.53 (1H, m), 3.60 (1H, m), 4.16 (2H, s), 4.24 (2H, q, J = 7.0 Hz), 6.95-7.01 (6H, m), 8.17 (2H, d, J = 9.0 Hz). 
               
               
                   
               
             
          
         
       
     
       Reference Example 14 
     Production of methyl 5-(4-benzylpiperazin-1-yl)-2-hydroxybenzoate 
       [0666]    To a solution of 400 mg of methyl 5-(4-benzylpiperazin-1-yl)-2-methoxymethoxybenzoate (1.1 mmol) in 1,4-dioxane (20 mL) was added a solution of 4 N hydrogen chloride in 1,4-dioxane (4 mL, 16 mmol), and the resulting solution was stirred for 2 hours at 100° C. The resulting reaction solution was subjected to distillation under reduced pressure to obtain a residue. This residue was purified by silica gel column chromatography (dichloromethane:methanol=30:1), to thereby yield 353 mg of the title compound. 
         [0667]    Appearance: Pale yellow powder 
         [0668]      1 H NMR (CD 3 OD) δ 3.29-3.40 (8H, m), 3.94 (3H, s), 4.39 (2H, s), 6.91 (1H, d, J=8.9 Hz), 7.28 (1H, dd, J=8.9 Hz, 3.0 Hz), 7.42 (1H, d, J=3.0 Hz), 7.49-7.60 (5H, m). 
         [0669]    The following compounds were produced in the same manner as in Reference Example 14. 
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 3 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 105   
                 R 106   
                 Form 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 15 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 (DMSO-d 6 ) 1.20 (3H, t, J = 7.0 Hz), 1.78 (2H, brs), 1.91 (2H, brs), 2.10 (1H, brs), 2.34 (2H, brs), 3.45 (2H, brs), 3.55 (2H, brs), 4.09 (2H, q, J = 7.0 Hz), 6.88 (2H, brs), 7.60 (2H, brs), 10.05 (1H, brs), 11.75 (1H, brs). 
               
               
                   
               
               
                 16 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 (DMSO-d 6 ) 1.20 (3H, t, J = 7.0 Hz), 1.64 (1H, brs), 1.93 (2H, brs), 2.08 (2H, brs), 3.30 (1H brs), 3.45 (2H, brs), 3.48 (2H, brs), 4.10 (2H, q, J = 7.0 Hz), 6.88 (2H, brs), 7.66 (2H, brs), 10.05 (1H, brs), 12.60 (1H, brs). 
               
               
                   
               
               
                 17 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 hydro- chloride 
                 (DMSO-d 6 ) 1.22 (3H, t, J = 7.1 Hz), 2.03-2.13 (4H, m), 2.14 (3H, s), 2.75 (1H, brs), 3.38-3.57 (4H, m), 4.12 (2H, q, J = 7.1 Hz), 6.89 (1H, d, J = 8.6 Hz), 7.46-7.53 (2H, m), 9.99 (1H, brs). 
               
               
                   
               
               
                 18 
                 —OCH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 (CDCl 3 ) 1.27 (3H, t, J = 7.1 Hz), 1.98-2.18 (3H,.m), 2.41-2.44 (4H, m), 3.30 (2H, t, J = 12.0 Hz), 3.66 (2H, d, J = 11.9 Hz), 3.95 (3H, s), 4.15 (2H, q, J = 7.1 Hz), 6.26 (1H, brs), 6.96-7.03 (2H, m), 7.85 (1H, s). 
               
               
                   
               
               
                 19 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 hydro- chloride 
                 (DMSO-d 6 ) 1.20 (3H, t, J = 7.1 Hz), 1.87 (4H, brs), 2.14 (4H, brs), 2.33 (2H, d, J = 6.4 Hz), 2.52 (2H, brs), 3.44 (2H, brs), 4.19 (2H, q, J = 7.1 Hz), 6.88 (1H, d, J = 8.6 Hz), 7.46-7.57 (2H, m), 9.98 (1H, brs), 12.04 (1H, brs). 
               
               
                   
               
             
          
         
       
     
       Reference Example 20 
     Production of ethyl N-(4-hydroxyphenyl)isonipecotate 
       [0670]    To a solution of ethyl N-(4-methoxyphenyl)-isonipecotate (2.63 g, 10 mmol) in dichloromethane (100 mL) was added a solution of 2 M boron tribromide in dichloromethane (20 mL, 40 mmol), and the resulting solution was stirred for 0.5 hours at room temperature. The resulting reaction solution was poured into ice water, then an aqueous solution of 1 M sodium hydroxide (110 mL) was added to the solution. After stirring, the resulting solution was separated. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure to thereby yield 2.43 g of the title compound. 
         [0671]    Appearance: Yellow oil 
         [0672]      1 H NMR (CDCl 3 ) δ 1.27 (3H, t, J=7.0 Hz), 1.91 (2H, m), 2.02 (2H, brd, J=11.5 Hz), 2.38 (1H, m), 2.68 (2H, dt, J=2.0 Hz, 11.5 Hz), 3.46 (2H, dt, J=12.0 Hz, 3.0 Hz), 4.16 (2H, q, J=7.0 Hz), 4.45 (1H, brs), 6.75 (2H, d, J=9.0 Hz), 6.86 (2H, d, J=9.0 Hz). 
         [0673]    The following compounds were produced in the same manner as in Reference Example 20. 
       Reference Example 21 
     4-(2-Fluoro-4-nitrophenoxy)phenol 
       [0674]      1 H NMR (DMSO-d 6 ) δ 6.80-7.10 (5H, m), 8.04 (1H, ddd, J=1.4 Hz, 2.7 Hz, 9.2 Hz), 8.29 (1H, dd, J=2.7 Hz, 10.9 Hz), 9.59 (1H, s). 
       Reference Example 22 
     1-Benzyl-3-(4-hydroxyphenyl)imidazolidin-2-one 
       [0675]      1 H NMR (DMSO-d 6 ) δ 3.18-3.40 (2H, m), 3.61-3.80 (2H, m), 4.35 (2H, s), 6.71 (2H, d, J=8.8 Hz), 7.15-7.48 (7H, m), 9.10 (1H, s). 
       Reference Example 23 
     Production of 2-(4-hydroxyphenylamino)-1-(4-piperonylpiperazin-1-yl)ethanone 
       [0676]    To a solution of N-(4-hydroxyphenyl)glycine (11.38 g, 68.1 mmol) in N,N-dimethylformamide (DMF) (150 mL) were added under ice cooling 1-piperonylpiperazine (15.0 g, 68.1 mmol), 1-hydroxybenzotriazole monohydrate (10.43 g, 68.1 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (15.66 g, 81.7 mmol), and the resulting solution was stirred for 30 minutes under ice cooling and for 4.5 hours at room temperature. The reaction solution was concentrated under reduced pressure. To the residue was added a saturated sodium bicarbonate solution (400 mL), and extracted with ethyl acetate (400 mL). The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and evaporated, to leave the resulting product solidified in a powdered form. Ethyl acetate was added, and the resulting product was filtered off and washed with ethyl acetate, to thereby yield 18.58 g of the title compound. 
         [0677]    Appearance: Brown powder 
         [0678]      1 H NMR (DMSO-d 6 ) δ 2.30 (2H, brs), 2.36 (2H, brs), 3.40 (2H, s), 3.47 (4H, t, J=14.5 Hz), 4.03 (2H, d, J=7.0 Hz), 4.90 (1H, brs), 5.99 (2H, s), 6.49 (2H, d, J=8.9 Hz), 6.54 (2H, d, J=8.9 Hz), 6.75 (1H, dd, J=8.0 Hz, 1.1 Hz), 6.85 (1H, d, J=8.0 Hz), 6.87 (1H, s), 8.42 (1H, s). 
         [0679]    The following compounds were produced in the same manner as in Reference Example 23. 
       Reference Example 24 
     6-Chloro-N-(3,4-dichlorophenyl)nicotinamide 
       [0680]      1 H NMR (CDCl 3 ) δ 7.64 (1H, d, J=8.9 Hz), 7.72 (1H, dd, J=8.7 Hz, 2.3 Hz), 7.73 (1H, dd, J=8.3 Hz, 0.7 Hz), 8.12 (1H, d, J=2.3 Hz), 8.35 (1H, dd, J=8.3 Hz, 2.5 Hz), 8.95 (1H, dd, J=2.5 Hz, 0.7 Hz), 10.71 (1H, brs). 
       Reference Example 25 
     4-(4-Piperonylpiperazine-1-carbonyl)-1-(4-hydroxyphenyl)pyrrolidin-2-one 
       [0681]      1 H NMR (CDCl 3 ) δ 2.43-2.45 (4H, m), 2.73-2.95 (2H, m), 3.45 (2H, s), 3.49-3.54 (4H, m), 3.65-3.72 (1H, m), 3.78-3.87 (1H, m), 4.17-4.23 (1H, m), 5.96 (2H, s), 6.71-6.80 (4H, m), 6.84-6.85 (1H, m), 7.29 (2H, d, J=8.9 Hz). 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 4 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
                   
               
               
                 Example 
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 Xa 1   
                 Xa 2   
                 R 107   
                 R 108   
                 Form 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 26 
                 —NH— 
                 —CH 2 — 
                 —H 
                 benzyl 
                 free 
                 (CDCl 3 ) 2.46-2.48 (4H, m), 3.45 (2H, t, J = 5.0 Hz), 3.54 (2H, s), 3.68 (2H, t, J = 5.0 Hz), 3.82 (2H, s), 6.53 (2H, d, J = 8.7 Hz), 6.70 (2H, d, J = 8.7 Hz), 7.27- 7.34 (5H, m). 
               
               
                 27 
                 —CH 2 — 
                 —CH 2 — 
                 —H 
                 benzyl 
                 free 
                 (CDCl 3 ) 2.30-2.33 (2H, m), 2.41- 2.45 (2H, m), 2.55-2.60 (2H, m), 2.85- 2.91 (2H, m), 3.36-3.40 (2H, m), 3.52 (2H, s), 3.62-3.66 (2H, m), 5.10 (1H, brs), 6.74-6.77 (2H, m), 7.03 (2H, d, J = 8.6 Hz), 7.27-7.32 (5H, m). 
               
               
                 28 
                 —CH 2 — 
                 —CH 2 — 
                 —H 
                 piperonyl 
                 hydro- chloride 
                 (DMSO-d 6 ) 2.56-3.47 (10H, m), 4.01- 4.07 (1H, m), 4.18-4.48 (3H, m), 6.07 (2H, s), 6.65-6.68 (2H, m), 7.00-7.03 (4H, m), 7.21 (1H, s), 9.18 (1H, brs), 11.04 (1H, brs). 
               
               
                 29 
                 —O— 
                 —CH 2 — 
                 —H 
                 piperonyl 
                 free 
                 (CDCl 3 ) 2.31-2.50 (4H, m), 3.41 (2H, s), 3.52-3.72 (4H, m), 4.63 (2H, s), 5.94 (2H, s), 6.25 (1H, brs), 6.70 (2H, d, J = 9.1 Hz), 6.69-6.77 (1H, m), 6.73 (1H, s), 6.77 (2H, d, J = 9.1 Hz), 6.83 (1H, d, J = 0.9 Hz). 
               
               
                 30 
                 —O— 
                 —CH 2 — 
                 —H 
                 benzyl 
                 free 
                 (CDCl 3 ) 2.40-2.52 (4H, m), 3.51 (2H, s), 3.53-3.73 (4H, m), 4.63 (2H, s), 5.89 (1H, brs), 6.70 (2H, d, J = 9.2 Hz), 6.78 (2H, d, J = 9.2 Hz), 7.22-7.43 (5H, m). 
               
               
                 31 
                 —CH(OH)— 
                 none 
                 —H 
                 benzyl 
                 free 
                 (CDCl 3 ) 1.89-2.03 (1H, m), 2.21- 2.32 (1H, m), 2.32-2.57 (2H, m), 3.00- 3.18 (1H, m), 3.20-3.35 (1H, m), 3.40 (1H, d, J = 13.1 Hz), 3.46 (1H, d, J = 13.1 Hz), 3.60-3.83 (2H, m), 5.13 (1H, s), 6.71 (2H, d, J = 8.6 Hz), 7.09 (2H, d, J = 8.6 Hz), 7.18-7.35 (5H, m). 
               
               
                 32 
                 none 
                 none 
                 —H 
                 3-pyridyl 
                 free 
                 (DMSO-d 6 ) 3.18-3.35 (4H, m), 3.64 (4H, brs), 6.82 (2H, d, J = 8.4 Hz), 7.21- 7.37 (4H, m), 8.02-8.03 (1H, m), 8.32 (1H, d, J = 2.4 Hz), 9.90 (1H, brs). 
               
               
                 33 
                 —CH 2 — 
                 —CO— 
                 —H 
                 —CO 2 C(CH 3 ) 3   
                 free 
                 (CDCl 3 ) 1.44 (9H, s), 2.93-3.15 (4H, m), 3.32 (2H, t, J = 5.2 Hz), 3.50 (2H, t, J = 5.2 Hz), 3.97 (2H, s), 5.48 (1H, brs), 6.81 (2H, d, J = 8.6 Hz), 7.11 (2H, d, J = 8.6 Hz). 
               
               
                 34 
                 —NH— 
                 —CH 2 — 
                 —CH 3   
                 piperonyl 
                 free 
                 (CDCl 3 ) 2.20 (3H, s), 2.41-2.46 (4H, m), 3.44 (4H, brs), 3.67 (2H, t, J = 4.8 Hz), 3.81 (2H, s), 4.34 (1H, brs), 4.52 (1H, brs), 5.95 (2H, s), 6.37 (1H, dd, J = 8.4 Hz, 2.6 Hz), 6.44 (1H, d, J = 2.8 Hz), 6.64 (1H, d, J = 8.4 Hz), 6.70-6.77 (2H, m), 6.85 (1H, s). 
               
               
                   
               
             
          
         
       
     
       Reference Example 35 
     Production of ethyl(4-hydroxy-3-methylphenylamino)acetate 
       [0682]    Potassium carbonate (5.04 g, 36.5 mmol) was added at room temperature to a solution of 4-amino-o-cresol (3.00 g, 24.4 mmol) and ethyl bromoacetate (2.70 mL, 24.4 mmol) in DMF (30 mL). The resulting solution was stirred at room temperature for 1.5 hours. Water was added to the reaction mixture, and extracted with ethyl acetate. The ethyl acetate layer was washed with brine. The ethyl acetate layer was dried over anhydrous sodium sulfate, and evaporated. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=3:1), to thereby yield 5.10 g of the title compound. 
         [0683]    Appearance: Yellow solid 
         [0684]      1 H NMR (CDCl 3 ) δ 1.28 (3H, t, J=7.1 Hz), 2.19 (3H, s), 3.84 (2H, s), 3.95 (1H, brs), 4.22 (2H, q, J=7.1 Hz), 4.59 (1H, brs), 6.36 (1H, dd, J=8.4 Hz, 2.9 Hz), 6.44 (1H, d, J=2.9 Hz), 6.63 (1H, d, J=8.4 Hz). 
         [0685]    The following compounds were produced in the same manner as in Reference Example 35. 
       Reference Example 36 
     Ethyl(3-hydroxyphenylamino)acetate 
       [0686]      1 H NMR (CDCl 3 ) δ 1.30 (3H, t, J=7.1 Hz), 3.88 (2H, s), 4.25 (2H, q, J=7.1 Hz), 4.29 (1H, brs), 4.85 (1H, s), 6.08-6.10 (1H, m), 6.18-6.24 (2H, m), 7.01-7.07 (1H, m). 
       Reference Example 37 
     Benzyl(4-hydroxy-3-methoxyphenylamino)acetate 
       [0687]      1 H NMR (CDCl 3 ) δ 3.81 (3H, s), 3.92 (2H, brs), 4.01 (1H, brs), 5.09 (1H, brs), 5.20 (2H, s), 6.11 (1H, dd, J==8.4 Hz, 2.6 Hz), 6.23 (1H, d, J=2.6 Hz), 6.76 (1H, d, J=58.4 Hz), 7.31-7.38 (5H, m). 
       Reference Example 38 
     t-Butyl[3-(4-benzyloxy-3-methylphenyl)-2-oxotetrahydropyrimidin-1-yl]acetate 
       [0688]      1 H NMR (CDCl 3 ) δ 1.47 (9H, s), 2.04-2.21 (2H, m), 2.25 (3H, s), 3.45 (2H, t, J=5.9 Hz), 3.67 (2H, t, J=5.9 Hz), 4.04 (2H, s), 5.06 (2H, s), 6.82 (1H, d, J=8.6 Hz), 7.01 (1H, dd, J=2.6 Hz, 8.6 Hz), 7.06-7.12 (1H, m), 7.26-7.48 (5H, m). 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 5 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
                   
               
               
                 Example 
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 109   
                 R 110   
                 R 111   
                 R 112   
                 R 113   
                   1 H NMR (CDCl 3 ) δ ppm or MS 
               
               
                   
               
               
                 39 
                 —CH 3   
                 —CH 3   
                 —H 
                 —H 
                 —H 
                   1 H NMR 1.30 (3H, t, J = 7.1 Hz), 2.14 (3H, s), 2.20 (3H, s), 3.87 (2H, s), 4.24 (2H, q, J = 7.1 Hz), 4.42 (1H, brs), 6.29 (1H, d, J = 8.6 Hz), 6.58 (1H, d, J = 8.6 Hz). 
               
               
                 40 
                 —F 
                 —H 
                 —F 
                 —H 
                 —H 
                   1 H NMR 1.30 (3H, t, J = 7.1 Hz), 3.85 (2H, s), 4.25 (2H, q, J = 7.1 Hz), 4.77 (1H, s), 6.37 (1H, dd, J = 7.9 Hz, 11.8 Hz), 6.73 (1H, dd, J = 7.9 Hz, 11.6 Hz). 
               
               
                 41 
                 —CH 3   
                 —H 
                 —CH 3   
                 —H 
                 —H 
                   1 H NMR 1.30 (3H, t, J = 7.1 Hz), 2.15 (3H, s), 2.19 (3H, s), 3.84 (1H, brs), 3.89 (2H, s), 4.17 (1H, s), 4.25 (2H, q, J = 7.1 Hz), 6.28 (1H, s), 6.57 (1H, s). 
               
               
                 42 
                 —H 
                 —CH 3   
                 —CH 3   
                 —H 
                 —H 
                 MS 223 (M + ) 
               
               
                 43 
                 —OCH 3   
                 —H 
                 —H 
                 —H 
                 —H 
                   1 H NMR 1.29 (3H, t, J = 7.1 Hz), 3.82 (3H, s), 3.85 (2H, s), 4.23 (2H, q, J = 7.1 Hz), 5.26 (1H, brs), 6.11 (1H, dd, J = 8.4 Hz, 2.6 Hz), 6.25 (1H, d, J = 2.6 Hz), 6.76 (1H, d, J = 8.4 Hz). 
               
               
                 44 
                 —F 
                 —H 
                 —H 
                 —H 
                 —H 
                   1 H NMR 1.30 (3H, t, J = 7.1 Hz), 3.83 (2H, s), 4.08 (1H, brs), 4.24 (2H, q, J = 7.1 Hz), 4.62 (1H, d, J = 3.3 Hz), 6.30-6.41 (2H, m), 6.85 (1H, t, J = 8.9 Hz). 
               
               
                 45 
                 —H 
                 —H 
                 —H 
                 —CH 3   
                 —CH 3   
                   1 H NMR 1.20 (3H, t, J = 7.1 Hz), 1.48 (6H, s), 4.15 (2H, q, J = 7.1 Hz), 6.60-6.69 (4H, m). 
               
               
                 46 
                 —CH 3   
                 —H 
                 —H 
                 —CH 3   
                 —H 
                   1 H NMR 1.24 (3H, t, J = 7.3 Hz), 1.44 (3H, d, J = 6.9 Hz), 2.18 (3H, s), 3.80 (1H, brs), 4.03 (1H, q, J = 6.9 Hz), 4.17 (2H, q, J = 7.3 Hz), 4.25 (1H, brs), 6.37 (1H, dd, J = 8.4 Hz, 3.0 Hz), 6.45 (1H, d, J = 2.8 Hz), 6.62 (1H, d, J = 8.4 Hz). 
               
               
                 47 
                 —H 
                 —H 
                 —H 
                 —CH 3   
                 —H 
                   1 H NMR 1.24 (3H, t, J = 7.1 Hz), 1.44 (3H, d, J = 6.7 Hz), 3.88 (1H, brs), 4.04 (1H, q, J = 6.9 Hz), 4.17 (2H, q, J = 7.1 Hz), 4.59 (1H, brs), 6.54 (2H, d, J = 8.9 Hz), 6.68 (2H, d, J = 8.9 Hz). 
               
               
                 48 
                 —CF 3   
                 —H 
                 —H 
                 —H 
                 —H 
                 MS 263 (M + ) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 6 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
                   
               
               
                 Example 
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 114   
                 R 115   
                 R 116   
                 R 117   
                 R 118   
                   1 H NMR (solvent) δ ppm or MS 
               
               
                   
               
               
                 49 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 —H 
                 —H 
                 —H 
                   1 H NMR (DMSO-d 6 ) 1.18 (3H, t, J = 7.1 Hz), 3.89 (2H, d, J = 6.2 Hz), 4.11 (2H, q, J = 7.1 Hz), 6.14 (1H, t, J = 6.2 Hz), 6.62 (2H, d, J = 8.8 Hz), 6.90 (1H, t, J = 9.0 Hz), 6.97 (2H, d, J = 8.8 Hz), 8.03 (1H, dd, J = 2.6 Hz, 9.0 Hz), 8.24 (1H, dd, J = 2.6 Hz, 10.9 Hz). 
               
               
                   
               
               
                 50 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 —H 
                 —F 
                 —CH 3   
                   1 H NMR (CDCl 3 ) 1.29 (3H, t, J = 7.1 Hz), 3.07 (3H, s), 4.03 (2H, s), 4.22 (2H, q, J = 7.1 Hz), 6.22- 6.35 (2H, m), 7.15 (1H, d, J = 9.0 Hz), 8.49 (1H, dd, J = 2.8 Hz, 9.0 Hz), 9.01 (1H, d, J = 2.8 Hz). 
               
               
                   
               
               
                 51 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 —F 
                 —H 
                 —CH 3   
                   1 H NMR (CDCl 3 ) 1.28 (3H, t, J = 7.1 Hz), 3.05 (3H, s), 4.06 (2H, s), 4.20 (2H, q, J = 7.1 Hz), 6.72 (1H, td, J = 2.2 Hz, 9.0 Hz), 6.90 (1H, td, J = 1.8 Hz, 9.4 Hz), 7.11 (1H, d, J = 9.0 Hz), 8.50 (1H, dd, J = 2.7 Hz, 9.0 Hz), 9.02 (1H, d, J = 2.7 Hz). 
               
               
                   
               
               
                 52 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 —H 
                 —H 
                 —SO 2 CH 3   
                   1 H NMR (CDCl 3 ) 1.31 (3H, t, J = 7.1 Hz), 3.17 (3H, s), 4.25 (2H, q, J = 7.1 Hz), 4.47 (2H, s), 7.09 (1H, d, J = 8.9 Hz), 7.20 (2H, d, J = 8.7 Hz), 7.60 (2H, d, J = 8.9 Hz), 8.51 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.03 (1H, d, J = 2.8 Hz). 
               
               
                   
               
               
                 53 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 —H 
                 —H 
                 —SO 2 CH 3   
                   1 H NMR (CDCl 3 ) 1.31 (3H, t, J = 7.1 Hz), 2.16 (3H, s), 3.17 (3H, s), 4.25 (2H, q, J = 7.1 Hz), 4.46 (2H, s), 7.07 (1H, dd, J = 9.1 Hz, 0.7 Hz), 7.08 (1H, d, J = 7.3 Hz), 7.40 (1H, d, J = 2.6 Hz), 7.44 (1H, dd, J = 7.3 Hz, 2.6 Hz), 8.50 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.01 (1H, dd, J = 2.8 Hz, 0.7 Hz). 
               
               
                   
               
               
                 54 
                 —H 
                 —CF 3   
                 —H 
                 —H 
                 —C 2 H 5   
                 MS 291 (M + ) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 7 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 119   
                 R 120   
                 R 121   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 55 
                 4-CF 3 Ph- 
                 —H 
                 —H 
                 1.30 (3H, t, J = 7.1 Hz), 3.89 (2H, d, J = 4.6 Hz), 3.95 (2H, s), 4.20 (1H, brs), 4.25 (2H, q, J = 7.1 Hz), 6.62 (2H, d, J = 8.9 Hz), 6.77 (1H, d, J = 8.4 Hz), 6.97 (2H, d, J = 8.9 Hz), 7.27 (2H, d, J = 7.9 Hz), 7.39 (1H, dd, J = 8.4 Hz, 2.5 Hz), 7.54 (2H, d, J = 7.9 Hz), 8.03 (1H, d, J = 2.5 Hz). 
               
               
                 56 
                 4-CF 3 PhO— 
                 —H 
                 —SO 2 CH 3   
                 1.30 (3H, t, J = 7.1 Hz), 3.15 (3H, s), 4.23 (2H, q, J = 7.1 Hz), 4.45 (2H, s), 5.06 (2H,s), 6.99- 7.04 (3H, m), 7.16 (2H, d, J = 8.9 Hz), 7.54 (2H, d, J = 8.9 Hz), 7.56 (2H, d, J = 9.2 Hz), 7.79-7.83 (1H, m), 8.23 (1H, d, J = 2.0 Hz). 
               
               
                 57 
                 4-CF 3 PhO— 
                 —CH 3   
                 —SO 2 CH 3   
                 1.30 (3H, t, J = 7.1 Hz), 2.19 (3H, s), 3.16 (3H, s), 4.24 (2H, q, J = 7.1 Hz), 4.44 (2H, s), 5.05 (2H, s), 6.96-7.07 (4H, m), 7.36 (1H, dd, J = 8.7 Hz, 2.6 Hz), 7.42 (1H, d, J = 2.3 Hz), 7.56 (2H, d, J = 8.9 Hz), 7.80 (1H, dd, J = 8.6 Hz, 2.3 Hz), 8.20 (1H, d, J = 2.3 Hz). 
               
               
                   
               
               
                 (Ph means a benzene ring having 1 to 4 free valences. Hereinafter Ph indicates the same meaning.) 
               
             
          
         
       
     
       Reference Example 58 
     t-Butyl(3-cyano-4-hydroxyphenylamino)acetate 
       [0689]    MS 248 (M + ) 
       Reference Example 59 
     Production of 2-[4-(2-fluoro-4-nitrophenoxy)phenoxy]-1-(4-piperonylpiperazin-1-yl)ethanone 
       [0690]    Potassium carbonate (0.350 g, 2.53 mmol) was added to a solution of 4-(2-fluoro-4-nitrophenoxy)phenol (0.420 g, 1.69 mmol) and 1-chloroacetyl-4-piperonylpiperazine (0.500 g, 1.70 mmol) in DMF (8 mL). The resulting reaction mixture was stirred for 40 minutes at 100° C. Water was added to the reaction mixture, and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous sodium sulfate, and evaporated, to thereby yield 0.860 of the title compound. 
         [0691]    Appearance: Brown oil 
         [0692]      1 H NMR (CDCl 3 ) δ 2.50-2.60 (4H, m), 3.43 (2H, s), 3.50-3.70 (4H, m), 4.71 (2H, s), 5.95 (2H, s), 6.65-6.75 (2H, m), 6.80-7.05 (6H, m), 7.94 (1H, dd, J=2.3 Hz, 9.1 Hz), 8.06 (1H, dd, J=2.3 Hz, 10.4 Hz). 
         [0693]    The following compound was produced in the same manner as in Reference Example 59. 
       Reference Example 60 
     2-[4-(2-fluoro-4-nitrophenoxy)phenylamino]-1-(4-piperonylpiperazin-1-yl)ethanone 
       [0694]      1 H NMR (DMSO-d 6 ) δ 2.25-2.40 (4H, m), 3.43 (2H, s), 3.45-3.50 (4H, m), 3.90 (2H, d, J=5.1 Hz), 5.75 (1H, t, J=5.1 Hz), 5.99 (2H, s), 6.70-6.75 (3H, m), 6.80-7.00 (5H, m), 8.05 (1H, ddd, J=1.4 Hz, 2.7 Hz, 10.5 Hz), 8.27 (1H, dd, J=2.7 Hz, 11.0 Hz). 
       Reference Example 61 
     Production of methyl 3-(4-benzyloxyphenylamino)-propionate 
       [0695]    Under nitrogen, 4-benzyloxyaniline (13.0 g, 65 mmol) was dissolved by heating at 70° C., and a boron trifluoride-diethyl ether complex (0.82 mL, 6.5 mmol) was added dropwise at the same temperature to the dissolved solution. Methyl acrylate (5.85 mL, 65 mmol) was then slowly added dropwise to the resulting solution. This solution was stirred for 10 hours at 70° C. After cooling with ice, ethyl acetate was added to the reaction mixture and washed with aqueous 1 N sodium hydroxide and brine. The organic layer was dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=5:1), to thereby yield 17.5 g of the title compound. 
         [0696]    Appearance: Brown powder 
         [0697]      1 H NMR (CDCl 3 ) δ 2.60 (2H, t, J=6.4 Hz), 3.39 (2H, t, J=6.4 Hz), 3.69 (3H, s), 3.77 (1H, brs), 4.98 (2H, s), 6.58 (2H, d, J=8.9 Hz), 6.85 (2H, d, J=8.9 Hz), 7.30-7.44 (5H, m). 
       Reference Example 62 
     Production of ethyl 3-(4-Methoxyphenylamino)propionate 
       [0698]    3-(4-hydroxyphenylamino)propionic acid (4.00 g, 20.5 mmol) was added to 48% hydrobromic acid (50 mL), and the resulting solution was stirred for 2.5 hours at 100° C. After concentration under reduced pressure, ethanol (10 mL) was added to the residue, and concentrated under reduced pressure. A saturated sodium bicarbonate solution was added to the residue, and extracted with dichloromethane. The dichloromethane layer was dried over anhydrous sodium sulfate and evaporated. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=2:1), to thereby yield 1.27 g of the title compound. 
         [0699]    Appearance: Yellow oil 
         [0700]      1 H NMR (CDCl 3 ) δ 1.27 (3H, t, J=7.2 Hz), 2.59 (2H, t, J=6.4 Hz), 3.38 (2H, t, J=6.4 Hz), 4.15 (2H, q, J=7.2 Hz), 6.55 (2H, d, J=8.8 Hz), 6.70 (2H, d, J=8.8 Hz). 
       Reference Example 63 
     Production of ethyl[(3-fluoro-4-hydroxyphenyl)methyl-amino]acetate 
       [0701]    Ethyl(3-fluoro-4-hydroxyphenylamino)acetate (1.06 g, 5.1 mmol) was dissolved in methanol (150 mL) and the resulting solution was cooled with ice. To the resulting solution were added aqueous 37% formaldehyde (1.5 mL), sodium triacetoxyborohydride (1 g, 16 mmol) and acetic acid (0.9 mL, 15 mmol), and then stirred at room temperature under a nitrogen atmosphere for 14 hours. The solvent was evaporated under reduced pressure. Water was added to the residue, and the resulting solution was neutralized with a saturated sodium bicarbonate solution and extracted with ethyl acetate. The organic layer was washed with brine, and then dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=1:2), to thereby yield 0.93 g of the title compound. 
         [0702]    Appearance: Light brown oil 
         [0703]      1 H NMR (CDCl 3 ) δ 1.24 (3H, t, J=7.1 Hz), 3.00 (3H, s), 3.98 (2H, s), 4.17 (2H, q, J=7.1 Hz), 4.68 (1H, brs), 6.31-6.52 (2H, m), 6.87 (1H, t, J=8.9 Hz). 
         [0704]    The following compounds were produced in the same manner as in Reference Example 63. 
       Reference Example 64 
     Ethyl(methyl{4-[5-(4-trifluoromethylbenzyl)pyridin-2-yloxy]phenyl}amino)acetate 
       [0705]      1 H NMR (CDCl 3 ) δ 1.25 (3H, t, J=7.1 Hz), 3.07 (3H, s), 3.95 (2H, s), 4.04 (2H, s), 4.18 (2H, q, J=7.1 Hz), 6.69 (2H, d, J=−9.1 Hz), 6.75 (1H, d, J=8.5 Hz), 7.00 (2H, d, J=9.1 Hz), 7.27 (2H, d, J=8.1 Hz), 7.39 (1H, dd, J=8.5 Hz, 2.5 Hz), 7.54 (2H, d, J=8.1 Hz) 8.04 (1H, d, J=2.5 Hz). 
       Reference Example 65 
       [0706]    Ethyl[(4-hydroxy-2-trifluoromethylphenyl)methylamino]-acetate MS 277 (M + ) 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 8 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
                   
               
               
                 Example 
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 122   
                 R 123   
                 R 124   
                 R 125   
                 M 
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 66 
                 —H 
                 —H 
                 —CH 3   
                 —CH 3   
                 1 
                 3.00 (3H, s), 3.71 (3H, s), 4.01 (2H, s), 4.55 (1H, brs), 6.62 (2H, d, J = 9.2 Hz), 6.75 (2H, d, J = 9.2 Hz). 
               
               
                 67 
                 Benzyl 
                 —H 
                 —CH 3   
                 —CH 3   
                 2 
                 2.51-2.57 (2H, m), 2.86 (3H, s), 3.56-3.62 (2H, m) 3 66 (3H, s), 5.00 (2H, s), 6.72 (2H, d, J = 9.1 Hz), 6.91 (2H, d, J = 9.1 Hz), 7.30- 7.45 (5H, m). 
               
               
                 68 
                 —H 
                 —F 
                 —C 2 H 5   
                 —C 2 H 5   
                 1 
                 1.18 (3H, t, J = 7 1 Hz), 1.26 (3H, t, J = 7.1 Hz), 3.38 (2H, q, J = 7.1 Hz) 3.94 (2H, s), 4.19 (2H, q, J = 7.1 Hz), 4.61 (1H, brs), 630-6.35 (1H, m), 6.43 (1H, dd, J = 13.7 Hz, 3.0 Hz), 6.86 (1H, t, J = 8.9 Hz). 
               
               
                 69 
                 —H 
                 —OCH 3   
                 —C 2 H 5   
                 —C 2 H 5   
                 1 
                 1.17 (3H, t, J = 7.1 Hz), 1.25 (3H, t, J = 7.1 Hz), 3.39 (2H, q, J = 7.1 Hz), 3.85 (3H, s), 3 .95 (2H, s) 4.18 (2H, q, J = 7.1 Hz), 5.30 (1H, brs), 6.21 ( 1H, dd, J = 8.6 Hz, 2.8 Hz), 6.33 (1H, d, J = 2.8 Hz), 6.79 (1H, d, J = 8.7 Hz). 
               
               
                   
               
               
                 70 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 —C 2 H 5   
                 —C 2 H 5   
                 1 
                 1.23 (3H, t, J = 7.1 Hz), 1.28 (3H, t, J = 7.1 Hz), 2.08 (3H, s), 3.47 (2H, q, J = 7.1 Hz), 4.01 (2H, s), 4.22 (2H, q, J = 7.1 Hz) 6.40- 6.59 (2H, m), 6.81-7.00 (2H, m), 8.43 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.06 (1H, d, J = 2.8 Hz). 
               
               
                   
               
               
                 71 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 —CH 3   
                 —C 2 H 5   
                 1 
                 1.27 (3H, t, J = 7.1 Hz), 2.10 (3H, s), 3.08 (3H, s), 4.06 (2H, s), 4.21 (2H, q, J = 7.1 Hz), 6.50- 6.62 (2H, m), 6.85-6.99 (2H, m), 8.43 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.05 (1H, d, J = 2.8 Hz). 
               
               
                   
               
               
                 72 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —OCH 3   
                 —CH 3   
                 —C 2 H 5   
                 1 
                 1.27 (3H, t, J = 7.1 Hz), 3.11 (3H, s), 3.74 (3H, s), 4.07 (2H, s), 4.21 (2H, q, J = 7.1 Hz), 6.27 (1H, dd, J = 8.7 Hz, 2.8 Hz), 6.34 (1H, d, J = 2.8 Hz), 6.95-7.01 (2H, m), 8.42 (1H, dd, J = 9.2 Hz, 3.0 Hz), 9.03 (1H, d, J = 2.8 Hz). 
               
               
                   
               
               
                 (M means the number of the methylene groups. Hereinafter M indicates the same meaning.) 
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 9 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
               
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 126   
                 R 127   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 73 
                 —H 
                 —CH 3   
                 2.41 (4H, brs), 2.88 (3H, s), 3.42 (2H, s), 3.50 (2H, brs), 3.60 (2H, brs), 3.94 (2H, s), 5.92 (2H, s), 6.55-6.69 (4H, m), 6.72 (2H, s), 6.82 (1H, s), 7.47 (1H, brs). 
               
               
                 74 
                 —H 
                 —C 2 H 5   
                 1.05 (3H, t, J = 7.1 Hz), 2.44 (4H, brs), 3.25 (2H, q, J = 7.1 Hz), 3.46 (2H, s), 3.60 (4H, brs), 3.91 (2H, s), 5.94 (2H, s), 6.63 (4H, s), 6.72-6.74 (2H, m), 6.82 (1H, s), 7.43 (1H, brs). 
               
               
                   
               
               
                 75 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 2.44 (4H, brs), 3.06 (3H, s), 3.44 (2H, s), 3.49 (2H, brs), 3.63 (2H, brs), 4.11 (2H, s), 5.94 (2H, s), 6.69-6.77 (4H, m), 6.85 (1H, s), 6.92-7.02 (3H, m), 8.41 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.04 (1H, d, J = 3.0 Hz). 
               
               
                   
               
               
                 76 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —C 2 H 5   
                 1.20 (3H, t, J = 7.1 Hz), 2.42-2.46 (4H, m), 3.44- 3.51 (6H, m), 3.64 (2H, q, J = 7.1 Hz), 4.06 (2H, s), 5.95 (2H, s), 6.67 (2H, d, J = 9.2 Hz), 6.74 (2H, brs), 6.85 (1H, brs), 6.94 (1H, d, J = 9.1 Hz), 6.99 (2H, d, J = 9.1 Hz), 8.42 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.05 (1H, d, J = 2.8 Hz). 
               
               
                   
               
             
          
         
       
     
       Reference Example 77 
     Production of 1-(4-piperonylpiperazin-1-yl)-2-[cyclopropyl(4-hydroxyphenyl)amino]ethanone 
       [0707]    To a solution of 1-(4-piperonylpiperazin-1-yl)-2-(4-hydroxyphenylamino)ethanone (1.00 g, 2.7 mmol) in methanol (10 mL) were added acetic acid (1.55 mL, 27 mmol), molecular sieves 3A1/16 (1.00 g), [(1-ethoxycyclopropyl)oxy]trimethylsilane (0.653 mL, 3.2 mmol) and sodium cyanoborohydride (770 mg, 12 mmol). The resulting solution was stirred for 16 hours at 60° C. This reaction solution was filtered and concentrated, and to the residue were added ethyl acetate and water. The aqueous layer was adjusted to pH 10 using aqueous 6 N sodium hydroxide. This layer was stirred for some time, and once insoluble matter had dissolved, the ethyl acetate layer was removed, and washed with aqueous 2 N sodium hydroxide and a saturated sodium bicarbonate solution, then dried over anhydrous magnesium sulfate. The solvent was evaporated, to thereby yield 770 mg of the title compound. 
         [0708]    Appearance: White powder 
         [0709]      1 H NMR (CDCl 3 ) δ 0.54-0.59 (2H, m), 0.72-0.79 (2H, m), 2.39-2.45 (4H, m), 2.70-2.77 (1H, m), 3.44 (2H, s), 3.48-3.51 (2H, m), 3.57-3.60 (2H, m), 4.12 (2H, s), 5.95 (2H, s), 6.62-6.67 (2H, m), 6.74-6.85 (5H, m). 
         [0710]    The following compound was produced in the same manner as in Reference Example 77. 
       Reference Example 78 
     Ethyl{cyclopropyl[3-methyl-4-(5-nitropyridin-2-yloxy)phenyl]amino}acetate 
       [0711]      1 H NMR (CDCl 3 ) δ 0.66-0.72 (2H, m), 0.83-0.89 (2H, m), 1.26 (3H, t, J=7.3 Hz), 2.10 (3H, s), 2.71-2.79 (1H, m), 4.08-4.22 (4H, m), 6.77-6.82 (2H, m), 6.91-6.95 (2H, m), 8.40-8.45 (1H, m), 9.05 (1H, d, J=2.8 Hz). 
       Reference Example 79 
     Production of ethyl[(3-hydroxyphenyl)methylamino]-acetate 
       [0712]    Potassium bicarbonate (1.42 mL, 14.19 mmol) was added to a solution of ethyl(3-hydroxyphenylamino)acetate (2.77 g, 14.19 mmol) in DMF (15 mL). To the resulting solution was further added methyl iodide (1.77 mL, 28.38 mmol), and then stirred at room temperature for 18 hours. To the resulting reaction solution was added brine (150 mL), and the obtained mixture was extracted with ethyl acetate (150 mL). The ethyl acetate layer was dried over anhydrous sodium sulfate, after which solvent was evaporated, to thereby yield 2.48 g of the title compound. 
         [0713]    Appearance: Pale yellow oil 
         [0714]      1 H NMR (CDCl 3 ) δ 1.24 (3H, t, J=7.1 Hz), 3.04 (3H, s), 4.03 (2H, s), 4.18 (2H, q, J=7.1 Hz), 5.17 (1H, brs), 6.17-6.27 (3H, m), 7.04-7.10 (1H, m). 
         [0715]    The following compounds were produced in the same manner as in Reference Example 79. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 10 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
               
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 128   
                 R 129   
                 R 130   
                 R 131   
                   1 H NMR (CDCl 3 ) δ ppm or MS 
               
               
                   
               
               
                 80 
                 —H 
                 —H 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.22 (3H, t, J = 7.1 Hz), 1.43 (3H, d, J = 7.1 Hz), 2.83 (3H, s), 4.16 (2H, q, J = 7.1 Hz), 4.33 (1H, q, J = 7.1 Hz), 4.84 (1H, brs), 6.75 (4H, s). 
               
               
                   
               
               
                 81 
                 —CH 3   
                 —H 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.23 (3H, t, J = 7.3 Hz), 1.42 (3H, d, J = 7.1 Hz), 2.22 (3H, s), 2.82 (3H, s), 4.08-4.21 (2H, m), 4.30 (1H, s), 4.33 (1H, q, J = 7.1 Hz), 6.58 (1H, dd, J = 8.6 Hz, 3.0 Hz), 6.65 (1H, d, J = 2.8 Hz), 6.68 (1H, d, J = 8.6 Hz). 
               
               
                   
               
               
                 82 
                 —OCH 3   
                 —H 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.17 (3H, t, J = 7.1 Hz), 3.39 (2H, q, J = 7.1 Hz), 3.75 (3H, s), 4.00 (2H, brs), 5.11 (1H, brs), 5.15 (2H, s), 6.21 (1H, dd, J = 8.6 Hz, 2.8 Hz), 6.27 (1H, d, J = 2.8 Hz), 6.77 (1H, d, J = 8.6 Hz), 7.27-7.37 (5H, m). 
               
               
                   
               
               
                 83 
                 —F 
                 —H 
                 —F 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.24 (3H, t, J = 7.1 Hz), 2.92 (3H, s), 3.93 (2H, s), 4.15 (2H, q, J = 7.1 Hz), 4.96 (1H, d, J = 2.8 Hz), 6.70 (1H, d, J = 8.2 Hz, 12.9 Hz), 6.77 (1H, d, J = 8.1 Hz, 12.2 Hz). 
               
               
                   
               
               
                 84 
                 —CH 3   
                 —H 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 0.99 (3H, t, J = 7.1 Hz), 1.21 (3H, t, J = 7.1 Hz), 2.18 (3H, s), 2.24 (3H, s), 3.10 (2H, q, J = 7.1 Hz), 3.68 (2H, s), 4.11 (2H, q, J = 7.1 Hz), 4.47 (1H, s), 6.59 (1H, s), 6.94 (1H, s). 
               
               
                   
               
               
                 85 
                 —H 
                 —H 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.26 (3H, t, J = 7.3 Hz), 1.33 (6H, s), 2.80 (3H, s), 4.18 (2H, q, J = 7.3 Hz), 5.15 (1H, brs), 6.71 (2H, d, J = 8.9 Hz), 7.00 (2H, d, J = 8.9 Hz). 
               
               
                   
               
               
                 86 
                 —H 
                 —CH 3   
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 237 (M + ) 
               
               
                   
               
               
                 87 
                 —CH 3   
                 —H 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.24 (3H, t, J = 7.1 Hz), 2.19 (3H, s), 2.24 (3H, s), 2.79 (3H, s), 3.64 (2H, s), 4.15 (2H, q, J = 7.1 Hz), 4.45 (1H, brs), 6.59 (1H, s), 6.89 (1H, s). 
               
               
                   
               
               
                 88 
                 —CF 3   
                 —H 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 277 (M + ) 
               
               
                   
               
               
                 89 
                 —CN 
                 —H 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 262 (M + ) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 11 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
                   
                   
               
               
                 Example 
                   
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 132   
                 R 133   
                 R 134   
                 R 135   
                 R 136   
                 M 
                   1 H NNMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 90 
                 —H 
                 —H 
                 —H 
                 —C 2 H 5   
                 —C 2 H 5   
                 1 
                 1.24 (3H, t, J = 7.1 Hz), 1.28 (3H, t, J = 7.0 Hz), 3.48 (2H, q, J = 7.1 Hz), 4.02 (2H, s), 4.21 (2H, q, J = 7.0 Hz), 6.67 (2H, d, J = 8.9 Hz), 6.95 (1H, d, J = 9.1 Hz), 7.00 (2H, d, J = 8.9 Hz), 8.42 (1H, dd, J = 2.8 Hz, 9.1 Hz), 9.06 (1H, d, J = 2.8 Hz). 
               
               
                 91 
                 —H 
                 —H 
                 —H 
                 —CH 3   
                 —C 2 H 5   
                 1 
                 1.27 (3H, t, J = 7.2 Hz), 3.10 (3H, s), 4.07 (2H, s), 4.20 (2H, q, J = 7.2 Hz), 6.71 (2H, d, J = 9.2 Hz), 6.95 (1H, d, J = 9.1 Hz), 7.02 (2H, d, J = 9.2 Hz), 8.43 (1H, dd, J = 2.8 Hz, 9.1 Hz), 9.05 (1H, d, J = 2.8 Hz). 
               
               
                 92 
                 —F 
                 —H 
                 —H 
                 allyl 
                 —C 2 H 5   
                 1 
                 1.29 (3H, t, J = 7.1 Hz), 4.02 (4H, brs), 4.23 (2H, q, J = 7.1 Hz), 5.21-5.30 (2H, m), 5.84-5.94 (1H, m), 6.40-6.52 (2H, m), 7.01-7.08 (2H, m), 8.47 (1H, dd, J = 8.9 Hz, 2.8 Hz), 9.03 (1H, d, J = 2.6 Hz). 
               
               
                 93 
                 —F 
                 —H 
                 —F 
                 —C 2 H 5   
                 —C 2 H 5   
                 1 
                 1.22 (3H, t, J = 7.1 Hz), 1.27 (3H, t, J = 7.1 Hz), 3.37 (2H, q, J = 7.1 Hz), 4.02 (2H, s), 4.20 (2H, q, J = 7.1 Hz), 6.77 (1H, dd, J = 8.1 Hz, 12.3 Hz), 6.92 (1H, dd, J = 7.3 Hz, 12.7 Hz), 7.09 (1H, d, J = 9.0 Hz), 8.49 (1H, dd, J = 2.8 Hz, 9.0 Hz), 9.02 (1H, d, J = 2.8 Hz). 
               
               
                 94 
                 —F 
                 —F 
                 —H 
                 —CH 3   
                 —C(CH 3 ) 3   
                 0 
                 1.45 (9H, s), 3.26 (3H, s), 6.90-7.11 (2H, m), 7.16 (1H, d, J = 9.0 Hz), 8.53 (1H, dd, J = 2.8 Hz, 9.0 Hz), 9.01 (1H, d, J = 2.8 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 12 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
                   
               
               
                 Example 
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 137   
                 R 138   
                 R 139   
                 Xa 3   
                 Xa 4   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 95 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 piperonyl 
                 none 
                 —CH 2 — 
                 2.44 (8H, brs), 2.96 (2H, s), 3.30 (3H, s), 3.38 (2H, s), 5.92 (2H, s), 6.72 (2H, brs), 6.82 (1H, s), 7.09 (1H, d, J = 9.1 Hz), 7.20 (2H, d, J = 8.9 Hz), 7.29 (2H, d, J = 8.9 Hz), 8.51 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.04 (1H, d, J = 2.8 Hz). 
               
               
                   
               
               
                 96 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 benzyl 
                 none 
                 none 
                 1.55-1.80 (3H, m), 1.81- 2.15 (3H, m), 2.23 (4H, t, J = 5.0 Hz), 3.16 (3H, s), 3.20 (4H, t, J = 5.0 Hz), 3.42 (2H, s), 3.55-3.69 (1H, m), 3.85-4.00 (1H, m), 5.36 (1H, t, J = 3.2 Hz), 6.99 (4H, s), 7.16-7.36 (5H, m). 
               
               
                   
               
               
                 97 
                 —H 
                 —CH 3   
                 piperonyl 
                 —CH 2 — 
                 none 
                 2.18 (3H, s), 2.38-2.42 (4H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 2.89 (3H, s), 3.41 (2H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 3.50 (2H, brs), 3.61 (2H, brs), 
               
               
                   
                   
                   
                   
                   
                   
                 3.95 (2H, brs), 5.93 (2H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 6.44-6.57 (3H, m), 6.73- 
               
               
                   
                   
                   
                   
                   
                   
                 6.76 (2H, m), 6.83 (1H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 13 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
               
               
                 Example 
                   
                   
               
               
                 No. 
                 R 140   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 98 
                 —NO 2   
                 1.07 (3H, t, J = 7.1 Hz), 2.15 (3H, s), 3.38 (3H, s), 4.19 (2H, q, 
               
               
                   
                   
                 J = 7.1 Hz), 7.06-7.20 (4H, m), 8.51 (1H, dd, J = 9.1 Hz, 2.8 
               
               
                   
                   
                 Hz), 8.97 (1H, d, J = 2.8 Hz). 
               
               
                 99 
                 4-CF 3 PhOCH 2 — 
                 1.07 (3H, t, J = 7.1 Hz), 2.18 (3H, s), 3.36 (3H, s), 4.08 (2H, q, 
               
               
                   
                   
                 J = 7.1 Hz), 5.04 (2H, s), 6.97 (1H, d, J = 8.6 Hz), 7.01- 
               
               
                   
                   
                 7.13 (4H, m), 7.16 (1H, d, J = 2.3 Hz), 7.57 (2H, d, J = 8.6 
               
               
                   
                   
                 Hz), 7.80 (1H, dd, J = 8.6 Hz, 2.3 Hz), 8.17 (1H, d, J = 2.3 
               
               
                   
                   
                 Hz). 
               
               
                   
               
             
          
         
       
     
       Reference Example 100 
     Production of ethyl[acetyl(3-fluoro-4-hydroxyphenyl)amino]acetate 
       [0716]    Ethyl(3-fluoro-4-hydroxyphenylamino)acetate (0.84 g, 4 mmol) was dissolved in N,N-dimethylacetamide (4 mL). To the resulting solution was added acetyl chloride (0.6 mL, 10 mmol), and the resulting solution was stirred at room temperature for 1 hour. Water (1 mL), methanol (10 mL) and saturated sodium carbonate (10 mL) were added, and the mixture was stirred at room temperature for 1 hour. Water was added to the solution. 10% hydrochloric acid was employed to turn the solution acidic, and then the solution was extracted with ethyl acetate. The organic layer was washed with water and brine, then dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (ethyl acetate: n-hexane 2:1), to thereby yield 0.84 g of the title compound. 
         [0717]    Appearance: Colorless powder 
         [0718]      1 H NMR (CDCl 3 ) δ 1.28 (3H, t, J=7.3 Hz), 1.94 (3H, s), 4.20 (2H, q, J=7.3 Hz), 4.32 (2H, s), 6.02 (1H, brs), 6.99-7.07 (2H, m), 7.13-7.18 (1H, m). 
         [0719]    The following compounds were produced in the same manner as in Reference Example 100. 
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 14 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 141   
                 R 142   
                 M 
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 101 
                 —H 
                 —CH 3   
                 1 
                 1.26 (3H, t, J = 7.1 Hz), 1.92 (3H, s), 
               
               
                   
                   
                   
                   
                 2.24 (3H, s), 4.19 (2H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 4.32 (2H, s), 5.38 (1H, brs), 6.78 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 8.4 Hz), 7.04 (1H, dd, J = 8.4 Hz, 
               
               
                   
                   
                   
                   
                 2.5 Hz), 7.10 (1H, d, J = 2.5 Hz). 
               
               
                 102 
                 —H 
                 —H 
                 2 
                 1.21 (3H, t, J = 7.2 Hz), 1.83 (3H, s), 
               
               
                   
                   
                   
                   
                 2.56 (2H, t, J = 7.4 Hz), 3.97 (2H, t, J = 
               
               
                   
                   
                   
                   
                 7.4 Hz), 4.06 (2H, q, J = 7.2 Hz), 
               
               
                   
                   
                   
                   
                 6.05 (1H, brs), 6.87 (2H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                 7.03 (2H, d, J = 8.7 Hz). 
               
               
                 103 
                 benzyl 
                 —H 
                 1 
                 1.26 (3H, t, J = 7.1 Hz), 1.91 (3H, s), 
               
               
                   
                   
                   
                   
                 4.18 (2H, q, J = 7.1 Hz), 4.33 (2H, s), 
               
               
                   
                   
                   
                   
                 5.07 (2H, s), 6.98 (2H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                 7.26 (2H, d, J = 8.9 Hz), 7.35-7.45 
               
               
                   
                   
                   
                   
                 (5H, m). 
               
               
                   
               
               
                 104 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 1 
                 1.24 (3H, t, J = 7.1 Hz), 1.89 (3H, s), 4.15 (2H, q, J = 7.1 Hz), 4.32 (2H, s), 6.95 (2H, d, J = 8.9 Hz), 7.12 (1H, t, J = 9.0 Hz), 7.27-7.32 (3H, m), 7.52- 7.60 (1H, m), 7.70-7.80 (2H, m), 7.99 (1H, s), 8.05 (1H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 15 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
               
               
                 Example 
                   
                   
               
               
                 No. 
                 R 143   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 105 
                 —C 2 H 5   
                 1.09 (3H, t, J = 7.4 Hz), 2.20 (2H, q, J = 7.4 Hz), 2.40-2.45 (4H, m), 
               
               
                   
                   
                 3.43 (4H, brs), 3.61 (2H, brs), 4.47 (2H, s), 5.94 (2H, s), 6.70-6.76 (2H, 
               
               
                   
                   
                 m), 6.84 (1H, s), 7.08 (1H, d, J = 9.0 Hz), 7.19 (2H, d, J = 8.7 Hz), 
               
               
                   
                   
                 7.52 (2H, d, J = 8.7 Hz), 8.51 (1H, dd, J = 2.8 Hz, 9.0 Hz), 9.04 (1H, 
               
               
                   
                   
                 d, J = 2.8 Hz). 
               
               
                 106 
                 —CH 2 Cl 
                 2.40-2.48 (4H, m), 3.43 (4H, s), 3.62 (2H, brs), 3.97 (2H, s), 4.49 (2H, 
               
               
                   
                   
                 s), 5.95 (2H, s), 6.70-6.77 (2H, m), 6.84 (1H, s), 7.11 (1H, d, J = 9.0 
               
               
                   
                   
                 Hz), 7.23 (2H, d, J = 8.7 Hz), 7.59 (2H, d, J = 8.7 Hz), 8.52 (1H, dd, 
               
               
                   
                   
                 J = 2.8 Hz, 9.0 Hz), 9.04 (1H, d, J = 2.8 Hz). 
               
               
                 107 
                 cyclopropyl 
                 0.65-1.52 (5H, m), 2.43 (4H, brs), 3.43 (4H, brs), 3.61 (2H, brs), 
               
               
                   
                   
                 4.50 (2H, brs), 5.95 (2H, s), 6.72-6.75 (2H, m), 6.84 (1H, s), 7.08 (1H, 
               
               
                   
                   
                 d, J = 9.1 Hz), 7.20 (1H, d, J = 8.8 Hz), 7.59 (2H, d, J = 8.8 Hz), 
               
               
                   
                   
                 8.50 (1H, dd, J = 2.9 Hz, 9.1 Hz), 9.04 (1H, d, J = 2.9 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 16 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
               
               
                 Example 
                   
                   
               
               
                 No. 
                 R 144   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 108 
                 —H 
                 1.44 (3H, t, J = 7.1 Hz), 4.43 (2H, q, J = 7.1 Hz), 5.05 (2H, s), 6.93 (1H, d, 
               
               
                   
                   
                 J = 8.6 Hz), 7.02 (2H, d, J = 8.6 Hz), 7.17 (2H, d, J = 8.9 Hz), 7.56 (2H, 
               
               
                   
                   
                 d, J = 8.4 Hz), 7.69 (2H, d, J = 8.9 Hz), 7.79 (1H, dd, J = 8.4 Hz, 2.5 Hz), 
               
               
                   
                   
                 8.22 (1H, d, J = 2.5 Hz), 8.90 (1H, brs). 
               
               
                 109 
                 —CH 3   
                 1.44 (3H, t, J = 7.1 Hz), 2.19 (3H, s), 4.43 (2H, q, J = 7.1 Hz), 5.03 (2H, 
               
               
                   
                   
                 s), 6.94 (1H, d, J = 8.4 Hz), 7.02 (2H, d, J = 8.4 Hz), 7.07 (1H, d, J = 8.6 
               
               
                   
                   
                 Hz), 7.51-7.58 (4H, m), 7.78 (1H, dd, J = 8.6 Hz, 2.5 Hz), 8.20 (1H, d, J = 
               
               
                   
                   
                 2.5 Hz), 8.84 (1H, brs). 
               
               
                   
               
             
          
         
       
     
       Reference Example 110 
     Production of (6-chloropyridin-3-yl)(4-trifluoromethylphenyl)methanone 
       [0720]    Under an argon gas flow, half of a solution of 4-bromobenzotrifluoride (1.20 g, 5.33 mmol) in THF (6 mL) was added to magnesium (156 mg, 6.41 mmol). The resulting solution was stirred, and further 1,2-dibromoethane (3 drops) was added. Once the reaction began, the balance of the 4-bromobenzotrifluoride in THF solution was added dropwise, and once dropping had finished, the resulting solution was stirred for 30 minutes at 60° C. A solution of 6-chloro-N-methoxy-N-methylnicotinamide (990 mg, 5.36 mmol) in THF (3 mL) was charged into a separate reaction vessel, into which the above reaction solution was added dropwise under an argon gas flow and ice cooling. After dropping had finished, the resulting solution was stirred for 30 minutes at room temperature, and then heated to reflux for 1 hour. The reaction solution was cooled with ice, then aqueous ammonium chloride and water were added. The resulting solution was extracted with ethyl acetate, and washed with brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=10:1), to thereby yield 610 mg of the title compound. 
         [0721]    Appearance: White powder 
         [0722]      1 H NMR (CDCl 3 ) δ 7.52 (1H, d, J=8.3 Hz), 7.80 (2H, d, J=8.0 Hz), 7.90 (2H, d, J=8.0 Hz), 8.11 (1H, dd, J=8.3 Hz, 2.0 Hz), 8.77 (1H, d, J=2.0 Hz). 
       Reference Example 111 
     Production of ethyl 3-[4-(4-nitrophenoxy)phenyl]-propionate 
       [0723]    To a solution of ethyl 3-(4-hydroxyphenyl)-propionate (6.00 g, 30.9 mmol) in DMF (60 mL) were added 4-fluoronitrobenzene (6.54 g, 46.3 mmol) and potassium carbonate (5.12 g, 37.1 mmol). The resulting reaction solution was stirred for 1 hour at 80° C. To the reaction solution was added water and extracted with ethyl acetate. The resulting ethyl acetate layer was washed with water and then with brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=5:1), to thereby yield 9.64 g of the title compound. 
         [0724]    Appearance: Pale yellow oil 
         [0725]      1 H NMR (CDCl 3 ) δ 1.23 (3H, t, J=7.1 Hz), 2.62 (2H, t, J=7.7 Hz), 2.96 (2H, t, J=7.7 Hz), 4.12 (2H, q, J=7.1 Hz), 6.93-7.06 (4H, m), 7.24 (2H, d, J=8.5 Hz), 8.17 (2H, d, J=9.2 Hz). 
         [0726]    The following compounds were produced in the same manner as in Reference Example 111. 
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 17 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
               
               
                 Example 
                   
                   
               
               
                 No. 
                 R 145   
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 112 
                 -Ac 
                 (DMSO-d 6 ) 2.58(3 H, s), 7.26(2 H, d, J = 8.8 Hz), 7.40(1 H, t, J = 
               
               
                   
                   
                 8.4 Hz), 8.04(2 H, d, J = 8.8 Hz), 8.15(1 H, ddd, J = 1.4 Hz, 
               
               
                   
                   
                 2.6 Hz, 8.4 Hz), 8.39(1 H, dd, J = 2.6 Hz, 10.7 Hz). 
               
               
                 113 
                 —CH 2 COOCH 3   
                 (DMSO-d 6 ) 3.63(3 H, s), 3.72(2 H, s), 7.11-7.17(3 H, m), 
               
               
                   
                   
                 7.38(2 H, d, J = 8.4 Hz), 8.09(1 H, ddd, J = 1.4 Hz, 2.7 Hz, 9.1 
               
               
                   
                   
                 Hz), 8.33(1 H, dd, J = 2.7 Hz, 10.2 Hz). 
               
               
                 114 
                 —(CH 2 ) 2 COOC 2 H 5   
                 (CDCl 3 ) 1.22(3 H, t, J = 7.1 Hz), 2.62(2 H, t, J = 7.6 Hz), 
               
               
                   
                   
                 2.96(2 H, t, J = 7.6 Hz), 4.12(2 H, q, J = 7.1 Hz), 6.92(1 H, dd, 
               
               
                   
                   
                 J = 9.0 Hz, 8.0 Hz), 6.99(2 H, d, J = 8.6 Hz), 7.24(2 H, d, J = 
               
               
                   
                   
                 8.6 Hz), 7.90-8.00(1 H, m), 8.06(1 H, dd, J = 10.3 Hz, 2.7 Hz). 
               
               
                 115 
                 —NHAc 
                 (DMSO-d 6 ) 2.05(3 H, s), 7.07(1 H, t, J = 8.6 Hz), 7.16(2 H, d, J = 
               
               
                   
                   
                 9.0 Hz), 7.67(2 H, d, J = 9.0 Hz), 8.06(1 H, ddd, J = 1.4 Hz, 
               
               
                   
                   
                 2.7 Hz, 8.6 Hz), 8.31(1 H, dd, 2.7 Hz, 10.9 Hz), 10.06(1 H, s). 
               
               
                 116 
                 —SCH 2 COOC 2 H 5   
                 (CDCl 3 ) 1.24(3 H, t, J = 7.1 Hz), 3.62(2 H, s), 4.18(2 H, q, J = 
               
               
                   
                   
                 7.1 Hz), 6.95-7.05(3 H, m), 7.49(2 H, d, J = 8.8 Hz), 8.00(1 H, 
               
               
                   
                   
                 ddd, J = 1.5 Hz, 2.6 Hz, 9.1 Hz), 8.08(1 H, dd, J = 2.6 Hz, 
               
               
                   
                   
                 10.2 Hz). 
               
               
                 117 
                 —OCH 3   
                 (DMSO-d 6 ) 3.77(3 H, s), 6.90-7.10(3 H, m), 7.16(2 H, d, J = 9.1 
               
               
                   
                   
                 Hz), 8.03(1 H, ddd, J = 1.4 Hz, 2.6 Hz, 9.2 Hz), 8.27(1 H, dd, J = 
               
               
                   
                   
                 2.6 Hz, 10.9 Hz). 
               
               
                 118 
                 —H 
                 (CDCl 3 ) 6.95(1 H, dd, J = 9.0 Hz, 8.0 Hz), 7.07(2 H, d, J = 7.9 
               
               
                   
                   
                 Hz), 7.24(2 H, t, J = 7.9 Hz), 7.42(2 H, t, J = 7.9 Hz), 
               
               
                   
                   
                 7.91-8.02(1 H, m), 8.07(1 H, dd, J = 10.3 Hz, 2.7 Hz). 
               
               
                 119 
                 —(CH 2 ) 3 COOC 2 H 5   
                 (CDCl 3 ) 1.25(3 H, t, J = 7.1 Hz), 1.88-2.03(2 H, m), 2.32(2 H, t, 
               
               
                   
                   
                 J = 7.4 Hz), 2.66(2 H, t, J = 7.4 Hz), 4.12(2 H, q, J = 7.1 Hz), 
               
               
                   
                   
                 6.91(1 H, dd, J = 9.0 Hz, 8.0 Hz), 6.99(2 H, d, J = 8.5 Hz), 
               
               
                   
                   
                 7.22(2 H, d, J = 8.5 Hz), 7.91-7.98(1 H, m), 8.06(1 H, dd, J = 
               
               
                   
                   
                 10.3 Hz, 2.7 Hz) 
               
               
                 120 
                 —CHO 
                 (DMSO-d 6 ) 7.33(2 H, d, J = 8.7 Hz), 7.47(1 H, t, J = 9.0 Hz), 
               
               
                   
                   
                 8.00(2 H, d, J = 8.7 Hz), 8.16(1 H, ddd, J = 1.4 Hz, 2.7 Hz, 9.0 
               
               
                   
                   
                 Hz), 8.40(1 H, dd, J = 2.7 Hz, 10.6 Hz), 9.99(1 H, s). 
               
               
                 121 
                 —COOC 2 H 5   
                 (DMSO-d 6 ) 1.32(3 H, t, J = 7.1 Hz), 4.31(2 H, q, J = 7.1 Hz), 
               
               
                   
                   
                 7.26(2 H, d, J = 8.9 Hz), 7.41(1 H, t, J = 8.4 Hz), 8.03(2 H, d, J = 
               
               
                   
                   
                 8.9 Hz), 8.14(1 H, ddd, J = 1.4 Hz, 2.6 Hz, 8.4 Hz), 8.39(1 H, 
               
               
                   
                   
                 dd, J = 2.6 Hz, 10.6 Hz). 
               
               
                   
               
               
                 (Ac means an acetyl group. Hereinafter Ac indicates the same meaning.) 
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 18 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
               
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 146   
                 R 147   
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 122 
                 4-NO 2   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (DMSO-d 6 ) 1.33(3 H, t, J = 7.1 Hz), 4.32(2 H, q, J = 7.1 Hz), 7.24-7.31(4 H, m), 8.05(2 H, d, J = 8.9 Hz), 8.29(2 H, d,J = 9.3 Hz). 
               
               
                   
               
               
                 123 
                 4-NO 2   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 3.10(3 H, s), 3.75(3 H, s), 4.10(2 H, s), 6.71(2 H, d, J = 9.2 Hz), 6.96(2 H, d, J = 9.2 Hz), 6.98(2 H, d, J = 9.2 Hz), 8.17(2 H, d, J = 9.2 Hz). 
               
               
                   
               
               
                 124 
                 2-NO 2   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 1.22(3 H, t, J = 7.1 Hz), 2.60(2 H, t, J = 7.7 Hz), 2.93(2 H, t, J = 7.7 Hz), 4.11(2 H, q, J = 7.1 Hz), 6.92-6.99(3 H, m), 7.13-7.23(3 H, m), 7.45(1 H, dt, J = 1.6 Hz, 8.2 Hz), 7.92(1 H, dd, J = 8.2 Hz, 1.6 Hz). 
               
               
                   
               
               
                 125 
                 4-NO 2   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 1.50(9 H, s), 2.53(2 H, brs), 3.66(2 H, m), 4.10 (2 H, brs), 6.05(1 H, brs), 7.02(2 H, d, J = 9.0 Hz), 7.06 (2 H, d, J = 8.5 Hz), 7.43(2 H, d, J = 8.5 Hz), 8.21(2 H, d, J = 9.0 Hz). 
               
               
                   
               
               
                 126 
                 4-NO 2   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 1.21(3 H, t, J = 7.1 Hz), 2.61(2 H, t, J = 7.7 Hz), 2.95(2 H, t, J = 7.7 Hz), 4.10(2 H, q, J = 7.1 Hz), 6.88-6.94(2 H, m), 6.98(2 H, d, J = 9.2 Hz), 7.08(1 H, d, J = 7.6 Hz), 7.32(1 H, t, J = 7.6 Hz), 8.18(2 H, d, J = 9.2 Hz). 
               
               
                   
               
               
                 127 
                 4-NO 2   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 2.58(2 H, t, J = 7.7 Hz), 2.87(2 H, t, J = 7.7 Hz), 3.62(3 H, s), 6.89-7.01(3 H, m), 7.13-7.37(3 H, m), 8.18(2 H, d, J = 9.2 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 19 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 148   
                 R 149   
                 R 150   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 128 
                 —H 
                 —H 
                 —C 2 H 5   
                 1.41(3 H, t, J = 7.3 Hz), 4.40(2 H, q, J = 7.3 Hz), 
               
               
                   
                   
                   
                   
                 7.09(1 H, d, J = 8.9 Hz), 7.22-7.26(2 H, m), 
               
               
                   
                   
                   
                   
                 8.14-8.17(2 H, m), 8.52(1 H, dd, J = 8.9 Hz, 3.0 Hz), 9.04(1 H, 
               
               
                   
                   
                   
                   
                 d, J = 3.0 Hz). 
               
               
                 129 
                 —H 
                 —H 
                 —CH 3   
                 3.94(3 H, s), 7.10(1 H, d, J = 8.9 Hz), 7.22-7.26(2 H, m), 
               
               
                   
                   
                   
                   
                 8.13-8.16(2 H, m), 8.52(1 H, dd, J = 8.9 Hz, 2.7 Hz), 
               
               
                   
                   
                   
                   
                 9.04(1 H, d, J = 2.7 Hz). 
               
               
                 130 
                 —F 
                 —H 
                 —CH 3   
                 3.95(3 H, s), 7.18(1 H, d, J = 8.8 Hz), 7.29-7.35(1 H, m), 
               
               
                   
                   
                   
                   
                 7.87-7.96(2 H, m), 8.54(1 H, dd, J = 8.8 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                   
                 8.99(1 H, d, J = 2.6 Hz). 
               
               
                 131 
                 —F 
                 —H 
                 —C 2 H 5   
                 1.41(3 H, t, J = 7.1 Hz), 4.41(2 H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 7.18(1 H, d, J = 9.1 .Hz), 7.29-7.35(1 H, m), 7.88-7.96(2 
               
               
                   
                   
                   
                   
                 H, m), 8.54(1 H, dd, J = 9.1 Hz, 2.8 Hz), 8.99(1 H, 
               
               
                   
                   
                   
                   
                 d, J = 2.8 Hz). 
               
               
                 132 
                 —CH 3   
                 —H 
                 —CH 3   
                 2.21(3 H, s), 3.93(3 H, s), 7.08-7.15(2 H, m), 7.97(1 H, dd, 
               
               
                   
                   
                   
                   
                 J = 8.4 Hz, 2.2 Hz), 8.02(1 H, d, J = 2.2 Hz), 8.52(1 H, 
               
               
                   
                   
                   
                   
                 dd, J = 8.9 Hz, 2.7.Hz), 9.01(1 H, d, J = 2.7 Hz). 
               
               
                 133 
                 —OCH 3   
                 —H 
                 —C 2 H 5   
                 1.41(3 H, t, J = 7.1 Hz), 3.80(3 H, s), 4.40(2 H, q, J = 7.1 
               
               
                   
                   
                   
                   
                 Hz), 7.09(1 H, d, J = 8.9 Hz), 7.21(1 H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                 7.71-7.77(2 H, m), 8.49(1 H, dd, J = 8.9 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                   
                 8.97(1 H, a, J = 2.8 H). 
               
               
                 134 
                 —H 
                 —OCH 3   
                 —CH 3   
                 3.90(3 H, s), 3.91(3 H, s), 6.77-6.81(2 H, m), 7.11(1 H, dd, 
               
               
                   
                   
                   
                   
                 J = 9.1 Hz, 0.5 Hz), 7.91-7.95(1 H, m), 8.53(1 H, dd, J = 
               
               
                   
                   
                   
                   
                 9.1 Hz, 2.7 Hz), 9.06(1 H, d, J = 2.7 Hz). 
               
               
                 135 
                 —H 
                 —CH 3   
                 —CH 3   
                 2.64(3 H, s), 3.91(3 H, s), 7.02-7.10(3 H, m), 8.03- 
               
               
                   
                   
                   
                   
                 8.06(1 H, m), 8.52(1 H, dd, J = 8.9 Hz, 2.7 Hz), 9.05(1 H, 
               
               
                   
                   
                   
                   
                 dd, J = 2.7 Hz, 0.5 Hz). 
               
               
                 136 
                 —Cl 
                 —H 
                 —CH 3   
                 3.95(3 H, s), 7.17-7.20(1 H, m), 7.31(1 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                 8.03-8.07(1 H, m), 8.20(1 H, a, J = 2.0 Hz), 8.55(1 H, dd, 
               
               
                   
                   
                   
                   
                 J = 9.1 Hz, 2.8 Hz), 8.98(1 H, dd, J = 2.8 Hz, 0.5 Hz). 
               
               
                 137 
                 —F 
                 —F 
                 —CH 3   
                 3.97(3 H, s), 7.06-7.16(1 H, m), 7.21(1 H, dd, J = 0.3 Hz, 
               
               
                   
                   
                   
                   
                 9.0 Hz), 7.77-7.88(1 H, m), 8.56(1 H, dd, J = 2.8 Hz, 9.0 
               
               
                   
                   
                   
                   
                 Hz), 8.99(1 H, dd, J = 0.3 Hz, 2.8 Hz) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 20 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 151   
                 R 152   
                 M 
                   1 H NMR (CD Cl 3 ) δ ppm 
               
               
                   
               
               
                 138 
                 —H 
                 —CH 3   
                 2 
                 2.64-2.70(2 H, m), 2.97-3.02(2 H, m), 3.69(3 H, s), 
               
               
                   
                   
                   
                   
                 7.01-7.10(3 H, m), 7.26-7.30(2 H, m), 8.47(1 H, dd, J = 8.9 Hz, 
               
               
                   
                   
                   
                   
                 2.6 Hz), 9.04(1 H, d, J = 2.6 Hz). 
               
               
                 139 
                 —OCH 3   
                 —C 2 H 5   
                 2 
                 1.26(3 H, t, J = 7.1. Hz), 2.67(2 H, t, J = 7.5 Hz), 2.99(2 H, 
               
               
                   
                   
                   
                   
                 t, J = 7.5 Hz), 3.74(3 H, s), 4.16(2 H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 6.76-6.91(2 H, m), 7.02(1 H, d, J = 9.1 Hz), 7.06(1 H, d, J = 8.0 
               
               
                   
                   
                   
                   
                 Hz), 8.45(1 H, dd, J = 9.1 Hz, 2.6 Hz), 9.01(1 H, d, J = 2.6 
               
               
                   
                   
                   
                   
                 Hz). 
               
               
                 140 
                 —H 
                 —CH 3   
                 1 
                 3.67(2 H, s), 3.72(3 H, s), 7.04(1 H, d, J = 8.9 Hz), 7.12(2 H, 
               
               
                   
                   
                   
                   
                 d, J = 8.6 Hz), 7.38(2 H, d, J = 8.6 Hz), 8.45-8.50(1 H, m), 
               
               
                   
                   
                   
                   
                 9.04(1 H, d, J = 3.0 Hz). 
               
               
                 141 
                 —H 
                 —C 2 H 5   
                 2 
                 1.23(3 H, t, J = 7.1 Hz), 2.63(2 H, t, J = 7.8 Hz), 2.97(2 H, 
               
               
                   
                   
                   
                   
                 t, J = 7.8 Hz), 4.11(2 H, q, J = 7.1 Hz), 7.00(1 H, d, J = 9.1 
               
               
                   
                   
                   
                   
                 Hz), 7.06(2 H, d, J = 8.5 Hz), 7.26(2 H, d, J = 8.5 Hz), 
               
               
                   
                   
                   
                   
                 8.45(1 H, dd, J = 9.1 Hz, 2.8 Hz), 9.02(1 H, d, J = 2.8 Hz). 
               
               
                 142 
                 —OCH 3   
                 —CH 3   
                 2 
                 2.66-2.71(2 H, m), 2.97-3.02(2 H, m), 3.70(3 H, s), 3.74(3 H, 
               
               
                   
                   
                   
                   
                 s), 6.83-6.88(2 H, m), 7.01-7.08(2 H, m), 8.45(1 H, dd, J = 
               
               
                   
                   
                   
                   
                 9.1 Hz, 2.8 Hz), 9.01(1 H, d, J = 2.8 Hz). 
               
               
                 143 
                 —OC 2 H 5   
                 —C 2 H 5   
                 2 
                 1.15(3 H, t, J = 7.0 Hz), 1.26(3 H, t, J = 7.1 Hz), 2.53- 
               
               
                   
                   
                   
                   
                 2.72(2 H, m), 2.87-3.05(2 H, m), 3.98(2 H, q, J = 7.0 Hz), 
               
               
                   
                   
                   
                   
                 4.15(2 H, q, J = 7.1 Hz), 6.73-6.93(2 H, m), 7.02(1 H, d, J = 
               
               
                   
                   
                   
                   
                 9.0 Hz), 7.07(1 H, d, J = 8.0 Hz), 8.45(1 H, dd, J = 9.0 Hz, 
               
               
                   
                   
                   
                   
                 2.8 Hz), 9.01(1 H, d, J = 2.8 Hz). 
               
               
                 144 
                 —F 
                 —C 2 H 5   
                 2 
                 1.26(3 H, t, J = 7.1 Hz), 2.57-2.71(2 H, m), 2.89-3.06(2 H, 
               
               
                   
                   
                   
                   
                 m), 4.15(2 H, q, J = 7.1 Hz), 6.98-7.21(4 H, m), 8.50(1 H, 
               
               
                   
                   
                   
                   
                 dd, J = 9.0 Hz, 2.8 Hz), 9.01(1 H, d, J = 2.8 Hz). 
               
               
                 145 
                 —H 
                 —C 2 H 5   
                 4 
                 1.26(3 H, t, J = 7.3 Hz), 1.60-1.80(4 H, m), 2.30-2.40(2 H, 
               
               
                   
                   
                   
                   
                 m), 2.60-2.75(2 H, m), 4.13(2 H, q, J = 7.3 Hz), 7.01(1 H, d, 
               
               
                   
                   
                   
                   
                 J = 9.0 Hz), 7.06(2 H, d, J = 8.6 Hz), 7.25(2 H, d, J = 8.6 
               
               
                   
                   
                   
                   
                 Hz), 8.46(1 H, dd, J = 9.0 Hz, 3.0 Hz), 9.04(1 H, d, J = 3.0 
               
               
                   
                   
                   
                   
                 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 21 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 153   
                 R 154   
                 M 
                   1 H NMR (CDCl 3 ) δ ppm or MS 
               
               
                   
               
               
                 146 
                 —CH 3   
                 —H 
                 1 
                   1 H NMR 1.32(3 H, t, J = 7.1 Hz), 2.08(3 H, s), 3.90(2 H, d, J = 
               
               
                   
                   
                   
                   
                 5.3 Hz), 4.15-4.39 (3 H, m), 6.39-6.59(2 H, m), 6.81-7.01(2 
               
               
                   
                   
                   
                   
                 H, m), 8.44(1 H, dd, J = 9.1 Hz, 2.8 Hz), 9.05(1 H, dd, 
               
               
                   
                   
                   
                   
                 J = 2.8 Hz, 0.4 Hz). 
               
               
                 147 
                 —CH 3   
                 -Ac 
                 1 
                   1 H NMR 1.29(3 H, t, J = 7.1 Hz), 1.99(3 H, s), 2.17(3 H, s), 
               
               
                   
                   
                   
                   
                 4.22(2 H, q, J = 7.1 Hz), 4.38(2 H, s), 7.05-7.12(2 H, m), 
               
               
                   
                   
                   
                   
                 7.22-7.28(2 H, m), 7.31(1 H, s), 8.50(1 H, d, J = 9.0 Hz), 
               
               
                   
                   
                   
                   
                 9.01(1 H, s). 
               
               
                 148 
                 —H 
                 —H 
                 1 
                   1 H NMR 1.32(3 H, t, J = 7.1 Hz), 3.91(2 H, d, J = 5.4 Hz),  
               
               
                   
                   
                   
                   
                 4.27(2 H, q, J = 7.1 Hz), 4.37(1 H, t, J = 5.4 Hz), 6.66(2 H, 
               
               
                   
                   
                   
                   
                 d, J = 8.9 Hz), 6.96(1 H, d, J = 9.1 Hz), 6.98(2 H, d, J = 8.9 
               
               
                   
                   
                   
                   
                 Hz), 8.43(1 H, dd, J = 2.8 Hz, 9.1 Hz), 9.05(1 H, d, J = 2.8 
               
               
                   
                   
                   
                   
                 Hz). 
               
               
                 149 
                 —H 
                 -Ac 
                 2 
                   1 H NMR 1.23(3 H, t, J = 7.1 Hz), 1.90(3 H, s), 2.62(2 H, t, J = 
               
               
                   
                   
                   
                   
                 7.3 Hz), 4.03(2 H, t, J = 7.3 Hz), 4.08(2 H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 7.10(1 H, d, J = 9.0 Hz), 7.21-7.28(4 H, m), 8.52(1 H, dd, J = 
               
               
                   
                   
                   
                   
                 2.8 Hz, 9.0 Hz), 9.04(1 H, d, J = 2.8 Hz). 
               
               
                 150 
                 —F 
                 —C 2 H 5   
                 1 
                   1 H NMR 1.21-1.32(6 H, m), 3.47(2 H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 4.01(2 H, s), 4.23(2 H, q, J = 7.1 Hz), 6.38-6.49(2 H, m), 
               
               
                   
                   
                   
                   
                 7.01-7.07(2 H, m), 8.46(1 H, dd, J = 9.1 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                   
                 9.03(1 H, d, J = 2.8 Hz). 
               
               
                 151 
                 —OCH 3   
                 —C 2 H 5   
                 1 
                   1 H NMR 1.25(3 H, t, J = 7.1 Hz), 1.28(3 H, t, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 3.50(2 H, q, J = 7.1 Hz), 3.72(3 H, s), 4.03(2 H, s), 4.22(2 H, 
               
               
                   
                   
                   
                   
                 q, J = 7.1 Hz), 6.23(1 H, dd, J = 8.9 Hz, 2.8 Hz), 6.30(1 H, 
               
               
                   
                   
                   
                   
                 d, J = 2.6 Hz), 6.95-6.99(2 H, m), 8.42(1 H, dd, J = 9.1 Hz, 
               
               
                   
                   
                   
                   
                 2.8 Hz), 9.04(1 H, d, J = 2.8 Hz). 
               
               
                 152 
                 —F 
                 —CH 3   
                 1 
                   1 H NMR 1.28(3 H, t, J = 7.1 Hz), 3.09(3 H, s), 4.06(2 H, s), 
               
               
                   
                   
                   
                   
                 4.21(2 H, q, J = 7.1 Hz), 6.42-6.54(2 H, m), 7.03-7.10(2 H, 
               
               
                   
                   
                   
                   
                 m), 8.47(1 H, dd, J = 9.1 Hz, 2.8 Hz), 9.03(1 H, d, J = 2.8 
               
               
                   
                   
                   
                   
                 Hz). 
               
               
                 153 
                 —OCH 3   
                 —H 
                 1 
                   1 H NMR 1.32(3 H, t, J = 7.1 Hz), 3.72(3 H, s), 3.92(2 H, d J = 
               
               
                   
                   
                   
                   
                 5.3 Hz), 4.27(2 H, q, J = 7.1 Hz), 4.41(1 H, brt), 6.19(1 H, 
               
               
                   
                   
                   
                   
                 dd, J = 8.4 Hz, 2.5 Hz), 6.29(1 H, d, J = 2.5 Hz), 6.96-7.00(2 
               
               
                   
                   
                   
                   
                 H, m), 8.42(1 H, dd, J = 9.1 Hz, 2.8 Hz), 9.03(1 H, d, 
               
               
                   
                   
                   
                   
                 J = 2.8 Hz). 
               
               
                 154 
                 —F 
                 -Ac 
                 1 
                   1 H NMR 1.30 (3 H, t, J = 7.1 Hz), 2.02(3 H, s), 4.23(2 H, q, J = 
               
               
                   
                   
                   
                   
                 7.1 Hz), 4.38(2 H, s), 7.16-7.33(4 H, m), 8.54(1 H, dd, J = 
               
               
                   
                   
                   
                   
                 9.1 Hz, 2.8 Hz), 9.01(1 H, dd, J = 2.8 Hz, 0.5 Hz). 
               
               
                 155 
                 —F 
                 —H            
                 1 
                   1 H NMR 1.32(3 H, t, J = 7.1 Hz), 3.89(2 H, d, J = 5.3 Hz), 4.28(2 H, q, J = 7.1 Hz), 4.35-4.55(1 H, m), 6.31-6.50(2 H, m), 6.91-7.11(2 H, m), 8.47(1 H, dd, J = 9.1 Hz, 2.8 Hz), 9.02(1 H, dd, J = 2.8 Hz, 0.4 Hz). 
               
               
                 156 
                 —CF 3   
                 —CH 3   
                 1 
                 MS 399(M + ) 
               
               
                 157 
                 —CF 3   
                 —C 2 H 5   
                 1 
                 MS 413(M + ) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 22 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
                   
                   
               
               
                 Example 
                   
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 155   
                 R 156   
                 R 157   
                 R 158   
                 R 159   
                 M 
                   1 H NMR or MS 
               
               
                   
               
               
                 158 
                 —H 
                 —H 
                 —H 
                 —CH 3   
                 —CH 3   
                 1 
                   1 H NMR (CDCl 3 ) δ 3.10(3 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 3.74(3 H, s), 4.09(2 H, s), 6.72(2 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 d, J = 9.1 Hz), 6.96 (1 H, d, J = 9.0 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz), 7.03(2 H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.43(1 H, dd, J = 9.0 Hz, 2.9 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 9.06(1 H, d, J = 2.9 Hz). 
               
               
                 159 
                 —H 
                 —H 
                 —H 
                 -Ac 
                 —C 2 H 5   
                 1 
                   1 H NMR (DMSO-d 6 ) δ 1.20(3 H, t, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 J = 7.1 Hz), 1.87(3 H, s), 4.12(2 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 q, J = 7.1 Hz), 4.37 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.28-7.35(3 H, m), 7.48(2 H, d, J = 8.7 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz), 8.65(1 H, dd, J = 2.9 Hz, 9.1 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz), 9.05 (1 H, d, J = 2.9 Hz). 
               
               
                 160 
                 —H 
                 —H 
                 —H 
                 —CH 3   
                 —CH 3   
                 2 
                   1 H NMR (CDCl 3 ) δ 2.59-2.64(2 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 m), 2.96 (3 H, s), 3.67-3.72(5 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.76(2 H, d, J = 9.1 Hz), 6.97(1 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 d, J = 9.1 Hz), 7.05(2 H, d, J = 8.9 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz), 8.43(1 H, dd, J = 9.1 Hz, 3.0 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz), 9.06(1 H, d, J = 2.8 Hz). 
               
               
                 161 
                 —F 
                 —H 
                 —F 
                 —H 
                 —C 2 H 5   
                 1 
                   1 H NMR (CDCl 3 ) δ 1.32(3 H, t, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.1 Hz), 3.91(2 H, d, J = 5.5 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 4.28(2 H, q, J = 7.1 Hz), 4.57-4.71(1 
               
               
                   
                   
                   
                   
                   
                   
                   
                 H, m), 6.43(1 H, dd, J = 7.9 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz, 11.6 Hz), 6.94(1 H, dd, J = 7.0 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz 11.0 Hz), 7.08(1 H, d, J = 9.0 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz), 8.49(1 H, dd, J = 2.8 Hz, 9.0 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz), 9.01(1 H, d, J = 2.8 Hz). 
               
               
                 162 
                 —F 
                 —F 
                 —H 
                 —CH 3   
                 —C(CH 3 ) 3   
                 0 
                   1 H NMR (CDCl 3 ) δ 1.51(9 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 3.30(3 H, s), 6.95-7.10(2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.21(1 H, d, J = 9.1 Hz), 8.54(1 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dd, J = 2.8 Hz, 9.1 Hz), 9.00(1 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 d, J = 2.8 Hz). 
               
               
                 163 
                 —CH 3   
                 —H 
                 —CH 3   
                 —C 2 H 5   
                 —C 2 H 5   
                 1 
                   1 H NMR (CDCl 3 ) δ 1.08(3 H, t, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.1 Hz), 1.24(3 H, t, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 2.07(3 H, s), 2.28(3 H, s), 3.21(2 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 q, J = 7.1 Hz), 3.78(2 H, s), 4.15 
               
               
                   
                   
                   
                   
                   
                   
                   
                 (2 H, q, J = 7.1 Hz), 6.86(1 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.95(1 H, d, J = 9.1 Hz), 7.07(1 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 s), 8.45(1 H, dd, J = 9.1 Hz, 2.8 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz), 9.06(1 H, d, J = 2.8 Hz). 
               
               
                 164 
                 —COOCH 3   
                 —H 
                 —H 
                 —C 2 H 5   
                 —C(CH 3 ) 3   
                 1 
                 MS 431(M + ) 
               
               
                 165 
                 —CH 3   
                 —H 
                 —CH 3   
                 —CH 3   
                 —C 2 H 5   
                 1 
                   1 H NMR (CDCl 3 ) δ 1.27(3 H, t, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.1 Hz), 2.08(3 H, s), 2.28(3 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 2.89(3 H, s), 3.73(2 H, s), 4.19(2 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 q, J = 7.1 Hz), 6.85(1 H, s), 6.96 
               
               
                   
                   
                   
                   
                   
                   
                   
                 (1 H,d, J = 9.1 Hz), 7.01(1 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.45(1 H, dd, J = 9.1 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 9.06(1 H, d, J = 2.8 Hz). 
               
               
                 166 
                 —CN 
                 —H 
                 —H 
                 —CH 3   
                 —C(CH 3 ) 3   
                 1 
                 MS 384(M + ) 
               
               
                 167 
                 —H 
                 —H 
                 —CF 3   
                 —C 2 H 5   
                 —C 2 H 5   
                 1 
                 MS 413(M + ) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 23 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
               
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 160   
                 R 161   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 168 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.27(3 H, t, J = 7.0 Hz), 1.41-1.48(2 H m), 1.85 (2 H, brd, J = 13.0 Hz), 1.95(1 H, m), 2.29(2 H, d, J = 7.0 Hz) 2 76(2 H, dt, J = 2.5 Hz, 12.0 Hz), 3.65 (2 H, brd, J = 12.0 Hz), 4.16(2 H, q, J = 7.0 Hz), 6.96-6.99(3 H, m), 7.03(2 H, d, J = 9.0 Hz), 8.44 (1 H, dd, J = 9.0 Hz, 3.0 Hz), 9.05(1 H, d, J = 3.0 Hz). 
               
               
                   
               
               
                 169 
                 —H 
                 morpholino 
                 3.16-3.19(4 H, m), 3.86-3.89(4 H, m), 
               
               
                   
                   
                   
                 6.94-7.01 (3 H, m), 7.05-7.11(2 H, m), 
               
               
                   
                   
                   
                 8.45(1 H, dd, J = 9.2 Hz, 3.0 Hz), 
               
               
                   
                   
                   
                 9.05(1 H, d, J = 3.0 Hz). 
               
               
                   
               
               
                 170 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2.47-2.62(4 H, m) 2 96-3.14(4 H, m), 3.49(2 H, s), 7.11(1 H, d, J = 9.0 Hz), 7.19-7.37(7 H, m), 7.81 (2 H, d, J = 8.7 Hz), 8.52(1 H, dd, J = 9.0 Hz, 2.0 Hz), 9.02(1 H, d, J = 2.0 Hz). 
               
               
                   
               
               
                 171 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.28(3 H, t, J = 7.0 Hz), 1.90(2 H, dq, J = 4.0 Hz, 11.5 Hz), 2.04(2 H, brd, J = 13.0 Hz), 2.43(1 H, m), 2.82(2 H, dt, J = 3.0 Hz, 12.0 Hz), 3.63(2 H, dt, J = 13.0 Hz, 3.0 Hz), 4.17(2 H, q, J = 7.0 Hz), 6.97-6.99(3 H, m), 7.04(2 H, d, J = 9.0 Hz), 8.44(1 H, dd, J = 9.0 Hz, 3.0 Hz), 9.05(1 H, d, J = 3.0 Hz). 
               
               
                   
               
               
                 172 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.28(3 H, t, J = 7.0 Hz), 1.70(2 H, m), 1.84(1 H, m), 2.04(1 H, m), 2.69(1 H, m), 2.86(1 H, m), 3.08(1 H, dd, J = 12.0 Hz, 10.0 Hz), 3.46(1 H, brd, J = 12.0 Hz), 3.69(1 H, dd, J = 12.0 Hz, 4.0 Hz), 4.18(2 H, q, J = 7.0 Hz), 6.97-7.05(5 H, m), 8.45(1 H, dd, J = 9.0 Hz, 3.0 Hz), 9.06(1 H, d, J = 3.0 Hz). 
               
               
                   
               
               
                 173 
                 —COOCH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2.61-2.64(4 H, m) 3.24-3.28(4 H, m), 3.58(2 H; s), 3.68(3 H, s), 7.03-7.16(3 H, m), 7.26-7.36(5 H, m), 7.54(1 H, d, J = 2.8 Hz), 8.46(1 H, d.d, J = 9.1 Hz, 2.8 Hz), 8.97(1 H, d, J = 2.8 Hz). 
               
               
                   
               
               
                 174 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2.43(4 H, t, J = 5.1 Hz), 3.40(4 H, t, J = 5.1 Hz), 3.43(2 H, s), 4.46(2 H, t, J = 5.5 Hz), 4.79(1 H, t, J = 5.5 Hz), 5.95(2 H, s), 6.74(2 H, s), 6.85(1 H, s), 7.05(1 H, d, J = 9.1 Hz), 7.12(2 H, d, J = 8.4 Hz), 7.40(2 H, d, J = 8.4 Hz), 8.48(1 H, dd, J = 9.1 Hz, 2.8 Hz), 9.03(1 H, d, J = 2.8 Hz). 
               
               
                   
               
               
                 175 
                 —CH 3   
                 —NHCOCOOC 2 H 5   
                 1.33(3 H, t, J = 7.1 Hz), 2.07(3 H, s), 
               
               
                   
                   
                   
                 4.32(2 H, q, J = 7.1 Hz), 7.15(1 H, d, J = 
               
               
                   
                   
                   
                 8.7 Hz), 7.27(1 H, cld, J = 9.2 Hz, 0.5 
               
               
                   
                   
                   
                 Hz), 7.63(1 H, cM, J = 8.6 Hz, 2.5 Hz), 
               
               
                   
                   
                   
                 7.71(1 H, d, J = 2.5 Hz), 8.62(1 H, dd, J = 
               
               
                   
                   
                   
                 9.1 Hz, 2 8 Hz), 9.01(1 H, dd, J = 2.8 Hz, 
               
               
                   
                   
                   
                 0.5 Hz), 10.82(1 H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 24 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 162   
                 R 163   
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
             
          
           
               
                 176 
                 —H 
                 —Ac 
                 (CDCl 3  ) 2.60 (3H, s), 7.10-9.00 (7H, m). 
               
               
                 177 
                 —H 
                 —CHO 
                 (CDCl 3 ) 7.14 (1H, d, J = 9.0 Hz), 7.35 (2H, 
               
               
                   
                   
                   
                 d, J = 8.7 Hz), 8.00 (2H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                 8.54 (1H, dd, J = 9.0 Hz, 1.8 Hz), 9.04 (1H, 
               
               
                   
                   
                   
                 d, J = 1.8 Hz), 10.03 (1H, s). 
               
               
                 178 
                 —H 
                 —C 2 H 5   
                 (CDCl 3 ) 1.28 (3H, t, J = 7.6 Hz), 2.70 (2H, 
               
               
                   
                   
                   
                 q, J = 7.6 Hz), 7.01 (1H, dd, J = 9.1 Hz, 
               
               
                   
                   
                   
                 0.7 Hz), 7.07 (2H, d, J = 8.7 Hz), 7.28 (2H, 
               
               
                   
                   
                   
                 d, J = 8.7 Hz), 8.46 (1H, dd, J = 9.1 Hz, 
               
               
                   
                   
                   
                 2.8 Hz), 9.05 (1H, dd, J = 2.8 Hz, 0.7 Hz). 
               
               
                 179 
                 —CH 3   
                 —CHO 
                 (CDCl 3 ) 2.25 (3H, s), 7.14 (1H, d, J = 8.9 
               
               
                   
                   
                   
                 Hz), 7.24 (1H, d, J = 8.2 Hz), 7.81 (1H, dd, 
               
               
                   
                   
                   
                 J = 8.2 Hz, 2.0 Hz), 7.85 (1H, s), 8.53 (1H, 
               
               
                   
                   
                   
                 dd, J = 8.9 Hz, 2.6 Hz), 9.00 (1H, d, J = 
               
               
                   
                   
                   
                 2.6 Hz), 10.00 (1H, s). 
               
               
                   
               
               
                 180 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 1.70-1.93 (4H, m), 2.45-2.56 (2H, m), 3.22-3.36 (2H, m), 4.62 (2H, s), 7.03 (1H, d, J = 9.2 Hz), 7.12 (2H, d, J = 8.6 Hz), 7.35 (2H, d, J = 8.6 Hz), 8.47 (1H, dd, J = 9.2 Hz, 2.6 Hz), 9.04 (1H, d, J = 2.6 Hz). 
               
               
                   
               
               
                 181 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 2.46-2.47 (4H, m), 2.77-2.99 (2H, m), 3.46 (2H, s), 3.51-3.57 (4H, m), 3.64- 3.73 (1H, m), 3.90-3.96 (1H, m), 4.30- 4.36 (1H, m), 5.96 (2H, s), 6.75-6.86 (3H, m), 7.04 (1H, d, J = 9.1 Hz), 7.17 (2H, d, J = 9.1 Hz), 7.70 (2H, d, J = 8.9 Hz), 8.48 (1H, dd, J = 2.8 Hz, 9.1 Hz), 9.03 (1H, d, J = 2.8 Hz). 
               
               
                   
               
               
                 182 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 1.51 (9H, s), 3.80 (4H, m), 4.27 (2H, s), 7.07 (1H, d, J = 9.1 Hz), 7.21 (2H, dd, J = 6.8 Hz, 2.1 Hz), 7.38 (2H, dd, J = 6.8 Hz, 2.1 Hz), 8.49 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.04 (1H, d, J = 2.8 Hz). 
               
               
                   
               
               
                 183 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 3.35-3.55 (4H, m), 3.96 (2H, s), 4.58 (2H, s), 5.96 (2H, s), 6.73-6.78 (2H, m), 6.81 (1H, s), 6.91 (2H, d, J = 9.1 Hz), 7.00 (1H, d, J = 9.1 Hz), 7.09 (2H, d, J = 9.1 Hz), 8.45 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.04 (1H, d, J = 2.8 Hz). 
               
               
                   
               
               
                 184 
                 —H 
                 —NHCONHPh 
                 (DMSO-d 6 ) 6.96 (1H, t, J = 6.5 Hz), 7.14 (2H, d, J = 8.8 Hz), 7.21 (1H, d, J = 9.1 Hz), 7.27 (2H, t, J = 8.3 Hz), 7.45 (2H, d, J = 8.3 Hz), 7.52 (2H, d, J = 8.8 Hz), 8.60 (1H, dd, J = 2.8 Hz, 9.1 Hz), 8.70 (1H, s), 8.77 (1H, s), 9.02 (1H, d, J = 2.8 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 25 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 164   
                 R 165   
                 R 166   
                 M 
                 mp (° C.) or  1 H NMR (solvent) δ ppm 
               
               
                   
               
             
          
           
               
                 185 
                 —NO 2   
                 —CH 3   
                 piperonyl 
                 2 
                 mp 142.0-143.0 
               
               
                 186 
                 —NO 2   
                 —H 
                 benzyl 
                 1 
                   1 H NMR (DMSO-d 6 ) 3.36 (2H, t, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 3.84 (2H, t, J = 8.1 Hz), 4.40 (2H, s), 7.15- 
               
               
                   
                   
                   
                   
                   
                 7.25 (3H, m), 7.26-7.34 (3H, m), 7.35- 
               
               
                   
                   
                   
                   
                   
                 7.41 (2H, m), 7.61-7.71 (2H, m), 8.59 (1H, dd, 
               
               
                   
                   
                   
                   
                   
                 J = 2.9 Hz, 9.1 Hz), 9.02 (1H, d, J = 9.1 Hz). 
               
               
                 187 
                 —NO 2   
                 —CH 3   
                 piperonyl 
                 1 
                   1 H NMR (DMSO-d 6 ) 2.05 (3H, s), 3.29- 
               
               
                   
                   
                   
                   
                   
                 3.41 (2H, m), 3.71-3.88 (2H, m), 4.29 (2H, s), 
               
               
                   
                   
                   
                   
                   
                 5.60 (2H, s), 6.74-6.81 (1H, m), 6.82-6.92 (2H, 
               
               
                   
                   
                   
                   
                   
                 m), 7.09 (1H, d, J = 8.8 Hz), 7.21 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 9.1 Hz), 7.49 (1H, d, J = 2.6 Hz, 8.8 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.51-7.57 (1H, m), 8.60 (1H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 9.00 (1H, d, J = 2.9 Hz). 
               
               
                 188 
                 —NO 2   
                 —CH 3   
                 3,4-(CH 3 O) 2 PhCH 2 — 
                 2 
                   1 H NMR (CDCl 3 ) 2.00-2.15 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 2.14 (3H, s), 3.31 (2H, t, J = 6.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 3.73 (2H, d, J = 6.0 Hz), 3.88 (3H, s), 
               
               
                   
                   
                   
                   
                   
                 3.89 (3H, s), 4.57 (2H, s), 6.83 (1H, d, J = 8.1 
               
               
                   
                   
                   
                   
                   
                 Hz), 6.87 (1H, dd, J = 1.9 Hz, 8.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.91 (1H, d, J = 1.9 Hz), 6.98-7.06 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 7.20 (1H, dd, J = 2.4 Hz, 8.6 Hz), 7.29 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 2.4 Hz), 8.46 (1H, dd, J = 2.8 Hz, 9.1 
               
               
                   
                   
                   
                   
                   
                 Hz), 9.04 (1H, d, J = 2.8 Hz). 
               
               
                 189 
                 —NO 2   
                 —CH 3   
                 —CH 2 COOC(CH 3 ) 3   
                 2 
                   1 H NMR (CDCl 3 ) 1.48 (9H, s), 2.12 (3H, s), 
               
               
                   
                   
                   
                   
                   
                 2.12-2.24 (2H, m), 3.48 (2H, t, J = 5.9 Hz), 
               
               
                   
                   
                   
                   
                   
                 3.77 (2H, t, J = 5.9 Hz), 4.05 (2H, s), 6.92- 
               
               
                   
                   
                   
                   
                   
                 7.06 (2H, m), 7.17 (1H, dd, J = 2.6 Hz, 8.6 
               
               
                   
                   
                   
                   
                   
                 Hz), 8.45 (1H, dd, J = 2.9 Hz, 9.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 9.04 (1H, d, J = 2.9 Hz). 
               
               
                 190 
                 —Br 
                 —CH 3   
                 piperonyl 
                 2 
                   1 H NMR (CDCl 3 ) 1.94-2.18 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 2.15 (3H, s), 3.30 (2H, d, J = 6.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 3.71 (2H, d, J = 6.0 Hz), 4.52 (2H, s), 
               
               
                   
                   
                   
                   
                   
                 5.95 (2H, s), 6.69-6.82 (3H, m), 6.88 (1H, s), 
               
               
                   
                   
                   
                   
                   
                 7.00 (1H, d, J = 8.6 Hz), 7.15 (1H, dd, J = 2.6 
               
               
                   
                   
                   
                   
                   
                 Hz, 8.6 Hz), 7.24 (1H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.73 (1H, dd, J = 2.5 Hz, 8.6 Hz), 8.20 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 2.5 Hz). 
               
               
                 191 
                 —Br 
                 —CH 3   
                 3,4-(CH 3 O) 2 PhCH 2 — 
                 2 
                   1 H NMR (CDCl 3 ) 1.95-2.11 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 2.14 (3H, s), 3.30 (2H, t, J = 5.9 Hz), 
               
               
                   
                   
                   
                   
                   
                 3.70 (2H, t, J = 5.9 Hz), 3.88 (3H, s), 
               
               
                   
                   
                   
                   
                   
                 3.88 (3H, s), 4.56 (2H, s), 6.74-6.92 (4H, s), 
               
               
                   
                   
                   
                   
                   
                 7.00 (1H, d, J = 8.5 Hz), 7.15 (1H, dd, J = 2.4 
               
               
                   
                   
                   
                   
                   
                 Hz, 8.5 Hz), 7.24 (1H, d, J = 2.4 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.73 (1H, dd, J = 2.6 Hz, 8.8 Hz), 8.19 (1H, 
               
               
                   
                   
                   
                   
                   
                 dd, J = 0.5 Hz, 2.6 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
               
               
               
             
           
               
                 TABLE 26 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 167   
                   1 H NMR (CDCl 3 ) δ ppm or MS 
               
               
                   
               
             
          
           
               
                 192 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.24 (3H, t, J = 7.1 Hz), 3.07 (3H, s), 4.05 (2H, s), 4.18 (2H, q, J = 7.1 Hz), 6.44-6.45 (1H, m), 6.49-6.53 (1H, m), 6.57-6.61 (1H, m), 6.97 (1H, d, J = 9.1 Hz), 7.25-7.31 (1H, m), 8.44 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.07 (1H, d, J = 2.8 Hz). 
               
               
                   
               
               
                 193 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 3.93 (3H, s), 7.08-7.11 (1H, m), 7.26-7.40 (1H, m), 7.51-7.57 (1H, m), 7.83-7.84 (1H, m), 7.96-8.00 (1H, m), 8.49-8.53 (1H, m), 9.02-9.03 (1H, m). 
               
               
                   
               
               
                 194 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 488 (M + ) 
               
               
                   
               
               
                 195 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 4.00 (3H, s), 7.14 (1H, d, J = 8.9 Hz), 7.37 (1H, dd, J = 8.9 Hz, 2.3 Hz), 7.67 (1H, d, J = 2.3 Hz), 7.87 (1H, d, J = 8.6 Hz), 8.04 (1H, d, J = 8.9 Hz), 8.11 (1H, dd, J = 8.6 Hz, 1.7 Hz), 8.51- 8.55 (1H, m), 8.64 (1H, brs), 9.05 (1H, d, J = 2.8 Hz). 
               
               
                   
               
               
                 196 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 4.03 (3H, s), 7.20 (1H, d, J = 9.1 Hz), 7.31 (1H, d, J = 8.1 Hz), 7.51- 7.57 (1H, m), 7.65-7.71 (1H, m), 7.94 (1H, d, J = 8.4 Hz), 8.29 (1H, d, J = 8.1 Hz), 8.55 (1H, dd, J = 9.1 Hz, 2.8 Hz), 8.99 (1H, d, J = 2.8 Hz), 9.05 (1H, d, J = 8.7 Hz). 
               
               
                   
               
               
                 197 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.47 (3H, t, J = 7.1 Hz), 4.49 (2H, t, J = 7.1 Hz), 7.11 (1H, d, J = 8.9 Hz), 7.42 (1H, dd, J = 9.4 Hz, 2.5 Hz), 7.52-7.58 (1H, m), 7.67 (1H, d, J = 2.5 Hz), 7.99 (1H, d, J = 8.2 Hz), 8.21 (1H, dd, J = 7.3 Hz, 1.2 Hz), 8.51 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.04-9.08 (2H, m). 
               
               
                   
               
               
                 198 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (CDCl 3 ) 2.11 (3H, s), 2.19 (2H, t, J = 5.9 Hz), 2.34-2.50 (4H, m), 3.42 (2H, s), 3.40-3.47 (2H, m), 3.51 (2H, t, J = 5.9 Hz), 3.56-3.76 (2H, m), 3.78 (2H, t, J = 5.7 Hz), 4.20 (2H, s), 5.94 (2H, s), 6.69-6.77 (2H, m), 6.84 (1H, d, J = 1.0 Hz), 6.96-7.02 (2H, m), 7.17 (1H, dd, J = 2.6 Hz, 8.5 Hz), 7.24- 7.28 (1H, m), 8.45 (1H, dd, J = 2.8 Hz, 9.1 Hz), 9.04 (1H, d, J = 2.8 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 27 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 168   
                 R 169   
                 M 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
             
          
           
               
                 199 
                 —H 
                 benzyl 
                 2 
                 (CDCl 3 ) 2.36-2.45 (4H, m), 2.63-2.68 (2H, m), 2.99- 
               
               
                   
                   
                   
                   
                 3.05 (2H, m), 3.41-3.45 (2H, m), 3.52 (2H, s), 3.64- 
               
               
                   
                   
                   
                   
                 3.67 (2H, m), 7.01-7.11 (3H, m), 7.29-7.34 (7H, m), 
               
               
                   
                   
                   
                   
                 8.47 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.05 (1H, d, J = 2.8 
               
               
                   
                   
                   
                   
                 Hz). 
               
               
                 200 
                 —H 
                 piperonyl 
                 2 
                 (CDCl 3 ) 2.33-2.41 (4H, m), 2.62-2.67 (2H, m), 2.98- 
               
               
                   
                   
                   
                   
                 3.04 (2H, m), 3.39-3.43 (4H, m), 3.62-3.65 (2H, m), 
               
               
                   
                   
                   
                   
                 5.94 (2H, s), 6.73-6.77 (2H, m), 6.84 (1H, s), 7.00- 
               
               
                   
                   
                   
                   
                 7.10 (3H, m), 7.26-7.31 (2H, m), 8.44-8.48 (1H, m), 
               
               
                   
                   
                   
                   
                 9.03 (1H, dd, J = 3.0 Hz, 0.5 Hz). 
               
               
                 201 
                 —F 
                 benzyl 
                 0 
                 (CDCl 3 ) 2.49 (4H, brs), 3.49-3.56 (4H, m), 3.79 (2H, 
               
               
                   
                   
                   
                   
                 brs), 7.15 (1H, d, J = 8.9 Hz), 7.24-7.38 (8H, m), 
               
               
                   
                   
                   
                   
                 8.53 (1H, dd, J = 9.1 Hz, 2.8 Hz), 8.99 (1H, d, J = 2.8 
               
               
                   
                   
                   
                   
                 Hz). 
               
               
                 202 
                 —H 
                 benzyl 
                 0 
                 (DMSO-d 6 ) 2.41 (4H, brs), 3.33 (2H, brs), 3.52 (4H, 
               
               
                   
                   
                   
                   
                 brs), 7.24-7.27 (8H, m), 7.50 (2H, d, J = 7.9 Hz), 
               
               
                   
                   
                   
                   
                 8.64 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.04 (1H, d, J = 2.8 
               
               
                   
                   
                   
                   
                 Hz). 
               
               
                 203 
                 —H 
                 4-CH 3 OPhCH 2 — 
                 0 
                 (CDCl 3 ) 2.46 (4H, brs), 3.44-3.90 (4H, m), 3.49 (2H, 
               
               
                   
                   
                   
                   
                 s), 3.81 (3H, s), 6.85-6.89 (2H, m), 7.06 (1H, d, J = 
               
               
                   
                   
                   
                   
                 8.9 Hz), 7.18-7.27 (4H, m), 7.48-7.53 (2H, m), 8.48- 
               
               
                   
                   
                   
                   
                 8.52 (1H, m), 9.03 (1H, d, J = 2.8 Hz). 
               
               
                 204 
                 —H 
                 piperonyl 
                 0 
                 (CDCl 3 ) 2.46 (4H, brs), 3.46 (2H, s), 3.52 (2H, brs), 
               
               
                   
                   
                   
                   
                 3.77 (2H, brs), 5.95 (2H, s), 6.75 (2H, s), 6.86 (1H, s), 
               
               
                   
                   
                   
                   
                 7.07 (1H, dd, J = 9.1 Hz, 0.5 Hz), 7.20 (2H, d, J = 8.6 
               
               
                   
                   
                   
                   
                 Hz), 7.51 (2H, d, J = 8.6 Hz), 8.50 (1H, dd, J = 8.9 
               
               
                   
                   
                   
                   
                 Hz, 2.8 Hz), 9.03 (1H, dd, J = 2.8 Hz, 0.5 Hz). 
               
               
                 205 
                 —H 
                 3-pyridyl 
                 0 
                 (CDCl 3 ) 3.27 (4H, brs), 3.84 (4H, brs), 7.08-7.12 (1H, 
               
               
                   
                   
                   
                   
                 m), 7.21-7.27 (4H, m), 7.54-7.59 (2H, m), 8.16- 
               
               
                   
                   
                   
                   
                 8.18 (1H, m), 8.34 (1H, brs), 8.52 (1H, dd, J = 9.1 Hz, 
               
               
                   
                   
                   
                   
                 2.8 Hz), 9.05 (1H, dd, J = 2.8 Hz, 0.5 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 28 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 Xa 5   
                 R 170   
                 M 
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
             
          
           
               
                 206 
                 —O— 
                 piperonyl 
                 1 
                 2.43 (4H, brs), 3.42 (2H, s), 3.58 (2H, t, J = 5.0 
               
               
                   
                   
                   
                   
                 Hz), 3.64 (2H, t, J = 5.0 Hz), 4.70 (2H, s), 
               
               
                   
                   
                   
                   
                 5.95 (2H, s), 6.70-6.79 (2H, m), 6.84 (1H, d, J = 
               
               
                   
                   
                   
                   
                 0.6 Hz), 7.01 (3H, d, J = 9.1 Hz), 7.09 (2H, d, 
               
               
                   
                   
                   
                   
                 J = 9.1 Hz), 8.46 (1H, dd, J = 9.1 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                   
                 9.04 (1H, d, J = 2.8 Hz). 
               
               
                 207 
                 —CH(OH)— 
                 benzyl 
                 0 
                 1.90-2.05 (1H, m), 2.21-2.68 (3H, m), 3.11- 
               
               
                   
                   
                   
                   
                 3.25 (1H, m), 3.28-3.40 (1H, m), 3.45 (2H, s), 
               
               
                   
                   
                   
                   
                 3.73 (2H, t, J = 5.1 Hz), 4.77 (1H, d, J = 6.3 Hz), 
               
               
                   
                   
                   
                   
                 5.24 (1H, d, J = 6.3 Hz), 7.04 (1H, d, J = 8.9 
               
               
                   
                   
                   
                   
                 Hz), 7.16 (2H, d, J = 8.7 Hz), 7.21-7.35 (5H, m), 
               
               
                   
                   
                   
                   
                 7.38 (2H, d, J = 8.7 Hz), 8.48 (1H, dd, J = 8.9 
               
               
                   
                   
                   
                   
                 Hz, 2.8 Hz), 9.03 (1H, d, J = 2.8 Hz). 
               
               
                   
               
               
                 208 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 piperonyl 
                 1 
                 0.65-0.70 (2H, m), 0.81-0.88 (2H, m), 2.41- 2.48 (4H, m), 2.77-2.85 (1H, m), 3.45 (2H, s), 3.49-3.52 (2H, m), 3.60-3.63 (2H, m), 4.20 (2H, s), 5.95 (2H, s), 6.71-6.78 (2H, m), 6.86 (1H, brs), 6.90-7.02 (5H, m), 8.39-8.44 (1H, m), 9.06 (1H, d, J = 2.8 Hz). 
               
               
                   
               
               
                 209 
                 —O— 
                 benzyl 
                 1 
                 2.45 (4H, t, J = 4.5 Hz), 3.52 (2H, s), 3.59 (2H, t, 
               
               
                   
                   
                   
                   
                 J = 4.9 Hz), 3.65 (2H, t, J = 4.9 Hz), 4.70 (2H, 
               
               
                   
                   
                   
                   
                 s), 7.00 (2H, d, J = 9.2 Hz), 7.01 (1H, d, J = 9.0 
               
               
                   
                   
                   
                   
                 Hz), 7.08 (2H, d, J = 9.2 Hz), 7.21-7.40 (5H, m), 
               
               
                   
                   
                   
                   
                 8.46 (1H, dd, J = 9.0 Hz, 2.8 Hz), 9.04 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 2.8 Hz). 
               
               
                 210 
                 —N(CH 3 )— 
                 benzyl 
                 0 
                 2.32 (4H, brs), 3.24 (3H, s), 3.28 (4H, brs), 
               
               
                   
                   
                   
                   
                 3.48 (2H, brs), 7.04 (1H, d, J = 9.1 Hz), 7.11 (2H, 
               
               
                   
                   
                   
                   
                 d, J = 9.0 Hz), 7.15 (2H, d, J = 9.0 Hz), 7.22- 
               
               
                   
                   
                   
                   
                 7.40 (5H, m), 8.48 (1H, dd, J = 9.1 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                   
                 9.04 (1H, d, J = 2.8 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 29 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
                   
                   
               
               
                 Example 
                   
                   
                   
                   
                   
                   
                   1 H NMR (CDCl 3 ) 
               
               
                 No. 
                 R 171   
                 R 172    
                 Xa 6   
                 R 173    
                 R 174   
                 R 175   
                 δ ppm or MS 
               
               
                   
               
             
          
           
               
                 211 
                 —NO 2   
                 —H 
                 —N(CH 3 )— 
                 —CH 3   
                 —H 
                 —C 2 H 5   
                   1 H NMR 1.25 (3H, t, J = 7.1 Hz), 1.50 (3H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 d, J = 7.1 Hz), 2.93 (3H, s), 4.18 (2H, q, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.1 Hz), 4.48 (1H, q, J = 7.3 Hz), 6.82 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 d, J = 9.2 Hz), 6.97 (1H, d, J = 9.1 Hz), 7.03 
               
               
                   
                   
                   
                   
                   
                   
                   
                 (2H, d, J = 9.0 Hz), 8.43 (1H, dd, J = 9.1 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz, 2.8 Hz), 9.06 (1H, d, J = 2.8 Hz). 
               
               
                 212 
                 —NO 2   
                 —H 
                 —N(CH 3 )— 
                 —CH 3   
                 —CH 3   
                 —C 2 H 5   
                   1 H NMR 1.24 (3H, t, J = 7.1 Hz), 1.46 (6H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 s), 2.94 (3H, s), 4.18 (2H, q, J = 7.1 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz), 6.97 (1H, dd, J = 9.1 Hz, 0.5 Hz), 7.00- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.08 (4H, m), 8.45 (1H, dd, J = 9.1 Hz, 3.0 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz), 9.05 (1H, dd, J = 2.8 Hz, 0.5 Hz). 
               
               
                 213 
                 —NO 2   
                 —CH 3   
                 —N(CH 3 )— 
                 —CH 3   
                 —H 
                 —C 2 H 5   
                   1 H NMR 1.26 (3H, t, J = 7.1 Hz), 1.49 (3H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 d, J = 7.3 Hz), 2.10 (3H, s), 2.91 (3H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 4.13-4.24 (2H, m), 4.48 (1H, q, J = 7.3 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.64-6.68 (2H, m), 6.91-6.96 (2H, m), 8.43 
               
               
                   
                   
                   
                   
                   
                   
                   
                 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.06 (1H, dd, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 J = 2.8 Hz, 0.5 Hz). 
               
               
                 214 
                 —NO 2   
                 —H 
                 none 
                 —CH 3   
                 —CH 3   
                 —CH 3   
                 MS 316 (M + ) 
               
               
                 215 
                 —Br 
                 —OCH 3   
                 —CH 2 — 
                 —H 
                 —H 
                 —C 2 H 5   
                   1 H NMR 1.26 (3H, t, J = 7.1 Hz), 2.63-2.68 
               
               
                   
                   
                   
                   
                   
                   
                   
                 (2H, m), 2.94-3.00 (2H, m), 3.75 (3H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 4.15 (2H, q, J = 7.1 Hz), 6.80-6.86 (3H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.03 (1H, d, J = 7.9 Hz), 7.73 (1H, dd, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.7 Hz, 2.6 Hz), 8.16 (1H, dd, J = 2.6 Hz, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 0.7 Hz). 
               
               
                 216 
                 3,4-Cl 2 PhCH 2 NHCO— 
                 —H 
                 —CH 2 — 
                 —H 
                 —H 
                 —C 2 H 5   
                 MS 472 (M + ) 
               
               
                 217 
                 4-CF 3 PhCH 2 NHCO— 
                 —H 
                 —CH 2 — 
                 —H 
                 —H 
                 —C 2 H 5   
                 MS 472 (M + ) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 30 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 176   
                 R 177   
                   1 H NMR (CDCl 3 ) δ ppm or MS 
               
               
                   
               
             
          
           
               
                 218 
                 4-CF 3 PhCO— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.26 (3H, t, J = 7.1 Hz), 2.64-2.69 (2H, m), 2.95-3.01 (2H, m), 3.76 (3H, s), 4.15 (2H, q, J = 7.1 Hz), 6.83-6.89 (2H, m), 7.03- 7.10 (2H, m), 7.73-7.76 (2H, m), 7.86-7.89 (2H, m), 8.21 (1H, dd, J = 8.6 Hz, 2.5 Hz), 8.55 (1H, dd, J = 2.5 Hz, 0.7 Hz). 
               
               
                   
               
               
                 219 
                 3.4-Cl 2 PhNHCO— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.20 (3H, t, J = 7.1 Hz), 3.44 (2H, q, J = 7.1 Hz), 3.56 (3H, s), 4.04 (2H, s), 5.17 (2H, s), 6.15- 6.18 (2H, m), 6.83 (1H, d, J = 8.7 Hz), 6.88 (1H, d, J = 8.9 Hz), 7.29-7.35 (6H, m), 7.44 (1H, dd, J = 8.7 Hz, 2.5 Hz), 7.82 (1H, d, J = 2.3 Hz), 8.10 (1H, dd, J = 8.7 Hz, 2.5 Hz), 8.59 (1H, d, J = 2.5 Hz), 8.72 (1H, brs). 
               
               
                   
               
               
                 220 
                 3,4-Cl 2 PhNHCO— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 501 (M + ) 
               
               
                   
               
               
                 221 
                 4-CF 3 PhNHCO— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 501 (M + ) 
               
               
                   
               
               
                 222 
                 —COOC 2 H 5   
                 4-NO 2 Ph- 
                   1 H NMR 1.40 (3H, t, J = 7.1 Hz), 
               
               
                   
                   
                   
                 4.40 (2H, q, J = 7.1 Hz), 7.08 (1H, 
               
               
                   
                   
                   
                 d, J = 8.6 Hz), 7.32 (2H, d, J = 9.0 
               
               
                   
                   
                   
                 Hz), 8.31 (2H, d, J = 9.0 Hz), 
               
               
                   
                   
                   
                 8.37 (1H, dd, J = 8.6 Hz, 2.3 Hz), 
               
               
                   
                   
                   
                 8.82 (1H, d, J = 2.3 Hz). 
               
               
                 223 
                 4-CF 3 PhNHCO— 
                 4-CHOPh- 
                 MS 386 (M + ) 
               
               
                   
               
               
                 224 
                 —COOC 2 H 5   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.39 (3H, t, J = 7.1 Hz), 2.28 (3H, s), 4.39 (2H, q, J = 7.1 Hz), 7.07 (1H, dd, J = 8.6 Hz, 0.5 Hz), 7.21 (1H, d, J = 8.9 Hz), 8.13 (1H, dd, J = 8.9 Hz, 2.8 Hz), 8.20 (1H, d, J = 2.8 Hz), 8.36 (1H, dd, J = 8.6 Hz, 2.3 Hz), 8.78 (1H, dd, J = 2.8 Hz, 0.5 Hz). 
               
               
                   
               
               
                 (CHOPh means a formylphenyl group. Hereinafter CHOPh indicates the same meaning.) 
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 31 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
               
               
                 Example 
                   
                   
                   
                   
                 mp (° C.) or  1 H NMR 
               
               
                 No. 
                 R 178   
                 R 179   
                 R 180   
                 Form 
                 (solvent) δ ppm 
               
               
                   
               
             
          
           
               
                 225 
                 4-CF 3 PhNHCO— 
                 —CH 3   
                 —NHCOCOOC 2 H 5   
                 free 
                   1 H NMR (DMSO-d 6 ) 
               
               
                   
                   
                   
                   
                   
                 1.33 (3H, t, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 2.08 (3H, s), 4.33 (2H, q, 
               
               
                   
                   
                   
                   
                   
                 J = 7.1 Hz), 7.12 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.7 Hz), 7.17 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.6 Hz), 7.63 (1H, dd, 
               
               
                   
                   
                   
                   
                   
                 J = 8.7 Hz, 2.5 Hz), 7.72- 
               
               
                   
                   
                   
                   
                   
                 7.75 (3H, m), 7.98 (2H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.7 Hz), 8.37 (1H, dd, 
               
               
                   
                   
                   
                   
                   
                 J = 8.6 Hz, 2.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.69 (1H, d, J = 2.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 10.62 (1H, brs), 10.81 (1H, 
               
               
                   
                   
                   
                   
                   
                 brs). 
               
               
                   
               
               
                 226 
                 3,4-Cl 2 PhNHCO— 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 hydro- bromide 
                 mp 132.0-134.0 
               
               
                   
               
               
                 227 
                 —NO 2   
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                   1 H NMR (CDCl 3 ) 1.28 (3H, t, J = 7.1 Hz), 1.86-1.95(2H, m), 2.02- 2.06 (2H, m), 2.10 (3H, s), 2.40-2.48 (1H, m), 2.76- 2.85 (2H, m), 3.61- 3.65 (2H, m), 4.17 (2H, q, J = 7.1 Hz), 6.79-6.97 (4H, m), 8.43 (1H, dd, J = 9.1 Hz, 3.0 Hz), 9.04 (1H, d, J = 2.8 Hz). 
               
               
                   
               
               
                 228 
                 —NO 2   
                 —OCH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                   1 H NMR (CDCl 3 ) 1.28 (3H, t, J = 7.1 Hz), 1.41-1.50 (2H, m), 1.84- 2.04 (3H, m), 2.30 (2H, d, J = 6.9 Hz), 2.78 (2H, dd, J = 12.0 Hz, 9.7 Hz), 3.65 (2H, d, J = 12.4 Hz), 3.73 (3H, s) 4.16 (2H, q, J = 7.3 Hz), 6.53 (1H, dd, J = 8.7 Hz, 2.6 Hz), 6.59 (1H, d, J = 2.6 Hz), 6.96- 7.02 (2H, m), 8.42 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.03 (1H, d, J = 2.8 Hz). 
               
               
                   
               
               
                 229 
                 —NO 2   
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                   1 H NMR (CDCl 3 ) 1.27 (3H, t, J = 7.1 Hz), 1.37-1.49 (2H, m), 1.83- 2.03 (3H, m), 2.10 (3H, s), 2.29 (2H, d, J = 6.9 Hz), 2.74 (2H, dd, J = 12.2 Hz, 10.1 Hz), 3.64 (2H, d, J = 12.4 Hz), 4.15 (2H, q, J = 7.3 Hz), 6.77-6.83 (2H, m), 6.91-6.97 (2H, m), 8.42 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.02 (1H, d, J = 2.8 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 32 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
                   
               
               
                 Example 
                   
                   
                   
                   
                   
                   1 H NMR (CDCl 3 ) 
               
               
                 No. 
                 R 181   
                 R 182    
                 R 183   
                 R 184   
                 R 185   
                 δ ppm or MS 
               
               
                   
               
             
          
           
               
                 230 
                 —Br 
                 —CH 3   
                 —H 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 2.09 (3H, s), 2.41-2.45 (4H, m), 3.01 (3H, s), 3.43 (2H, s), 3.49 (2H, brs), 3.63 (2H, brs), 4.07 (2H, brs), 5.93 (2H, s), 6.51-6.56 (2H, m), 6.68-6.77 (3H, m), 6.85-6.91 (2H, m), 7.68 (1H, dd, J = 8.7 Hz, 2.5 Hz), 8.19 (1H, d, J = 2.5 Hz). 
               
               
                   
               
               
                 231 
                 3,4-Cl 2 PhNHCO— 
                 —H 
                 —CF 3   
                 —H 
                 —N(CH 3 )CH 2 COOC 2 H 5   
                 MS 541 (M + ) 
               
               
                 232 
                 4-CF 3 PhNHCO— 
                 —H 
                 —CF 3   
                 —H 
                 —N(CH 3 )CH 2 COOC 2 H 5   
                 MS 541 (M + ) 
               
               
                 233 
                 3,4-Cl 2 PhCH 2 NHCO— 
                 —H 
                 —CF 3   
                 —H 
                 —N(CH 3 )CH 2 COOC 2 H 5   
                 MS 555 (M + ) 
               
               
                 234 
                 4-CF 3 CH 2 NHCO— 
                 —H 
                 —CF 3   
                 —H 
                 —N(CH 3 )CH 2 COOC 2 H 5   
                 MS 555 (M + ) 
               
               
                 235 
                 —Br 
                 —F 
                 —H 
                 —F 
                 —N(CH 3 )CH 2 COOC 2 H 5   
                   1 H NMR 1.26 (3H, t, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 7.1 Hz), 2.99 (3H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 4.03 (2H, s), 4.18 (2H, q 
               
               
                   
                   
                   
                   
                   
                   
                 J = 7.1 Hz), 6.76 (1H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.2 Hz, 12.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 6.84-6.95 (2H, m), 7.77 
               
               
                   
                   
                   
                   
                   
                   
                 (1H, dd, J = 2.6 Hz, 8.7 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 8.17 (1H, d, J = 2.6 
               
               
                   
                   
                   
                   
                   
                   
                 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 33 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 186   
                 Xa 7   
                 R 187   
                 M 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
             
          
           
               
                 236  
                 —COOC 2 H 5   
                 —CH 2 — 
                 piperonyl 
                 1 
                 (DMSO-d 6 ) 1.31 (3H, t, J = 7.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 2.28 (4H, brs), 2.60-2.66 (2H, m), 2.80- 
               
               
                   
                   
                   
                   
                   
                 2.86 (2H, m), 3.38 (2H, s), 3.40- 
               
               
                   
                   
                   
                   
                   
                 3.46 (4H, m), 4.31 (2H, q, J = 7.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 5.98 (2H, s), 6.72-6.76 (1H, m), 
               
               
                   
                   
                   
                   
                   
                 6.84 (2H, d, J = 8.4 Hz), 7.06-7.11 (3H, 
               
               
                   
                   
                   
                   
                   
                 m), 7.30 (2H, d, J = 8.4 Hz), 8.30 (1H, 
               
               
                   
                   
                   
                   
                   
                 dd, J = 8.6 Hz, 2.4 Hz), 8.68 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 2.4 Hz). 
               
               
                 237 
                 —COOC 2 H 5   
                 none 
                 benzyl 
                 0 
                 (CDCl 3 ) 1.39 (3H, t, J = 7.3 Hz), 
               
               
                   
                   
                   
                   
                   
                 2.48 (4H, brs), 3.55-3.91 (6H, m), 
               
               
                   
                   
                   
                   
                   
                 4.38 (2H, q, J = 7.3 Hz), 6.97 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.6 Hz), 7.17-7.19 (2H, m), 7.20- 
               
               
                   
                   
                   
                   
                   
                 7.34 (5H, m), 7.46-7.49 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 8.31 (1H, dd, J = 8.6 Hz, 2.4 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.82 (1H, d, J = 2.4 Hz). 
               
               
                 238 
                 —Br 
                 —N(CH 3 )— 
                 piperonyl 
                 1 
                 (CDCl 3 ) 2.41-2.45 (4H, m), 3.03 (3H, s), 
               
               
                   
                   
                   
                   
                   
                 3.43 (2H, s), 3.47-3.51 (2H, m), 3.61- 
               
               
                   
                   
                   
                   
                   
                 3.65 (2H, m), 4.09 (2H, s), 5.95 (2H, s), 
               
               
                   
                   
                   
                   
                   
                 6.68-6.85 (6H, m), 6.96-7.02 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 7.70 (1H, dd, J = 8.7 Hz, 2.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.20 (1H, d, J = 2.5 Hz). 
               
               
                 239 
                 —Br 
                 —CH 2 — 
                 piperonyl 
                 1 
                 (CDCl 3 ) 2.31-2.41 (4H, m), 2.59- 
               
               
                   
                   
                   
                   
                   
                 2.65 (2H, m), 2.95-3.00 (2H, m), 3.38- 
               
               
                   
                   
                   
                   
                   
                 3.42 (4H, m), 3.61-3.65 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 5.95 (2H, s), 6.70-6.77 (2H, m), 6.81- 
               
               
                   
                   
                   
                   
                   
                 6.84 (2H, m), 7.01-7.06 (2H, m), 7.22- 
               
               
                   
                   
                   
                   
                   
                 7.27 (2H, m), 7.76 (1H, dd, J = 8.7 Hz, 
               
               
                   
                   
                   
                   
                   
                 2.6 Hz), 8.20-8.21 (1H, m). 
               
               
                 240 
                 —Br 
                 none 
                 benzyl 
                 0 
                 (CDCl 3 ) 2.47 (4H, brs), 3.49-3.55 (6H, 
               
               
                   
                   
                   
                   
                   
                 m), 6.86 (1H, d, J = 8.6 Hz), 7.14 (2H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.6 Hz), 7.28-7.33 (5H, m), 
               
               
                   
                   
                   
                   
                   
                 7.45 (2H, d, J = 8.6 Hz), 7.80 (1H, dd, 
               
               
                   
                   
                   
                   
                   
                 J = 8.6 Hz, 2.5 Hz), 8.22 (1H, d, J = 2.5 
               
               
                   
                   
                   
                   
                   
                 Hz). 
               
               
                 241 
                 —COOCH 3   
                 —N(CH 3 )— 
                 piperonyl 
                 1 
                 (CDCl 3 ) 2.41-2.45 (4H, m), 3.04 (3H, s), 
               
               
                   
                   
                   
                   
                   
                 3.43 (2H, s), 3.47-3.49 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 3.63 (2H, s), 3.91 (3H, s), 4.10 (2H, s), 
               
               
                   
                   
                   
                   
                   
                 5.95 (2H, s), 6.69-6.75 (4H, m), 
               
               
                   
                   
                   
                   
                   
                 6.84 (1H, dd, J = 8.7 Hz, 0.7 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.85 (1H, brs), 7.02 (2H, d, J = 9.2 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.21 (1H, dd, J = 8.7 Hz, 2.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.82 (1H, dd, J = 2.5 Hz, 0.7 Hz). 
               
               
                 242 
                 —COOC 2 H 5   
                 none 
                 piperonyl 
                 0 
                 (CDCl 3 ) 1.39 (3H, t, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 2.45 (4H, brs), 3.45 (2H, s), 3.54- 
               
               
                   
                   
                   
                   
                   
                 3.75 (4H, m), 4.38 (2H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 5.95 (2H, s), 6.71-6.75 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 6.86 (1H, s), 6.97 (1H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.19 (2H, d, J = 8.6 Hz), 7.48 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.7 Hz), 8.30 (1H, dd, J = 2.3 Hz, 8.6 
               
               
                   
                   
                   
                   
                   
                 Hz), 8.82 (1H, d, J = 2.3 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
               
               
               
             
           
               
                 TABLE 34 
               
               
                   
               
               
                 Reference 
                   
                   
               
               
                 Example 
               
               
                 No. 
                 Chemical Structure 
                 MS (M + ) 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 243 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 413 
               
               
                   
               
               
                 244 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 504 
               
               
                   
               
               
                 245 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 413 
               
               
                   
               
               
                 246 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 574 
               
               
                   
               
             
          
         
       
     
       Reference Example 247 
     Production of 4-(5-nitropyridin-2-yloxy)phenylamine 
       [0727]    To a solution of sodium hydroxide (730 mg, 18.25 mmol) in methanol was added 4-aminophenol (2.00 g, 18.32 mmol). After the resulting mixture was made to dissolve, methanol was evaporated under reduced pressure. To the residue was added DMF (20 mL), and then 2-chloro-5-nitropyridine (2.91 g, 18.35 mmol). The reaction solution was stirred for 1.5 hours at 70° C., and then concentrated under reduced pressure. Water was added to the residue, and the resulting solution was extracted with ethyl acetate. The ethyl acetate layer was washed with brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, after which solvent was evaporated, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=1:1), to thereby yield 3.37 g of the title compound. 
         [0728]    Appearance: Black-red powder 
         [0729]      1 H NMR (DMSO-d 6 ) δ 5.10 (2H, s), 6.61 (2H, d, J=8.9 Hz), 6.85 (2H, d, J=8.9 Hz), 7.08 (1H, d, J=9.0 Hz), 8.55 (1H, dd, J=9.0 Hz, 3.0 Hz), 9.01 (1H, d, J=3.0 Hz). 
         [0730]    The following compounds were produced in the same manner as in Reference Example 247. 
         [0000]    
       
         
               
               
               
             
           
               
                 TABLE 35 
               
               
                   
               
               
                 Reference 
                   
                   
               
               
                 Example 
                   
                   
               
               
                 No. 
                 Chemical Structure 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
             
             
               
                 248 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (DMSO-d 6 ) 4.03 (2H, s), 6.96 (1H, d, J = 8.4 Hz), 7.10 (2H, d, J = 8.9 Hz), 7.17 (2H, d, J = 8.9 Hz), 7.48 (2H, d, J = 8.1 Hz), 7.66 (2H, d, J = 8.1 Hz), 7.71 (1H, dd, J = 8.4 Hz, 2.5 Hz), 8.08 (1H, d, J = 2.5 Hz), 9.12 (2H, brs). 
               
               
                   
               
               
                 249 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 1.47 (9H, s), 2.94 (2H, d, J = 5.1 Hz), 3.10-3.80 (9H, m), 4.62 (1H, d, J = 5.1 Hz), 7.03 (1H, d, J = 9.1 Hz), 7.10 (2H, d, J = 8.5 Hz), 7.31 (2H, d, J = 8.5 Hz), 8.46 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.01 (1H, d, J = 2.8 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 36 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
               
               
                 Example 
                   
                   
               
               
                 No. 
                 R 188   
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 250 
                 —CH 2 OH 
                 (CDCl 3 ) 4.74 (2H, s), 7.04 (1H, d, J = 8.9 Hz), 7.13-7.18 (2H, 
               
               
                   
                   
                 m), 7.46 (2H, d, J = 8.3 Hz), 8.48 (1H, dd, J = 8.9 Hz, 2.6 
               
               
                   
                   
                 Hz), 9.03 (1H, d, J = 2.6 Hz). 
               
               
                 251 
                 —(CH 2 ) 2 OH 
                 (CDCl 3 ) 2.91 (2H, t, J = 6.6 Hz), 3.91 (2H, t, J = 6.6 Hz), 
               
               
                   
                   
                 7.03 (1H, d, J = 9.2 Hz), 7.09-7.13 (2H, m), 7.32 (2H, d, J = 
               
               
                   
                   
                 8.6 Hz), 8.47 (1H, dd, J = 9.2 Hz, 3.0 Hz), 9.04 (1H, d, J = 
               
               
                   
                   
                 3.0 Hz). 
               
               
                 252 
                 —(CH 2 ) 2 COOH 
                 (CDCl 3 ) 2.73 (2H, t, J = 7.9 Hz), 3.01 (2H, t, J = 7.9 Hz), 
               
               
                   
                   
                 7.03 (1H, d, J = 8.9 Hz), 7.09 (2H, d, J = 8.6 Hz), 7.30 (2H, 
               
               
                   
                   
                 d, J = 8.6 Hz), 8.47 (1H, dd, J = 9.2 Hz, 3.0 Hz), 9.04 (1H, 
               
               
                   
                   
                 d, J = 2.6 Hz). 
               
               
                 253 
                 —(CH 2 ) 3 COOH 
                 (DMSO-d 6 ) 2.01 (2H, dq, J = 15.0 Hz, 7.2 Hz), 2.46 (2H, t, 
               
               
                   
                   
                 J = 7.2 Hz), 2.72 (2H, t, J = 7.2 Hz), 7.02 (1H, d, J = 8.6 Hz), 
               
               
                   
                   
                 7.08 (2H, d, J = 8.6 Hz), 7.27 (2H, d, J = 8.6 Hz), 8.46 (1H, 
               
               
                   
                   
                 dd, J = 8.6 Hz, 3.0 Hz), 9.04 (1H, d, J = 3.0 Hz). 
               
               
                   
               
             
          
         
       
     
       Reference Example 254 
     Production of ethyl 3-[4-(3-nitrophenoxy)phenyl]-propionate 
       [0731]    Under argon; to a solution of 3-iodonitrobenzene (3.00 g, 12.0 mmol) in pyridine (15 mL) were added ethyl 3-(4-hydroxyphenyl)propionate (2.81 g, 14.5 mmol), copper oxide (3.35 g, 42.2 mmol), and potassium carbonate (4.16 g, 30.1 mmol), and the resulting solution was heated to reflux for 40 hours. The reaction solution was concentrated under reduced pressure. Water and ethyl acetate were added to the residue, and once insoluble matter had been filtered off, and the filtrate was extracted with ethyl acetate out. The ethyl acetate layer was washed with 1 M hydrochloric acid, water and a saturated sodium bicarbonate solution, and then washed with brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=9:1-&gt;6:1), to thereby yield 1.12 g of the title compound. 
         [0732]    Appearance: Pale yellow oil 
         [0733]      1 H NMR (CDCl 3 ) δ 1.23 (3H, t, J=7.1 Hz), 2.62 (2H, t, J=7.7 Hz), 2.95 (2H, t, J=7.7 Hz), 4.12 (2H, q, J=7.1 Hz), 6.96 (2H, d, J=8.6 Hz), 7.22 (2H, d, J=8.6 Hz), 7.29 (1H, dd, J=8.2 Hz, 2.3 Hz), 7.43 (1H, t, J=8.2 Hz), 7.74 (1H, s), 7.90 (1H, dd, J=8.2 Hz, 2.3 Hz). 
       Reference Example 255 
     Production of 1-(t-butoxycarbonyl)-4-[4-(4-nitrophenoxy)phenyl]piperazine 
       [0734]    Potassium carbonate (15.7 g, 114 mmol) was added to a solution of 2-chloro-5-nitropyridine (4.50 g, 28.4 mmol) and 1-(4-hydroxyphenyl)piperazine dihydrochloride (7.13 g, 28.4 mmol) in DMF (80 mL). The resulting solution was stirred at room temperature for 8 hours. To this reaction solution was added di-t-butyl dicarbonate (6.81 g, 31.2 mmol), and stirred at room temperature for 2.5 days. To the reaction solution was charged with ethyl acetate, washed with water, and dried with anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=1:3), to thereby yield 7.05 g of the title compound. 
         [0735]    Appearance: Yellow needles 
         [0736]      1 H NMR (CDCl 3 ) δ 1.49 (9H, s), 3.15 (4H, t, J=5.0 Hz). 
       3.59 (4H, t, J=5.0 Hz), 6.98 (2H, d, J=9.0 Hz), 7.00 (1H, d, J=9.0 Hz), 7.07 (2H, d, J=9.0 Hz), 8.45 (1H, dd, J=9.0 Hz, 2.5 Hz), 9.05 (1H, d, J=2.5 Hz). 
     Reference Example 256 
     Production of (ethyl{3-methoxy-4-[5-(4-trifluoromethylphenylcarbamoyl)pyridin-2-yloxy]phenyl}amino)acetate 
       [0737]    Benzyl[ethyl(4-hydroxy-3-methoxyphenyl)amino]acetate (9.46 g, 30 mmol) and 6-chloro-N-(4-trifluoromethylphenyl)nicotinamide (9.02 g, 30 mmol) were dissolved in DMF (100 mL). To the resulting solution was added potassium carbonate (6.22 g, 45 mmol), and then stirred for 12 hours at 120° C. The reaction solution was concentrated under reduced pressure. To the residue was added ethyl acetate and extracted with water. The pH of the aqueous layer was adjusted from 3 to 4 with 1 M hydrochloric acid, after which the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate, and evaporated to thereby yield 4.2 g of the title compound. 
         [0738]    Appearance: Brown powder 
         [0739]      1 H NMR (DMSO-d 6 ) δ 1.19 (3H, t, J=7.1 Hz), 3.40 (2H, q, J=7.1 Hz), 3.63 (3H, s), 4.01 (2H, s), 6.17 (1H, d, J=8.9 Hz), 6.22 (1H, brs), 6.25 (1H, d, J=2.5 Hz), 6.87-6.90 (2H, m), 7.53 (2H, d, J=8.6 Hz), 7.76 (2H, d, J=8.4 Hz), 8.18 (1H, dd, J=8.7 Hz, 2.3 Hz), 8.67 (1H, d, J=2.1 Hz), 8.88 (1H, brs). 
       Reference Example 257 
     Production of ethyl methyl[2,5-difluoro-4-(5-nitropyridin-2-yloxy)phenyl]aminoacetate 
       [0740]    To a solution of ethyl(2,5-difluoro-4-hydroxyphenyl)aminoacetate (1.1 g, 4.8 mmol) in DMF (25 mL) were added sodium bicarbonate (0.44 g, 5.2 mmol) and methyl iodide (1.69 mL, 28.6 mmol), and the resulting reaction solution was stirred for 2 days at room temperature. Water was added to the reaction mixture, and extracted with ethyl acetate. Once the ethyl acetate layer had been washed with water, the ethyl acetate layer was dried with anhydrous magnesium sulfate, and evaporated. The residue was dissolved in DMF (30 mL), and to this resulting solution were added potassium carbonate (0.72 g, 5.2 mmol) and 2-chloro-5-nitropyridine (0.79 g, 5.0 mmol). The reaction solution was stirred for 2.5 days at room temperature. Water was added to the reaction mixture, and extracted with ethyl acetate. The ethyl acetate layer was washed with water, and dried over anhydrous magnesium sulfate. The solvent was then evaporated, and the residue was purified by silica gel chromatography (n-hexane:ethyl acetate=8:1), to thereby yield 1.41 g of the title compound. 
         [0741]    Appearance: Yellow oil 
         [0742]      1 H NMR (CDCl 3 ) δ 1.27 (3H, t, J=7.1 Hz), 3.01 (3H, s), 4.05 (2H, s), 4.19 (2H, q, J=7.1 Hz), 6.77 (1H, dd, J=8.2 Hz, 12.2 Hz), 6.92 (1H, dd, J=7.2 Hz, 12.8 Hz), 8.49 (1H, dd, J=2.8 Hz, 9.0 Hz), 9.02 (1H, d, J=2.8 Hz). 
         [0743]    The following compounds were produced in the same manner as in Reference Example 257. 
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 37 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 189   
                 R 190   
                 R 191   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 258 
                 —NO 2   
                 —CH 3   
                 —CH 3   
                 1.27 (3H, t, J = 7.1 Hz), 2.05 (3H, s), 2.29 (3H, s), 
               
               
                   
                   
                   
                   
                 2.87 (3H, s), 3.71 (2H, s), 4.18 (2H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 6.87 (1H, d, J = 8.7 Hz), 6.97 (1H, dd, J = 9.1 Hz, 
               
               
                   
                   
                   
                   
                 0.3 Hz), 7.08 (1H, d, J = 8.7 Hz), 8.45 (1H, dd, 
               
               
                   
                   
                   
                   
                 J = 9.1 Hz, 2.8 Hz), 9.04 (1H, dd, J = 2.8 Hz, 
               
               
                   
                   
                   
                   
                 0.3 Hz). 
               
               
                 259 
                 4-CF 3 PhCO— 
                 —H 
                 —C 2 H 5   
                 1.23 (3H, t, J = 7.1 Hz), 1.28 (3H, t, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 2.12 (3H, s), 3.46 (2H, q, J = 7.1 Hz), 4.01 (2H, s), 
               
               
                   
                   
                   
                   
                 4.21 (2H, q, J = 7.1 Hz), 6.49-6.53 (2H, m), 6.92- 
               
               
                   
                   
                   
                   
                 6.96 (2H, m), 7.73-7.77 (2H, m), 7.86-7.89 (2H, 
               
               
                   
                   
                   
                   
                 m), 8.17 (1H, dd, J = 8.7 Hz, 2.5 Hz), 8.59 (1H, 
               
               
                   
                   
                   
                   
                 dd, J = 2.5 Hz, 0.7 Hz). 
               
               
                   
               
             
          
         
       
     
       Reference Example 260 
     Production of ethyl 4-{3-[3-methyl-4-(5-nitropyridin-2-yloxy)phenyl]-2-oxotetrahydropyrimidin-1-yl}benzoate 
       [0744]    Under a nitrogen atmosphere, to a solution of ethyl 4-[3-(4-benzyloxy-3-methyl)phenyl-2-oxotetrahydropyrimidin-1-yl]benzoate (1.82 g, 3.1 mmol) in ethanol-DMF (70 mL-30 mL) was added 10% palladium-carbon (0.4 g), and the resulting solution was stirred under a hydrogen atmosphere for 4 hours at room temperature. The resulting solution was filtered through Celite, and ethanol was evaporated under reduced pressure so as to give a DMF (30 mL) solution. To this solution was addded 2-chloro-5-nitropyridine (0.52 g, 3.3 mmol) and stirred under a nitrogen atmosphere for 14 hours at room temperature, and then for 3 hours at 40° C. Water was added to the reaction mixture, and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel chromatography (n-hexane:ethyl acetate=10:1), to thereby yield 1.8 g of the title compound. 
         [0745]    Appearance: White powder 
         [0746]      1 H NMR (CDCl 3 ) δ 1.39 (3H, t, J=7.1 Hz), 2.14 (3H, s), 2.21-2.40 (2H, m), 3.75-3.97 (4H, m), 4.36 (2H, q, J=7.1 Hz), 7.01 (1H, d, J=9.1 Hz), 7.06 (1H, d, J=8.6 Hz), 7.23 (1H, dd, J=2.6 Hz, 8.6 Hz), 7.32 (1H, d, J=2.6 Hz), 7.40-7.49 (2H, m), 7.97-8.07 (2H, m), 8.46 (1H, dd, J=2.8 Hz, 9.1 Hz), 9.04 (1H, d, J=2.8 Hz). 
       Reference Example 261 
     Production of 3-[4-(5-nitropyridin-2-ylsulfanyl)phenyl]propionic acid 
       [0747]    To a solution of 2-chloro-5-nitropyridine (1.74 g, 11.0 mmol) and 4-mercaptohydrocinnamic acid (2.00 g, 11.0 mmol) in DMF (30 mL) was added potassium carbonate (4.55 g, 32.9 mmol), and the resulting solution was stirred for 1 hour at 80° C. To the reaction solution were added water and concentrated hydrochloric acid, and then cooled with ice. The precipitated solid matter was collected by filtration, to thereby yield 3.29 g of the title compound. 
         [0748]    Appearance: Pale yellow powder 
         [0749]      1 H NMR (DMSO-d 6 ) δ 2.60 (2H, t, J=7.5 Hz), 2.91 (2H, t, J=7.5 Hz), 7.07 (1H, d, J=9.0 Hz), 7.43 (2H, d, J=8.2 Hz), 7.57 (2H, d, J=8.2 Hz), 8.39 (1H, dd, J=2.8 Hz, 9.0 Hz), 9.17 (1H, d, J=2.8 Hz), 12.19 (1H, s). 
       Reference Example 262 
     Production of ethyl 3-[3-methoxy-4-(5-nitropyridin-2-ylamino)phenyl]propionate 
       [0750]    To 2-chloro-5-nitropyridine (3.11 g, 20 mmol) were added ethyl 3-(4-amino-3-methoxyphenyl)propionate (4.38 g, 20 mmol) and acetic acid (10 mL), and the resulting solution was stirred for 13 hours at 100° C. To the reaction solution were added ethyl acetate and water. The ethyl acetate layer was separated, washed with brine, a saturated sodium bicarbonate solution and brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=2:1), to thereby yield 3.78 g of the title compound. 
         [0751]    Appearance: Yellow powder 
         [0752]      1 H NMR (CDCl 3 ) δ 1.26 (3H, t, J=7.1 Hz), 2.61-2.67 (2H, m), 2.93-2.99 (2H, m), 3.89 (3H, s), 4.15 (2H, q, J=7.1 Hz), 6.73 (1H, d, J=9.2 Hz), 6.81-6.87 (2H, m), 7.43 (1H, brs), 7.92 (1H, d, J=8.1 Hz), 8.23 (1H, dd, J=9.2 Hz, 2.8 Hz), 9.11 (1H, d, J=2.8 Hz). 
         [0753]    The following compounds were produced in the same manner as in Reference Example 262. 
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 38 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
               
               
                 Example 
                   
                   
               
               
                 No. 
                 R 192   
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 263 
                 —COOC 2 H 5   
                 (DMSO-d 6 ) 1.32 (3H, t, J = 7.1 Hz), 4.29 (2H, q, J = 7.1 
               
               
                   
                   
                 Hz), 7.01 (1H, d, J = 9.3 Hz), 7.89 (2H, d, J = 8.9 Hz), 
               
               
                   
                   
                 8.36 (1H, dd, J = 2.9 Hz, 9.3 Hz), 9.09 (1H, d, J = 2.9 
               
               
                   
                   
                 Hz), 10.43 (1H, s). 
               
               
                 264 
                 —(CH 2 ) 2 COOC 2 H 5   
                 (CDCl 3 ) 1.25 (3H, t, J = 7.1 Hz), 2.64 (2H, t, J = 7.6 Hz), 
               
               
                   
                   
                 2.97 (2H, t, J = 7.6 Hz), 4.14 (2H, q, J = 7.1 Hz), 
               
               
                   
                   
                 6.73 (1H, d, J = 9.3 Hz), 7.20-7.40 (4H, m), 8.23 (1H, dd, 
               
               
                   
                   
                 J = 2.7 Hz, 9.3 Hz), 9.07 (1H, d, J = 2.7 Hz). 
               
               
                   
               
               
                 265 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 1.30 (3H, t, J = 7.1 Hz), 2.77 (4H, t, J = 5.0 Hz), 3.28 (4H, t, J = 5.0 Hz), 3.28 (2H, s), 4.22 (2H, q, J = 7.1 Hz), 6.61 (1H, d, J = 9.4 Hz), 6.95 (2H, d, J = 9.0 Hz), 7.11 (1H, brs), 7.22 (2H, d, J = 9.0 Hz), 8.18 (1H, dd, J = 9.4 Hz, 2.5 Hz), 9.05 (1H, d, J = 2.5 Hz). 
               
               
                   
               
               
                 266 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 1.28 (3H, t, J = 7.1 Hz), 1.32-1.60 (2H, m), 1.75- 2.12 (3H, m), 2.29 (2H, d, J = 6.9 Hz), 2.77 (2H, td, J = 12.4 Hz, 2.4 Hz), 3.68 (2H, d, J = 12.4 Hz), 4.16 (2H, q, J = 7.1 Hz), 6.60 (1H, d, J = 9.2 Hz), 6.96 (2H, d, J = 8.9 Hz), 7.16 (1H, brs), 7.20 (2H, d, J = 8.9 Hz), 8.18 (1H, dd, J = 9.2 Hz, 2.6 Hz), 9.05 (1H, d, J = 2.6 Hz). 
               
               
                   
               
             
          
         
       
     
       Reference Example 267 
     Production of 4-[(5-nitro-2-pyridyl)oxy]benzaldehyde ethylene acetal 
       [0754]    To a solution of 4-[(5-nitro-2-pyridyl)oxy]benzaldehyde (5.00 g, 20.5 mmol) in benzene (100 mL) were added ethylene glycol (2.28 mL, 41.0 mmol) and p-toluenesulfonic acid (0.50 g), and the resulting solution was heated to reflux for 3 hours while removing water with a Dean-Stark. The reaction solution was washed with a saturated sodium bicarbonate solution, and subsequently washed with brine. The benzene layer was dried over anhydrous magnesium sulfate, and evaporated, to thereby yield 5.88 g of the title compound. 
         [0755]    Appearance: Yellow powder 
         [0756]      1 H NMR (CDCl 3 ) δ 4.00-4.19 (4H, m), 5.83 (1H, s), 7.00 (1H, d, J=9.0 Hz), 7.15 (2H, d, J=8.5 Hz), 7.55 (2H, d, J=8.5 Hz), 8.45 (1H, dd, J=9.0 Hz, 2.0 Hz), 9.01 (1H, d, J=2.0 Hz). 
         [0757]    The following compound was produced in the same manner as in Reference Example 267. 
       Reference Example 268 
     4-(2-Fluoro-4-nitrophenoxybenzaldehyde ethylene acetal 
       [0758]      1 H NMR (DMSO-d 6 ) δ 3.90-4.10 (4H, m), 5.76 (1H, s), 7.15-7.25 (3H, m), 7.54 (2H, d, J=8.7 Hz), 8.10 (1H, ddd, J=1.3 Hz, 2.7 Hz, 9.1 Hz), 8.35 (1H, dd, J=2.7 Hz, 10.8 Hz). 
       Reference Example 269 
     Production of t-butyl[4-(5-nitropyridin-2-yloxy)phenyl]carbamate 
       [0759]    To a solution of 4-(5-nitropyridin-2-yloxy)phenylamine (2.97 g, 12.85 mmol) in THF was added di-t-butyl dicarbonate (5.60 g, 25.66 mmol), and the resulting solution was stirred under reflux for 4 hours. The reaction solution was concentrated under reduced pressure. Water was added to the residue, and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, evaporated, and to the resulting product was added diethyl ether. The obtained white powder was filtered, and the resulting product was washed with diethyl ether, to thereby yield 3.04 g of the title compound. 
         [0760]    Appearance: Yellow powder 
         [0761]      1 H NMR (CDCl 3 ) δ 1.53 (9H, s), 6.53 (1H, brs), 7.00 (1H, d, J=9.2 Hz), 7.09 (2H, d, J=8.9 Hz), 7.45 (2H, d, J=8.9 Hz), 8.46 (1H, dd, J=9.2 Hz, 3.0 Hz), 9.03 (1H, d, J=3.0 Hz). 
       Reference Example 270 
     Production of 5-[3-methyl-4-(5-nitropyridin-2-yloxy)benzylidene]thiazolidine-2,4-dione 
       [0762]    To a solution of 3-methyl-4-(5-nitropyridin-2-yloxy)benzaldehyde (600 mg, 2.32 mmol) in toluene (35 mL) were added 2,4-thiazolidinedione (270 mg, 2.31 mmol) and piperidine acetate (135 mg, 0.93 mmol). The resulting solution was attached to a Dean Stark, and stirred under reflux for 1.5 hours. After being left to cool for 17 hours at room temperature, the precipitated yellow powder was filtered, to thereby yield 600 mg of the title compound. 
         [0763]    Appearance: Yellow powder 
         [0764]      1 H NMR (DMSO-d 6 ) δ 2.15 (3H, s), 7.33 (1H, d, J=8.4 Hz), 7.35 (1H, d, J=9.1 Hz), 7.52 (1H, dd, J=8.4 Hz, 2.0 Hz), 7.59 (1H, d, J=2.0 Hz), 7.79 (1H, s), 8.65 (1H, dd, J=9.1 Hz, 3.0 Hz), 9.02 (1H, d, J=3.0 Hz), 12.63 (1H, brs). 
         [0765]    The following compounds were produced in the same manner as in Reference Example 270. 
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 39 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
               
               
                 Example 
                   
                   
               
               
                 No. 
                 R 193   
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 271 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (DMSO-d 6 ) 7.35 (1H, d, J = 9.0 Hz), 7.42 (2H, d, J = 8.6 Hz), 7.71 (2H, d, J = 8.6 Hz), 7.84 (1H, s), 8.65 (1H, dd, J = 9.0 Hz, 2.9 Hz), 9.04 (1H, d, J = 2.9 Hz), 12.64 (1H, brs). 
               
               
                   
               
               
                 272 
                 —CH═C(COOCH 3 ) 2   
                 (CDCl 3 ) 3.87 (6H, s), 7.09 (1H, d, J = 9.0 Hz), 7.20 (2H, d, 
               
               
                   
                   
                 J = 8.5 Hz), 7.53 (2H, d, J = 8.5 Hz), 7.77 (1H, s), 
               
               
                   
                   
                 8.51 (1H, dd, J = 9.0 Hz, 2.8 Hz), 9.04 (1H, d, J = 2.8 Hz). 
               
               
                   
               
             
          
         
       
     
       Reference Example 273 
     Production of N-[4-(2-fluoro-4-nitrophenoxy)phenyl]-N-[2-(4-piperonylpiperazin-1-yl)-2-oxyethyl]acetamide 
       [0766]    To a solution of N-[4-(2-fluoro-4-nitrophenoxy)phenyl]acetamide (0.800 g, 2.76 mmol) in DMF (5 mL) was added 60% sodium hydride (0.118 g, 2.95 mmol). The resulting solution was stirred for 10 minutes at room temperature, after which a solution of 1-chloroacetyl-4-piperonylpiperazine (0.870 g, 2.96 mmol) in DMF (4 mL) was added to the reaction solution. The reaction solution was stirred for 2 hours at 60° C., and then for 1 hour at 100° C. Water was added to the reaction mixture, and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous sodium sulfate, evaporated, and the residue was purified by silica gel column chromatography (dichloromethane:methanol=5:1), to thereby yield 0.730 g of the title compound. 
         [0767]    Appearance: Yellow oil 
         [0768]      1 H NMR (DMSO-d 6 ) δ 1.82 (3H, s), 2.20-2.40 (4H, m), 3.30-3.50 (6H, m), 4.43 (2H, s), 5.98 (2H, s), 6.70-6.85 (3H, m), 7.20-7.30 (3H, m), 7.48 (2H, d, J=8.8 Hz), 8.12 (1H, ddd, J=1.4 Hz, 2.7 Hz, 10.5 Hz), 8.36 (1H, dd, J=2.7 Hz, 10.7 Hz). 
         [0769]    The following compound was produced in the same manner as in Reference Example 273. 
       Reference Example 274 
     3-(4-Benzyloxy-3-methylphenyl)-1-[2-oxo-2-(4-piperonylpiperazin-1-yl)ethyl]tetrahydropyrimidin-2-one 
       [0770]      1 H NMR (DMSO-d 6 ) δ 1.92-2.08 (2H, m), 2.15 (3H, s), 2.22-2.40 (4H, m), 3.25-3.49 (8H, m), 3.56 (2H, d, J=5.6 Hz), 4.08 (2H, s), 5.09 (2H, s), 5.97 (2H, s), 6.74 (1H, dd J=1.3 Hz, 7.9 Hz), 6.84 (1H, d, J=7.9 Hz), 6.85 (1H, d, J=1.3 Hz), 6.91 (1H, d, J=8.7 Hz), 6.95 (1H, dd, J=2.5 Hz, 8.6 Hz), 7.01 (1H, d, J=2.5 Hz), 7.28-7.34 (1H, m), 7.36-7.41 (2H, m), 7.42-7.48 (2H, m). 
       Reference Example 275 
     Production of 2-dimethylamino-N-[4-(5-nitropyridin-2-yloxy)phenyl]-N-[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]acetamide 
       [0771]    To a solution of 2-chloro-N-[4-(5-nitropyridin-2-yloxy)phenyl]-N-[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]acetamide (0.300 g, 0.528 mmol) in acetonitrile (3 mL) was added at room temperature dimethylamine (0.150 mL, 1.63 mmol), and the resulting solution was stirred for 2 hours at 50° C. Water was added to the reaction mixture, and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous sodium sulfate, evaporated, and the residue was purified by silica gel column chromatography (dichloromethane:methanol=10:1), to thereby yield 0.270 g of the title compound. 
         [0772]    Appearance: Yellow powder 
         [0773]      1 H NMR (CDCl 3 ) δ 2.29 (6H, s), 2.40-2.45 (4H, m), 3.02 (2H, s), 3.40-3.46 (4H, m), 3.61 (2H, s), 4.48 (2H, s), 5.95 (2H, s), 6.70-6.77 (2H, m), 6.84 (1H, s), 7.09 (1H, d, J=9.0 Hz), 7.19 (2H, d, J=8.7 Hz), 7.51 (2H, d, J=8.7 Hz), 8.51 (1H, dd, J=2.8 Hz, 9.0 Hz), 9.04 (1H, d, J=2.8 Hz). 
       Reference Example 276 
     Production of methyl 2-[4-(5-nitropyridin-2-yloxy)phenyl]propionate 
       [0774]    To a solution of methyl 2-[4-(5-nitropyridin-2-yloxy)phenyl]acetate (0.50 g, 1.7 mmol) in DMF (10 mL) were added 60% sodium hydride (0.153 g, 3.8 mmol) and methyl iodide (0.13 mL, 2.1 mmol), and the resulting reaction solution was stirred for 1 hour at 0° C. To the reaction solution was added saturated aqueous ammonium chloride, and extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated aqueous sodium chloride. The ethyl acetate layer was dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by silica gel chromatography (n-hexane:ethyl acetate=8:1), to thereby yield 0.32 g of the title compound. 
         [0775]    Appearance: Colorless oil 
         [0776]      1 H NMR (CDCl 3 ) δ 1.54 (3H, d, J=7.4 Hz), 3.69 (3H, s), 3.78 (1H, q, J=7.2 Hz), 7.03 (1H, d, J=9.1 Hz), 7.09-7.15 (2H, m), 7.36-7.41 (2H, m), 8.48 (1H, dd, J=9.1, 2.8 Hz), 9.05 (1H, d, J=2.8 Hz). 
       Reference Example 277 
     Production of ethyl 3-{3-methoxy-4-[methyl(5-nitropyridin-2-yl)amino]phenyl}propionate 
       [0777]    To a solution of ethyl 3-[3-methoxy-4-(5-nitropyridin-2-ylamino)phenyl]propionate (3.70 g, 11 mmol) in DMF (60 mL) were added under ice-cooling sodium hydride (60%, 490 mg, 12 mmol) and methyl iodide (0.77 mL, 12 mmol), and the resulting reaction solution was stirred for 2 hours gradually warming up to room temperature. The reaction solution was concentrated under reduced pressure. To the residue was added ethyl acetate, washed with water and brine, and then dried with anhydrous magnesium sulfate. The solvent was evaporated, to thereby yield 4.27 g of the title compound. 
         [0778]    Appearance: Yellow oil substance 
         [0779]      1 H NMR (CDCl 3 ) δ 1.27 (3H, t, J=7.1 Hz), 2.66-2.71 (2H, m), 2.98-3.04 (2H, m), 3.46 (3H, s), 3.78 (3H, s), 4.17 (2H, q, J=7.1 Hz), 6.12 (1H, brd, J=9.5 Hz), 6.87-6.90 (2H, m), 7.11-7.14 (1H, m), 7.97-8.02 (1H, m), 9.11 (1H, d, J=2.7 Hz). 
         [0780]    The following compounds were produced in the same manner as in Reference Example 277. 
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 40 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 194   
                 R 195   
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
             
          
           
               
                 278 
                 —CH 3   
                 —COOC 2 H 5   
                 (DMSO-d 6 ) 1.34 (3H, t, J = 7.1 
               
               
                   
                   
                   
                 Hz), 3.56 (3H, s), 4.34 (2H, q, J = 
               
               
                   
                   
                   
                 7.1 Hz), 6.70 (1H, d, J = 9.5 Hz), 
               
               
                   
                   
                   
                 7.55 (2H, d, J = 8.6 Hz), 8.06 (2H, 
               
               
                   
                   
                   
                 d, J = 8.6 Hz), 8.21 (1H, dd, J = 
               
               
                   
                   
                   
                 2.8 Hz, 9.5 Hz), 9.05 (1H, d, J = 
               
               
                   
                   
                   
                 2.8 Hz). 
               
               
                 279 
                 —CH 3   
                 —(CH 2 ) 2 COOC 2 H 5   
                 (CDCl 3 ) 1.26 (3H, t, J = 7.1 Hz), 
               
               
                   
                   
                   
                 2.67 (2H, t, J = 7.6 Hz), 3.01 (2H, 
               
               
                   
                   
                   
                 t, J = 7.6 Hz), 3.55 (3H, s), 
               
               
                   
                   
                   
                 4.15 (2H, q, J = 7.1 Hz), 6.32 (1H, 
               
               
                   
                   
                   
                 d, J = 9.5 Hz), 7.17 (2H, d, J = 8.3 
               
               
                   
                   
                   
                 Hz), 7.32 (2H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                 8.01 (1H, dd, J = 2.7 Hz, 9.5 Hz), 
               
               
                   
                   
                   
                 9.11 (1H, d, J = 2.7 Hz). 
               
               
                 280 
                 benzyl 
                 —(CH 2 ) 2 COOC 2 H 5   
                 (CDCl 3 ) 1.24 (3H, t, J = 7.2 Hz), 
               
               
                   
                   
                   
                 2.64 (2H, t, J = 7.7 Hz), 2.97 (2H, 
               
               
                   
                   
                   
                 t, J = 7.7 Hz), 4.14 (2H, q, J = 7.2 
               
               
                   
                   
                   
                 Hz), 5.27 (2H, s), 6.26 (1H, d, J = 
               
               
                   
                   
                   
                 9.5 Hz), 7.06 (2H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                 7.20-7.30 (7H, m), 8.02 (1H, dd, 
               
               
                   
                   
                   
                 J = 2.7 Hz, 9.5 Hz), 9.12(1H, d, 
               
               
                   
                   
                   
                 J = 2.7 Hz). 
               
               
                   
               
               
                 281 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 1.30 (3H, t, J = 7.1 Hz), 2.78 (4H, t, J = 5.0 Hz), 3.30 (2H, s), 3.31 (4H, t, J = 5.0 Hz), 3.53 (3H, s), 4.22 (2H, q, J = 7.1 Hz), 6.30 (1H, d, J = 9.5 Hz), 6.99 (2H, d, J = 8.9 Hz), 7.12 (2H, d, J = 8.9 Hz), 7.99 (1H, dd, J = 9.5 Hz, 2.8 Hz), 9.10 (1H, d, J = 2.8 Hz). 
               
               
                   
               
               
                 282 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 1.28 (3H, t, J = 7.1 Hz), 1.45 (2H, qd, J = 12.2 Hz, 3.7 Hz), 1.80-2.17 (3H, m), 2.30 (2H, d, J = 6.9 Hz), 2.80 (2H, td, J = 12.2 Hz, 2.3 Hz), 3.52 (3H, s), 3.72 (2H, d, J = 12.4 Hz), 4.16 (2H, q, J = 7.1 Hz), 6.30 (1H, d, J = 9.5 Hz), 6.98 (2H, d, J = 8.9 Hz), 7.10 (2H, d, J = 8.9 Hz), 7.98 (1H, dd, J = 9.5 Hz, 2.8 Hz), 9.10 (1H, d, J = 2.8 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
               
               
               
             
           
               
                 TABLE 41 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 196   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
             
          
           
               
                 283  
                 —(CH 2 ) 2 CH 3   
                 0.93 (3H, t, J = 7.4 Hz), 1.60-1.70 (2H, m), 
               
               
                   
                   
                 2.35-2.43 (4H, m), 2.66 (2H, t, J = 8.1 Hz), 
               
               
                   
                   
                 3.03 (2H, t, J = 8.1 Hz), 3.42 (2H, s), 3.43- 
               
               
                   
                   
                 3.45 (2H, m), 3.62-3.65 (2H, m), 3.96 (2H, 
               
               
                   
                   
                 t, J = 7.7 Hz), 5.95 (2H, s), 6.16 (1H, d, J = 
               
               
                   
                   
                 9.5 Hz), 6.70-6.80 (2H, m), 6.84 (1H, d, J = 
               
               
                   
                   
                 1.3 Hz), 7.14 (2H, d, J = 8.3 Hz), 7.33 (2H, 
               
               
                   
                   
                 d, J = 8.3 Hz), 7.96 (1H, dd, J = 2.8 Hz, 9.5 
               
               
                   
                   
                 Hz), 9.08 (1H, d, J = 2.8 Hz). 
               
               
                 284 
                 cyclopentyl 
                 1.30-1.40 (2H, m), 1.55-1.65 (4H, m), 1.95- 
               
               
                   
                   
                 2.00 (2H, m), 2.35-2.45 (4H, m), 2.67 (2H, 
               
               
                   
                   
                 t, J = 7.4 Hz), 3.04 (2H, t, J = 7.4 Hz), 3.42 
               
               
                   
                   
                 (2H, s), 3.43-3.47 (2H, m), 3.55-3.68 (2H, 
               
               
                   
                   
                 m), 5.18-5.28(1H, m), 5.88 (1H, d, J = 9.5 
               
               
                   
                   
                 Hz), 5.95 (2H, s), 6.70-6.78 (2H, m), 6.84 
               
               
                   
                   
                 (1H, s), 7.04 (2H, d, J = 8.2 Hz), 7.34 (2H, 
               
               
                   
                   
                 d, J = 8.2 Hz), 7.92 (1H, dd, J = 2.8 Hz, 9.5 
               
               
                   
                   
                 Hz), 9.09 (1H, d, J = 2.8 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
               
               
               
             
           
               
                 TABLE 42 
               
               
                   
               
               
                 Reference 
                   
                   
               
               
                 Example 
               
               
                 No. 
                 Chemical Structure 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 285 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 1.91-2.06 (2H, m), 2.27 (3H, s), 3.31-3.44 (2H, m), 3.58 (2H, t, J = 6.3 Hz), 4.69-4.85 (1H, m), 5.07 (2H, s), 6.04 (1H, s), 6.84 (1H, d, J = 10.1 Hz), 7.01 (1H, dd, J = 8.5 Hz, 2.5 Hz), 7.04 (1H, d, J = 2.5 Hz), 7.30-7.36 (1H, m), 7.37- 7.46 (4H, m). 
               
               
                   
               
               
                 286 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 1.96-2.11 (2H, m), 2.27 (3H, s), 3.20-3.34 (2H, m), 3.56-3.68 (2H, m), 4.50 (2H, s), 5.07 (2H, s), 5.94 (2H, s), 6.72-6.80 (2H, m), 6.84 (1H, d, J = 8.6 Hz), 6.88 (1H, d, J = 1.2 Hz), 7.04 (1H, dd, J = 2.6 Hz, 8.6 Hz), 7.11 (1H, d, J = 2.6 Hz), 7.28-7.34 (1H, m), 7.35- 7.41 (2H, m), 7.42-7.48 (2H, m). 
               
               
                   
               
               
                 287 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (DMSO-d 6 ) 3.20-3.40 (2H, m), 3.71 (3H, s), 3.64-3.83 (2H, m), 4.36 (2H, s), 6.84-6.95 (2H, m), 7.22- 7.41 (5H, m), 7.42-7.53 (2H, m). 
               
               
                   
               
               
                 288 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (DMSO-d 6 ) 2.18 (3H, s), 3.35 (2H, t, J = 8.7 Hz), 3.69-3.84 (2H, m), 5.05 (2H, s), 6.74 (1H, s), 6.93 (1H, d, J = 8.9 Hz), 7.23 (1H, dd, J = 2.8 Hz, 8.9 Hz), 7.27-7.48 (6H, m). 
               
               
                   
               
               
                 289 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 2.29 (3H, s), 3.28-3.39 (2H, m), 3.68-3.81 (2H, m), 4.36 (2H, s), 5.06 (2H, s), 5.95 (2H, s), 6.77 (2H, s), 6.78-6.91 (2H, m), 7.20-7.35 (2H, m), 7.36-7.51 (5H, m). 
               
               
                   
               
               
                 290 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 1.93-2.12 (2H, m), 2.27 (3H, s), 3.28 (2H, t, J = 5.9 Hz), 3.63 (2H, t, J = 5.9 Hz), 3.88 (6H, s), 4.55 (2H, s), 5.07 (2H, s), 6.71-6.92 (4H, m), 6.96-7.08 (1H, m), 7.11 (1H, d, J = 2.1 Hz), 7.25-7.51 (5H, m). 
               
               
                   
               
             
          
         
       
     
       Reference Example 291 
     Production of N-[4-(5-nitropyridin-2-yloxy)phenyl]-2-(4-piperonylpiperazin-1-yl)acetamide 
       [0781]    A solution of (4-piperonylpiperazin-1-yl)acetic acid (13.9 g, 50 mmol) was suspended in DMF (400 mL), and to the resulting suspension were added 1-hydroxybenzotriazole monohydrate (8.42 g, 55 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (10.5 g, 55 mmol) and 4-(5-nitropyridin-2-yloxy)phenylamine (11.6 g, 50 mmol) under ice cooling. The resulting solution was stirred for 6 hours at room temperature. The reaction solution was concentrated under reduced pressure. To the residue was added ethyl acetate, and washed with a saturated sodium bicarbonate solution and brine. The organic layer was left for standing overnight at room temperature, and the resulting precipitated crystals were collected by suction filtration, to thereby yield 12.8 g of the title compound. 
         [0782]    Appearance: White powder 
         [0783]      1 H NMR (CDCl 3 ) δ 2.53 (4H, brs), 2.64-2.65 (4H, m), 3.15 (2H, s), 3.46 (2H, s), 5.95 (2H, s), 6.76 (2H, brs), 6.86 (1H, s), 7.04 (1H, d, J=9.1 Hz), 7.14 (2H, d, J=8.7 Hz), 7.67 (2H, d, J=8.9 Hz), 8.47 (1H, dd, J=9.1 Hz, 2.8 Hz), 9.03 (1H, d, J=2.8 Hz), 9.24 (1H, brs). 
       Reference Example 292 
     Production of ethyl{methanesulfonyl[3-methoxy-4-(5-nitropyridin-2-yloxy)phenyl]amino}acetate 
       [0784]    A solution of ethyl[3-methoxy-4-(5-nitropyridin-2-yloxy)phenylamino]acetate (2.43 g, 7.00 mmol) was dissolved in THF (15 mL), dichloromethane (20 mL) and DMF (10 mL), and to the resulting solution were added triethylamine (1.95 mL, 13.99 mmol), 4-dimethylaminopyridine (0.86 g, 7.00 mmol) and methanesulfonyl chloride (1.08 mL, 13.99 mmol) under ice cooling. The resulting solution was stirred for 14 hours at 30° C. Water was added to the reaction mixture, and extracted with dichloromethane. The dichloromethane layer was washed with water and brine. The dichloromethane layer was dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=1:2), to thereby yield 1.10 g of the title compound. 
         [0785]    Appearance: Yellow oil 
         [0786]    1H NMR (CDCl 3 ) δ 1.32 (3H, t, J=7.3 Hz), 3.18 (3H, s), 3.75 (3H, s), 4.26 (2H, q, J=7.3 Hz), 4.49 (2H, s), 7.09 (1H, d, J=9.1 Hz), 7.15 (2H, d, J=1.2 Hz), 7.25 (1H, s), 8.48 (1H, dd, J=9.1 Hz, 2.8 Hz), 8.98 (1H, d, J=2.8 Hz). 
         [0787]    The following compounds were produced in the same manner as in Reference Example 292. 
         [0000]    
       
         
               
               
               
             
           
               
                 TABLE 43 
               
               
                   
               
               
                 Reference 
                   
                   
               
               
                 Example 
                   
                   
               
               
                 No. 
                 Chemical Structure 
                   1 H NMR (solvent) δ ppm or MS 
               
               
                   
               
             
             
               
                 293 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (DMSO-d 6 ) 3.00 (3H, s), 5.17 (2H, s), 7.05 (1H, d, J = 8.4 Hz), 7.12 (2H, d, J = 8.9 Hz), 7.19-7.26 (4H, m), 7.67 (2H, d, J = 8.9 Hz), 7.95 (1H, dd, J = 8.4 Hz, 2.5 Hz), 8.25 (1H, d, J = 2.3 Hz), 9.69 (1H, brs). 
               
               
                   
               
               
                 294 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (CDCl 3 ) 2.18 (3H, s), 3.04 (3H, s), 5.04 (2H, s), 6.56 (1H, brs), 6.96 (1H, d, J = 8.6 Hz), 7.01-7.09 (4H, m), 7.15 (1H, d, J = 2.6 Hz), 7.56 (2H, d, J = 8.4 Hz), 7.79 (1H, dd, J = 8.6 Hz, 2.5 Hz), 8.19 (1H, d, J = 2.5 Hz). 
               
               
                   
               
               
                 295 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 364 (M + ) 
               
               
                   
               
             
          
         
       
     
       Reference Example 296 
     Production of 3-[4-(5-nitropyridin-2-yloxy)phenyl]-n-propanol 
       [0788]    To a solution of 3-[4-(5-nitropyridin-2-yloxy)phenyl]propionic acid (2.64 g, 9.2 mmol) in THF (50 mL) was added dropwise a 1 M borane-THF complex THF solution (38.4 mL, 38.4 mmol) under ice cooling. The reaction solution was stirred for 2 hours at room temperature. Water was added to the reaction mixture, and extracted with ethyl acetate, and the ethyl acetate layer was washed with water and then brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, after which solvent was evaporated, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=1:1), to thereby yield 1.17 g of the title compound. 
         [0789]    Appearance: Green oil 
         [0790]      1 H NMR (CDCl 3 ) δ 1.90-1.96 (2H, m), 2.73-2.79 (2H, m), δ 3.69-3.74 (2H, m), 7.00-7.09 (3H, m), 7.26-7.30 (2H, m), 8.44-8.49 (1H, m), 9.05 (1H, d, J=2.6 Hz). 
       Reference Example 297 
     Production of 2-{4-[3-(t-butyldimethylsilanyloxy)-propyl]phenoxy}-5-nitropyridine 
       [0791]    To a solution of 3-[4-(5-nitropyridin-2-yloxy)phenyl]-n-propanol (1.17 g, 4.3 mmol) in DMF (10 mL) were added imidazole (580 mg, 8.5 mmol) and t-butylchlorodimethylsilane (640 mg, 4.2 mmol), and the resulting solution was stirred for 13 hours at room temperature. Water was added to the reaction mixture, and extracted with diethyl ether, and the diethyl ether layer was washed with water and then brine. The diethyl ether layer was dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=5:1), to thereby yield 1.14 g of the title compound. 
         [0792]    Appearance: Pale yellow powder 
         [0793]      1 H NMR (CDCl 3 ) δ 0.07 (6H, s), 0.92 (9H, s), 1.84-1.89 (2H, m), 2.69-2.75 (2H, m), 3.66 (2H, t, J=6.3 Hz), 6.99-7.08 (3H, m), 7.27 (2H, d, J=7.6 Hz), 8.46 (1H, dd, J=8.9 Hz, 3.0 Hz), 9.05 (1H, d, J=3.0 Hz). 
         [0794]    The following compound was produced in the same manner as in Reference Example 297. 
       Reference Example 298 
     2-{4-[2-(t-Butyldimethylsilanyloxy)ethyl]phenoxy}-5-nitropyridine 
       [0795]      1 H NMR (CDCl 3 ) δ 0.00 (6H, s), 0.88 (9H, s), 2.86 (2H, t, J=6.9 Hz), 3.84 (2H, t, J=6.9 Hz), 7.00 (1H, d, J=9.2 Hz), 7.05-7.08 (2H, m), 7.26-7.31 (2H, m), 8.46 (1H, dd, J=9.2 Hz, 3.0 Hz), 9.05 (1H, d, J=3.0 Hz). 
       Reference Example 299 
     Production of ethyl 4-[4-(5-nitropyridin-2-yloxy)phenyl]butanoate 
       [0796]    To a solution of 4-[4-(5-nitropyridin-2-yloxy)phenyl]butanoic acid (9.98 g, 33.01 mmol) in dichloromethane were added ethanol (5.59 mL, 99.01 mmol), 4-dimethylaminopyridine (400 mg, 3.27 mmol), triethylamine (13.81 mL, 99.08 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (7.6 g, 39.65 mmol) under ice cooling, and the resulting solution was stirred for 20 minutes under ice cooling and then for 1 hour at room temperature. The reaction solution was concentrated under reduced pressure. Water was added to the residue, and extracted with ethyl acetate, and the ethyl acetate layer was washed with 1 N hydrochloric acid, a saturated sodium bicarbonate solution and brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=5:1), to thereby yield 6.77 g of the title compound. 
         [0797]    Appearance: Colorless oil 
         [0798]      1 H NMR (CDCl 3 ) δ 1.27 (3H, t, J=7.0 Hz), 1.99 (2H, dt, J=15.0 Hz, 7.5 Hz), 2.36 (2H, t, J=7.5 Hz), 2.70 (2H, t, J=7.5 Hz), 4.14 (2H, q, J=7.0 Hz), 7.01 (1H, d, J=9.0 Hz), 7.08 (2H, d, J=8.5 Hz), 7.26 (2H, d, J=8.5 Hz), 8.46 (1H, dd, J=9.0 Hz, 3.0 Hz), 9.04 (1H, d, J=3.0 Hz). 
       Reference Example 300 
     Production of methyl 3-[4-(5-nitropyridin-2-ylsulfanyl)phenyl]propionate 
       [0799]    To a solution of 3-[4-(5-nitropyridin-2-ylsulfanyl)phenyl]propionic acid (86.0 g, 0.283 mmol) in DMF (1 mL) were added potassium carbonate (59.0 mg, 0.424 mmol) and methyl iodide (0.0260 mL, 0.424 mmol), and the resulting solution was stirred for 1 hour at room temperature. Water was added to the reaction mixture, and then cooled with ice. The precipitated solid matter was collected by filtration, to thereby yield 76.9 mg of the title compound. 
         [0800]    Appearance: Light brown powder 
         [0801]      1 H NMR (DMSO-d 6 ) δ 2.70 (2H, t, J=7.6 Hz), 2.94 (2H, t, J=7.6 Hz), 3.60 (3H, s), 7.07 (1H, d, J=8.9 Hz), 7.43 (2H, d, J=8.1 Hz), 7.57 (2H, d, J=8.1 Hz), 8.39 (1H, dd, J=2.7 Hz, 8.9 Hz), 9.17 (1H, d, J=2.7 Hz). 
       Reference Example 301 
     Production of ethyl(Z)-3-[4-(5-nitro-2-pyridyloxy)phenyl]-2-butenoate 
       [0802]    To a suspension of 60% sodium hydride (1.28 g, 32.0 mmol) in THF (80 mL) was added dropwise a solution of triethyl phosphonoacetate (8.71 g, 38.8 mmol) in THF (40 mL) under ice cooling, and the resulting solution was stirred for 10 minutes at the same temperature. To the reaction solution was added 4-[(5-nitro-2-pyridyl)oxy]acetophenone (5.90 g, 22.8 mmol) and the resulting solution was stirred at the same temperature for 10 minutes, and then stirred at room temperature for 60 hours. To the reaction solution was added saturated ammonium chloride and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution, and then washed with brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=5:1), to thereby yield 1.17 g of the title compound. 
         [0803]    Appearance: Colorless needles 
         [0804]      1 H NMR (CDCl 3 ) δ 1.13 (3H, t, J=7.1 Hz), 2.20 (3H, d, J=1.4 Hz), 4.02 (2H, q, J=7.1 Hz), 5.93 (1H, q, J=1.4 Hz), 7.02 (1H, d, J=9.0 Hz), 7.12 (2H, d, J=8.6 Hz), 7.29 (2H, d, J=8.6 Hz), 8.45 (1H, dd, J=9.0 Hz, 2.8 Hz), 9.03 (1H, d, J=2.8 Hz). 
         [0805]    The following compounds were produced in the same manner as in Reference Example 301. 
       Reference Example 302 
     Ethyl(E)-3-{4-[4-(3,4-dichlorobenzoylamino)-2-fluorophenoxy]phenyl}acrylate 
       [0806]    Melting point: 166-167° C. 
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 44 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
               
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 197   
                 R 198   
                   1 H NMR (CDCl 3 ) δ ppm or MS 
               
               
                   
               
               
                 303 
                 —H 
                 —H 
                   1 H NMR 1.35 (3H, t, J = 7.1 Hz), 4.28 (2H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                 6.43 (1H, d, J = 16.0 Hz), 7.09 (1H, d, J = 8.9 Hz), 7.20 (2H, d, 
               
               
                   
                   
                   
                 J = 8.7 Hz), 7.62 (2H, d, J = 8.7 Hz), 7.70 (1H, d, J = 16.0 Hz), 
               
               
                   
                   
                   
                 8.50 (1H, dd, J = 8.9 Hz, 2.5 Hz), 9.04 (1H, d, J = 2.5 Hz). 
               
               
                 304 
                 —H 
                 —CH 3   
                   1 H NMR 1.31 (3H, t, J = 7.1 Hz), 2.58 (3H, d, J = 1.2 Hz), 
               
               
                   
                   
                   
                 4.21 (2H, q, J = 7.1 Hz), 6.14 (1H, q, J = 1.2 Hz), 7.05 (1H, d, 
               
               
                   
                   
                   
                 J = 9.0 Hz), 7.16 (2H, d, J = 8.7 Hz), 7.55 (2H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                 8.48 (1H, dd, J = 9.0 Hz, 2.8 Hz), 9.03 (1H, d, J = 2.8 Hz). 
               
               
                 305 
                 —CH 3   
                 —H 
                 MS 328 (M + ) 
               
               
                   
               
             
          
         
       
     
       Reference Example 306 
     Production of ethyl 3-[4-(5-nitropyridine-2-carbonyl)phenyl]propionate 
       [0807]    A solution of bis(tributyltin) (1.37 g, 2.36 mmol) in toluene (7 mL) was added under an argon atmosphere to 2-chloro-5-nitropyridine (0.325 g, 2.05 mmol), bis(dibenzylideneacetone)palladium(0) (18.1 mg, 0.0315 mmol), tri(2-furyl)phosphine (29.3 mg, 0.126 mmol) and molecular sieves 4A (1.90 g), and the resulting solution was heated to reflux for 1 hour. To the reaction solution was added bis(dibenzylideneacetone)palladium(0) (27.2 mg, 0.0472 mmol) and tri(2-furyl)phosphine (43.9 mg, 0.189 mmol), and subsequently added a solution of 4-[2-ethoxycarbonyl]ethyl]benzoyl chloride (0.379 g, 1.57 mmol) in toluene (5 mL). The resulting reaction solution was stirred for 4 hours at 80° C. To the reaction solution was added saturated aqueous potassium fluoride and stirred for 0.5 hours at room temperature. Insoluble matter was then filtered off. The filtrate was extracted with ethyl acetate, and the ethyl acetate layer was washed with brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by silica gel column chromatography (n-hexane→n-hexane:ethyl acetate=4:1), to thereby yield 0.323 g of the title compound. 
         [0808]    Appearance: Pale yellow powder 
         [0809]      1 H NMR (CDCl 3 ) δ 1.22 (3H, t, J=7.1 Hz), 2.65 (2H, t, J=7.7 Hz), 3.03 (2H, t, J=7.7 Hz), 4.12 (2H, q, J=7.1 Hz), 7.34 (2H, d, J=8.3 Hz), 8.00 (2H, d, J=8.3 Hz), 8.18 (1H, d, J=8.5 Hz), 8.65 (1H, dd, J=8.5 Hz, 2.6 Hz), 9.49 (1H, d, J=2.6 Hz). 
       Reference Example 307 
     Production of ethyl 3-[4-(4-aminophenoxy)phenyl]propionate 
       [0810]    To a suspension of 5% palladium-carbon (0.50 g) in ethanol (50 mL) was added ethyl 3-[4-(4-nitrophenoxy)phenyl]propionate (5.00 g, 15.9 mmol), and the resulting solution was subjected to catalytic reduction at atmospheric pressure and at room temperature. Once the absorption of hydrogen had stopped, the catalyst was removed by filtration, and the filtrate was concentrated under reduced pressure, to thereby yield 4.52 g of the title compound. 
         [0811]    Appearance: Light brown oil 
         [0812]      1 H NMR (CDCl 3 ) δ 1.22 (3H, t, J=7.1 Hz), 2.57 (2H, t, J=7.8 Hz), 2.88 (2H, t, J=7.8 Hz), 3.55 (2H, brs), 4.10 (2H, q, J=7.1 Hz), 6.64 (2H, d, J=8.8 Hz), 6.78-6.86 (4H, m), 7.08 (2H, d, J=8.6 Hz). 
         [0813]    The following compounds were produced in the same manner as in Reference Example 307. 
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 45 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
               
               
                 Example No. 
                 R 199   
                 R 200   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 308 
                 4-NH 2 Ph- 
                 2-(CH 2 ) 2 COOCH 3   
                 2.66 (2H, t, J = 7.8 Hz), 3.00 (2H, t, J = 7.8 
               
               
                   
                   
                   
                 Hz), 3.54 (2H, brs), 3.63 (3H, s), 6.65 (2H, d, 
               
               
                   
                   
                   
                 J = 8.8 Hz), 6.70 (1H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                 6.79 (2H, d, J = 8.8 Hz), 6.94 (1H, t, J = 8.1 
               
               
                   
                   
                   
                 Hz), 7.08 (1H, t, J = 8.1 Hz), 7.19 (1H, d, J = 
               
               
                   
                   
                   
                 8.1 Hz). 
               
               
                 309 
                 4-NH 2 Ph- 
                 3-(CH 2 ) 2 COOC 2 H 5   
                 1.21 (3H, t, J = 7.2 Hz), 2.56 (2H, t, J = 7.9 
               
               
                   
                   
                   
                 Hz), 2.87 (2H, t, J = 7.9 Hz), 3.54 (2H, brs), 
               
               
                   
                   
                   
                 4.10 (2H, q, J = 7.2 Hz), 6.66 (2H, d, J = 8.8 
               
               
                   
                   
                   
                 Hz), 6.70-6.76 (2H, m), 6.79-6.87 (3H, m), 
               
               
                   
                   
                   
                 7.16 (1H, t, J = 7.8 Hz). 
               
               
                 310 
                 2-NH 2 Ph- 
                 4-(CH 2 ) 2 COOC 2 H 5   
                 1.22 (3H, t, J = 7.2 Hz), 2.56 (2H, t, J = 7.8 
               
               
                   
                   
                   
                 Hz), 2.89 (2H, t, J = 7.8 Hz), 3.55 (2H, brs), 
               
               
                   
                   
                   
                 4.11 (2H, q, J = 7.2 Hz), 6.72 (1H, t, J = 7.8 
               
               
                   
                   
                   
                 Hz), 6.79-6.92 (4H, m), 6.93 (1H, t, J = 7.8 
               
               
                   
                   
                   
                 Hz), 7.12 (2H, d, J = 8.5 Hz). 
               
               
                 311 
                 4-NH 2 Ph- 
                 4-COOC 2 H 5   
                 1.37 (3H, t, J = 7.1 Hz), 4.36 (2H, q, J = 7.1 
               
               
                   
                   
                   
                 Hz), 4.00-4.50 (2H, m), 6.78 (2H, d, J = 8.9 
               
               
                   
                   
                   
                 Hz), 6.89-6.95 (4H, m), 7.97 (2H, d, J = 8.9 
               
               
                   
                   
                   
                 Hz). 
               
               
                 312 
                 3-NH 2 Ph- 
                 4-(CH 2 ) 2 COOC 2 H 5   
                 1.22 (3H, t, J = 7.2 Hz), 2.59 (2H, t, J = 7.8 
               
               
                   
                   
                   
                 Hz), 2.91 (2H, t, J = 7.8 Hz), 3.65 (2H, brs), 
               
               
                   
                   
                   
                 4.12 (2H, q, J = 7.2 Hz), 6.29 (1H, t, J = 2.2 
               
               
                   
                   
                   
                 Hz), 6.32-6.41 (2H, m), 6.92 (2H, d, J = 8.6 
               
               
                   
                   
                   
                 Hz), 7.06 (1H, t, J = 8.0 Hz), 7.13 (2H, d, J = 
               
               
                   
                   
                   
                 8.6 Hz). 
               
               
                   
               
               
                 313 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 3-COOCH 3   
                 3.56 (2H, brs), 3.89 (3H, s), 6.80 (1H, dd, J = 8.6 Hz, 0.7 Hz), 7.11 (1H, dd, J = 8.6 Hz, 3.0 Hz), 7.25-7.29 (1H, m), 7.39-7.44 (1H, m), 7.69-7.72 (2H, m), 7.78-7.82 (1H, m). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 46 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
               
               
                 Example No. 
                 R 201   
                 Form 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 314 
                 —Ac 
                 hydrochloride 
                 (DMSO-d 6 ) 2.53 (3H, s), 3.30-4.20 (3H, m), 
               
               
                   
                   
                   
                 6.88 (1H, d, J = 8.8 Hz), 6.99-7.05 (3H, m), 
               
               
                   
                   
                   
                 7.22 (1H, t, J = 8.8 Hz), 7.96 (1H, d, J = 8.9 Hz). 
               
               
                 315 
                 —CH 2 COOCH 3   
                 free 
                 (CDCl 3 ) 3.57 (2H, s), 3.60-3.80 (5H, m), 
               
               
                   
                   
                   
                 6.41 (1H, ddd, J = 1.2 Hz, 2.6 Hz, 8.6 Hz), 
               
               
                   
                   
                   
                 6.50 (1H, dd, J = 2.6 Hz, 12.0 Hz), 6.80- 
               
               
                   
                   
                   
                 6.95 (3H, m), 7.18 (2H, d, J = 8.4 Hz). 
               
               
                 316 
                 —(CH 2 ) 2 COOC 2 H 5   
                 free 
                 (CDCl 3 ) 1.21 (3H, t, J = 7.1 Hz), 2.56 (2H, t, J = 
               
               
                   
                   
                   
                 7.8 Hz), 2.87 (2H, t, J = 7.8 Hz), 3.66 (2H, 
               
               
                   
                   
                   
                 brs), 4.10 (2H, q, J = 7.1 Hz), 6.34-6.43 (1H, 
               
               
                   
                   
                   
                 m), 6.48 (1H, dd, J = 12.0 Hz, 2.7 Hz), 6.77- 
               
               
                   
                   
                   
                 6.93 (3H, m), 7.08 (2H, d, J = 8.7 Hz). 
               
               
                 317 
                 —H 
                 free 
                 (CDCl 3 ) 3.66 (2H, brs), 6.35-6.44 (1H, m), 
               
               
                   
                   
                   
                 6.49 (1H, dd, J = 12.0 Hz, 2.7 Hz), 6.83- 
               
               
                   
                   
                   
                 6.96 (3H, m), 7.01 (1H, dd, J = 9.0 Hz, 8.0 
               
               
                   
                   
                   
                 Hz), 7.26 (2H, t, J = 8.0 Hz). 
               
               
                 318 
                 —(CH 2 ) 3 COOC 2 H 5   
                 free 
                 (CDCl 3 ) 1.23 (3H, t, J = 7.1 Hz), 1.83- 
               
               
                   
                   
                   
                 1.97 (2H, m), 2.28 (2H, t, J = 7.5 Hz), 
               
               
                   
                   
                   
                 2.57 (2H, t, J = 7.6 Hz), 3.66 (2H, brs), 
               
               
                   
                   
                   
                 4.09 (2H, q, J = 7.1 Hz), 6.34-6.43 (1H, m), 
               
               
                   
                   
                   
                 6.48 (1H, dd, J = 12.0 Hz, 2.7 Hz), 6.81 (2H, 
               
               
                   
                   
                   
                 d, J = 8.5 Hz), 6.88 (1H, dd, J = 9.0 Hz, 8.0 
               
               
                   
                   
                   
                 Hz), 7.05 (2H, d, J = 8.5 Hz). 
               
               
                 319 
                 —COOC 2 H 5   
                 free 
                 (DMSO-d 6 ) 1.29 (3H, t, J = 7.1 Hz), 4.27 (2H, 
               
               
                   
                   
                   
                 q, J = 7.1 Hz), 5.42 (2H, brs), 6.41 (1H, dt, J = 
               
               
                   
                   
                   
                 1.6 Hz, 8.6 Hz), 6.50 (1H, dd, J = 2.5 Hz, 13.3 
               
               
                   
                   
                   
                 Hz), 6.90-7.00 (3H, m), 7.91 (2H, d, J = 9.7 Hz). 
               
               
                 320 
                 —NHCH 2 COOC 2 H 5   
                 free 
                 (CDCl 3 ) 1.29 (3H, t, J = 7.1 Hz), 3.62 (2H, s), 
               
               
                   
                   
                   
                 3.86 (2H, s), 4.12 (1H, s), 4.23 (2H, q, J = 7.1 
               
               
                   
                   
                   
                 Hz), 6.35-6.39 (1H, m), 6.48 (1H, dd, J = 2.7 
               
               
                   
                   
                   
                 Hz, 12.1 Hz), 6.55 (2H, d, J = 8.9 Hz), 6.80- 
               
               
                   
                   
                   
                 6.85 (3H, m). 
               
               
                 321 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 (CDCl 3 ) 3.70 (2H, brs), 3.95-4.15 (4H, m), 5.76 (1H, s), 6.38-6.42 (1H, m), 6.49 (1H, dd, J = 2.7 Hz, 14.7 Hz), 6.85-6.93 (3H, m), 7.39 (2H, d, J = 8.7 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 47 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example No. 
                 R 202   
                 R 203   
                 R 204   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 322 
                 —H 
                 —H 
                 —C 2 H 5   
                 1.38 (3H, t, J = 7.3 Hz), 4.35 (2H, q, J = 7.3 Hz), 
               
               
                   
                   
                   
                   
                 6.82 (1H, d, J = 8.6 Hz), 7.04-7.14 (3H, m), 7.75 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 3.0 Hz), 8.01-8.04 (2H, m). 
               
               
                 323 
                 —H 
                 —H 
                 —CH 3   
                 3.30 (2H, brs), 3.89 (3H, s), 6.82 (1H, d, J = 8.6 
               
               
                   
                   
                   
                   
                 Hz), 7.04-7.13 (3H, m), 7.75 (1H, d, J = 3.0 Hz), 
               
               
                   
                   
                   
                   
                 8.02 (2H, dd, J = 6.6 Hz, 2.0 Hz). 
               
               
                 324 
                 —F 
                 —H 
                 —CH 3   
                 3.57 (2H, brs), 3.91 (3H, s), 6.87 (1H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                 7.10-7.23 (2H, m), 7.64 (1H, d, J = 3.0 Hz), 7.80- 
               
               
                   
                   
                   
                   
                 7.82 (1H, m), 7.83-7.85 (1H, m). 
               
               
                 325 
                 —F 
                 —H 
                 —C 2 H 5   
                 1.38 (3H, t, J = 7.1 Hz), 4.37 (2H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 6.87 (1H, d, J = 8.6 Hz), 7.12 (1H, dd, J = 8.6 Hz, 3.0 
               
               
                   
                   
                   
                   
                 Hz), 7.15-7.22 (1H, m), 7.64 (1H, d, J = 3.0 Hz), 7.81- 
               
               
                   
                   
                   
                   
                 7.86 (2H, m). 
               
               
                 326 
                 —CH 3   
                 —H 
                 —CH 3   
                 2.29 (3H, s), 3.56 (2H, brs), 3.89 (3H, s), 6.79 (1H, d, J = 
               
               
                   
                   
                   
                   
                 8.6 Hz), 6.92 (1H, d, J = 8.6 Hz), 7.11 (1H, dd, J = 8.6 
               
               
                   
                   
                   
                   
                 Hz, 3.0 Hz), 7.71 (1H, d, J = 3.0 Hz), 7.85 (1H, dd, J = 
               
               
                   
                   
                   
                   
                 8.6 Hz, 2.4 Hz), 7.94 (1H, d, J = 2.4 Hz). 
               
               
                 327 
                 —OCH 3   
                 —H 
                 —C 2 H 5   
                 1.38 (3H, t, J = 7.1 Hz), 3.55 (2H, brs), 3.85 (3H, s), 
               
               
                   
                   
                   
                   
                 4.37 (2H, q, J = 7.1 Hz), 6.79-6.83 (1H, m), 7.02 
               
               
                   
                   
                   
                   
                 7.10 (2H, m), 7.63-7.67 (3H, m). 
               
               
                 328 
                 —H 
                 —OCH 3   
                 —CH 3   
                 3.63 (2H, brs), 3.86 (6H, s), 6.54-6.58 (1H, m), 6.68 (1H, 
               
               
                   
                   
                   
                   
                 d, J = 2.2 Hz), 6.81-6.84 (1H, m), 7.13 (1H, dd, J = 8.6 
               
               
                   
                   
                   
                   
                 Hz, 3.0 Hz), 7.77 (1H, dd, J = 3.0 Hz, 0.5 Hz), 7.83 (1H, 
               
               
                   
                   
                   
                   
                 d, J = 8.9 Hz). 
               
               
                 329 
                 —H 
                 —CH 3   
                 —CH 3   
                 2.58 (3H, s), 3.63 (2H, brs), 3.86 (3H, s), 6.80-6.88 (3H, 
               
               
                   
                   
                   
                   
                 m), 7.13 (1H, dd, J = 8.6 Hz, 3.0 Hz), 7.75 (1H, d, J = 
               
               
                   
                   
                   
                   
                 3.0 Hz), 7.92-7.96 (1H, m). 
               
               
                 330 
                 —Cl 
                 —H 
                 —CH 3   
                 3.62 (2H, brs), 3.91 (3H, s), 6.88 (1H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                 7.08-7.15 (2H, m), 7.68 (1H, d, J = 3.0 Hz), 7.91 (1H, dd, 
               
               
                   
                   
                   
                   
                 J = 8.6 Hz, 2.1 Hz), 8.13 (1H, d, J = 2.1 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 48 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 205   
                 R 206   
                 M 
                   1 H NMR (CDCl 3 ) δ ppm or MS 
               
               
                   
               
               
                 331 
                 —H 
                 —CH 3   
                 2 
                 MS 272 (M + ) 
               
               
                 332 
                 —OCH 3   
                 —C 2 H 5   
                 2 
                   1 H NMR 1.25 (3H, t, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 2.63 (2H, t, J = 7.5 Hz), 2.94 
               
               
                   
                   
                   
                   
                 (2H, t, J = 7.5 Hz), 3.43 (2H, brs), 
               
               
                   
                   
                   
                   
                 3.77 (3H, s), 4.14 (2H, q, J = 7.1 
               
               
                   
                   
                   
                   
                 Hz), 6.71-6.86 (3H, m), 6.98 (1H, 
               
               
                   
                   
                   
                   
                 d, J = 8.0 Hz), 7.06 (1H, dd, J = 
               
               
                   
                   
                   
                   
                 8.6 Hz, 2.9 Hz), 7.65 (1H, d, J = 
               
               
                   
                   
                   
                   
                 2.9 Hz). 
               
               
                 333 
                 —H 
                 —CH 3   
                 1 
                   1 H NMR 3.60 (2H, s), 3.69 (3H, 
               
               
                   
                   
                   
                   
                 s), 6.76 (1H, d, J = 8.6 Hz), 6.99- 
               
               
                   
                   
                   
                   
                 7.10 (3H, m), 7.24-7.27 (2H, m), 
               
               
                   
                   
                   
                   
                 7.71 (1H, d, J = 3.0 Hz). 
               
               
                 334 
                 —H 
                 —C 2 H 5   
                 2 
                   1 H NMR 1.21 (3H, t, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 2.58 (2H, t, J = 7.7 Hz), 2.90 (2H, 
               
               
                   
                   
                   
                   
                 t, J = 7.7 Hz), 4.11 (2H, q, J = 7.1 
               
               
                   
                   
                   
                   
                 Hz), 6.72 (1H, d, J = 8.6 Hz), 6.95 
               
               
                   
                   
                   
                   
                 (2H, d, J = 8.5 Hz), 7.05 (1H, dd, 
               
               
                   
                   
                   
                   
                 J = 8.6 Hz, 3.0 Hz), 7.14 (2H, d, 
               
               
                   
                   
                   
                   
                 J = 8.5 Hz), 7.68 (1H, d, J = 
               
               
                   
                   
                   
                   
                 3.0 Hz). 
               
               
                 335 
                 —OCH 3   
                 —CH 3   
                 2 
                   1 H NMR 2.62-2.68 (2H, m), 2.91- 
               
               
                   
                   
                   
                   
                 2.97 (2H, m), 3.45 (2H, brs), 3.69 
               
               
                   
                   
                   
                   
                 (3H, s), 3.77 (3H, s), 6.74-6.79 
               
               
                   
                   
                   
                   
                 (2H, m), 6.82 (1H, d, J = 1.8 Hz), 
               
               
                   
                   
                   
                   
                 6.98 (1H, d, J = 7.9 Hz), 
               
               
                   
                   
                   
                   
                 7.04-7.26 (1H, m), 7.64 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 3.0 Hz). 
               
               
                 336 
                 —OC 2 H 5   
                 —C 2 H 5   
                 2 
                   1 H NMR 1.20 (3H, t, J = 7.0 
               
               
                   
                   
                   
                   
                 Hz), 1.25 (3H, t, J = 7.1 Hz), 2.51- 
               
               
                   
                   
                   
                   
                 2.68 (2H, m), 2.81-3.01 (2H, m), 
               
               
                   
                   
                   
                   
                 3.19-3.63 (2H, m), 3.98 (2H, q, J = 
               
               
                   
                   
                   
                   
                 7.0 Hz), 4.14 (2H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 6.69-6.83 (3H, m), 6.95-7.09 (2H, 
               
               
                   
                   
                   
                   
                 m), 7.60-7.67 (1H, m). 
               
               
                 337 
                 —F 
                 —C 2 H 5   
                 2 
                   1 H NMR 1.25 (3H, t, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 2.52-2.71 (2H, m), 2.86-3.02 
               
               
                   
                   
                   
                   
                 (2H, m), 3.47 (2H, brs), 4.14 
               
               
                   
                   
                   
                   
                 (2H, q, J = 7.1 Hz), 6.81 (1H, 
               
               
                   
                   
                   
                   
                 d, J = 8.6 Hz), 6.93-7.04 (2H, m), 
               
               
                   
                   
                   
                   
                 7.05-7.13 (2H, m), 7.63 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 2.9 Hz). 
               
               
                 338 
                 —H 
                 —C 2 H 5   
                 4 
                   1 H NMR 1.25 (3H, t, J = 7.2 Hz), 
               
               
                   
                   
                   
                   
                 1.55-1.80 (4H, m), 2.32 (2H, t, 
               
               
                   
                   
                   
                   
                 J = 7.0 Hz), 2.60 (2H, t, J = 7.0 
               
               
                   
                   
                   
                   
                 Hz), 3.49 (2H, brs), 4.12 (2H, q, 
               
               
                   
                   
                   
                   
                 J = 7.2 Hz), 6.74 (1H, d, J = 8.5 
               
               
                   
                   
                   
                   
                 Hz), 6.97 (2H, d, J = 8.5 Hz), 7.06 
               
               
                   
                   
                   
                   
                 (1H, dd, J = 8.5 Hz, 3.0 Hz), 
               
               
                   
                   
                   
                   
                 7.14 (2H, d, J = 8.5 Hz), 7.71 
               
               
                   
                   
                   
                   
                 (1H, d, J = 3.0 Hz). 
               
               
                 339 
                 —H 
                 —C 2 H 5   
                 3 
                   1 H NMR 1.26 (3H, t, J = 7.5 Hz), 
               
               
                   
                   
                   
                   
                 1.94 (2H, dt, J = 15.0 Hz, 7.5 Hz), 
               
               
                   
                   
                   
                   
                 2.33 (2H, t, J = 7.5 Hz), 2.63 (2H, 
               
               
                   
                   
                   
                   
                 t, J = 7.5 Hz), 3.50 (2H, brs), 4.13 
               
               
                   
                   
                   
                   
                 (2H, q, J = 7.0 Hz), 6.75 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 8.5 Hz), 6.98 (2H, d, J = 8.5 
               
               
                   
                   
                   
                   
                 Hz), 7.07 (1H, dd, J = 8.5 Hz, 3.0 
               
               
                   
                   
                   
                   
                 Hz), 7.15 (2H, d, J = 8.5 Hz), 7.72 
               
               
                   
                   
                   
                   
                 (1H, d, J = 3.0 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
               
             
           
               
                 TABLE 49 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 Xa 8   
                 M 
                 Form 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
             
          
           
               
                 340 
                 —NH— 
                 2 
                 free 
                 (CDCl 3 ) 1.24 (3H, t, J = 7.1 Hz), 2.60 (2H, 
               
               
                   
                   
                   
                   
                 t, J = 7.6 Hz), 2.90 (2H, t, J = 7.6 Hz), 
               
               
                   
                   
                   
                   
                 3.35 (2H, brs), 4.13 (2H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 6.16 (1H, brs), 6.77 (1H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                 6.98 (1H, dd, J = 2.9 Hz, 8.6 Hz), 7.00- 
               
               
                   
                   
                   
                   
                 7.15 (4H, m), 7.78 (1H, d, J = 2.9 Hz). 
               
               
                 341 
                 —N(CH 3 )— 
                 0 
                 hydrochloride 
                 (DMSO-d 6 ) 1.30 (3H, t, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 3.43 (3H, s), 4.28 (2H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 7.03 (1H, d, J = 9.1 Hz), 7.30 (2H, d, J = 
               
               
                   
                   
                   
                   
                 8.6 Hz), 7.55 (1H, d, J = 9.1 Hz), 7.93 (2H, 
               
               
                   
                   
                   
                   
                 d, J = 8.6 Hz), 8.05 (1H, s). 
               
               
                 342 
                 —N(CH 3 )— 
                 2 
                 free 
                 (CDCl 3 ) 1.24 (3H, t, J = 7.2 Hz), 2.63 (2H, 
               
               
                   
                   
                   
                   
                 t, J = 7.7 Hz), 2.95 (2H, t, J = 7.7 Hz), 
               
               
                   
                   
                   
                   
                 3.53 (3H, s), 4.14 (2H, q, J = 7.2 Hz), 
               
               
                   
                   
                   
                   
                 6.52 (1H, d, J = 9.5 Hz), 7.07 (1H, dd, J = 
               
               
                   
                   
                   
                   
                 2.7 Hz, 9.5 Hz), 7.10 (2H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                   
                 7.22 (2H, d, J = 8.3 Hz), 7.83 (1H, d, J = 
               
               
                   
                   
                   
                   
                 2.7 Hz). 
               
               
                 343 
                 —N(CH 2 Ph)— 
                 2 
                 dihydrochloride 
                 (CDCl 3 ) 1.22 (3H, t, J = 7.1 Hz), 2.57 (2H, 
               
               
                   
                   
                   
                   
                 t, J = 7.7 Hz), 2.90 (2H, t, J = 7.7 Hz), 
               
               
                   
                   
                   
                   
                 4.11 (2H, q, J = 7.1 Hz), 5.28 (2H, s), 
               
               
                   
                   
                   
                   
                 6.65 (1H, d, J = 8.8 Hz), 7.08 (2H, d, J = 
               
               
                   
                   
                   
                   
                 7.8 Hz), 7.15-7.24 (7H, m), 8.27 (1H, d, J = 
               
               
                   
                   
                   
                   
                 8.8 Hz), 8.80 (1H, s). 
               
               
                 344 
                 —CO— 
                 2 
                 free 
                 (CDCl 3 ) 1.21 (3H, t, J = 7.1 Hz), 2.63 (2H, 
               
               
                   
                   
                   
                   
                 t, J = 7.7 Hz), 2.98 (2H, t, J = 7.7 Hz), 
               
               
                   
                   
                   
                   
                 4.10 (2H, q, J = 7.1 Hz), 7.18 (2H, brs), 
               
               
                   
                   
                   
                   
                 7.27 (2H, d, J = 8.1 Hz), 7.32 (1H, d, J = 
               
               
                   
                   
                   
                   
                 8.3 Hz), 7.88-7.99 (3H, m), 8.27 (1H, s). 
               
               
                   
               
             
          
           
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 50 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 207   
                 R 208   
                 R 209   
                 M 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 345 
                 —H 
                 —H 
                 —C(CH 3 ) 3   
                 0 
                 (CDCl 3 ) 1.51 (9H, s), 3.49 (2H, brs) 641 (1H, 
               
               
                   
                   
                   
                   
                   
                 brs), 6.72 (1H, d, J = 8.6 Hz), 7.00 (2H, d, J = 8.9 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.06 (1H, dd, J = 8.6 Hz, 3 0 Hz) 7 32 (2H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.9 Hz), 7.69 (1H, d, J = 3.0 Hz). 
               
               
                 346 
                 —H 
                 —Ac 
                 —C 2 H 5   
                 1 
                 (CDCl 3 ) 1.27 (3H, t, J = 7.1 Hz), 1.94 (3H, s) 
               
               
                   
                   
                   
                   
                   
                 3.60 (2H, brs), 4.18 (2H q, J = 7.1 Hz), 4.35 (2H, 
               
               
                   
                   
                   
                   
                   
                 s), 6.82 (1H, d, J = 8.6 Hz), 7.07 (2H, d, J = 8.8 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.12 (1H, dd, J = 3.0 Hz, 8.6 Hz) 7.31 (2H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.8 Hz), 7.73 (1H, d, J = 3.0 Hz), 
               
               
                 347 
                 —H 
                 —Ac 
                 —C 2 H 5   
                 2 
                 (CDCl 3 ) 1.23 (3H, t, ,J = 7.1 Hz), 1.85 (3H, s), 
               
               
                   
                   
                   
                   
                   
                 2.57 (2H, t, J = 7.4 Hz), 3.60 (2H, s), 3.98 (2H, t, J = 
               
               
                   
                   
                   
                   
                   
                 7.4 Hz), 4.07 (2H, q, J = 7.1 Hz), 6.82 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.6 Hz), 7.08 (2H, d, J = 8.8 Hz), 7.10-7.15 
               
               
                   
                   
                   
                   
                   
                 (3H, m), 7.74 (1H, d, J = 3.0 Hz). 
               
               
                 348 
                 —CH 3   
                 —Ac 
                 —C 2 H 5   
                 1 
                 (CDCl 3 ) 1.28 (3H, t, J = 7.1 Hz), 1.95 (3H, s), 
               
               
                   
                   
                   
                   
                   
                 2.23 (3H, s), 3.52 (2H, s), 4.19 (2H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 4.34 (2H, s), 6.73 (1H, d, J = 8.6 Hz) 6.91 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.4 Hz), 7.05-7.15 (2H, m), 7.20 (1H, s), 
               
               
                   
                   
                   
                   
                   
                 7.66 (1H, s). 
               
               
                 349 
                 —H 
                 —CH 3   
                 —CH 3   
                 1 
                 (CDCl 3 ) 3.05 (3H, s), 3.45 (2H, brs), 3.72 (3H, s), 
               
               
                   
                   
                   
                   
                   
                 4.05 (2H, s), 6.67 (3H, d, J = 9.0 Hz), 6.98 (2H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 2.0 Hz), 7.04 (1H, dd, J = 8.6 Hz, 3.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.69 (1H, d, J = 2.0 Hz). 
               
               
                 350 
                 —H 
                 —CH 3   
                 —C 2 H 5   
                 1 
                 (CDCl 3 ) 1.25 (3H, t, J = 7.1 Hz), 3.05 (3H, s), 
               
               
                   
                   
                   
                   
                   
                 3.45 (2H, brs), 4.03 (2H, s), 4.18 (2H, q, J = 7.1. 
               
               
                   
                   
                   
                   
                   
                 Hz), 6.65-6.69 (3H, m), 6.96 (2H, d, J = 9.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.04 (1H, dd, J = 2.9 Hz, 8.6 Hz), 7.69 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 2.9 Hz). 
               
               
                 351 
                 —H 
                 —C 2 H 5   
                 —C 2 H 5   
                 1 
                 (CDCl 3 ) 1.20 (3H, t, J = 7.2 Hz), 1.26 (3H, t, J = 
               
               
                   
                   
                   
                   
                   
                 7.2 Hz), 3.40-3.46 (4H, m), 3.99 (2H, s), 4.19 (2H, 
               
               
                   
                   
                   
                   
                   
                 q, J = 7.2 Hz), 6.63 (2H, d, J = 9.1 Hz), 6.67 (1H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.6 Hz), 6.95 (2H, d, J = 9.1 Hz), 7.04 (1H, 
               
               
                   
                   
                   
                   
                   
                 dd, J = 3.2 Hz, 8.6 Hz), 7.69 (1H, d, J = 3.2 Hz). 
               
               
                 352 
                 —CH 3   
                 —CH 3   
                 —C 2 H 5   
                 1 
                 (CDCl 3 ) 1.26 (3H, t, J = 7.1 Hz), 2.13 (3H, s), 
               
               
                   
                   
                   
                   
                   
                 3.05 (3H, s), 3.41 (2H, brs), 4.02 (2H, s), 4.19 (2H, 
               
               
                   
                   
                   
                   
                   
                 q, J = 7.1 Hz), 6.46-6.68 (3H, m), 6.89 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.6 Hz), 7.03 (1H, dd, J = 8.6 Hz, 3.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.67 (1H, d, J = 3.0 Hz). 
               
               
                 353 
                 —OCH 3   
                 —CH 3   
                 —C 2 H 5   
                 1 
                 (CDCl 3 ) 1.26 (3H, t, J = 7.1 Hz), 3.07 (3H, s), 
               
               
                   
                   
                   
                   
                   
                 3.42 (2H, brs), 3.75 (3H, s), 4.04 (2H, s), 4.19 (2H, 
               
               
                   
                   
                   
                   
                   
                 q, J = 7.1 Hz), 6.24 (1H, dd, J = 8.7 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.33 (1H, d, J = 2.8 Hz), 6.67 (1H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.95 (1H, d, J = 8.7 Hz), 7.02 (1H, dd, J = 8.6 Hz, 
               
               
                   
                   
                   
                   
                   
                 3.0 Hz), 7.63 (1H, d, J = 2.8 Hz). 
               
               
                 354 
                 —OCH 3   
                 —C 2 H 5   
                 —C 2 H 5   
                 1 
                 (DMSO-d 6 ) 1.13 (3H, t, J = 7.1 Hz), 1.20 (3H, t, J = 
               
               
                   
                   
                   
                   
                   
                 7.1 Hz), 3.41 (2H, q, J = 7.1 Hz), 3.63 (3H, s), 
               
               
                   
                   
                   
                   
                   
                 4.09-4.17 (4H, m), 4.81 (2H, brs), 6.11 (1H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 8.7 Hz, 2.8 Hz), 6.26 (1H d, J = 2.8 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.55 (1H, d, J = 8.6 Hz), 6.79 (1H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.99 (1H, dd, J = 8.7 Hz, 3.0 Hz), 7.40 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 2.3 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 51 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 210   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 355 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.48 (9H, s), 3.04 (4H, t, J = 5.0 Hz), 3.54 (2H, brs), 3.57 (4H, t, J = 5.0 Hz), 6.65 (2H, d, J = 9.0 Hz), 6.82 (2H, d, J = 9.0 Hz), 6.88 (4H, ABq, J = 9.0 Hz). 
               
               
                   
               
               
                 356 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.78 (2H, m), 2.03 (2H, m), 2.86 (2H, m), 3.39 (3H, s), 3.42 (2H, m), 3.52 (2H, brs), 3.70 (1H, m), 4.72 (2H; s), 6.64 (2H, d, J = 9.0 Hz), 6.82 (2H, d, J = 9.0 Hz), 6.88 (4H, ABq, J = 9.0 Hz). 
               
               
                   
               
               
                 357 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.27 (3H, t, J = 7.0 Hz), 1.88 (2H, dq, J = 3.5 Hz, 12.5 Hz), 2.03 (2h, dd, J = 12.5 Hz, 3.0 Hz), 2.40 (1H, m), 2.72 (2H, dt, J = 2.5 Hz, 12.0 Hz), 3.51-3.53 (4H, m), 4.16 (2H, q, J = 7.0 Hz), 6.65 (2H, d, J = 8.5 Hz), 6.82 (2H, d, J = 8.5 Hz), 6.88 (4H, s). 
               
               
                   
               
               
                 358 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.48 (9H, s), 1.74 (2H, brd, J = 11.5 Hz), 1.85 (2H, m), 2.74 (2H, m), 2.77 (3H, s), 3.53 (2H, brs), 3.60 (2H, brd, J = 12.0 Hz), 4.12 (1H, brs), 6.65 (2H, d, J = 8.5 Hz), 6.82 (2H, d, J = 8.5 Hz), 6.87 (4H, s). 
               
               
                   
               
               
                 359 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.30 (3H, t, J = 7.0 Hz), 1.81 (2H, m), 2.03 (2H, m), 2.84 (1H, m), 2.95 (1H, m), 3.35 (1H, m), 3.44 (1H, m), 3.54 (3H, m), 4.15 (2H, s), 4.23 (2H, q, J = 7.0 Hz), 6.65 (2H, d, J = 9.0 Hz), 6.82 (2H, d, J = 9.0 Hz), 6.88 (4H, s). 
               
               
                   
               
               
                 360 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.48 (9H, s), 1.60 (2H, m), 1.80 (2H, m), 2.59 (1H, m), 2.78 (2H, brs), 3.57 (2H, brs), 4.23 (2H, brs), 4.12 (1H, brs), 6.67 (2H, d, J = 9.0 Hz), 6.86 (2H, d, J = 9.0 Hz), 6.87 (2H, d, J = 9.0 Hz), 7.09 (2H, d, J = 9.0 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 52 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 211   
                 R 212   
                   1 H NMR (CDCl 3 ) δ ppm or MS 
               
               
                   
               
               
                 361 
                 —H 
                 —Ac 
                   1 H NMR 2.50 (3H, s), 3.60 (2H, brs), 6.80-7.90 (7H, m). 
               
               
                   
               
               
                 362 
                 —H 
                 —NHCONHPh 
                   1 H NMR 3.55 (2H, s), 6.76 (1H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                 6.89 (1H, s), 6.95-7.02 (3H, m), 7.03-7.12 (2H, m), 
               
               
                   
                   
                   
                 7.21-7.36 (6H, m), 6.68 (1H, d, J = 2.9 Hz). 
               
               
                   
               
               
                 363 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.70-1.90 (4H, m), 2.18 (2H, brs), 2.40- 2.50 (2H, m), 3.13-3.29 (2H, m), 4.56 (2H, s), 6.76 (1H, d, J = 8.6 Hz), 7.01 (2H, d, J = 8.6 Hz), 7.09 (1H, dd, J = 8.6 Hz, 3.0 Hz), 7.23 (2H, d, J = 8.6 Hz), 7.72 (1H, d, J = 3.0 Hz). 
               
               
                   
               
               
                 364 
                 —H 
                 —CH(CH 3 )COOCH 3   
                 MS 272 (M + ) 
               
               
                 365 
                 —H 
                 —C(CH 3 ) 2 COOCH 3   
                 MS 286 (M + ) 
               
               
                   
               
               
                 366 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.50 (9H, s), 3.55 (2H, brs), 3.72 (2H, m), 3.78 (2H, m), 4.25 (2H, s), 6.80 (1H, d, J = 8.6 Hz), 7.08 (2H, d, J = 8.9 Hz), 7.10 (1H, dd, J = 8.6 Hz, 3.0 Hz), 7.24 (2H, d, J = 8.9 Hz), 7.72 (1H, d, J = 3.0 Hz). 
               
               
                   
               
               
                 367 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.48 (9H, s), 3.07 (4H, brs), 3.47 (2H, brs), 3.57 (4H, t, J = 5.0 Hz), 6.72 (1H, d, J = 8.5 Hz), 6.92 (2H, d, J = 9.0 Hz), 7.00 (2H, d, J = 9.0 Hz), 7.06 (1H, dd, J = 8.5 Hz, 3.0 Hz), 7.70 (1H, d, J = 3.0 Hz). 
               
               
                   
               
               
                 368 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.27 (3H, t, J = 7.0 Hz), 1.44 (2H, dq, J = 4.0 Hz, 12.5 Hz), 1.83 (2H, brd, J = 13.0 Hz), 1.91 (1H, m), 2.28 (2H, d, J = 7.0 Hz), 2.70 (2H, dt, J = 2.5 Hz, 12.0 Hz), 3.46 (2H, brs), 3.57 (2H, brd, J = 12.0 Hz), 4.15 (2H, q, J = 7.0 Hz), 6.69 (1H, d, J = 8.5 Hz), 6.92 (2H, d, J = 9.0 Hz), 6.97 (2H, d, J = 9.0 Hz), 7.05 (2H, dd, J = 8.5 Hz, 3.0 Hz), 7.70 (1H, d, J = 3.0 Hz). 
               
               
                   
               
               
                 369 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.27 (3H, t, J = 7.1 Hz), 1.86-2.05 (4H, m), 2.14 (3H, s), 2.35-2.44 (1H, m), 2.69-2.79 (2H, m), 3.43 (2H, brs), 3.55-3.59 (2H, m), 4.16 (2H, q, J = 7.1 Hz), 6.62 (1H, d, J = 8.6 Hz), 6.74-6. 82 (2H, m), 6.89 (1H, d, J = 8.6 Hz), 7.03 (1H, dd, J = 8.6 Hz, 3.0 Hz), 7.68 (1H, d, J = 3.0 Hz). 
               
               
                   
               
               
                 370 
                 —OCH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.27 (3H, t, J = 7.1 Hz), 1.38-1.50 (2H, m), 1.87-2.06 (3H, m), 2.29 (2H, d, J = 7.1 Hz), 2.69- 2.77 (2H, m), 3.42 (2H, brs), 3.58 (2H, d, J = 12.2 Hz), 3.75 (3H, s), 4.15 (2H, q, J = 7.1 Hz), 6.49 (1H, dd, J = 8.6 Hz, 2.6 Hz), 6.59 (1H, d, J = 2.6 Hz), 6.70 (1H, d, J = 8.6 Hz), 6.96 (1H, d, J = 8.6 Hz), 7.04 (1H, dd, J = 8.6 Hz, 3.0 Hz), 7.65 (1H, d, J = 3.0 Hz). 
               
               
                   
               
               
                 371 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.27 (3H, t, J = 7.1 Hz), 1.37-1.49 (2H, m), 1.80-2.04 (3H, m), 2.13 (3H, s), 2.28 (2H, d, J = 6.9 Hz), 2.69 (2H, dd, J = 12.0 Hz, 9.9 Hz), 3.41- 3.59 (4H, m), 4.15 (2H, q, J = 7.3 Hz), 6.60 (1H, d, J = 8.6 Hz), 6.73-6.81 (2H, m), 6.88 (1H, d, J = 8.6 Hz), 7.02 (1H, dd, J = 8.6 Hz, 3.0 Hz), 7.66 (1H, d, J = 2.8 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 53 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 213   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 372 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 3.51 (2H, brs), 3.94-4.12 (4H, m), 5.78 (1H, s), 6.73 (1H, d, J = 8.6 Hz), 6.99-7.09 (3H, m), 7.43 (2H, d, J = 8.5 Hz), 7.70 (1H, d, J = 2.7 Hz). 
               
               
                   
               
               
                 373 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 0.05 (6H, s), 0.91 (9H, s), 1.77-1.88 (2H, m), 2.62- 2.68 (2H, m), 3.62-3.66 (2H, m), 6.73 (1H, d, J = 8.9 Hz), 6.95-7.17 (5H, m), 7.72 (1H, d, J = 3.0 Hz). 
               
               
                   
               
               
                 374 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 −0.07 (6H, s), 0.81 (9H, s), 2.73 (2H, t, J = 7.3 Hz), 3.72 (2H, t, J = 7.3 Hz), 6.66 (1H, dd, J = 8.6 Hz, 0.7 Hz), 6.88-6.92 (2H, m), 6.99 (1H, dd, J = 8.6 Hz, 3.0 Hz), 7.10 (2H, d, J = 8.6 Hz), 7.64 (1H, d, J = 3.0 Hz). 
               
               
                   
               
               
                 375 
                 morpholino 
                 3.09-3.13 (4H, m), 3.84-3.87 (4H, m), 6.71 (1H, d, J = 
               
               
                   
                   
                 8.6 Hz), 6.90 (2H, d, J = 8.9 Hz), 7.02 (2H, d, J = 9.2 
               
               
                   
                   
                 Hz), 7.05 (1H, dd, J = 8.6 Hz, 3.0 Hz), 7.69 (1H, d, J = 
               
               
                   
                   
                 3.0 Hz) 
               
               
                   
               
               
                 376 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 3.12 (1H, dd, J = 14.2 Hz, 9.8 Hz), 3.52 (1H, dd, J = 14.2 Hz, 3.8 Hz), 3.70 (2H, s), 4.51 (1H, dd, J = 9.8 Hz, 3.8 Hz), 6.78 (1H, d, J = 8.6 Hz), 7.02 (2H, d, J = 8.6 Hz), 7.09 (1H, dd, J = 8.6 Hz, 3.1 Hz), 7.20 (2H, d, J = 8.6 Hz), 7.71 (1H, d, J = 3.1 Hz), 7.98 (1H, brs). 
               
               
                   
               
               
                 377 
                 —CH═C(COOCH 3 ) 2   
                 3.84 (3H, s), 3.85 (3H, s), 6.82 (1H, d, J = 8.3 Hz), 
               
               
                   
                   
                 7.03 (2H, d, J = 8.9 Hz), 7.02-7.10 (1H, m), 7.42 (2H, 
               
               
                   
                   
                 d, J = 8.9 Hz), 7.70-7.76 (2H, m). 
               
               
                   
               
               
                 378 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.27 (3H, t, J = 7.0 Hz), 1.88 (2H, m), 2.02 (2H, m), 2.40 (1H, m), 2.75 (2H, dt, J = 3.0 Hz, 12.0 Hz), 3.46 (2H, brs), 3.56 (2H, dt, J = 13.0 Hz, 3.0 Hz), 4.15 (2H, q, J = 7.0 Hz), 6.70 (1H, d, J = 8.5 Hz), 6.92 (2H, d, J = 9.0 Hz), 6.98 (2H, d, J = 9.0 Hz), 7.05 (1H, dd, J = 8.5 Hz, 3.0 Hz), 7.70 (1H, d, J = 3.0 Hz). 
               
               
                   
               
               
                 379 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.28 (3H, t, J = 7.0 Hz), 1.66-1.72 (2H, m), 1.82 (1H, m), 2.01 (1H, m), 2.68 (1H, m), 2.78 (1H, m), 2.99 (1H, dd, J = 12.0 Hz, 10.0 Hz), 3.39 (1H, brd, J = 12.0 Hz), 3.47 (2H, brs), 3.62 (1H, dd, J = 12.0 Hz, 4.0 Hz), 4.17 (2H, q, J = 7.0 Hz), 6.70 (1H, d, J = 8.5 Hz), 6.94 (2H, d, J = 9.0 Hz), 6.98 (2H, d, J = 9.0 Hz), 7.06 (1H, dd, J = 8.5 Hz, 3.0 Hz), 7.70 (1H, d, J = 3.0 Hz). 
               
               
                   
               
               
                 380 
                 —CH(CH 3 )CH 2 COOC 2 H 5   
                 1.18 (3H, t, J = 7.2 Hz), 1.27 (3H, d, J = 7.0 Hz), 2.43- 
               
               
                   
                   
                 2.60 (2H, m), 3.19-3.29 (1H, m), 3.48 (2H, brs), 
               
               
                   
                   
                 4.06 (2H, q, J = 7.2 Hz), 6.72 (1H, d, J = 8.7 Hz), 
               
               
                   
                   
                 6.96 (2H, d, J = 8.6 Hz), 7.05 (1H, dd, J = 8.7 Hz, 3.0 
               
               
                   
                   
                 Hz), 7.16 (2H, d, J = 8.6 Hz), 7.70 (1H, d, J = 3.0 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 54 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 214    
                   1 H NMR (CDCl 3 ) δ ppm or MS 
               
               
                   
               
               
                 381 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 460 (M + ) 
               
               
                   
               
               
                 382 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.90-2.03 (1H, m), 2.20- 2.55 (3H, m), 3.11-3.25 (1H, m) 3.25- 3.38 (1H, m), 3.43 (2H, s), 3.57 (2H, s), 3.60-3.88 (2H, m), 4.70 (1H, d, J = 6.5 Hz), 5.18 (1H, d, J = 6.5 Hz), 6.76 (1H, d, J = 8.6 Hz), 7.02 (2H, d, J = 8.5 Hz), 7.08 (1H, dd, J = 8.5 Hz, 3.0 Hz), 7.20- 7.35 (7H, m), 7.73 (1H, dd, J = 3.1 Hz, 0.5 Hz). 
               
               
                   
               
               
                 383 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 2.25 (4H, t, J = 5.0 Hz), 3.19 (3H, s), 3.22 (4H, t, J = 5.0 Hz), 3.43 (2H, s), 3.56 (2H, brs), 6.77 (1H, d, J = 8.6 Hz), 7.00 (2H, d, J = 9.2 Hz), 7.05 (2H, d, J = 9.2 Hz), 7.09 (1H, dd, J = 8.6 Hz, 2.8 Hz), 7.17-7.35 (5H, m), 7.72 (1H, d, J = 2.8 Hz). 
               
               
                   
               
               
                 384 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 2.20 (3H, s), 3.07 (1H, dd, J = 14.2 Hz, 10.1 Hz), 3.50 (2H, brs), 3.52 (1H, dd, J = 14.2 Hz, 3.8 Hz), 4.51 (1H, dd, J = 10.1 Hz, 3.8 Hz), 6.73 (1H, d, J = 8.5 Hz), 6.90 (1H, d, J = 8.5 Hz), 7.03 (1H, dd, J = 8.5 Hz, 3.0 Hz), 7.08 (1H, dd, J = 8.5 Hz, 3.0 Hz), 7.10 (1H, d, J = 3.0 Hz), 7.67 (1H, d, J = 3.0 Hz), 8.10 (1H, brs). 
               
               
                   
               
               
                 385 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 3.62 (2H, brs), 3.97 (3H, s), 6.86 (1H, d, J = 8.6 Hz), 7.12 (1H, dd, J = 8.6 Hz, 3.0 Hz), 7.32 (1H, dd, J = 8.9 Hz, 2.5 Hz), 7.41 (1H, d, J = 2.1 Hz), 7.72-7.75 (2H, m), 7.92 (1H, d, J = 8.9 Hz), 8.02 (1H, dd, J = 8.6 Hz, 1.7 Hz), 8.56 (1H, s). 
               
               
                   
               
               
                 386 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 3.63 (2H, brs), 3.98 (3H, s), 6.90 (1H, d, J = 8.6 Hz), 6.94 (1H, d, J = 8.2 Hz), 7.15 (1H, dd, J = 8.7 Hz, 3.0 Hz), 7.54-7.57 (1H, m), 7.62-7.68 (1H, m), 7.77 (1H, d, J = 3.0 Hz), 8.18 (1H, d, J = 8.2 Hz), 8.32-8.35 (1H, m), 9.03 (1H, d, J = 8.7 Hz). 
               
               
                   
               
               
                 387 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.45 (3H, t, J = 7.1 Hz), 3.57 (2H, brs), 4.47 (2H, q, J = 7.1 Hz), 6.83 (1H, d, J = 8.6 Hz), 7.12 (1H, dd, J = 8.6 Hz, 3.1 Hz), 7.38 (1H, dd, J = 9.4 Hz, 2.6 Hz), 7.43-7.49 (2H, m, 7.75 (1H, d, J = 3.0 Hz), 7.89 (1H, d, J = 8.2 Hz), 8.10 (1H, dd, J = 7.3 Hz, 1.3 Hz), 8.93 (1H, d, J = 9.4 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 55 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 215   
                 R 216   
                 R 217   
                 Xa 9   
                 Xa 10   
                   1 H NMR (CDCl 3 ) δ ppm or MS 
               
               
                   
               
               
                 388 
                 —H 
                 —CH 3   
                 piperonyl 
                 —CH 2 — 
                 —CH 2 — 
                 MS 474 (M + ) 
               
               
                 389 
                 —H 
                 —F 
                 benzyl 
                 none 
                 none 
                   1 H NMR 2.46 (4H, brs), 
               
               
                   
                   
                   
                   
                   
                   
                 3.54 (6H, brs), 6.83 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.7 Hz), 7.09 (1H, dd, J = 8.6 
               
               
                   
                   
                   
                   
                   
                   
                 Hz, 3.0 Hz), 7.16-7.36 (8H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.61 (1H, d, J = 3.0 Hz). 
               
               
                 390 
                 —H 
                 —OCH 3   
                 piperonyl 
                 —CH 2 — 
                 —CH 2 — 
                   1 H NMR 2.31-2.41 (4H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 2.59-2.65 (2H, m), 2.92- 
               
               
                   
                   
                   
                   
                   
                   
                 2.98 (2H, m), 3.41 (4H, brs), 
               
               
                   
                   
                   
                   
                   
                   
                 3.62-365 (2H, m), 3.76 (3H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 5.95 (2H, s), 6.71-6.79 (4H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 6.83-6.85 (2H, m), 6.97 (1H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.1 Hz), 7.06 (1H, dd, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.7 Hz, 3.0 Hz), 7.63 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 2.8 Hz). 
               
               
                 391 
                 —H 
                 —H 
                 —COOC(CH 3 ) 3   
                 —CH 2 — 
                 —CH(OH)— 
                   1 H NMR 1.47 (9H, s), 2.81- 
               
               
                   
                   
                   
                   
                   
                   
                 2.98 (2H, m), 301-3.20 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 3.29 (3H, brs), 3.39 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs), 3.51 (2H, brs), 3.58- 
               
               
                   
                   
                   
                   
                   
                   
                 3.78 (3H, m), 4.58 (1H, q, J = 
               
               
                   
                   
                   
                   
                   
                   
                 7.0 Hz), 6.75 (1H, d, J = 8.8 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 6.99 (2H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.07 (1H, dd, J = 8.8 Hz, 3.0 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.19 (2H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.67 (1H, d, J = 3.0 Hz). 
               
               
                 392 
                 —CH 3 — 
                 —H 
                 piperonyl 
                 —CH 2 — 
                 —CH 2 — 
                 MS 474 (M + ) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 56 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 218   
                 R 219   
                 R 220   
                   1 H NMR (CDCl 3 ) δ ppm or MS 
               
               
                   
               
               
                 393 
                 —H 
                 —H 
                 —H 
                   1 H NMR 2.42-2.49 (4H, m), 3.42-3.48 (4H, 
               
               
                   
                   
                   
                   
                 m), 3.66-3.72 (2H, m), 3.86 (2H, d, J = 4.3 
               
               
                   
                   
                   
                   
                 Hz), 4.82 (1H, t, J = 4.3 Hz), 5.96 (2H, s), 
               
               
                   
                   
                   
                   
                 6.62 (2H, d, J = 8.8 Hz), 6.68 (1H, d, J = 8.6 
               
               
                   
                   
                   
                   
                 Hz), 6.73-6.78 (2H, m), 6.86 (1H, d, J = 1.0 
               
               
                   
                   
                   
                   
                 Hz), 6.95 (1H, d, J = 8.8 Hz), 7.05 (1H, dd, J = 
               
               
                   
                   
                   
                   
                 3.0 Hz, 8.6 Hz), 7.69 (1H, d, J = 3.0 Hz) 
               
               
                 394 
                 —H 
                 —H 
                 —Ac 
                   1 H NMR 1.94 (3H, s), 2.45-2.55 (4H, m), 
               
               
                   
                   
                   
                   
                 3.45-3.70 (8H, m), 4.42 (2H, s), 5.95 (2H, s), 
               
               
                   
                   
                   
                   
                 6.75-6.85 (3H, m, 6.92 (1H, s), 7.04 (2H, d, 
               
               
                   
                   
                   
                   
                 J = 8.8 Hz), 7.12 (1H, dd, J = 3.0 Hz, 8.6 
               
               
                   
                   
                   
                   
                 Hz), 7.36 (2H, d, J = 8.8 Hz), 7.72 (1H, d, J = 
               
               
                   
                   
                   
                   
                 3.0 Hz). 
               
               
                 395 
                 —H 
                 —H 
                 —COC 2 H 5   
                   1 H NMR 1.06 (3H, t, J = 7.5 Hz), 2.17 (2H, 
               
               
                   
                   
                   
                   
                 q, J = 7.5 Hz), 2.40-2.45 (4H, m), 3.41 (4H, 
               
               
                   
                   
                   
                   
                 s), 3.59 (2H, d), 4.42 (2H, s), 5.94 (2H, s), 
               
               
                   
                   
                   
                   
                 6.70-6.75 (2H, m), 6.80-6.85 (2H, m), 
               
               
                   
                   
                   
                   
                 7.04 (2H, d, J = 8.7 Hz), 7.11 (1H, dd, J = 3.1 
               
               
                   
                   
                   
                   
                 Hz, 8.6 Hz), 7.36 (2H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                 7.72 (1H, d, J = 3.1 Hz). 
               
               
                   
               
               
                 396 
                 —H 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 0.60-1.55 (5H, m), 2.39 (4H, brs), 3.42 (4H1, brs), 3.55 (2H, brs), 4.46 (2H, brs), 5.94 (2H, s), 6.69-6.75 (2H, m), 6.77- 6.85 (2H, m,) 7.00-7.15 (2H, m), 7.40- 7.46 (2H, m), 7.72 (1H, s). 
               
               
                   
               
               
                 397 
                 —H 
                 —H 
                 cyclopropyl 
                   1 H NMR 0.60-0.66 (2H, m), 0.77-0.83 (2H, 
               
               
                   
                   
                   
                   
                 m), 2.42-2.44 (4H, m), 2.77-2.79 (1H, m), 
               
               
                   
                   
                   
                   
                 3.43-3.52 (6H, m), 3.59-3.62 (2H, m), 
               
               
                   
                   
                   
                   
                 4.16 (2H, s), 5.95 (2H, s), 6.66 (1H, d, J = 8.6 
               
               
                   
                   
                   
                   
                 Hz), 6.75 (2H, s), 6.86-6.97 (5H, m), 7.03 (1H, 
               
               
                   
                   
                   
                   
                 dd, J = 8.6 Hz, 2.8 Hz), 7.70 (1H, d, J = 2.8 
               
               
                   
                   
                   
                   
                 Hz). 
               
               
                 398 
                 —CH 3   
                 —CH 3   
                 —C 2 H 5   
                 MS 517(M + ) 
               
               
                 399 
                 —COOCH 3   
                 —H 
                 —C 2 H 5   
                 MS 547(M + ) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 57 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 Xa 11    
                 M 
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 400 
                 —NH— 
                 0 
                 2.40-2.50 (4H; m), 3.40-3.55 (6H, m), 3.68 (2H, brs), 
               
               
                   
                   
                   
                 5.95 (2H, s), 6.27 (1H, s), 6.30-6.55 (2H, m), 6.65-6.95 (5H, 
               
               
                   
                   
                   
                 m), 7.20-7.30 (2H, m). 
               
               
                 401 
                 —NH— 
                 1 
                 2.40-2.50 (4H, m), 3.35-3.45 (4H, m), 3.55-3.70 (4H, m), 
               
               
                   
                   
                   
                 3.83 (2H, d, J = 4.4 Hz), 4.72 (1H, t, J = 4.4 Hz), 5.95 (2H, 
               
               
                   
                   
                   
                 s), 6.30-6.40 (1H, m), 6.45-6.60 (3H, m), 
               
               
                 402 
                 —N(Ac)— 
                 1 
                 1.91 (3H, s), 2.40-2.50 (4H, m), 3.45-3.75 (8H, m), 4.41 (2H, 
               
               
                   
                   
                   
                 s), 5.94 (2H, s), 6.40-6.52 (2H, m), 6.70-6.75 (2H, m), 6.80- 
               
               
                   
                   
                   
                 6.95 (4H, m), 7.28 (2H, d, J = 9.0 Hz). 
               
               
                 403 
                 —O— 
                 1 
                 2.41 (4H, brs), 3.42 (2H, s), 3.50-3.80 (6H, m), 4.63 (2H, s), 
               
               
                   
                   
                   
                 5.94 (2H, s), 6.40 (1H, ddd, J = 1.2 Hz, 2.6 Hz, 7.4 Hz), 
               
               
                   
                   
                   
                 6.50 (1H, dd, J = 2.6 Hz, 12.1 Hz), 6.65-6.75 (2H, m), 6.80- 
               
               
                   
                   
                   
                 6.95 (6H, m). 
               
               
                   
               
             
          
         
       
     
       Reference Example 404 
     Production of methyl 3-[(4-hydroxyphenyl)methylamino]-propionate 
       [0814]    Methyl 3-[(4-benzyloxyphenyl)methylamino]-propionate (27.3 g, 91.1 mmol) was dissolved in ethanol (300 mL), and the resulting solution was cooled with ice and 10% palladium-carbon (3.0 g) was added. The resulting solution was stirred for 4.5 hours at room temperature under a hydrogen atmosphere. The reaction solution was filtered through Celite to remove insoluble matter, and the filtrate was concentrated under reduced pressure to thereby yield 19.1 g of the title compound. 
         [0815]    Appearance: Red oil 
         [0816]      1 H NMR (CDCl 3 ) δ 2.51-2.56 (2H, m), 2.83 (3H, brs), 3.57 (2H, brs), 3.66 (3H, s), 4.99 (1H, brs), 6.71-6.74 (4H, m). 
         [0817]    The following compounds were produced in the same manner as in Reference Example 404. 
       Reference Example 405 
     Ethyl[acetyl(4-hydroxyphenyl)amino]acetate 
       [0818]      1 H NMR (CDCl 3 ) δ 1.26 (3H, t, J=7.1 Hz), 1.92 (3H, s), 4.19 (2H, q, J=7.1 Hz), 4.34 (2H, s), 6.16 (1H, s), 6.87 (2H, d, J=8.8 Hz), 7.21 (2H, d, J=8.8 Hz). 
         [0000]    
       
         
               
               
               
             
           
               
                 TABLE 58 
               
               
                   
               
               
                 Reference 
                   
                   
               
               
                 Example 
                   
                   
               
               
                 No. 
                 Chemical Structure 
                 mp (° C.) or  1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
             
             
               
                 406 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 mp 172.0-173.0 
               
               
                   
               
               
                 407 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 2.24 (3H, s), 3.25-3.39 (2H, m), 3.66-3.81 (2H, m), 4.36 (2H, s), 4.93 (1H, s), 5.95 (2H, s), 6.71 (1H, d, J = 8.6 Hz), 6.77 (2H, d, J = 0.6 Hz), 6.83 (1H, s), 7.15 (1H, dd, J = 2.8 Hz, 8.6 Hz), 7.32 (1H, d, J = 2.8 Hz). 
               
               
                   
               
               
                 408 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.94-2.12 (2H, m), 2.08 (3H, s), 3.29 (2H, t, J = 6.0 Hz), 3.58 (2H, t, J = 6.0 Hz), 3.89 (3H, s), 3.93 (3H, s), 4.57 (2H, s), 6.34 (1H, d, J = 8.4 Hz), 6.71 (1H, dd, J = 2.6 Hz, 8.4 Hz), 6.75-6.93 (3H, m), 6.96 (1H, d, J = 1.3 Hz), 7.61 (1H, s). 
               
               
                   
               
               
                 409 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 2.07 (3H, s), 2.09-2.18 (2H, m), 2.37-2.50 (4H, m), 3.41 (2H, s), 3.43-3.54 (4H, m), 3.54-3.68 (4H, m), 4.22 (2H, s), 5.94 (2H, s), 6.35 (1H, d, J = 8.4 Hz), 6.62- 6.77 (3H, m), 6.83 (1H, d, J = 1.1 Hz), 6.88 (1H, d, J = 2.4 Hz). 
               
               
                   
               
               
                 410 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.49 (9H, s), 2.07 (3H, s), 2.07-2.21 (2H, m), 3.45 (2H, t, J = 5.9 Hz), 3.61 (2H, t, J = 5.9 Hz), 4.07 (2H, s), 6.33 (1H, d, J = 8.4 Hz), 6.71 (1H, dd, J = 2.6 Hz, 8.4 Hz), 6.87 (1H, d, J = 2.6 Hz), 7.26 (1H, s). 
               
               
                   
               
             
          
         
       
     
       Reference Example 411 
     Production of [4-(5-aminopyridin-2-yloxy)phenyl](4-piperonylpiperazin-1-yl)methanone 
       [0819]    [4-(5-nitropyridin-2-yloxy)phenyl](4-piperonylpiperazin-1-yl)methanone (0.36 g, 0.78 mmol) was dissolved in a mixed solvent consisting of ethanol (5 mL) and THF (5 mL). To the resulting solution was added 5% platinum-carbon (0.06 g), and stirred at room temperature under a hydrogen atmosphere. Two hours later, the 5% platinum-carbon was removed by filtration, and the solvent was evaporated under reduced pressure, to thereby yield 0.32 g of the title compound. 
         [0820]    Appearance: Pale yellow amorphous powder 
         [0821]      1 H NMR (CDCl 3 ) δ 2.43 (4H, brs), 3.44 (2H, s), 3.58 (6H, brs), 5.95 (2H, s), 6.74 (2H, s), 6.80 (1H, d, J=8.6 Hz), 6.85 (1H, s), 7.05 (2H, d, J=8.6 Hz), 7.10 (1H, dd, J=8.6 Hz, 3.0° Hz), 7.40 (2H, d, J=8.7 Hz), 7.74 (1H, d, J=2.6 Hz). 
         [0822]    The following compounds were produced in the same manner as in Reference Example 411. 
       Reference Example 412 
     4-[5-(4-Trifluoromethylphenoxymethyl)pyridin-2-yloxy]phenylamine 
       [0823]      1 H NMR (CDCl 3 ) δ 3.63 (2H, brs), 5.02 (2H, s), 6.70 (2H, d, J=8.9 Hz), 6.88 (1H, d, J=8.4 Hz), 6.94 (2H, d, J=8.9 Hz), 7.01 (2H, d, J=8.6 Hz), 7.55 (2H, d, J=8.4 Hz), 7.72 (1H, dd, J=8.4 Hz, 2.5 Hz), 8.22 (1H, d, J=2.3 Hz). 
       Reference Example 413 
     3-Methyl-4-[5-(4-trifluoromethylphenoxymethyl)pyridin-2-yloxy]phenylamine 
       [0824]      1 H NMR (CDCl 3 ) δ 2.08 (3H, s), 3.58 (2H, brs), 5.02 (2H, s), 6.65 (1H, dd, J=8.2 Hz, 2.8 Hz), 6.60 (1H, d, J=2.8 Hz), 6.83-6.87 (2H, m), 7.02 (2H, d, J=8.9 Hz), 7.56 (2H, d, J=9.1 Hz), 7.72 (1H, dd, J=8.6 Hz, 2.5 Hz), 8.21 (1H, d, J=2.5 Hz). 
       Reference Example 414 
     2-{[4-(4-Aminophenoxy)phenyl]methylamino}-1-(4-piperonylpiperazin-1-yl)ethanone 
       [0825]      1 H NMR (CDCl 3 ) δ 2.41 (4H, t, J=5.1 Hz), 2.99 (3H, s), 3.42 (2H, s), 3.48 (2H, t, J=4.8 Hz), 3.50 (2H, brs), 3.62 (2H, t, J=4.8 Hz), 4.04 (2H, s), 5.95 (2H, s), 6.61-6.68 (4H, m), 6.73-6.88 (7H, m). 
       Reference Example 415 
     2-{[3-(5-Aminopyridin-2-yloxy)phenyl]methylamino}-1-(4-piperonylpiperazin-1-yl)ethanone 
       [0826]      1 H NMR (CDCl 3 ) δ 2.40 (4H, t, J=4.9 Hz), 3.00 (3H, s), 3.41 (2H, s), 3.44-3.46 (2H, m), 3.51 (2H, brs), 3.59-3.61 (2H, m), 4.06 (2H, s), 5.95 (2H, s), 6.35-6.45 (3H, m), 6.70-6.74 (3H, m), 6.85 (1H, s), 7.05 (1H, dd, J=8.6 Hz, 3.1 Hz), 7.12-7.18 (1H, m), 7.73 (1H, d, J=3.1 Hz). 
         [0827]    The following compound were produced in the same manner as in Reference Example 415. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 59 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 221   
                 R 222   
                 R 223   
                 R 224   
                 R 225   
                   1 H NMR (CDCl 3 ) δ ppm or MS 
               
               
                   
               
               
                 416 
                 —H 
                 —H 
                 —CH 3   
                 —CH 3   
                 —CH 3   
                   1 H NMR 1.25 (3H, t, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 1.38 (6H, s), 2.86 (3H, s), 3.50 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs), 4.17 (2H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 6.73 (1H, dd, J = 8.6 Hz, 0.3 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 6.93 (2H, d, J = 9.1 Hz), 7.02- 
               
               
                   
                   
                   
                   
                   
                   
                 7.09 (3H, m), 7.73 (1H, d, J = 3.0 Hz). 
               
               
                 417 
                 —F 
                 —H 
                 —CH 3   
                 —H 
                 —H 
                   1 H NMR 1.26 (3H, t, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 3.05 (3H, s), 3.44 (2H, brs), 4.02 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                 s), 4.19 (2H, q, J = 7.1 Hz), 6.38- 
               
               
                   
                   
                   
                   
                   
                   
                 6.51 (2H, m), 6.75 (1H, d, J = 8.6 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.01-7.13 (2H, m), 7.63 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 3.0 Hz). 
               
               
                 418 
                 —F 
                 —H 
                 —C 2 H 5   
                 —H 
                 —H 
                   1 H NMR 1.16-1.30 (6H, m), 3.43 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs), 3.43 (2H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 3.98 (2H, s), 4.21 (2H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 6.33-6.47 (2H, m), 6.75 (1H, d, J = 8.6 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 6.99-7.09 (2H, m), 7.64 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 3.0 Hz). 
               
               
                 419 
                 —F 
                 —H 
                 —(CH 2 ) 2 CH 3   
                 —H 
                 —H 
                   1  H NMR 0.95 (3H, t, J = 7.4 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 1.27 (3H, t, J = 7.3 Hz), 1.59- 
               
               
                   
                   
                   
                   
                   
                   
                 1.70 (2H, m), 3.31 (2H, t, J = 7.6 z), 
               
               
                   
                   
                   
                   
                   
                   
                 3.45 (2H, brs), 3.99 (2H, s), 4.20 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                 q, J = 7.1 Hz), 6.32-6.45 (2H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 6.75 (1H, dd, J = 8.7 Hz, 0.7 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.04 (1H, t, J = 9.1 Hz), 7.05 (1H, dd, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 7.4 Hz, 5.8 Hz), 7.64 (1H, dd, J = 
               
               
                   
                   
                   
                   
                   
                   
                 3.0 Hz, 0.7 Hz). 
               
               
                 420 
                 —F 
                 —H 
                 —Ac 
                 —H 
                 —H 
                   1 H NMR 1.29 (3H, t, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 1.98 (3H, s), 3.55 (2H, brs), 4.21 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                 q, J = 7.1 Hz), 4.35 (2H, s), 6.87 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 8.7 Hz), 7.10-7.29 (4H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.63 (1H, d, J = 3.0 Hz). 
               
               
                 421 
                 —H 
                 —CF 3   
                 —C 2 H 5   
                 —H 
                 —H 
                 MS 383 (M + ) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 60 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 Xa 12   
                 R 226   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 422 
                 —O— 
                 —CH 2 CN 
                 3.54 (2H, brs), 3.72 (2H, s), 6.79 (1H, d, 
               
               
                   
                   
                   
                 J = 8.5 Hz), 7.06 (2H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                 7.09 (1H, dd, J = 8.5 Hz, 3.0 Hz), 
               
               
                   
                   
                   
                 7.30 (2H, d, J = 8.9 Hz), 7.71 (1H, d, J = 
               
               
                   
                   
                   
                 3.0 Hz). 
               
               
                   
               
               
                 423 
                 —O— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2.41 (4H, t, J = 5.1 Hz),3.38 (4H, t, J = 5.1 Hz), 3.42 (2H, s), 3.54 (2H, brs), 4.37 (2H, d, J = 5.1 Hz), 4.72 (1H, t, J = 5.1 Hz), 5.94 (2H, s), 6.74 (2H, s), 6.77 (1H, d, J = 8.7 Hz), 6.85 (1H, s), 7.01 (2H, d, J = 8.5 Hz), 7.08 (1H, dd, J = 8.7 Hz, 3.0 Hz), 7.28 (2H, d, J = 8.5 Hz), 7.68 (1H, d, J = 2.8 Hz). 
               
               
                   
               
               
                 424 
                 —O— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2.45-2.47 (4H, m), 2.73-2.98 (2H, m), 3.45 (2H, s), 3.49-3.72 (7H, m), 3.85- 3.91 (1H, m), 4.24-4.30 (1H, m), 5.96 (2H, s), 6.74-6.78 (3H, m), 6.86 (1H, s), 7.05-7.11 (3H, m), 7.53- 7.58 (2H, m), 7.70 (1H, d, J = 3.0 Hz). 
               
               
                   
               
               
                 425 
                 —O— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.35 (3H, d, J = 6.6 Hz), 2.37-2.52 (4H, m), 3.31 (1H, q, J = 6.6 Hz), 3.67- 3.72 (4H, m), 6.76 (1H, d, J = 8.6 Hz), 6.99 (2H, d, J = 8.3 Hz), 7.08 (1H, dd, J = 8.6 Hz, 2.3 Hz), 7.27 (2H, d, J = 8.4 Hz), 7.72 (1H, d, J = 3.0 Hz). 
               
               
                   
               
               
                 426 
                 —N(CH 3 )— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.30 (3H, t, J = 7.1 Hz), 2.76 (4H, t, J = 5.0 Hz), 3.24 (4H, t, J = 5.0 Hz), 3.28 (3H, s), 3.35 (4H, s), 4.21 (2H, q, J = 7.1 Hz), 6.42 (1H, dd, J = 8.8 Hz, 0.7 Hz), 6.83 (1H, dd, J = 8.8 Hz, 2.9 Hz), 6.92 (2H, d, J = 8.9 Hz), 7.10 (2H, d, J = 8.9 Hz), 7.79 (1H, dd, J = 2.9 Hz, 0.7 Hz). 
               
               
                   
               
               
                 427 
                 —N(CH 3 )— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.28 (3H, t, J = 7.1 Hz), 1.46 (2H, qd, J = 12.3 Hz, 3.6 Hz), 1.77-2.10 (3H, m), 2.29 (2H, d, J = 6.9 Hz), 2.73 (2H, td, J = 12.3 Hz, 2.4 Hz), 3.23 (2H, brs), 3.35 (3H, s), 3.63 (2H, d, J = 12.3 Hz), 4.15 (2H, q, J = 7.1 Hz), 6.41 (1H, d, J = 8.9 Hz), 6.82 (1H, dd, J = 8.9 Hz, 3.0 Hz), 6.92 (2H, d, J = 8.9 Hz), 7.09 (2H, d, J = 8.9 Hz), 7.79 (1H, d, J = 2.5 Hz). 
               
               
                   
               
               
                 428 
                 —O— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 3.28-3.42 (2H, m), 3.43-3.59 (2H, m), 3.71-3.88 (2H, m), 4.47 (2H, s), 6.73 (1H, d, J = 8.6 Hz), 7.01-7.11 (3H, m), 7.25-7.39 (5H, m), 7.51-7.59 (2H, m), 7.70 (1H, d, J = 2.9 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 61 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 227   
                 R 228   
                   1 H NMR (CDCl 3 ) δ ppm or MS 
               
               
                   
               
               
                 429 
                 —F 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 478 (M + ) 
               
               
                   
               
               
                 430 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.96-2.11 (2H, m), 2.19 (3H, s), 3.29 (2H, t, J = 5.9 Hz), 3.46 (2H, s), 3.68 (2H, t, J = 5.9 Hz), 4.52 (2H, s), 5.95 (2H, s), 6.67 (1H, d, J = 8.6 Hz), 6.73-6.81 (2H, m), 6.88 (1H, s), 6.93 (1H, d, J = 8.6 Hz), 7.05 (1H, dd, J = 3.0 Hz, 8.6 Hz), 7.09 (1H, dd, J = 2.6 Hz, 8.6 Hz), 7.18-7.22 (1H, m), 7.00 (1H, d, J =3.0 Hz). 
               
               
                   
               
               
                 431 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.99-2.11 (2H, m), 2.19 (3H, s), 3.29 (2H, t, J = 6.0 Hz), 3.47 (2H, s), 3.68 (2H, d, J = 6.0 Hz), 3.88 (3H, s), 3.88 (3H, s), 4.56 (2H, s), 6.68 (1H, d, J = 8.6 Hz), 6.82 (1H, d, J = 8.1 Hz), 6.86 (1H, dd, J = 1.8 Hz, 8.1 Hz), 6.91 (1H, d, J = 1.8 Hz), 6.93 (1H, d, J = 8.6 Hz), 7.05 (1H, dd, J = 3.0 Hz, 8.6 Hz), 7.09 (1H, dd, J = 2.6 Hz, 8.6 Hz), 7.19 (1H, d, J = 2.6 Hz), 7.69 (1H, d, J = 3.0 Hz). 
               
               
                   
               
               
                 432 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 2.10-2.21 (2H, m), 2.35-2.48 (4H, m), 3.42 (2H, s), 3.43-3.54 (6H, m), 3.57-3.66 (2H, m), 3.73 (2H, t, J = 5.7 Hz), 4.21 (2H, s), 5.95 (2H, s), 6.66 (1H, d, J = 8.6 Hz), 6.69-6.77 (2H, m), 6.84 (1H, d, J = 1.2 Hz), 6.92 (1H, d, J = 8.6 Hz), 7.02-7.09 (2H, m), 7.17 (1H, d, J = 2.4 Hz), 7.69 (1H, d, J = 2.8 Hz). 
               
               
                   
               
               
                 433 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.38 (3H, t, J = 7.1 Hz), 2.19 (3H, s), 2.19-2.38 (2H, m), 3.47 (2H, s), 3.73-3.93 (4H, m), 4.36 (2H, q, J = 7.1 Hz), 6.67 (1H, d, J = 8.6 Hz), 6.94 (1H, d, J = 8.6 Hz), 7.05 (1H, dd, J = 3.0 Hz, 8.6 Hz), 7.12 (1H, dd, J = 2.6 Hz, 8.6 Hz), 7.22 (1H, d, J = 2.6 Hz), 7.40-7.48 (2H, m), 7.69 (1H, d, J = 3.0 Hz), 7.95 8.04 (2H, m). 
               
               
                   
               
               
                 434 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.47 (9H, s), 2.05-2.24 (5H, m), 3.34-3.54 (4H, m), 3.77 (2H, t, J = 5.8 Hz), 4.04 (2H, s), 6.65 (1H, d, J = 8.6 Hz), 6.90 (1H, d, J = 8.6 Hz), 6.99-7.10 (2H, m), 7.17 (1H, d, J = 2.4 Hz), 7.68 (1H, d, J = 3.0 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 62 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 229   
                 Xa 13   
                 R 230   
                 Xa 14   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 435 
                 —H 
                 —CO— 
                 3-pyridyl 
                 —CH 2 — 
                 3.23 (4H, brs), 3.62 (2H, brs), 
               
               
                   
                   
                   
                   
                   
                 3.81 (4H, brs), 6.83 (1H, d, J = 8.6 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.09 (2H, d, J 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.12 (1H, dd, J = 8.6 Hz, 3.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.20-7.21 (2H, m), 7.45 (2H, d, J = 8.7 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.55 (1H, d, J = 3.0 Hz), 8.14- 
               
               
                   
                   
                   
                   
                   
                 8.17 (1H, m), 8.31-8.33 (1H, m). 
               
               
                 436 
                 —H 
                 none 
                 piperonyl 
                 —CO— 
                 3.37 (4H, s), 3.48 (2H, brs), 3.90 (2H, 
               
               
                   
                   
                   
                   
                   
                 s), 4.57 (2H, s), 5.95 (2H, s), 6.72 (1H, 
               
               
                   
                   
                   
                   
                   
                 dd, J = 8.5 Hz, 0.7 Hz), 6.74- 
               
               
                   
                   
                   
                   
                   
                 6.78 (2H, m), 6.78-6.82 (1H, m), 
               
               
                   
                   
                   
                   
                   
                 6.86 (2H, d, J = 9.1 Hz), 7.02 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                 9.1 Hz), 7.06 (1H, dd, 4 = 8.5 Hz, 
               
               
                   
                   
                   
                   
                   
                 2.9 Hz), 7.69 (1H, d, J = 2.9 Hz). 
               
               
                 437 
                 —COOCH 3   
                 none 
                 benzyl 
                 —CH 2 — 
                 2.58-2.62 (4H, m), 3.14-3.18 (4H, m), 
               
               
                   
                   
                   
                   
                   
                 3.61 (2H, s), 3.65 (3H, s), 6.63 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.7 Hz), 6.95 (1H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.12-7.18 (2H, m), 7.25-7.36 (5H, m, 
               
               
                   
                   
                   
                   
                   
                 7.41 (1H, d, J = 3.0 Hz), 7.51 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 2.8 Hz). 
               
               
                 438 
                 —H 
                 —CH 2 — 
                 —COOC(CH 3 ) 3   
                 —CH 2 — 
                 1.45 (9H, s), 2.36-2.40 (4H, m), 3.40- 
               
               
                   
                   
                   
                   
                   
                 3.44 (4H, m), 3.47 (2H, s), 3.56 (2H, 
               
               
                   
                   
                   
                   
                   
                 brs), 6.76 (1H, d, J = 8.6 Hz), 6.97- 
               
               
                   
                   
                   
                   
                   
                 7.02 (2H, m), 7.08 (1H, dd, J = 8.6 Hz, 
               
               
                   
                   
                   
                   
                   
                 3.0 Hz), 7.25-7.29 (2H, m), 7.71 (1H, 
               
               
                   
                   
                   
                   
                   
                 d J = 3.0 Hz). 
               
               
                 439 
                 —H 
                 —CO— 
                 benzyl 
                 —CH 2 — 
                 2.38 4H, brs); 3.33 2H, brs), 
               
               
                   
                   
                   
                   
                   
                 3.50 (4H, brs), 5.17 (2H, brs), 
               
               
                   
                   
                   
                   
                   
                 6.82 (1H, d, J = 8.6 Hz), 6.96 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.7 Hz), 7.10 (1H, dd, J = 8.6 Hz, 
               
               
                   
                   
                   
                   
                   
                 3.0 Hz), 7.27-7.33 (5H, m), 7.36 (2H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.7 Hz), 7.57 (1H, d, J = 3.0 
               
               
                   
                   
                   
                   
                   
                 Hz). 
               
               
                 440 
                 —H 
                 —CO— 
                 4-CH 3 OPhCH 2 — 
                 —CH 2 — 
                 2.44 (4H, brs), 3.48 (2H, s), 3.59 (4H, 
               
               
                   
                   
                   
                   
                   
                 brs), 3.81 (3H, s), 6.80 (1H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 8.6 Hz, 0.7 Hz), 6.85-6.89 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 7.03-7.08 (2H, m), 7.11 (1H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 8.6 Hz, 3.0 Hz), 7.21-7.26 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 7.38-7.43 (2H, m), 7.73-7.75 (1H, m). 
               
               
                 441 
                 —H 
                 —SO 2 — 
                 benzyl 
                 —CH 2 13  
                 2.42-2.57 (4H, m), 2.91-3.10 (4H, m), 
               
               
                   
                   
                   
                   
                   
                 3.47 (2H, s), 3.63 (2H, brs), 6.83 (1H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.6 Hz), 7.07-7.14 (3H, m), 
               
               
                   
                   
                   
                   
                   
                 7.18-7.31 (5H, m), 7.68 (2H, d, J = 8.8 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.74 (1H, d, J = 2.0 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 63 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 231   
                 R 232   
                 R 233   
                 R 234   
                 R 235   
                   ′ H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 442 
                 —F 
                 —H 
                 —H 
                 —H 
                 —H 
                 2.43-2.48 (4H, m), 3.44-3.47 (6H, m) 3.67- 
               
               
                   
                   
                   
                   
                   
                   
                 3.68 (2H, m), 3.82 (2H, d, J = 4.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 4.96 (1H, brs), 5.96 (2H, s), 6.36-6.43 (2H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 6.71-6.78 (3H, m), 6.86 (1H, brs), 6.97- 
               
               
                   
                   
                   
                   
                   
                   
                 7.03 (1H, m), 7.06 (1H, dd, J = 8.7 Hz, 3.0 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.63 (1H, d, J = 3.0 Hz). 
               
               
                 443 
                 —F 
                 —H 
                 —H 
                 —H 
                 —CH 3   
                 2.43-2.45 (4H, m), 3.01 (3H, s), 3.44 (2H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 3.47 (2H, brs), 3.63 (2H, brs), 4.07 (2H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 5.95 (2H, s), 6.39-6.50 (2H, m), 6.72-6.76 (3H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 6.85 (1H, s), 7.00-7.08 (2H, m), 7.63 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 dd, J = 3.0 Hz, 0.5 Hz). 
               
               
                 444 
                 —F 
                 —H 
                 —H 
                 —H 
                 —C 2 H 5   
                 1.18 (3H, t, J = 7.1 Hz), 2.43 (4H, t, J = 5.0 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 3.37-3.48 (8H, m), 3.63 (2H, brs), 
               
               
                   
                   
                   
                   
                   
                   
                 4.01 (2H, s), 5.95 (2H, s), 6.35-6.46 (2H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 6.72-6.77 (3H, m), 6.85 (1H, s), 6.99 (1H d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.9 Hz), 7.05 (1H, dd, J = 8.7 Hz, 3.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.63 (1H, d, J = 3.0 Hz). 
               
               
                 445 
                 —F 
                 —H 
                 —H 
                 —F 
                 CH 3   
                 2.33-2.49 (4H, m), 2.93 (3H s), 3.38-3.68 (8H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 4.00 (2H, s), 5.95 (2H, s), 6.71-6.77 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                 s), 6.78-6.82 (2H, m), 6.83-6.91 (2H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.08 (1H, dd, J = 2.9 Hz, 8.6 Hz), 7.62 (1H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 2.9 Hz). 
               
               
                 446 
                 —F 
                 —H 
                 —H 
                 —F 
                 —C 2 H 5   
                 1.11 (3H, t, J = 7.1 Hz), 2.31-2.49 (4H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 3.29 (2H, q, J = 7.1 Hz), 3.41 (2H, s), 3.42- 
               
               
                   
                   
                   
                   
                   
                   
                 3.69 (6H, m), 3.96 (2H, s), 6.70-6.78 (2H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 6.79-6.91 (4H m), 7.08 (1H, dd, J = 2.9 Hz, 
               
               
                   
                   
                   
                   
                   
                   
                 8.6 Hz), 7.62 (1H, d, J = 2.9 Hz). 
               
               
                 447 
                 —F 
                 —H 
                 —F 
                 —H 
                 —CH 3   
                 2.36-2.52 (4H, m), 3.01 (3H, s), 3.34-3.54 (6H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 3.55-3.71 (2H, m), 4.05 (2H, s), 5.95 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                 s), 6.18-6.29 (2H, m), 6.70-6.79 (2H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 6.82 (1H, d, J = 8.6 Hz), 6.85 (1H, d, J = 0.98 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.07 (1H, dd, J = 2.9 Hz, 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.59 (1H, d, J = 2.9 Hz). 
               
               
                 448 
                 —F 
                 —F 
                 —H 
                 —H 
                 —CH 3   
                 2.29-2.55 (4H, m), 2.95 (3H s), 3.30-3.75 (8H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 4.01 (2H, s), 5.95 (2H, s), 6.60-6.95 (6H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 7.09 (1H, dd, J = 3.0 Hz, 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.62 (1H, d, J = 3.0 Hz). 
               
               
                 449 
                 —CH 3   
                 —CH 3   
                 —H 
                 —H 
                 —CH 3   
                 2.11 (3H, s), 2.25 (3H, s), 2.36-2.42 (4H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 2.66 (3H, s) 3.41 (2H, s), 3.45 (2H, brs), 3.53- 
               
               
                   
                   
                   
                   
                   
                   
                 3.56 (2H, m), 3.61-3.64 (2H, m), 3.73 (2H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 5.95 (2H, s) 6.67 (1H, d, J = 8.7 Hz) 6.70- 
               
               
                   
                   
                   
                   
                   
                   
                 6.85 (4H, m), 6.95 (1H, d, J = 8.7 Hz), 7.03- 
               
               
                   
                   
                   
                   
                   
                   
                 7.08 (1H, m), 7.67 (1H, d, J = 3.0 Hz). 
               
               
                   
               
               
                 450 
                 —CH 3   
                 —H 
                 —H 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 0.62-0.66 (2H, m), 0.76-0.83 (2H, m), 2.12 (3H, s), 2.40-2.46 (4H, m), 2.73-2.81 (1H, m), 3.43 (2H, s), 3.48-3.63 (4H, m), 4.15 (2H, s), 5.94 (2H, s) 6.58 (1H, d, J = 8.7 Hz), 6.68- 6.77 (4H, m), 6.87 (2H, d, J = 8.6 Hz), 7.01 (1H, dd, J = 8.7 Hz, 3.0 Hz), 7.67 (1H, d, J = 3.0 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 64 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 236   
                 R 237   
                 R 238   
                 Xa 15   
                   1 H NMR (CDCl 3 ) δppm or MS 
               
               
                   
               
             
          
           
               
                 451 
                 —CH 3   
                 —H 
                 —H 
                 —CO— 
                   1 H NMR 2.20 (3H, s), 2.48-2.54 (4H, m), 
               
               
                   
                   
                   
                   
                   
                 3.44 (4H, s), 3.67-3.75 (2H, m), 4.23-4.27 (2H, 
               
               
                   
                   
                   
                   
                   
                 m), 5.95 (2H, s), 6.68-6.78 (3H, m), 6.86 (1H, 
               
               
                   
                   
                   
                   
                   
                 brs), 6.95 (1H, d, J = 8.7 Hz), 7.07 (1H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 8.6 Hz, 3.0 Hz), 7.37 (1H, dd, J = 8.7 Hz, 
               
               
                   
                   
                   
                   
                   
                 2.6 Hz), 7.52 (1H, d, J = 2.5 Hz), 7.66 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 3.0 Hz), 9.13 (1H, brs). 
               
               
                 452 
                 —CH 3   
                 —H 
                 —CH 3   
                 —CO— 
                   1 H NMR 2.21-2.31 (7H, m), 3.28-3.40 (9H, m), 
               
               
                   
                   
                   
                   
                   
                 3.53 (2H, brs), 5.93 (2H, s), 6.66-6.80 (4H, m,) 
               
               
                   
                   
                   
                   
                   
                 6.91 (1H, d, J = 8.6 Hz), 7.03-7.12 (3H, m), 
               
               
                   
                   
                   
                   
                   
                 7.66 (1H, d, J = 3.0 Hz). 
               
               
                 453 
                 —H 
                 —H 
                 —SO 2 CH 3   
                 —CH 2 — 
                   1 H NMR 2.41 (4H, brs), 3.19 (3H, s), 3.34- 
               
               
                   
                   
                   
                   
                   
                 3.38 (2H, m), 3.42 (2H, s), 3.57-3.60 (4H, m), 
               
               
                   
                   
                   
                   
                   
                 4.51 (2H, s), 5.95 (2H, s), 6.70-6.77 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 6.80 (1H, d, J = 8.6 Hz), 6.84 (1H, brs), 
               
               
                   
                   
                   
                   
                   
                 7.02 (2H, d, J = 8.7 Hz), 7.10 (1H, dd, J = 8.6 
               
               
                   
                   
                   
                   
                   
                 Hz, 3.0 Hz), 7.59 (2H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.71 (1H, d, J = 3.0 Hz). 
               
               
                 454 
                 —CH 3   
                 —H 
                 —SO 2 CH 3   
                 —CH 2 — 
                   1 H NMR 2.21 (3H, s), 2.41 (4H, brs), 3.20 (3H, 
               
               
                   
                   
                   
                   
                   
                 s), 3.34-3.38 (2H, m), 3.42 (2H, s), 3.53 (2H, 
               
               
                   
                   
                   
                   
                   
                 brs), 3.59-3.61 (2H, m), 4.51 (2H, s), 5.94 (2H, 
               
               
                   
                   
                   
                   
                   
                 s), 6.70-6.77 (3H, m), 6.83 (1H, brs), 6.90 (1H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.6 Hz), 7.09 (1H, dd, J = 8.6 Hz, 3.0 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.36 (1H, dd, J = 8.6 Hz, 2.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.42 (1H, d, J = 2.3 Hz), 7.66 (1H, d, J = 3.0 
               
               
                   
                   
                   
                   
                   
                 Hz). 
               
               
                 455 
                 —CF 3    
                 —H 
                 —C 2 H 5   
                 —CH 2 — 
                 MS 557 (M + ) 
               
               
                 456 
                 —CF 3   
                 —H 
                 —CH 3   
                 —CH 2 — 
                 MS 543 (M + ) 
               
               
                 457 
                 —CN 
                 —H 
                 —CH 3   
                 —CH 2 — 
                 MS 500 (M + ) 
               
               
                 458 
                 —OCH 3   
                 —H 
                 —SO 2 CH 3   
                 —CH 2 — 
                   1 H NMR 2.48 (4H, brs), 3.26 (3H, s), 3.42- 
               
               
                   
                   
                   
                   
                   
                 3.66 (8H, m), 3.82 (3H, s), 4.58 (2H, s), 
               
               
                   
                   
                   
                   
                   
                 5.99 (2H, s), 6.77-6.79 (2H, m), 6.81-6.88 (2H, 
               
               
                   
                   
                   
                   
                   
                 m), 7.06-7.30 (4H, m), 7.67 (1H, d, J = 2.3 
               
               
                   
                   
                   
                   
                   
                 Hz). 
               
               
                 459 
                 —CH 3   
                 —CH 3   
                 —CH 3   
                 —CH 2 — 
                 MS 503 (M + ) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 65 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 239   
                 R 240   
                 R 241   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
             
          
           
               
                 460 
                 —H 
                 —CH 3   
                 —H 
                 2.40-2.44 (4H, m), 3.00 (3H, s), 3.49 (4H, brs), 3.63 (2H, brs), 
               
               
                   
                   
                   
                   
                 4.05 (2H, s), 5.95 (2H, s), 6.67 (1H, d, J = 8.6 Hz), 6.69 (2H, d, 
               
               
                   
                   
                   
                   
                 J = 9.1 Hz), 6.74 (2H, brs), 6.85 (1H, brs), 6.97 (2H, d, J = 9.1 
               
               
                   
                   
                   
                   
                 Hz), 7.03 (1H, dd, J = 8.6 Hz, 3.0 Hz), 7.68 (1H, d, J = 3.0 
               
               
                   
                   
                   
                   
                 Hz). 
               
               
                 461 
                 —H 
                 —CH 3   
                 —CH 3   
                 1.28 (3H, d, J = 6.6 Hz , 2.14-2.21 1H, m), 2.28-2.35 (2H, m) 
               
               
                   
                   
                   
                   
                 2.47-2.49 (1H, m), 2.75 (3H, s), 3.24-3.54 (3H, m), 3.38 (2H, 
               
               
                   
                   
                   
                   
                 s), 3.45 (2H, s), 3.78-3.84 (1H, m), 4.54 (1H, q, J = 6.8 Hz), 
               
               
                   
                   
                   
                   
                 5.93 (2H, s), 6.68-6.75 (5H, m), 6.82 (1H, s), 6.99 (2H, d, J = 
               
               
                   
                   
                   
                   
                 9.1 Hz), 7.05 (1H, dd, J = 8.6 Hz, 3.0 Hz), 7.69 (1H, dd, J = 
               
               
                   
                   
                   
                   
                 3.1 Hz, 0.7 Hz). 
               
               
                 462 
                 —CH 3   
                 —CH 3   
                 —CH 3   
                 1.28(3H, d, J 6.6 Hz), 2.15(3H, s), 2.15-2.21(1H, in), 2.33- 
               
               
                   
                   
                   
                   
                 2.36 (2H, m), 2.49 (1H, brs), 2.74 (3H, s), 3.25-3.55 (3H, m), 
               
               
                   
                   
                   
                   
                 3.39 (2H, s), 3.42 (2H, s), 3.80 (1H, brs), 4.55 (1H, q, J = 6.4 
               
               
                   
                   
                   
                   
                 Hz), 5.93 (2H, s), 6.55-6.59 (2H, m), 6.64 (1H, dd, J = 8.6 Hz, 
               
               
                   
                   
                   
                   
                 0.5 Hz), 6.69-6.75 (2H, m), 6.83 (1H, brs), 6.90 (1H, d, J = 8.7 
               
               
                   
                   
                   
                   
                 Hz), 7.04 (1H, dd, J = 8.7 Hz, 3.0 Hz), 7.67 (1H, dd, J = 3.0 
               
               
                   
                   
                   
                   
                 Hz, 0.7 Hz). 
               
               
                 463 
                 —OCH 3   
                 —CH 3   
                 —H 
                 2.31-2.50 (4H, m), 3.02 (3H, s), 3.31-3.57 (6H, m), 3.58- 
               
               
                   
                   
                   
                   
                 3.70 (2H, m), 3.76 (3H, s), 4.06 (2H, s), 5.95 (2H, s), 6.24 (1H, 
               
               
                   
                   
                   
                   
                 dd, J = 8.7 Hz, 2.8 Hz), 6.37 (1H, d, J = 2.8 Hz), 6.68 (1H, d, J = 
               
               
                   
                   
                   
                   
                 8.6 Hz), 6.69-6.79 (2H, m), 6.85 (1H, s), 6.94 (1H, d, J = 8.7 
               
               
                   
                   
                   
                   
                 Hz), 7.02 (1H, dd, J = 8.6 Hz, 3.0 Hz), 7.65 (1H, d, J = 3.0 
               
               
                   
                   
                   
                   
                 Hz). 
               
               
                 464 
                 —OCH 3   
                 —C 2 H 5   
                 —H 
                 1.18 (3H, t, J = 7.0 Hz), 2.31-2.51 (4H, m), 3.28-3.70 (10 H, 
               
               
                   
                   
                   
                   
                 m), 3.74 (3H, s), 4.01 (2H, s), 5.95 (2H, s), 6.22 (1H, dd, J = 
               
               
                   
                   
                   
                   
                 8.7 Hz, 2.8 Hz), 6.35 (1H, d, J = 2.8 Hz), 6.68 (1H dd, J = 
               
               
                   
                   
                   
                   
                 8.7 Hz, 0.5 Hz), 6.69-6.79 (2H, m), 6.81-6.88 (1H, m), 
               
               
                   
                   
                   
                   
                 6.93 (1H, d, J = 8.7 Hz), 7.03 (1H, dd, J = 8.7 Hz, 3.0 Hz), 
               
               
                   
                   
                   
                   
                 7.65 (1H, dd, J = 3.0 Hz, 0.5 Hz). 
               
               
                 465 
                 —CH 3   
                 —CH 3   
                 —H 
                 2.13 (3H, s), 2.42 (4H, t, J = 3.0 Hz), 2.99 (3H, s), 3.35- 
               
               
                   
                   
                   
                   
                 3.57 (6H, m), 3.58-3.70 (2H, m), 4.05 (2H, s), 5.95 (2H, s), 
               
               
                   
                   
                   
                   
                 6.53 (1H, dd, J = 8.8 Hz, 3.1 Hz), 6.57 (1H, d, J = 3.1 Hz), 
               
               
                   
                   
                   
                   
                 6.60 (1H, d, J = 8.8 Hz), 6.71-6.78 (2H, m), 6.85 (1H, brs), 
               
               
                   
                   
                   
                   
                 6.88 (1H, d, J = 8.7 Hz), 7.02 (1H, dd, J = 8.7 Hz, 3.0 Hz), 
               
               
                   
                   
                   
                   
                 7.67 (1H, d, J = 3.0 Hz). 
               
               
                 466 
                 —CH 3   
                 —C 2 H 5   
                 —H 
                 1.15 (3H, t, J = 7.0 Hz), 2.12 (3H, s), 2.42 (4H, t, J = 5.1 Hz), 
               
               
                   
                   
                   
                   
                 3.27-3.70 (10H, m), 4.00 (2H, s), 5.95 (2H, s), 6.46-6.57 (2H, 
               
               
                   
                   
                   
                   
                 m), 6.60 (1H, dd, J = 8.7 Hz, 0.5 Hz), 6.69-6.78 (2H, m), 6.82- 
               
               
                   
                   
                   
                   
                 6.90 (2H, m), 7.02 (1H, dd, J = 8.7 Hz, 3.0 Hz), 7.68 (1H, dd, J = 
               
               
                   
                   
                   
                   
                 3.0 Hz, 0.5 Hz). 
               
               
                 467 
                 —CH 3   
                 —Ac 
                 —H 
                 1.95 (3H, s), 2.23 (3H, s), 2.31-2.52 (4H, m), 3.29-3.70 (8H, m), 
               
               
                   
                   
                   
                   
                 4.43 (2H, s), 5.94 (2H, s), 6.69-6.79 (3H, m), 6.84 (1H, s), 
               
               
                   
                   
                   
                   
                 6.92 (1H, d, J = 8.5 Hz), 7.10 (1H, dd, J = 8.6 Hz, 3.0 Hz), 
               
               
                   
                   
                   
                   
                 7.19 (1H, dd, J = 8.5 Hz, 2.5 Hz), 7.28 (1H, d, J = 2.2 Hz), 
               
               
                   
                   
                   
                   
                 7.68 (1H, d, J = 2.5 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 66 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 242   
                 R 243   
                 Xa 16   
                 M 
                 E 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
             
          
           
               
                 468 
                 —OCH 3   
                 —H 
                 —CH 2 — 
                 1 
                 1 
                 (DMSO-d 6 ) 2.32-2.40 (4H, m), 3.32 (2H, brs), 
               
               
                   
                   
                   
                   
                   
                   
                 3.50 (4H, brs), 3.61 (3H, s), 3.88 (2H, brs), 
               
               
                   
                   
                   
                   
                   
                   
                 4.88 (2H, brs), 5.44 (1H, brs), 5.99 (2H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 6.15 (1H, dd, J = 8.6 Hz, 2.5 Hz), 6.44 (1H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 2.3 Hz), 6.51 (1H, d, J = 8.6 Hz), 6.71- 
               
               
                   
                   
                   
                   
                   
                   
                 6.88 (4H, m), 6.98 (1H, dd, J = 8.6 Hz, 2.8 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.40 (1H, d, J = 2.6 Hz). 
               
               
                 469 
                 —OCR 3   
                 —H 
                 —CH 2 — 
                 1 
                 2 
                 (DMSO-d 6 ) 2.32 (2H, brs), 2.40 (2R, brs), 
               
               
                   
                   
                   
                   
                   
                   
                 3.39 (2H, s), 3.49 (4H, brs), 3.61 (3H s), 
               
               
                   
                   
                   
                   
                   
                   
                 3.89 (2H, brd), 4.22 (4H, s), 4.82 (2R, brs), 
               
               
                   
                   
                   
                   
                   
                   
                 5.44 (1R, brt), 6.15 (1H, dd, J = 8.6 Hz, 2.5 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 6.44-6.52 (2H, m), 6.70-6.81 (4H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 6.98 (1H, dd, J = 8.7 Hz, 3.0 Hz), 7.39 (1H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 2.8 Hz). 
               
               
                 470 
                 —H 
                 —CH 3   
                 —CH 2 — 
                 2 
                 1 
                 (CDCl 3 ) 2.35 (4H, tt, ,J = 5.0 Hz, 5.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 2.52-2.58 (2R, m), 2.91 (3H, s), 3.36-3.39 (4R, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 3.59-3.62 (2H, m), 3.65-3.73 (4R, m), 
               
               
                   
                   
                   
                   
                   
                   
                 5.93 (2H, s), 6.64-6.76 (5H, m), 6.83 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 1.0 Hz), 6.97 (2H, d, J = 9.1 Hz), 7.03 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 dd, J = 8.6 Hz; 3.1 Hz), 7.66 (1H, dd, J = 3.1 
               
               
                   
                   
                   
                   
                   
                   
                 Hz, 0.5 Hz). 
               
               
                 471 
                 —CH 3   
                 —CH 3   
                 —CO— 
                 1 
                 1 
                 (CDCl 3 ) 2.12 (3R, s), 2.88-3.10 (3H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 3.26 (2H, t, J = 5.3 Hz), 340 (2H, brs), 3.60- 
               
               
                   
                   
                   
                   
                   
                   
                 3.90 (2H, m), 4.00-4.15 (2R, m), 4.20- 
               
               
                   
                   
                   
                   
                   
                   
                 4.40 (2H, m), 4.52 (2H, s), 5.95 (2H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 6.53 (1H, dd, J = 8.5 Hz, 3.0 Hz), 6.60 (1H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 6.60 (1H, d, J = 8.5 Hz), 6.71 (1H, d, J = 8.5 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 6.74 (1R, s), 6.76 (1H, d, J = 8.5 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 6.88 (1H, d, J = 8.8 Hz), 7.02 (1R, dd, J = 8.5 
               
               
                   
                   
                   
                   
                   
                   
                 Hz, 2.8 Hz), 7.66 (1H, d, J = 2.8 Hz). 
               
               
                 472 
                 —OCH 3   
                 —C 2 H 5   
                 —CO— 
                 1 
                 1 
                 (CDCl 3 ) 1.17 (3H, t, J = 7.0 Hz), 3.20- 
               
               
                   
                   
                   
                   
                   
                   
                 3.31 (2H, m), 3.40-3.60 (2H, m), 3.41 (2H, q, J = 
               
               
                   
                   
                   
                   
                   
                   
                 7.0 Hz), 3.61-3.82 (2H, m), 3.74 (3R, s), 
               
               
                   
                   
                   
                   
                   
                   
                 4.02 (2R, s), 4.30 (2R, s), 4.50 (2H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 5.95 (2R, s), 6.24 (1H, dd, J = 8.7 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 6.40 (1H, s), 6.68 (1H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 6.70 (1H, dd, J = 7.9 Hz, 1.5 Hz), 6.76 (1H, s, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 1.5 Hz), 6.76 (1H, d, J = 7.9 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 6.93 (1H, d, J = 8.6 Hz), 7.03 (1H, dd, J = 8.5 
               
               
                   
                   
                   
                   
                   
                   
                 Hz, 2.8 Hz), 7.64 (1H, d, J = 2.8 Hz). 
               
               
                   
               
               
                 (E means the number of the methylene groups. 
               
               
                 Hereinafter E indicates the same meaning.) 
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 67 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 Xa 17   
                 M 
                 E 
                 R 244   
                 Form 
                 mp (° C.) or  1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
             
          
           
               
                 473 
                 —CH 2 — 
                 1 
                 0 
                 benzyl 
                 free 
                   1 H NMR 2.33-2.43 (4H, m), 2.57-2.63 
               
               
                   
                   
                   
                   
                   
                   
                 (2H, m), 2.91-2.97 (2H, m), 3.38- 
               
               
                   
                   
                   
                   
                   
                   
                 3.42 (4H, m), 3.50 (2H, s), 3.62- 
               
               
                   
                   
                   
                   
                   
                   
                 3.65 (2H, m), 6.75 (1H, dd, J = 8.6 Hz, 
               
               
                   
                   
                   
                   
                   
                   
                 0.5 Hz), 6.95-7.00 (2H, m), 7.07 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 dd, J = 8.6 Hz, 3.0 Hz), 7.15-7.20 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 7.28-7.33 (5H, m), 7.70 (1H, dd, J = 
               
               
                   
                   
                   
                   
                   
                   
                 3.0 Hz, 0.5 Hz). 
               
               
                 474 
                 —CH 2 — 
                 1 
                 0 
                 piperonyl 
                 trihydro- 
                 mp 179-180 dec 
               
               
                   
                   
                   
                   
                   
                 chloride 
               
               
                 475 
                 —O— 
                 1 
                 0 
                 piperonyl 
                 free 
                   1 H NMR 2.41 (4H, brs), 3.42 (2H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 3.48 (2H, brs), 3.50-3.70 (4H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 4.65 (2H, s), 5.95 (2H, s), 6.72 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.6 Hz), 6.74 (2H, brs), 6.85 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs, 6.91 (2H, d, J = 9.2 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.00 (2H, d, J = 9.2 Hz), 7.06 (1H, dd, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.6 Hz, 3.0 Hz), 7.69 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 3.0 Hz). 
               
               
                 476 
                 —O— 
                 1 
                 0 
                 benzyl 
                 free 
                   1 H NMR 2.44 (4H, t, J = 5.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 3.51 (4H, s), 3.58 (2H, t, J = 5.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 3.64 (2H, t, J = 5.0 Hz), 4.65 (2H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 6.72 (1H, d, J = 8.5 Hz), 6.92 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 9.2 Hz), 7.00 (2H, d, J = 9.2 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.06 (1H, dd, J = 8.5 Hz, 3.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.22-7.35 (5H, m), 7.69 (1H, d, J = 3.0 
               
               
                   
                   
                   
                   
                   
                   
                 Hz). 
               
               
                 477 
                 —NH— 
                 0 
                 1 
                 piperonyl 
                 free 
                   1 H NMR 2.51 (4H, brs), 2.62-2.63 (4H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 3.12 (2H, s), 3.45 (2H, s), 3.52 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs), 5.94 (2H, s), 6.74 (1H, dd, J = 8.7 
               
               
                   
                   
                   
                   
                   
                   
                 Hz, 0.7 Hz), 6.75 (2H, brs), 6.85 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 s), 7.03 (2H, d, J = 8.9 Hz), 7.07 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 dd, J = 8.7 Hz, 3.0 Hz), 7.54 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 9.1 Hz), 7.69 (1H, dd, J = 3.0 Hz, 
               
               
                   
                   
                   
                   
                   
                   
                 0.7 Hz), 9.10 (1H, brs). 
               
               
                 478 
                 —N(CH 3 )— 
                 0 
                 1 
                 piperonyl 
                 free 
                   1 H NMR 2.44 (8H, brs), 2.93 (2H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 3.24 (3H, s), 3.38 (2H, s), 3.62 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs), 5.92 (2H, s), 6.72 (2H, brs), 6.80- 
               
               
                   
                   
                   
                   
                   
                   
                 6.84 (2H, m), 7.06 (2H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.12 (1H, dd, J = 8.6 Hz, 3.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.15 (2H, d, J = 8.9 Hz), 7.73 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 3.0 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 68 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 245   
                 R 246   
                 R 247   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
             
          
           
               
                 479 
                 —CH 3   
                 —H 
                 —CH 3   
                 1.12 (3H, d, J = 6.3 Hz), 2.10-2.12 (1H, m), 2.47 (1H, 
               
               
                   
                   
                   
                   
                 brs), 2.67-2.72 (1H, m), 2.80-3.11 (6H, m), 3.47- 
               
               
                   
                   
                   
                   
                 3.60 (3H, m), 3.84-4.10 (4H, m), 5.94 (2H, s), 6.64- 
               
               
                   
                   
                   
                   
                 6.74 (5H, m), 6.85 (1H, brs), 6.94-6.98 (2H, m), 7.00- 
               
               
                   
                   
                   
                   
                 7.05 (1H, m), 7.68 (1H, d, J = 2.8 Hz). 
               
               
                 480 
                 —CH 3   
                 —CH 3   
                 —H 
                 1.28-1.37 (3H, m), 1.94-2.03 (1H, m), 2.11-2.15 (1H, m), 
               
               
                   
                   
                   
                   
                 2.63-2.67 (1H, m), 2.79-2.82 (1H, m), 2.95-3.00 (4H, m), 
               
               
                   
                   
                   
                   
                 3.30-3.46 (5H, m), 4.03-4.69 (3H, m), 5.94 (2H, s), 
               
               
                   
                   
                   
                   
                 6.66 (1H, d, J = 8.7 H), 6.68 (2H, d, J = 9.1 H), 6.74 (2H, 
               
               
                   
                   
                   
                   
                 brs), 6.87 (1H, brs), 6.96 (2H, d, J = 9.1 Hz), 7.03 (1H, 
               
               
                   
                   
                   
                   
                 dd, J = 8.7 Hz, 3.0 Hz), 7.68 (1H, d, J = 3.0 Hz). 
               
               
                 481 
                 —C 2 H 5   
                 —H 
                 —CH 3   
                 1.11-1.18 (6H, m), 2.04-2.13 (1H, m), 2.45-2.47 (1H, m), 
               
               
                   
                   
                   
                   
                 2.66-2.73 (1H, m), 2.85-3.64 (8H, m), 3.84-4.11 (4H, m), 
               
               
                   
                   
                   
                   
                 5.94 (2H, s), 6.64-6.69 (3H, m), 6.74 (2H, brs), 6.85 (1H, 
               
               
                   
                   
                   
                   
                 brs), 6.93-6.96 (2H, m), 7.03 (1H, dd, J = 8.7 Hz, 3.0 Hz), 
               
               
                   
                   
                   
                   
                 7.69 (1H, d, J = 3.0 Hz). 
               
               
                 482 
                 —C 2 H 5   
                 —CH 3   
                 —H 
                 1.15 (3H, t, J = 7.1 Hz), 1.26-1.70 (3H, m), 1.94- 
               
               
                   
                   
                   
                   
                 2.04 (1H, m), 2.14-2.17 (1H, m), 2.63-2.67 (1H, m), 
               
               
                   
                   
                   
                   
                 2.80 (1H, brs), 3.01-3.59 (8H, m), 3.73-4.71 (3H, m), 
               
               
                   
                   
                   
                   
                 5.95 (2H, s), 6.63-6.70 (3H, m), 6.74 (2H, brs), 6.87 (1H, 
               
               
                   
                   
                   
                   
                 brs), 6.95 (2H, d, J = 9.1 Hz), 7.03 (1H, dd, J = 8.6 Hz, 
               
               
                   
                   
                   
                   
                 3.0 Hz), 7.69 (1H, dd, J = 3.0 Hz, 0.7 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
               
               
               
             
           
               
                 TABLE 69 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 248   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
             
          
           
               
                 483 
                 piperonyl 
                 1.36-1.46 (2H, m), 1.82-1.99 (3H, m), 2.13 (3H, s), 2.28 (2H, d, J = 6.8 
               
               
                   
                   
                 Hz), 2.41 (4H, brs), 2.70 (2H, t, J = 12.0 Hz), 3.41-3.76 (10 H, m), 
               
               
                   
                   
                 5.94 (2H, s), 6.59-6.89 (7H, m), 7.03 (1H, dd, J = 8.6 Hz, 3.0 Hz), 7.67- 
               
               
                   
                   
                 7.69 (1H, m). 
               
               
                 484 
                 benzyl 
                 1.33-1.42 (2H, m), 1.82-1.98 (3H, m), 2.04 (3H, s), 2.28 (2H, d, J = 6.8 
               
               
                   
                   
                 Hz), 2.41-2.45 (4H, m), 2.70 (2H, t, J = 12.0 Hz), 3.51-3.78 (10 H, m), 
               
               
                   
                   
                 6.60 (1H, d, J = 8.6 Hz), 6.69-6.92 (3H, m), 7.03 (1H, dd, J = 8.6 Hz, 
               
               
                   
                   
                 3.0 Hz), 7.28-7.33 (5H, m), 7.67 (1H, d, J = 2.5 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 70 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 249   
                 R 250   
                 R 251   
                 MS (M + ) 
               
               
                   
               
             
          
           
               
                 485 
                 —H 
                 —H 
                 —C 2 H 5   
                 557 
               
               
                 486 
                 —H 
                 —CH 3   
                 —CH 3   
                 557 
               
               
                 487 
                 —CH 3   
                 —H 
                 —CH 3   
                 557 
               
               
                   
               
             
          
         
       
     
       Reference Example 488 
     Production of ethyl[4-(4-amino-2-fluorophenoxy)phenylsulfanyl]acetate 
       [0828]    To a solution of ethyl[4-(2-fluoro-4-nitrophenoxy)phenylsulfanyl]acetate (4.93 g, 14.0 mmol) in ethanol (100 mL) was added tin chloride dihydrate (9.50 g, 42.1 mmol), and the resulting solution was stirred for 8 hours at 50° C. Water was added to the reaction mixture and extracted with ethyl acetate. The ethyl acetate layer was washed with 1 M hydrochloric acid, a saturated sodium bicarbonate solution, and brine, dried over anhydrous sodium sulfate, and evaporated, to thereby yield 3.45 g of the title compound. 
         [0829]    Appearance: Brown oil 
         [0830]      1 H NMR (CDCl 3 ) δ 1.20 (3H, t, J=7.1 Hz), 3.53 (2H, s), 3.80-4.20 (4H, m), 6.37-6.45 (1H, m), 6.49 (1H, dd, J=2.6 Hz, 12.0 Hz), 6.80-7.00 (3H, m&gt;, 7.38 (2H, d, J=8.9 Hz). 
         [0831]    The following compounds were produced in the same manner as in Reference Example 488. 
       Reference Example 489 
     2-{Allyl[4-(5-aminopyridin-2-yloxy)-3-fluorophenyl]amino}-1-(4-piperonylpiperazin-1-yl)ethanone 
       [0832]      1 H NMR (CDCl 3 ) δ 2.44-2.46 (4H, m), 3.44 (4H, brs), 3.44 (2H, s), 3.83 (2H, brs), 3.98 (2H, d, J=4.8 Hz), 4.03 (2H, s), 5.16-5.30 (2H, m), 5.82-5.95 (1H, m), 5.95 (2H, s), 6.35-6.46 (2H, m), 6.71-6.74 (3H, m), 6.85-6.87 (1H, m), 6.96-7.07 (2H, m), 7.63-7.64 (1H, m). 
       Reference Example 490 
     (E)-3-[3-(5-Aminopyridin-2-yloxy)phenyl]-1-(4-piperonylpiperazin-1-yl)propenone 
       [0833]    MS 458 (M + ). 
       Reference Example 491 
     Production of methyl 3-[4-(5-aminopyridin-2-ylsulfanyl)phenyl]propionate 
       [0834]    To a solution of methyl 3-[4-(5-nitropyridin-2-ylsulfanyl)phenyl]propionate (2.97 g, 9.33 mmol) in methanol (50 mL) were added sodium borohydride (0.590 g, 15.6 mmol) and 10% palladium-carbon (1.80 g), and the resulting solution was stirred for 24 hours at room temperature under a hydrogen atmosphere at atmospheric pressure. The reaction solution was filtered through Celite, and to the resulting filtrate was added concentrated hydrochloric acid (1.5 mL), and concentrated under reduced pressure. To the residue was added a saturated sodium bicarbonate solution, and extracted with ethyl acetate, and the ethyl acetate layer was washed with brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and evaporated, to thereby yield 2.49 g of the title compound. 
         [0835]    Appearance: Yellow powder 
         [0836]      1 H NMR (CDCl 3 ) δ 2.62 (2H, t, J=7.6 Hz), 2.93 (2H, t, J=7.6 Hz), 3.67 (3H, s), 6.87 (1H, dd, J=2.9 Hz, 8.4 Hz), 6.98 (1H, d, J=8.4 Hz), 7.15 (2H, d, J=8.2 Hz), 7.35 (2H, d, J=&gt;8.2 Hz), 8.01 (1H, d, J=2.9 Hz). 
       Reference Example 492 
     Production of ethyl 3-[4-(5-aminopyridin-2-yloxy)phenyl]acrylate 
       [0837]    To a solution of ethyl 3-[4-(5-nitropyridin-2-yloxy)phenyl]acrylate (2.02 g, 6.43 mmol) in methanol (100 mL) were added zinc (6.3 g, 96.3 mmol) and ammonium chloride (710 mg, 13.27 mmol). The resulting reaction solution was stirred for 2.5 hours under reflux, then acetic acid (5 mL) was added, and stirred for 20 minutes under reflux. Insoluble matter was filtered off through Celite, after which the filtrate was concentrated under reduced pressure. To the residue was added 5% potassium hydrogensulfate (150 mL), the mixture was extracted with dichloromethane, and the dichloromethane layer was washed with a saturated sodium bicarbonate solution and brine. The dichloromethane layer was dried over anhydrous magnesium sulfate, and evaporated, to thereby yield 1.78 g of the title compound. 
         [0838]    Appearance: Yellow oil 
         [0839]      1 H NMR (CDCl 3 ) δ 1.34 (3H, t, J=7.1 Hz), 3.58 (2H, brs), 4.26 (2H, q, J=7.1 Hz), 6.35 (1H, dd, J=16.0 Hz, 2.0 Hz), 6.81 (1H, d, J=8.6 Hz), 7.05 (2H, d, J=8.6 Hz), 7.10 (1H, dd, J=8.6 Hz, 3.0 Hz), 7.50 (2H, d, J=8.6 Hz), 7.66 (1H, dd, J=16.0 Hz, 3.0 Hz), 7.73 (1H, d, J=3.0 Hz). 
       Reference Example 493 
     Production of 3-(4-(5-amino-4-methylpyridin-2-yloxy)phenyl)-1-(4-piperonylpiperazin-1-yl)propan-1-one 
       [0840]    3-(4-hydroxyphenyl)-1-(4-piperonylpiperazin-1-yl)propan-1-one (0.38 g, 1.0 mmol) was dissolved in DMF (6 mL). To the resulting solution was added 60% sodium hydride (0.05 g, 1.2 mmol) and 2-chloro-4-methyl-5-nitropyridine (0.196 g, 1.1 mmol), and the resulting reaction solution was stirred overnight at room temperature. To the reaction solution was added saturated aqueous ammonium chloride, and extracted with ethyl acetate. The ethyl acetate layer was washed with water and brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by silica gel column chromatography (ethyl acetate), to thereby yield the intermediate product 3-(4-(4-methyl-5-nitropyridin-2-yloxy)phenyl)-1-(4-piperonylpiperazin-1-yl)propan-1-one. 
         [0841]    The 3-(4-(4-methyl-5-nitropyridin-2-yloxy)phenyl)-1-(4-piperonylpiperazin-1-yl)propan-1-one was dissolved in a mixed solvent consisting of ethanol (4 mL) and dioxane (1 mL). To this solution was added 10% palladium-carbon (0.034 g), and the resulting solution was subjected to catalytic reduction for 8 hours at atmospheric pressure and room temperature. The catalyst was removed by filtration, and the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel chromatography (dichloromethane:methanol=20:1), to thereby yield 0.22 g of the title compound. 
         [0842]    Appearance: Slightly yellow oil 
         [0843]      1 H NMR (CDCl 3 ) δ 2.18 (3H, s), 2.30-2.45 (4H, m), 2.56-2.63 (2H, m), 2.91-2.97 (2H, m), 3.30-3.50 (6H, m), 3.55-3.70 (2H, m), 5.95 (2H, s), 6.65-6.80 (3H, m), 6.84 (1H, s), 6.95-7.05 (2H, m), 7.15-7.20 (2H, m), 7.64 (1H, s). 
       Reference Example 494 
     Production of ethyl 3-{4-[4-(3,4-dichlorobenzoylamino)-phenoxy]phenyl}propionate 
       [0844]    A solution of 3,4-dichlorobenzoyl chloride (3.65 g, 17.4 mmol) was added dropwise under ice cooling to a solution of ethyl 3-[4-(4-aminophenoxy)phenyl]propionate (4.52 g, 15.9 mmol) and triethylamine (2.65 mL, 19.0 mmol) in THF (80 mL), and the resulting solution was stirred for 1 hour at the same temperature. Water was added to the reaction mixture, and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate and evaporated. The residue was recrystallized from water-containing ethanol to thereby yield 6.67 g of the title compound. 
         [0845]    Appearance: Colorless needles 
         [0846]    Melting point: 139-141° C. 
         [0847]    The following compounds were produced in the same manner as in Reference Example 494. 
       Reference Example 495 
     Ethyl 3-[4-(5-phenoxycarbonylaminopyridin-2-yloxy)phenyl]propionate 
       [0848]    MS 406 (M + ). 
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 71 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
               
               
                 Example 
                   
                   
                 mp.(° C.) or 
               
               
                 No. 
                 Xa 18   
                 R 252   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
             
          
           
               
                 496 
                 p-phenylene 
                 2-(CH 2 ) 2 COOCH 3   
                 mp 117-119 
               
               
                 497 
                 p-phenylene 
                 3-(CH 2 ) 2 COOC 2 H 5   
                 mp 111-113 
               
               
                 498 
                 o-phenylene 
                 4-(CH 2 ) 2 COOC 2 H 5   
                 mp 72-73 
               
               
                 499 
                 m-phenylene 
                 4-(CH 2 ) 2 COOC 2 H 5   
                   1 H NMR 1.22 (3H, t, J = 
               
               
                   
                   
                   
                 7.2 Hz), 2.59 (2H, t, J = 
               
               
                   
                   
                   
                 7.7 Hz), 2.91 (2H, t, J = 
               
               
                   
                   
                   
                 7.7 Hz), 4.10 (2H, q, J = 
               
               
                   
                   
                   
                 7.2 Hz), 6.78 (1H, dt, J = 
               
               
                   
                   
                   
                 8.1 Hz, 1.1 Hz), 
               
               
                   
                   
                   
                 6.93 (2H, d, J =8.5 Hz), 
               
               
                   
                   
                   
                 7.14 (2H, d, J = 8.5 Hz), 
               
               
                   
                   
                   
                 1H, d, J = 8.3 Hz), 7.81 
               
               
                   
                   
                   
                 (1H; brs), 7.91 (1H, d, 
               
               
                   
                   
                   
                 J = 2.1 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 72 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 253   
                 R 254   
                 mp (° C.) or  1 H NMR (solvent) δ ppm 
               
               
                   
               
             
          
           
               
                 500 
                 —F 
                 —H 
                 mp 168-169 
               
               
                 501 
                 —H 
                 —COOC 2 H 5   
                 mp 144-145 
               
               
                 502 
                 —F 
                 —COOC 2 H 5   
                 mp 145-146 
               
               
                 503 
                 —F 
                 —CH 2 COOCH 3   
                 mp 127-129 
               
               
                 504 
                 —F 
                 —(CH 2 ) 2 COOC 2 H 5   
                 mp 131-133 
               
               
                 505 
                 —F 
                 —(CH 2 ) 3 COOC 2 H 5   
                 mp 110-111 
               
               
                 506 
                 —F 
                 —SCH 2 COOC 2 H 5   
                   1 H NMR (CDCl 3 ) 1.23 (3H, t, J = 7.1 Hz), 3.56 (2H, 
               
               
                   
                   
                   
                 s), 4.15 (2H, q, J = 7.1 Hz), 6.90 (2H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                 7.08 (1H, t, J = 8.7 Hz), 7.20-7.30 (1H, m), 7.42 (2H, 
               
               
                   
                   
                   
                 d, J = 8.7 Hz), 7.58 (1H, d, J = 8.3 Hz), 7.65- 
               
               
                   
                   
                   
                 7.80 (2H, m), 7.82 (1H, s), 7.96 (1H, d, J = 2.1 Hz). 
               
               
                 507 
                 —F 
                 —NHCH 2 COOC 2 H 5   
                   1  H NMR (DMSO-d 6 ) 1.19 (3H, t, J = 7.1 Hz), 
               
               
                   
                   
                   
                 3.87 (2H, d, J = 6.4 Hz), 4.11 (2H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                 5.93 (1H, t, J = 6.4 Hz), 6.56 (2H, d, J = 9.0 Hz), 
               
               
                   
                   
                   
                 6.81 (2H, d, J = 9.0 Hz), 6.98 (1H, t, J = 9.2 Hz), 
               
               
                   
                   
                   
                 7.44-7.47 (1H, m), 7.82-7.86 (2H, m), 7.93 (1H, dd, 
               
               
                   
                   
                   
                 J = 2.0 Hz, 8.4 Hz), 8.20 (1H, d, J = 2.0 Hz), 
               
               
                   
                   
                   
                 10.50 (1H, s). 
               
               
                 508 
                 —H 
                 —Br 
                   1 H NMR (DMSO-d 6 ) 6.96 (2H, d, J = 9.0 Hz), 
               
               
                   
                   
                   
                 7.08 (2H, d, J = 9.0 Hz), 7.55 (2H, d, J = 8.5 Hz), 
               
               
                   
                   
                   
                 7.79 (2H, d, J = 8.5 Hz), 7.83 (1H, d, J = 8.5 Hz), 
               
               
                   
                   
                   
                 7.94 (1H, dd, J = 8.5 Hz, 2.0 Hz), 8.21 (1H, d, J = 
               
               
                   
                   
                   
                 2.0 Hz), 10.44 (1H, brs). 
               
               
                 509 
                 —F 
                 —Ac 
                 mp 143 
               
               
                   
               
               
                 510 
                 —F 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (CDCl 3 ) 4.00-4.15 (4H, m), 5.78 (1H, s), 6.96 (2H, d, J = 8.7 Hz), 7.00-7.10 (1H, m), 7.20- 7.30 (1H, m), 7.43 (2H, d, J = 8.7 Hz), 7.57 (1H, d, J = 8.3 Hz), 7.82 (1H, s), 7.95 (1H, d, J = 2.1 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 73 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 255   
                 R 256   
                 R 257   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
             
          
           
               
                 511 
                 —Cl 
                 —Cl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 3.98 (3H, s), 7.06 (1H, d, J = 8.7 Hz), 7.33-7.37 (1H, m), 7.56-7.59 (2H, m, 7.70-7.73 (1H, m), 7.80 (1H, d, J = 8.5 Hz), 7.95-8.07 (4H, m), 8.23-8.30 (2H, m), 8.60 (1H, s). 
               
               
                   
               
               
                 512 
                 —CF 3   
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 3.98 (3H, s), 7.07-7.10 (1H, m), 7.37 (1H, dd, J = 8.9 Hz, 2.3 Hz), 7.58 (1H, d, J = 2.3 Hz), 7.76- 7.82 (3H, m), 7.93-8.08 (5H, m), 8.27- 8.31 (2H, m), 8.60 (1H, s). 
               
               
                   
               
               
                 513 
                 —Cl 
                 —Cl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.46 (3H, t, J = 7.1 Hz), 4.47 (2H, q, J = 7.1 Hz), 7.04 (1H, d, J = 8.7 Hz), 7.41 (1H, dd, J = 9.4 Hz, 2.5 Hz), 7.47-7.60 (3H, m), 7.70 (1H, dd, J = 8.4 Hz, 2.1 Hz), 7.82 (1H, brs), 7.94 (1H, d, J = 8.6 Hz), 7.98 (1H, d, J = 2.1 Hz), 8.14 (1H, dd, J = 7.3 Hz, 1.2 Hz), 8.20-8.27 (2H, m), 8.92 (1H, d, J = 9.4 Hz). 
               
               
                   
               
               
                 514 
                 —CF 3   
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.46 (3H, t, J = 7.1 Hz), 4.47 (2H, q, J = 7.1 Hz), 7.04 (1H, d, J = 8.7 Hz), 7.40 (1H, dd, J = 9.4 Hz, 2.5 Hz), 7.47-7.53 (1H, m), 7.59 (1H, d, J = 2.5 Hz), 7.75 (2H, d, J = 8.2 Hz), 7.92- 8.00 (4H, m), 8.14 (1H, dd, J = 7.3 Hz, 1.2 Hz), 8.23-8.29 (2H, m), 8.97 (1H, d, J = 9.4 Hz). 
               
               
                   
               
               
                 515 
                 —C1 
                 —Cl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 4.00 (3H, s), 7.09 (1H, d, J = 9.6 Hz), 7.16 (1H, d, J = 8.1 Hz), 7.50- 7.57 (2H, m), 7.62-7.72 (2H, m), 7.98 (2H, d, J = 2.1 Hz), 8.15- 8.29 (4H, m), 9.01 (1H, d, J = 8.7 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
               
               
               
             
           
               
                 TABLE 74 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 258   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
             
          
           
               
                 516 
                 —COOCH 3   
                 3.91 (3H, s), 7.03 (1H, d, J = 8.9 Hz), 7.15-7.18 (2H, m), 
               
               
                   
                   
                 7.58 (1H, d, J = 8.3 Hz), 7.69-7.73 (1H, m), 7.89 (1H, brs), 
               
               
                   
                   
                 7.99 (1H, d, J = 2.0 Hz), 8.06-8.09 (2H, m), 8.23-8.30 (2H, 
               
               
                   
                   
                 m). 
               
               
                 517 
                 —COOC 2 H 5   
                 1.39 (3H, t, J = 7.3 Hz), 4.37 (2H, q, J = 7.3 Hz), 7.02 (1H, 
               
               
                   
                   
                 d, J = 8.6 Hz), 7.15-7.18 (2H, m), 7.57 (1H, d, J = 8.6 Hz); 
               
               
                   
                   
                 7.70-7.73 (1H, m), 7.97-7.99 (2H, m), 8.06-8.09 (2H, m), 
               
               
                   
                   
                 8.23-8.30 (2H, m). 
               
               
                 518 
                 —CH 2 COOCH 3   
                 3.63 (2H, s), 3.71 (3H, s), 6.94 (1H, d, J = 8.9 Hz), 7.07 (2H, 
               
               
                   
                   
                 d, J = 8.2 Hz), 7.30 (2H, d, J = 8.6 Hz), 7.55 (1H, d, J = 8.6 
               
               
                   
                   
                 Hz), 7.70 (1H, dd, J = 8.2 Hz, 2.0 Hz), 7.97-8.08 (2H, m), 
               
               
                   
                   
                 8.17 (1H, dd, J = 8.9 Hz, 2.6 Hz), 8.24 (1H, d, J = 2.6 Hz). 
               
               
                 519 
                 —(CH 2 ) 2 COOCH 3   
                 2.62-2.67 (2H, m), 2.93-2.98 (2H, m), 3.68 (3H, s), 6.93 (1H, 
               
               
                   
                   
                 d, J = 8.9 Hz), 7.03-7.06 (2H, m), 7.20-7.23 (2H, m), 
               
               
                   
                   
                 7.56 (1H, d, J = 8.3 Hz), 7.68-7.72 (1H, m), 7.96-7.98 (2H, 
               
               
                   
                   
                 m), 8.17 (1H, dd, J = 8.9 Hz, 2.6 Hz), 8.24 (1H, d, J = 2.6 
               
               
                   
                   
                 Hz). 
               
               
                 520 
                 —(CH 2 ) 3 COOC 2 H 5   
                 1.26 (3H, t, J = 7.0 Hz), 1.96 (2H, dt, J = 15.0 Hz, 7.5 Hz), 
               
               
                   
                   
                 2.34 (2H, t, J = 7.5 Hz), 2.66 (2H, t, J = 7.5 Hz), 4.13 (2H, 
               
               
                   
                   
                 q, J = 7.0 Hz), 6.93 (1H, d, J = 8.8 Hz), 7.04 (2H, d, J = 8.6 
               
               
                   
                   
                 Hz), 7.20 (2H, d, J = 8.6 Hz), 7.56 (1H, d, J = 8.3 Hz), 
               
               
                   
                   
                 7.70 (1H, dd, J = 8.3 Hz, 2.0 Hz), 7.89 (1H, s), 7.98 (1H, d, 
               
               
                   
                   
                 J = 2.0 Hz), 8.16 (1H, dd, J = 8.8 Hz, 2.6 Hz), 8.24 (1H, d, 
               
               
                   
                   
                 J = 2.6 Hz). 
               
               
                 521 
                 —(CH 2 ) 4 COOC 2 H 5   
                 1.26 (3H, t, J = 7.2 Hz), 1.60-1.75 (4H, m), 2.33 (2H, t, J = 
               
               
                   
                   
                 7.0 Hz), 2.64 (2H, t, J = 7.0 Hz), 4.13 (2H, q, J = 7.2 Hz), 
               
               
                   
                   
                 6.94 (1H, d, J = 8.9 Hz), 7.04 (2H, d; J = 8.5 Hz), 7.20 (2H, 
               
               
                   
                   
                 d, J = 8.5 Hz), 7.58 (1H, d, J = 8.3 Hz), 7.70 (1H, dd, J = 
               
               
                   
                   
                 8.3 Hz, 2.3 Hz), 7.78 (1H, brs), 7.98 (1H, d, J = 2.3 Hz), 
               
               
                   
                   
                 8.16 (1H, dd, J = 8.9 Hz, 2.6 Hz), 8.24 (1H, d, J = 2.6 Hz). 
               
               
                 522 
                 —CH 2 CN 
                 3.76 (2H, s), 7.00 (1H, d, J = 8.8 Hz), 7.16 (2H, d, J = 8.7 
               
               
                   
                   
                 Hz), 7.37 (2H, d, J = 8.7 Hz), 7.58 (1H, d, J = 8.4 Hz), 
               
               
                   
                   
                 7.70 (1H, dd, J = 8.4 Hz, 2.1 Hz), 7.81 (1H, s), 7.98 (1H, d, 
               
               
                   
                   
                 J = 2.1 Hz), 8.20 (1H, dd, J = 8.8 Hz, 2.3 Hz), 8.25 (1H, d, 
               
               
                   
                   
                 J =2.3 Hz). 
               
               
                 523 
                 —NHCOOC(CH 3 ) 3   
                 1.52 (9H, s), 6.49 (1H, brs), 6.90 (1H, d, J = 8.6 Hz), 
               
               
                   
                   
                 7.05 (2H, d, J = 8.9 Hz), 7.37 (2H, d, J = 8.9 Hz), 7.56 (1H, 
               
               
                   
                   
                 d, J = 8.6 Hz), 7.69 (1H, dd, J = 8.6 Hz, 2.3 Hz), 7.92 (1H, 
               
               
                   
                   
                 brs), 7.97 (1H, d, J = 2.3 Hz), 8.14 (1H, dd, J = 8.6 Hz, 2.6 
               
               
                   
                   
                 Hz), 8.22 (1H, d, J = 2.6 Hz). 
               
               
                 524 
                 —CH═C(COOCH 3 ) 2   
                 3.85 (3H, s), 3.86 (3H, s), 7.02 (1H, d, J = 8.8 Hz), 7.13 (2H, 
               
               
                   
                   
                 d, J = 8.5 Hz), 7.46 (2H, d, J = 8.5 Hz), 7.59 (1H, d, J = 8.2 
               
               
                   
                   
                 Hz), 7.70 (1H, dd, J = 8.2 Hz, 2.0 Hz), 7.74 (1H, s), 
               
               
                   
                   
                 7.88 (1H, brs), 7.97 (1H, d, J = 2.0 Hz), 8.22 (1H, dd, J = 
               
               
                   
                   
                 8.8 Hz, 2.5 Hz), 8.24 (1H, d, J = 2.5 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 75 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 259   
                 R 260   
                 R 261   
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
             
          
           
               
                 525 
                 —OCH 3   
                 —H 
                 —COOC 2 H 5   
                 (CDCl 3 ) 1.40 (3H, t, J = 7.1 Hz), 3.81 (3H, s), 
               
               
                   
                   
                   
                   
                 4.39 (2H, q, J = 7.1 Hz), 6.99-7.02 (1H, m), 
               
               
                   
                   
                   
                   
                 7.16 (1H, d, J = 8.1 Hz), 7.56 (1H, d, J = 8.4 
               
               
                   
                   
                   
                   
                 Hz), 7.67-7.72 (3H, m), 7.97-8.01 (2H, m), 
               
               
                   
                   
                   
                   
                 8.17- 8.22 (2H, m). 
               
               
                 526 
                 —CH 3   
                 —H 
                 —COOCH 3   
                 (CDCl 3 ) 2.24 (3H, s), 3.91 (3H, s), 6.97- 
               
               
                   
                   
                   
                   
                 7.01 (1H, m), 7.07 (1H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                 7.57 (1H, d, J = 8.4 Hz), 7.69-7.73 (1H, m), 
               
               
                   
                   
                   
                   
                 7.91 (1H, dd, J = 8.4 Hz, 2.4 Hz), 7.97- 
               
               
                   
                   
                   
                   
                 7.99 (3H, m), 8.21-8.26 (2H, m). 
               
               
                 527 
                 —Cl 
                 —H 
                 —COOCH 3   
                 (ODCl 3 ) 3.93 (3H, s), 7.08 (1H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                 7.26 (1H, d, J = 1.7 Hz), 7.56 (1H, d, J = 8.2 
               
               
                   
                   
                   
                   
                 Hz), 7.69-7.73 (1H, m), 7.95-7.99 (2H, m), 
               
               
                   
                   
                   
                   
                 8.10 (1H, brs), 8.15 (1H, d, J = 2.0 Hz), 8.22- 
               
               
                   
                   
                   
                   
                 8.24 (1H, m), 8.27 (1H, d, J = 2.8 Hz). 
               
               
                 528 
                 —F 
                 —H 
                 —COOCH 3   
                 (CDCl 3 ) 3.92 (3H, s), 7.07 (1H, dd, J = 7.8 Hz, 
               
               
                   
                   
                   
                   
                 1.8 Hz), 7.25-7.31 (1H, m), 7.56 (1H, d, J = 8.4 
               
               
                   
                   
                   
                   
                 Hz), 7.71 (1H, dd, J = 8.2 Hz, 2.1 Hz), 7.82- 
               
               
                   
                   
                   
                   
                 7.89 (2H, m), 7.97 (1H, d, J = 2.1 Hz), 
               
               
                   
                   
                   
                   
                 8.08 (1H, brs), 8.21-8.25 (2H, m). 
               
               
                 529 
                 —H 
                 —OCH 3   
                 —COOCH 3   
                 (ODCl 3 ) 3.83 (3H, s), 3.87 (3H, s), 6.70 (1H, dd, 
               
               
                   
                   
                   
                   
                 J = 8.6 Hz, 2.2 Hz), 6.74 (1H, d, J = 2.2 Hz), 
               
               
                   
                   
                   
                   
                 7.01 (1H, d, J = 8.6 Hz), 7.56 (1H, d, J = 8.1 
               
               
                   
                   
                   
                   
                 Hz), 7.75 (1H, dd, J = 8.6 Hz, 2.2 Hz), 
               
               
                   
                   
                   
                   
                 7.87 (1H, d, J = 8.6 Hz), 8.01 (1H, d, J = 2.2 
               
               
                   
                   
                   
                   
                 Hz), 8.25-8.33 (3H, m). 
               
               
                 530 
                 —H 
                 —CH 3   
                 —COOCH 3   
                 (ODCl 3 ) 2.63 (3H, s), 3.91 (3H, s), 6.98- 
               
               
                   
                   
                   
                   
                 7.05 (3H, m), 7.60 (1H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                 7.75 (1H, dd, J = 8.4 Hz, 2.2 Hz), 7.97- 
               
               
                   
                   
                   
                   
                 8.03 (3H, m), 8.23-8.28 (1H, m), 8.30-8.32 (1H, 
               
               
                   
                   
                   
                   
                 m). 
               
               
                 531 
                 —H 
                 —COOCH 3   
                 —H 
                 (DMSO-d6 6 ) 3.85 (3H, s), 7.17 (1H, d, J = 8.9 
               
               
                   
                   
                   
                   
                 Hz), 7.43-7.47 (1H, m), 7.56-7.62 (2H, m), 
               
               
                   
                   
                   
                   
                 7.78-7.86 (2H, m), 7.93-7.97 (1H, m), 8.22- 
               
               
                   
                   
                   
                   
                 8.27 (2H, m), 8.50 (1H, d, J = 2.3 Hz), 
               
               
                   
                   
                   
                   
                 10.60 (1H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 76 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 262   
                 R 263   
                 R 264   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
             
          
           
               
                 532 
                 —OCH 3   
                 —H 
                 —COOC 2 H 5   
                 1.40 (3H, t, J = 7.1 Hz), 3.82 (3H, s), 
               
               
                   
                   
                   
                   
                 4.39 (2H, q, J = 7.1 Hz), 7.00-7.03 (1H, 
               
               
                   
                   
                   
                   
                 m), 7.17 (1H, d, J = 8.1 Hz), 7.68- 
               
               
                   
                   
                   
                   
                 7.76 (4H, m), 8.01 (2H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                 8.16 (1H, brs), 8.22-8.25 (2H, m). 
               
               
                 533 
                 —OCH 3   
                 —H 
                 —(CH 2 ) 2 COOCH 3   
                 2.63-2.69 (2H, m), 2.93-2.99 (2H, m), 
               
               
                   
                   
                   
                   
                 3.69 (3H, s), 3.74 (3H, s), 6.78-6.84 (2H, 
               
               
                   
                   
                   
                   
                 m), 6.93 (1H, d, J = 8.7 Hz), 7.03 (1H, d, 
               
               
                   
                   
                   
                   
                 J =8.1 Hz), 7.73 (2H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                 7.96-7.99 (3H, m), 8.14-8.20 (2H, m). 
               
               
                 534 
                 —CH 3   
                 —H 
                 —COOCH 3   
                 2.25 (3H, s), 3.91 (3H, s), 6.99-7.03 (1H, 
               
               
                   
                   
                   
                   
                 m), 7.07 (1H, d, J = 8.4 Hz), 7.75- 
               
               
                   
                   
                   
                   
                 7.78 (2H, m), 7.88-7.92 (1H, m), 7.98- 
               
               
                   
                   
                   
                   
                 8.01 (4H, m), 8.26-8.29 (2H, m). 
               
               
                 535 
                 —Cl 
                 —H 
                 —COOCH 3   
                 3.93 (3H, s), 7.09 (1H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                 7.24-7.27 (1H, m), 7.76 (2H, d, J = 8.7 
               
               
                   
                   
                   
                   
                 Hz), 7.96-8.03 (4H, m), 8.16 (1H, d, J = 
               
               
                   
                   
                   
                   
                 2.1 Hz), 8.24 (1H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                 8.29 (1H, dd, J = 8.7 Hz, 2.6 Hz). 
               
               
                 536 
                 —F 
                 —H 
                 —COOCH 3   
                 3.92 (3H, s), 7.08 (1H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                 7.26-7.32 (1H, m), 7.75 (2H, d, J = 8.4 
               
               
                   
                   
                   
                   
                 Hz), 7.83-7.90 (2H, m), 7.98 (3H, d, J = 
               
               
                   
                   
                   
                   
                 8.2 Hz), 8.22-8.28 (2H, m). 
               
               
                 537 
                 —H 
                 —OCH 3   
                 —COOCH 3   
                 3.87 (3H, s), 3.88 (3H, s), 6.71 (1H, dd, J = 
               
               
                   
                   
                   
                   
                 8.6 Hz, 2.2 Hz), 6.77 (1H, d, J = 2.2 
               
               
                   
                   
                   
                   
                 Hz), 7.04 (1H, d, J = 8.9 Hz), 7.77 (2H, d, 
               
               
                   
                   
                   
                   
                 J = 8.1 Hz), 7.88 (1H, d, J = 8.6 Hz), 8.02 
               
               
                   
                   
                   
                   
                 (2H, d, J = 8.1 Hz), 8.17 (1H, brs), 8.29- 
               
               
                   
                   
                   
                   
                 8.35 (2H, m). 
               
               
                 538 
                 —H 
                 —CH 3   
                 —COOCH 3   
                 2.63 (3H, s), 3.91 (3H, s), 6.98-7.06 (3H, 
               
               
                   
                   
                   
                   
                 m), 7.79 (2H, d, J = 8.1 Hz), 8.00- 
               
               
                   
                   
                   
                   
                 8.04 (4H, m), 8.27-8.34 (2H, m). 
               
               
                 539 
                 —H 
                 —COOCH 3   
                 —H 
                 3.91 (3H, s), 6.99-7.04 (1H, m), 7.32- 7.37 (1H, m), 7.45-7.50 (1H, m, 7.74- 7.80 (3H, m), 7.86-7.90 (1H, m), 7.96- 8.01 (3H, m), 8.22-8.27 (2H, m). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 77 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 265   
                 R 266   
                 R 267   
                 R 268   
                   1 H NMR (CDCl 3 ) δ ppm or mp (° C.) 
               
               
                   
               
             
          
           
               
                 540 
                 —CF 3   
                 —H 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.17 (3H, t, J = 7.1 Hz) 1.26 (3H, d, J = 7.0 Hz), 2.44-2.61 (2H, m), 3.19-3.29 (1H, m), 4.05 (2H, q, J = 7.1 Hz), 6.88 (1H, d, J = 8.8 Hz), 7.01 (2H, d, J =8.5 Hz), 7.19 (2H, d, J = 8.5 Hz), 7.68 (2H, d, J =8.3 Hz), 7.94 (2H, d, J = 8.3 Hz), 8.15 (1H, dd, J = 8.8 Hz, 2.7 Hz), 8.23 (1H, d, J = 2.7 Hz), 8.29 (1H, brs). 
               
               
                   
               
               
                 541 
                 —Cl 
                 —Cl 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.17 (3H, t, J = 7.1 Hz), 1.26 (3H, d, J = 7.0 Hz), 2.43-2.60 (2H, m), 3.18-3.28 (1H, m), 4.05 (2H, q, J = 7.1 Hz), 6.85 (1H, d, J = 8.9 Hz), 6.99 (2H, d, J =8.4 Hz), 7.18 (2H, d, J = 8.4 Hz), 7.48 (1H, d, J = 8.3 Hz), 7.66 (1H, dd, J = 8.3 Hz, 2.0 Hz), 7.92 (1H, d, J = 2.0 Hz), 8.10 (1H, dd, J = 8.9 Hz, 2.7 Hz), 8.20 (1H, d, J =2.7 Hz), 8.39 (1H, brs). 
               
               
                   
               
               
                 542 
                 —CF 3   
                 —H 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.35 (3H, t, J = 7.1 Hz), 4.27 (2H, q, J = 7.1 Hz), 6.39 (1H, dd, J = 16.0 Hz, 2.6 Hz), 7.03 (1H, d, J = 8.9 Hz), 7.16 (2H, d, J = 8.8 Hz), 7.56 (2H, d, J = 8.8 Hz), 7.68 (1H, dd, J = 16.0 Hz, 3.2 Hz), 7.77 (2H, d, J = 8.1 Hz), 7.93 (1H, brs), 8.01 (2H, d, J = 8.1 Hz), 8.26 (1H, dd, J =8.9  Hz, 2.6 Hz) 8.29 (1H, d, J = 2.6 Hz). 
               
               
                   
               
               
                 543 
                 —CF 3   
                 —H 
                 —H 
                 —CH 2 COOCH 3   
                   1 H NMR 3.62 (2H, s), 3.70 (3H, s,) 
               
               
                   
                   
                   
                   
                   
                 6.94 (1H, d, J = 8.7 Hz), 7.05-7.09 (2H, 
               
               
                   
                   
                   
                   
                   
                 m), 7.26-7.32 (2H, m), 7.72 (2H, d, J =8.6 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.97 (2H, d, J = 8.2 Hz), 8.17-8.26 
               
               
                   
                   
                   
                   
                   
                 (3H, m). 
               
               
                 544 
                 —CF 3   
                 —H 
                 —H 
                 —(CH 2 ) 2 COOC 2 H 5   
                   1 H NMR 1.25 (3H, t, J = 7.1 Hz), 2.62 
               
               
                   
                   
                   
                   
                   
                 (2H, t, J = 7.7 Hz), 2.95 (2H, t, J = 7.7 
               
               
                   
                   
                   
                   
                   
                 Hz), 4.13 (2H, q, J = 7.1 Hz), 6.94 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.8 Hz), 7.04 (2H, d, J = 8.6 Hz), 7.22 
               
               
                   
                   
                   
                   
                   
                 (2H, d, J = 8.6 Hz), 7.75 (2H, d, J = 8.3 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.98 (2H, d, J = 8.3 Hz), 8.03 (1H, 
               
               
                   
                   
                   
                   
                   
                 brs), 8.19 (1H, dd, J = 8.8 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.26 (1H, d, J = 2.6 Hz). 
               
               
                   
               
               
                 545 
                 —Cl 
                 —Cl 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 0.01 (3H, s), 0.89 (9H, s), 2.83 (2H, t, J = 6.9 Hz), 3.82 (2H, t, J = 6.9 Hz), 6.92 (1H, d, J = 8.9 Hz), 7.05 (2H, dd, J = 6.3 Hz, 2.0 Hz), 7.24 (2H, d, J = 8.6 Hz), 7.58 (1H, d, J = 8.3 Hz), 7.71 (1H, dd, J = 8.3 Hz, 2.0 Hz), 7.80 (1H, brs), 7.98 (1H, d, J = 2.0 Hz), 8.15-8.19 (1H, m), 8.25 (1H, d, J = 2.6 Hz). 
               
               
                   
               
               
                 546 
                 —Cl 
                 —Cl 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 0.07 (6H, s), 0.91 (9H, s), 1.82- 1.87 (2H, m), 2.65-2.71 (2H, m), 3.63- 3.68 (2H, m), 6.92 (1H, d, J = 8.9 Hz), 7.02-7.05 (2H, m), 7.21 (2H, d, J = 8.6 Hz) 7.57 (1H, d, J = 8.3 Hz), 7.68-7.72 (1H, m), 7.86 (1H, brs), 7.97 (1H, d, J = 2.0 Hz), 8.14-8.18 (1H, m), 8.24 (1H, d, J = 2.3 Hz). 
               
               
                   
               
               
                 547 
                 —H 
                 —F 
                 —CF 3   
                 —COOC 2 H 5   
                 mp 133-134 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 78 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 269   
                 R 270   
                 Xa 19   
                 R 271   
                 M 
                 mp (° C.) or  1 H NMR (solvent) δ ppm 
               
               
                   
               
             
          
           
               
                 548 
                 —Cl 
                 —Cl 
                 —S— 
                 —CH 3   
                 2 
                 mp 141-142 
               
               
                 549 
                 —Cl 
                 —Cl 
                 —NH— 
                 —C 2 H 5   
                 2 
                 mp 170-171 
               
               
                 550 
                 —Cl 
                 —Cl 
                 —N(CH 3 )— 
                 —C 2 H 5   
                 2 
                   1 H NMR DMSO-d 6 ) 1.17 (3H, t, J = 7.1 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 2.63 (2H, t, J = 7.7 Hz), 2.85 (2H, t, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 7.7 Hz), 3.36 (3H, s), 4.07 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 7.1 Hz), 6.56 (1H, d, J = 9.5 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.18 (2H, d, J = 8.3 Hz), 7.27 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.3 Hz), 7.75-7.95 (3H, m), 8.20 (1H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 8.47 (1H, s), 10.26 (1H, s). 
               
               
                 551 
                 —CF 3   
                 —H 
                 —N(CH 3 )— 
                 —C 2 H 5   
                 0 
                 mp 135-136 
               
               
                 552 
                 —CF 3   
                 —H 
                 —N(CH 3 )— 
                 —C 2 H 5   
                 2 
                   1 H NMR (CDCl 3 ) 1.26 (3H, t, J = 7.2 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 2.65 (2H, t, J = 8.0 Hz), 2.97 (2H, t, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.0 Hz), 3.45 (3H, s), 4.16 (2H, q, J = 
               
               
                   
                   
                   
                   
                   
                   
                 7.2 Hz), 6.57 (1H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.18 (2H, d, J = 8.3 Hz), 7.24 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.3 Hz), 7.35-7.45 (1H, m), 7.65- 
               
               
                   
                   
                   
                   
                   
                   
                 7.78 (3H, m), 7.98 (2H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 8.28 (1H, d, J = 2.5 Hz). 
               
               
                 553 
                 —Cl 
                 —Cl 
                 —N(CH 2 Ph)— 
                 —C 2 H 5   
                 2 
                   1 H NMR (CDCl 3 ) 1.23 (3H, t, J = 7.2 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 2.61 (2H, t, J = 7.6 Hz), 2.92 (2H, t, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 7.6 Hz), 4.12 (2H, q, J = 7.2 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 5.20 (2H, s), 6.54 (1H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.10-7.30 (8H, m), 7.53 (1H, d, J = 8.4 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.60-7.75 (3H, m), 7.94 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 1.3 Hz), 8.22 (1H, d, J = 2.3 Hz). 
               
               
                 554 
                 —Cl 
                 —H 
                 —O— 
                 —CH 3   
                 0 
                   1 H NMR (CDCl 3 ) 3.91 (3H, s), 7.04 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 9.9 Hz), 7.17 (2H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.49 (2H, d, J = 8.6 Hz), 7.79 (1H, brs), 
               
               
                   
                   
                   
                   
                   
                   
                 7.83 (2H, d, J = 8.6 Hz), 8.08 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.6 Hz), 8.27-8.29 (2H, m). 
               
               
                 555 
                 —CF 3   
                 —H 
                 —O— 
                 —C 2 H 5   
                 0 
                   1 H NMR (CDCl 3 ) 1.39 (3H, t, J = 7.3 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 4.37 (2H, q, J = 7.3 Hz), 7.04 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 dd, J = 8.3 Hz, 1.3 Hz), 7.15-7.19 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 7.78 (2H, d, J = 8.3 Hz), 7.91 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs), 8.00 (2H, d, J = 6.9 Hz), 8.07- 
               
               
                   
                   
                   
                   
                   
                   
                 8.10 (2H, m), 8.27-8.31 (2H, m). 
               
               
                 556 
                 —H 
                 —OCF 3   
                 —O— 
                 —CH 3   
                 0 
                   1 H NMR (CDCl 3 ) 3.91 (3H, s), 7.04 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 8.7 Hz), 7.16 (2H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.42 (1H, d, J = 8.2 Hz), 7.53 (1H, t, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.1 Hz), 7.76-7.81 (2H, m), 8.05- 
               
               
                   
                   
                   
                   
                   
                   
                 8.08 (3H, m), 8.25-8.31 (2H m). 
               
               
                 557 
                 —H 
                 —CF 3   
                 —O— 
                 —C 2 H 5   
                 0 
                   1 H NMR CDCl 3  1.39 (3H, t, J = 7.2 Hz), 4.37 (2H, q, J = 7.2 Hz), 7.40 (1H, d, J = 8.7 Hz), 7.09-7.20 (2H, m), 7.66 (1H, t, J = 7.8 Hz), 7.76-7.90 (1H, m), 8.00 (1H, brs), 8.00-8.10 (3H, m), 8.10-8.18 (1H, m), 8.20-8.35 (2H, m). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 79 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 272   
                 R 273   
                 M 
                 mp (° C.) or  1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
             
          
           
               
                 558 
                 —H 
                 —Ac 
                 1 
                 mp 178-179 
               
               
                 559 
                 —H 
                 —Ac 
                 2 
                   1 H NMR 1.22 (3H, t, J = 7.2 Hz), 1.86 (3H, s), 2.58 (2H, t, J = 
               
               
                   
                   
                   
                   
                 7.3 Hz), 3.99 (2H, t, J = 7.3 Hz), 4.07 (2H, q, J = 7.2 Hz), 7.02 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 8.9 Hz), 7.15-7.20 (4H, m), 7.58 (1H, d, J = 8.4 Hz), 7.75 (1H, dd, 
               
               
                   
                   
                   
                   
                 J = 2.1 Hz, 8.4 Hz), 8.02 (1H, d, J = 2.1 Hz), 8.24 (1H, dd, J = 2.7 Hz, 
               
               
                   
                   
                   
                   
                 8.9 Hz), 8.28 (1H, s), 8.32 (1H, d, J = 2.7 Hz). 
               
               
                 560 
                 —H 
                 —CH 3   
                 1 
                   1 H NMR 1.26 (3H, t, J = 7.1 Hz), 3.06 (3H, s), 4.04 (2H, s), 4.18 (2H; 
               
               
                   
                   
                   
                   
                 q, J = 7.1 Hz), 6.68 (2H, d, J = 9.1 Hz), 6.85 (1H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                 7.00 (2H, d, J = 9.1 Hz), 7.55 (1H, d, J = 8.4 Hz), 7.70 (1H, dd, J = 
               
               
                   
                   
                   
                   
                 1.9 Hz, 8.4 Hz), 7.94 (1H, s), 7.97 (1H, d, J = 1.9 Hz), 8.10 (1H, dd, J = 
               
               
                   
                   
                   
                   
                 2.6 Hz, 8.9 Hz), 8.21 (1H, d, J = 2.6 Hz). 
               
               
                 561 
                 —H 
                 —C 2 H 5   
                 1 
                   1 H NMR 1.22 (3H, t, J = 7.1 Hz), 1.27 (3H, t, J = 7.1 Hz), 3.46 (2H, 
               
               
                   
                   
                   
                   
                 q, J = 7.1 Hz), 4.01 (2H, s), 4.20 (2H; q, J = 7.1 Hz), 6.64 (2H, d, 4 = 
               
               
                   
                   
                   
                   
                 9.1 Hz), 6.86 (1H, d, J = 8.9 Hz), 6.98 (2H, d, J = 9.1 Hz), 7.56 (1H, 
               
               
                   
                   
                   
                   
                 d, J = 8.4 Hz), 7.70 (1H, dd, J = 1.9 Hz, 8.4 Hz), 7.82 (1H, s), 
               
               
                   
                   
                   
                   
                 7.97 (1H, d, J = 1.9 Hz), 8.11 (1H, dd, J = 2.6 Hz, 8.9 Hz), 8.22 (1H, 
               
               
                   
                   
                   
                   
                 d, J = 2.6 Hz). 
               
               
                 562 
                 —OCH 3   
                 —CH 3   
                 1 
                   1 H NMR 1.25 (3H, t, J = 7.1 Hz) 3.03 (3H, s), 3.65 (3H, s), 4.01 (2H, 
               
               
                   
                   
                   
                   
                 s), 4.17 (2H, q, J = 7.1 Hz), 6.16 (1H, d, J = 8.7 Hz), 6.21 (1H, s), 
               
               
                   
                   
                   
                   
                 6.76 (1H, d, J = 8.9 Hz), 6.88 (1H, d, J = 8.6 Hz), 7.43 (1H, d, J = 
               
               
                   
                   
                   
                   
                 8.4 Hz), 7.67 (1H, d, J = 8.4 Hz), 7.94 (1H, d, J = 1.8 Hz), 8.02 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 8.9 Hz), 8.13 (1H, d, J = 2.3 Hz), 8.88 (1H, s). 
               
               
                 563 
                 —OCH 3   
                 —C 2 H 5   
                 1 
                   1 H NMR 1.21 (3H, t, J = 7.1 Hz), 1.27 (3H, t, J = 7.1 Hz), 3.44 (2H, 
               
               
                   
                   
                   
                   
                 q, J = 7.1 Hz), 3.68 (3H, s), 3.98 (2H, s), 4.20 (2H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 6.17 (1H, dd, J = 8.9 Hz, 3.0 Hz), 6.24 (1H, d, J = 2.8 Hz), 6.81 (1H, 
               
               
                   
                   
                   
                   
                 d, J = 8.9 Hz), 6.91 (1H, d, J = 8.7 Hz), 7.48 (1H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                 7.68 (1H, dd, J = 8.4 Hz, 2.2 Hz), 7.96 (1H, d, J = 2.0 Hz), 8.04 (1H, 
               
               
                   
                   
                   
                   
                 dd, J = 8.9 Hz), 2.8 Hz), 8.15 (1H, d, J = 2.3 Hz), 8.34 (1H, s). 
               
               
                 564 
                 —CH 3   
                 —Ac 
                 1 
                   1 H NMR 1.26 (3H, t, J = 7.1 Hz), 1.96 (3H, s), 2.22 (3H, s), 4.20 (2H, 
               
               
                   
                   
                   
                   
                 q, J = 7.1 Hz), 4.37 (2H, s), 6.99 (1H, d, J = 8.9 Hz), 7.07 (1H, d, J = 
               
               
                   
                   
                   
                   
                 8.4 Hz), 7.19 (1H, dd, J = 2.4 Hz, 8.4 Hz), 7.59 (1H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                 7.72 (1H, d, J = 8.4 Hz), 7.90-8.12 (2H, m), 8.21 (1H, dd, J = 2.0 Hz, 
               
               
                   
                   
                   
                   
                 8.4 Hz), 8.27 (1H, s). 
               
               
                 565 
                 —CH 3   
                 —CH 3   
                 1 
                   1 H NMR 1.26 (3H, t, J = 7.1 Hz), 2.12 (3H, s), 3.06 (3H, s), 4.04 (2H, 
               
               
                   
                   
                   
                   
                 s), 4.20 (2H, q, J = 7.1 Hz), 6.49-6.61 (2H, m), 6.83 (1H, d, J = 
               
               
                   
                   
                   
                   
                 8.9 Hz), 6.93 (1H, d, J = 8.5 Hz), 7.57 (1H, d, J = 8.5 Hz), 7.70 (1H, 
               
               
                   
                   
                   
                   
                 dd, J = 8.5 Hz, 2.1 Hz), 7.73 (1H, s), 7.97 (1H, d, J = 2.1 Hz), 
               
               
                   
                   
                   
                   
                 8.12 (1H, dd, J = 8.9 Hz, 2.8 Hz), 8.21 (1H, d, J = 2.8 Hz). 
               
               
                 566 
                 —F 
                 —Ac 
                 1 
                   1 H NMR 1.29 (3H, t, J = 7.1 Hz), 2.00 (3H, s), 4.21 (2H, q, J = 
               
               
                   
                   
                   
                   
                 7.1 Hz), 4.37 (2H, s), 7.09 (1H, dd, J = 7.9 Hz, 1.8 Hz), 7.18-7.32 (3H, 
               
               
                   
                   
                   
                   
                 m), 7.59 (1H, d, J = 8.4 Hz), 7.72 (1H, dd, J = 8.3 Hz, 2.1 Hz), 
               
               
                   
                   
                   
                   
                 7.83 (1H, brs), 7.99 (1H, d, J = 2.0 Hz), 8.20-8.24 (2H, m). 
               
               
                 567 
                 —F 
                 —CH 3   
                 1 
                   1 H NMR 1.27 (3H, t, J = 7.1 Hz), 3.06 (3H, s), 4.04 (2H, s), 4.20 (2H, 
               
               
                   
                   
                   
                   
                 q, J = 7.1 Hz), 6.40-6.52 (2H, m), 6.96 (1H, d, J = 9.2 Hz), 7.07 (1H, 
               
               
                   
                   
                   
                   
                 t, 4 = 9.1 Hz), 7.57 (1H, d, J = 8.2 Hz), 7.70 (1H, dd, J = 8.2 Hz, 
               
               
                   
                   
                   
                   
                 2.0 Hz), 7.82 (1H, brs), 7.97 (1H, d, J = 2.1 Hz), 8.13-8.19 (2H, m). 
               
               
                 568 
                 —F 
                 —C 2 H 5   
                 1 
                   1 H NMR 1.23 (3H, t, J = 7.1 Hz), 1.28 (3H, t, J = 7.1 Hz), 3.45 (2H, 
               
               
                   
                   
                   
                   
                 q, J = 7.1 Hz), 4.00 (2H, s), 4.22 (2H, q, J = 7.1 Hz), 6.37-6.48 (2H, 
               
               
                   
                   
                   
                   
                 m), 6.97 (1H, d, J = 8.7 Hz), 7.05 (1H, t, J = 9.1 Hz), 7.57 (1H, d, J = 
               
               
                   
                   
                   
                   
                 8.4 Hz), 7.70 (1H, dd, J = 8.4 Hz, 2.2 Hz), 7.79 (1H, brs), 7.98 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 2.0 Hz), 8.13-8.20 (2H, m). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 80 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
               
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 274   
                 R 275   
                 M 
                 E 
                 mp (° C.) or  1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 569 
                 —H 
                 -Ac 
                 1 
                 2 
                 mp 163-164 
               
               
                 570 
                 —H 
                 -Ac 
                 2 
                 2 
                   1 H NMR 1.22(3 H, t, J = 7.2 Hz), 1.87(3 H, s), 2.59(2 H, t, J = 
               
               
                   
                   
                   
                   
                   
                 7.3 Hz), 4.00(2 H, t, J = 7.3 Hz), 4.08(2 H, q, J = 7.2 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.03(1 H, d, J = 8.8 Hz), 7.19(4 H, s), 7.78(2 H, d, J = 8.3 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.95(1 H, brs), 8.01(2 H, d, J = 8.3 Hz), 8.27(1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.8 Hz), 8.31(1 H, s). 
               
               
                 571 
                 —H 
                 —CH 3   
                 1 
                 1 
                   1 H NMR 3.06(3 H, s), 3.73(3 H, s), 4.07(2 H, s), 6.68(2 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 9.1 Hz), 6.86 (1 H, d, J = 8.9 Hz), 7.00(2 H, d, J = 9.1 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.74(2 H, d, J = 8.0 Hz), 7.98(2 H, d, J = 8.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.07(1 H, s), 8.15(1 H, dd, J = 8.9 Hz, 2.5 Hz), 8.24(1 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 2.5 Hz). 
               
               
                 572 
                 —H 
                 —C 2 H 5   
                 1 
                 2 
                   1 H NMR 1.18(3 H, t, J = 7.1 Hz), 1.25(3 H, t, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 3.41(2 H, q, J = 7.1 Hz), 3.98(2 H, s), 4.17(2 H, q, J = 7.1 
               
               
                   
                   
                   
                   
                   
                 Hz), 6.59(2 H, d, J = 9.1 Hz), 6.79(1 H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.92(2 H, d, ,J = 9.1 Hz), 7.64(2 H, d, J = 8.4 Hz), 7.94(2 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.1 Hz), 8.07(1 H, dd, J = 8.9 Hz, 2.6 Hz), 8.22(1 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 2.8 Hz), 8.75(1 H, s). 
               
               
                 573 
                 —OCH 3   
                 —CH 3   
                 1 
                 2 
                   1 H NMR 1.24(3 H, t, J = 7.1 Hz), 3.03(3 H, s), 3.65(3 H, s), 
               
               
                   
                   
                   
                   
                   
                 4.01(2 H, s), 4.17 (2 H, q, J = 7.1 Hz), 6.17(1 H, dd, J = 8.7 
               
               
                   
                   
                   
                   
                   
                 Hz, 2.6 Hz), 6.24(1 H, d, J = 2.5 Hz), 6.77(1 H, d, J = 8.9 
               
               
                   
                   
                   
                   
                   
                 Hz), 6.89(1 H, d, J = 8.7 Hz), 7.63(2 H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.96(2 H, d, J = 8.1 Hz), 8.06(1 H, d, J = 8.7 Hz), 8.16(1 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 2.5 Hz), 8.91(1 H, s). 
               
               
                 574 
                 —OCH 3   
                 —C 2 H 5   
                 1 
                 2 
                   1 H NMR 1.19 3 H, t, J = 7.1 Hz , 1.26 3 H, t, J = 7.1 Hz 
               
               
                   
                   
                   
                   
                   
                 3.42(2 H, q, J = 7.1 Hz), 3.64(3 H, s), 3.97(2 H, s), 4.18(2 H, 
               
               
                   
                   
                   
                   
                   
                 q, J = 7.1 Hz), 6.14(1 H, dd, J = 8.7 Hz, 2.8 Hz), 6.21(1 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 2.8 Hz), 6.76(1 H, d, J = 8.9 Hz), 6.87(1 H, d, J = 8.7 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.62(2 H, d, J = 8.4 Hz), 7.96(2 H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.05(1 H, dd, J = 8.9 Hz, 2.5 Hz), 8.18(1 H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 9.01(1 H, s). 
               
               
                 575 
                 —CH 3   
                 -Ac 
                 1 
                 2 
                   1 H NMR 1.25(3 H, t, J = 7.0 Hz), 1.93(3 H s) 2.21(3 H, s), 
               
               
                   
                   
                   
                   
                   
                 4.18(2 H, q, J = 7.0 Hz), 4.35(2 H, s), 6.98(1 H, d, J = 8.7 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.06(1 H, d, J = 8.5 Hz), 7.18(1 H, d, J = 8.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.23-7.28(1 H, m), 7.75(2 H, d, J = 7.8 Hz), 8.02(2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 7.8 Hz), 8.22-8.33(2 H, m). 
               
               
                 576 
                 —CH 3   
                 —CH 3   
                 1 
                 2 
                   1 H NMR 1.26(3 H, t, J = 7.1 Hz), 2.11(3 H, s), 3.05(3 H, s), 
               
               
                   
                   
                   
                   
                   
                 4.04(2 H, s), 4.19 (2 H, q, J = 7.1 Hz), 6.46-6.60(2 H, m), 
               
               
                   
                   
                   
                   
                   
                 6.80(1 H, d, J = 8.9 Hz), 6.91(1 H, d, J = 8.5 Hz), 7.74(2 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.4 Hz), 7.98(2 H, d, J = 8.2 Hz), 8.07(1 H, s), 8.15 
               
               
                   
                   
                   
                   
                   
                 (1 H, dd, J = 8.9 Hz, 2.7 Hz), 8.23(1 H, d, J = 2.7 Hz). 
               
               
                 577 
                 —F 
                 -Ac 
                 1 
                 2 
                   1 H NMR 1.28(3 H, t, J = 7.1 Hz), 1.98(3 H, s), 4.20(2 H, q, 
               
               
                   
                   
                   
                   
                   
                 J = 7.1 Hz), 4.36 (2 H, s), 7.09(1 H, dd, J = 6.4 Hz, 3.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.13-7.32(3 H, m), 7.77(2 H, d, J = 8.3 Hz), 8.01(2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.1 Hz), 8.12(1 H, s), 8.23-8.28(2 H, m). 
               
               
                 578 
                 —F 
                 —CH 3   
                 1 
                 2 
                   1 H NMR 1.27(3 H, t, J = 7.1 Hz), 3.07(3 H, s), 4.04(2 H, s), 
               
               
                   
                   
                   
                   
                   
                 4.20(2 H, q, J = 7.1 Hz), 6.41-6.53(2 H, m), 6.98(1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 9.7 Hz), 7.07(1 H, t, J = 9.1 Hz), 7.76 (2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.84(1 H, s), 7.99(2 H, d, J = 8.1 Hz), 8.19-8.21(2 H, m). 
               
               
                 579 
                 —F 
                 —C 2 H 5   
                 1 
                 2 
                   1 H NMR 1.20-1.31(6 H, m), 3.45(2 H, q, J = 7.3 Hz), 
               
               
                   
                   
                   
                   
                   
                 4.00(2 H, s), 4.22(2 H, q, J = 7.1 Hz), 6.37-6.49(2 H, m), 
               
               
                   
                   
                   
                   
                   
                 6.97-7.09(2 H, m), 7.76-7.79(3 H, m), 7.99(2 H, d, J = 7.9 
               
               
                   
                   
                   
                   
                   
                 Hz), 8.19-8.21(2 H, m). 
               
               
                   
               
             
          
         
       
     
       Reference Example 580 
     Production of ethyl 3-{4-[5-(3,4-dichlorobenzoylamino)-pyridin-2-yloxy]-3-methoxyphenyl}propionate 
       [0849]    Under ice cooling, to a solution of ethyl 3-(4-(5-aminopyridin-2-yloxy)-3-methoxyphenyl)propionate (1.43 g, 4.5 mmol) in dichloromethane (30 mL) was added pyridine (0.44 mL, 5.4 mmol), and then 3,4-dichlorobenzoyl chloride (0.99 g, 4.7 mmol). The resulting solution was stirred for 1 hour under ice cooling, and then for 10 hours at room temperature. To the resulting reaction solution was added 10% hydrochloric acid, and extracted with dichloromethane. The dichloromethane layer was washed with water, dried over anhydrous magnesium sulfate, and evaporated. To the residue was added diethyl ether, and stirred. The precipitates were collected by filtration. After washing with water and diethyl ether, the precipitates were air dried at 60° C., to thereby yield 0.52 g of the title compound. 
         [0850]    Appearance: White powder 
         [0851]      1 H NMR (CDCl 3 ) δ 1.26 (3H, t, J=7.1 Hz), 2.56-2.79 (2H, m), 2.91-3.09 (2H, m), 3.75 (3H, s), 4.15 (2H, q, J=7.1 Hz), 6.75 (3H, m), 7.10 (1H, d, J=8.0 Hz), 7.56 (1H, d, J=8.2 Hz), 7.99 (1H, d, J=8.1 Hz), 8.17 (1H, s), 8.69 (1H, d, J=9.2 Hz), 8.79 (1H, s), 9.52 (1H, brs). 
         [0852]    The following compounds were produced in the same manner as in Reference Example 580. 
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 81 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 276   
                 R 277   
                 Xa 20   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 581 
                 3,4-Cl 2 Ph- 
                 —H 
                 —CO— 
                 1.23 (3H, t, J = 7.2 Hz), 2.64 (2H, t, J = 7.6 Hz), 
               
               
                   
                   
                   
                   
                 3.01 (2H, t, J = 7.6 Hz), 4.12 (2H, q, J = 7.2 Hz), 
               
               
                   
                   
                   
                   
                 7.30 (2H, d, J = 8.2 Hz), 7.57 (1H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                   
                 7.73 (1H, dd, J = 8.3 Hz, 2.2 Hz), 7.95-8.04 
               
               
                   
                   
                   
                   
                 (3H, m), 8.09 (1H, d, J = 8.6 Hz), 8.16 (1H, brs), 
               
               
                   
                   
                   
                   
                 8.41 (1H, dd, J = 8.6 Hz, 2.6 Hz), 8.80 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 2.6 Hz). 
               
               
                 582 
                 4-CF 3 Ph- 
                 —OC 2 H 5   
                 —O— 
                 1.22 (3H, t, J = 6.9 Hz), 1.26 (3H, t, J = 7.2 Hz), 
               
               
                   
                   
                   
                   
                 251-2.73 (2H, m), 2.87-3.06 (2H, m), 4.02 (2H, 
               
               
                   
                   
                   
                   
                 q, J = 6.9 Hz), 4.15 (2H, q, J = 7.2 Hz), 6.71- 
               
               
                   
                   
                   
                   
                 6.96 (3H, m), 7.17 (1H, d, J = 7.9 Hz), 7.75 (2H, 
               
               
                   
                   
                   
                   
                 d, J = 7.6 Hz), 8.43 (2H, d, J = 7.6 Hz), 9.15- 
               
               
                   
                   
                   
                   
                 9.32 (1H, m), 9.42 (1H, s), 11.14 (1H, brs). 
               
               
                 583 
                 3,4-Cl 2 Ph- 
                 —F 
                 —O— 
                 1.26 (3H, t, J = 7.1 Hz), 2.53-2.70 (2H, m), 2.85- 
               
               
                   
                   
                   
                   
                 3.03 (2H, m), 4.15 (2H, q, J = 7.1 Hz), 6.97- 
               
               
                   
                   
                   
                   
                 7.09 (3H, m), 7.10-7.19 (1H, m), 7.58 (1H, d, J = 
               
               
                   
                   
                   
                   
                 8.3 Hz), 7.70 (1H, dd, J = 8.3 Hz, 2.1 Hz), 7.72 
               
               
                   
                   
                   
                   
                 (1H, brs), 7.97 (1H, d, J = 2.1 Hz), 8.15- 
               
               
                   
                   
                   
                   
                 8.23 (2H, m). 
               
               
                 584 
                 PhCH 2 O— 
                 —H 
                 —O— 
                 1.25 (3H, t, J = 7.1 Hz), 2.53-2.71 (2H, m), 2.84- 
               
               
                   
                   
                   
                   
                 3.04 (2H, m), 4.14 (2H, q, J = 7.1 Hz), 6.51- 
               
               
                   
                   
                   
                   
                 6.64 (1H, m), 6.88 (1H, d, J = 8.8 Hz), 6.98- 
               
               
                   
                   
                   
                   
                 7.06 (2H, m), 7.17-7.24 (2H, m), 7.30-7.43 (5H, 
               
               
                   
                   
                   
                   
                 m), 7.87-8.02 (1H, m), 8.05 (1H, d, J = 2.5 Hz). 
               
               
                 585 
                 4-CF 3 Ph- 
                 —F 
                 —O— 
                 1.26 (3H, t, J = 7.1 Hz), 2.56-2.71 (2H, m), 2.89- 
               
               
                   
                   
                   
                   
                 3.02 (2H, m), 4.15 (2H, q, J = 7.1 Hz), 6.97- 
               
               
                   
                   
                   
                   
                 7.08 (3H, m), 7.10-7.19 (1H, m), 7.77 (2H, d, J = 
               
               
                   
                   
                   
                   
                 8.2 Hz), 7.82 (1H, brs), 7.99 (2H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                 8.17-8.26 (2H, m). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 82 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
                   
               
               
                 Example 
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 278   
                 R 279   
                 R 280   
                 R 281   
                 R 282   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 586 
                 4-CF 3 PhCO— 
                 —F 
                 —(CH 2 ) 2 CH 3   
                 —H 
                 —H 
                 0.96 (3H, t, J = 7.3 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 1.28 (3H, t, J = 7.1 Hz), 1.63- 
               
               
                   
                   
                   
                   
                   
                   
                 1.74 (2H, m), 3.32 (2H, t, J = 
               
               
                   
                   
                   
                   
                   
                   
                 7.6 Hz), 4.01 (2H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 4.21 (2H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 6.35-6.47 (2H, m), 6.97 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 7.8 Hz), 7.01 (1H, t, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.9 Hz), 7.77 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.2 Hz), 7.81 (1H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 7.99 (2H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 8.19-8.22 (2H, m). 
               
               
                 587 
                 4-CF 3 PhCO— 
                 —H 
                 —CH 3   
                 —CH 3   
                 —CH 3   
                 1.25 (3H, t, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 1.42 (6H, s), 2.91 (3H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 4.18 (2H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 6.92 (1H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.00 (2H, d, J = 9.2 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.07 (2H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.77 (2H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.81 (1H, s), 8.00 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.1 Hz), 8.20 (1H, dd, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.7 Hz, 2.8 Hz), 8.28 (1H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 2.5 Hz). 
               
               
                 588 
                 3,4-Cl 2 PhSO 2 — 
                 —F 
                 —CH 3   
                 —H 
                 —H 
                 1.29 (3H, t, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 3.05 (3H, s), 4.03 (2H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 4.22 (2H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 6.38-6.49 (2H, m), 6.82 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs), 6.88 (1H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.02 (1H, t, J = 8.8 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.48 (1H, dd, J = 8.4, 1.6 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.52 (1H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.57 (1H, dd, J = 8.7 Hz, 2.6 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.70 (1H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.82 (1H, d, J = 1.8 Hz). 
               
               
                   
               
             
          
         
       
     
       Reference Example 589 
     Production of ethyl 4-[5-(3,4-dimethylbenzoylamino)-pyridin-2-yloxy]benzoate 
       [0853]    To a solution of ethyl 4-(5-aminopyridin-2-yloxy)benzoate (14.15 g, 54.8 mmol) in DMF (100 mL) were added 3,4-dimethylbenzoic acid (8.23 g, 54.8 mmol), 1-hydroxybenzotriazole monohydrate (8.4 g, 54.8 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (12.6 g, 65.7 mmol) under ice cooling, and then stirred for 30 minutes under ice cooling and for 17 hours at room temperature. The reaction solution was concentrated under reduced pressure. To the residue was added water (200 mL), and extracted with ethyl acetate (250 mL). The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=2:1), to thereby yield 16.15 g of the title compound. 
         [0854]    Appearance: White powder 
         [0855]      1 H NMR (CDCl 3 ) δ 1.39 (3H, t, J=7.1 Hz), 2.33 (6H, s), 4.37 (2H, q, J=7.1 Hz), 6.99 (1H, d, J=9.7 Hz), 7.15 (2H, d, J=8.7 Hz), 7.24 (1H, d, J=7.7 Hz), 7.59 (1H, dd, J=7.7 Hz, 2.0 Hz), 7.65 (1H, d, J=2.0 Hz), 7.90 (1H, brs), 8.07 (2H, d, J=8.7 Hz), 8.25-8.35 (2H, m). 
         [0856]    The following compounds were produced in the same manner as in Reference Example 589. 
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 83 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 283   
                 R 284   
                 R 285   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
             
          
           
               
                 590 
                 —Cl 
                 —Cl 
                 —Ac 
                 2.58 (3H, s), 7.19 (1H, d, J = 8.7 Hz), 7.22 (2H, d, J = 
               
               
                   
                   
                   
                   
                 8.7 Hz), 6.06 (2H, s), 7.84 (1H, d, J = 8.4 Hz), 7.97 (1H, 
               
               
                   
                   
                   
                   
                 dd, J = 8.4 Hz, 2.1 Hz), 8.01 (1H; d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                 8.24 (1H, d, J = 2.1 Hz), 8.28 (1H, dd, J = 8.7 Hz, 2.6 
               
               
                   
                   
                   
                   
                 Hz), 8.56 (1H, d, J = 2.6 Hz), 10.64 (1H, brs). 
               
               
                 591 
                 —CN 
                 —H 
                 —COOCH 3   
                 3.92 (3H, s), 7.05 (1H, d, J = 8.9 Hz), 7.18 (2H, d, J = 
               
               
                   
                   
                   
                   
                 8.6 Hz), 7.81 (2H, d, J = 8.6 Hz), 7.90 (1H, brs), 
               
               
                   
                   
                   
                   
                 8.00 (2H, d, J = 8.6 Hz), 8.08 (2H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                 8.27 (1H, dd, J = 8.6 Hz, 2.6 Hz), 8.30 (1H, d, J = 2.3 
               
               
                   
                   
                   
                   
                 Hz). 
               
               
                   
               
             
          
         
       
     
       Reference Example 592 
     Production of ethyl 3-{4-[5-(3,4-dichlorobenzoylamino)-pyridin-2-yloxy]-3-ethoxyphenyl}propionate 
       [0857]    To a solution of ethyl 3-[3-ethoxy-4-(5-nitropyridin-2-yloxy)phenyl]propionate (0.82 g, 2.3 mmol) in ethanol (40 mL) was added 10% palladium-carbon (0.15 g) under a nitrogen atmosphere, and the resulting solution was stirred under a hydrogen atmosphere at atmospheric pressure for 1 hour at room temperature. 
         [0858]    The palladium-carbon was removed by filtration, and the filtrate was concentrated. The obtained filtrate (0.58 g) was dissolved in dichloromethane (30 mL), and to the resulting solution were added pyridine (0.17 mL, 2.1 mmol) and 3,4-dichlorobenzoyl chloride (0.39 g, 1.84 mmol) under ice cooling. The resulting solution was stirred under ice cooling for 1 hour, and then stirred for 12 hours at room temperature. The reaction solution was made acidic by adding 10% hydrochloric acid, and extracted with dichloromethane. The dichloromethane layer was washed with a saturated sodium bicarbonate solution, dried over anhydrous magnesium sulfate, and evaporated, to thereby yield 0.94 g of the title compound. 
         [0859]    Appearance: Yellow amorphous powder 
         [0860]      1 H NMR (CDCl 3 ) δ 1.18 (3H, t, J=7.0 Hz), 1.26 (3H, t, J=7.1 Hz), 2.53-2.71 (2H, m), 2.86-3.01 (2H, m), 3.98 (2H, q, J=7.0 Hz), 4.15 (2H, q, J=7.1 Hz), 6.78-6.88 (2H, m), 6.95 (1H, d, J=8.8 Hz), 7.06 (1H, d, J=7.9 Hz), 7.58 (1H, d, J=8.3 Hz), 7.65-7.77 (2H, m), 7.98 (1H, d, J=2.1 Hz), 8.14 (1H, dd, J=8.8 Hz, 2.7 Hz), 8.19 (1H, d, J=2.3 Hz). 
         [0861]    The following compound was produced in the same manner as in Reference Example 592. 
       Reference Example 593 
     N-{6-[4-(3-hydroxypropyl)phenoxy]pyridin-3-yl}-4-trifluoromethylbenzamide 
       [0862]      1 H NMR (CDCl 3 ) δ 1.86-1.97 (2H, m), 2.70-2.75 (2H, m), 3.68-3.73 (2H, m), 6.95 (1H, d, J=8.7 Hz), 7.03-7.08 (2H, m), 7.23 (2H, d, J=8.4 Hz), 7.77 (2H, d, J=8.2 Hz), 7.84 (1H, brs), 7.99 (2H, d, J=8.2 Hz), 8.20-8.23 (1H, m), 8.26 (1H, d, J=2.6 Hz). 
       Reference Example 594 
     Production of methyl 2-(4-{5-[3-(3,4-dichlorophenyl)-ureido]pyridin-2-yloxy}phenyl)acetate 
       [0863]    To a solution of methyl 2-[4-(5-aminopyridin-2-yloxy)phenyl]acetate (0.44 g, 1.7 mmol) in dichloro-methane (7 mL) was added 3,4-dichlorophenylisocyanate (0.353 g, 1.9 mmol), and the resulting reaction solution was stirred for 1 hour at room temperature. To the reaction solution was added diisopropyl ether. Insoluble matter was removed by filtration, to thereby yield 0.60 g of the title compound. 
         [0864]    Appearance: White powder 
         [0865]      1 H NMR (DMSO-d 6 ) δ 3.63 (3H, s), 3.69 (2H, s), 6.99-7.05 (3H, m), 7.26-7.30 (2H, m), 7.35 (1H, dd, J=8.8, 2.4 Hz), 7.52 (1H, d, J=8.8 Hz), 7.86 (1H, d, J=2.4 Hz), 7.98 (1H, dd, J=8.8, 2.8 Hz), 8.18 (1H, d, J=2.7 Hz), 8.91 (1H, s), 9.10 (1H, s). 
         [0866]    The following compounds were produced in the same manner as in Reference Example 594. 
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 84 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
               
               
                 Example 
                   
                   
               
               
                 No. 
                 R 286   
                 MS (M + ) 
               
               
                   
               
               
                 595 
                 —H 
                 459 
               
               
                 596 
                 —CH 3   
                 473 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 85 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
               
               
                 Example 
                   
                   
               
               
                 No. 
                 R 287   
                   1 H NMR (CDCl 3 ) δ ppm or MS 
               
               
                   
               
               
                 597 
                 4-CF 3 Ph- 
                   1 H NMR 1.18(3 H, t, J = 7.1 Hz), 1.25(3 H, t, J = 7.1 Hz), 
               
               
                   
                   
                 2.62-2.68(2 H, m), 2.96-3.01(2 H, m), 3.76(2 H, q, J = 7.1 Hz), 4.14(2 H, 
               
               
                   
                   
                 q, J = 7.1 Hz), 6.17(1 H, brs), 7.05(1 H, dd, J = 8.7 Hz, 0.7 Hz), 
               
               
                   
                   
                 7.11(2 H, d, J = 8.6 Hz), 7.28(2 H, d, J = 8.6 Hz), 7.40(2 H, d, J = 
               
               
                   
                   
                 8.7 Hz), 7.49(2 H, d,J = 8.6 Hz), 7.63(1 H, dd, J = 8.7 Hz, 2.6 Hz), 
               
               
                   
                   
                 8.14(1 H, dd, J = 2.6 Hz, 0.7 Hz). 
               
               
                 598 
                 3,4-Cl 2 Ph- 
                 MS 501(M + ) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 86 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
               
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 288   
                 M 
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 599 
                 —H 
                 3 
                 1.90-2.11(2 H, m), 2.28-2.50(4 H, m), 2.51-2.72(2 H, m), 
               
               
                   
                   
                   
                 2.82-3.07(2 H, m), 3.28-3.51(4 H, m), 3.52-3.78(4 H, m), 5.25-5.40(1 H, 
               
               
                   
                   
                   
                 m), 5.96(2 H, s), 6.69-6.81(2 H, m), 6.82-6.94(2 H, m), 
               
               
                   
                   
                   
                 6.95-7.08(2 H, m), 7.09-7.26(3 H, m), 7.88-8.07(2 H, m). 
               
               
                 600 
                 —H 
                 2 
                 2.20-2.46(4 H, m), 2.52-2.70(2 H, m), 2.82-3.02(2 H, m), 
               
               
                   
                   
                   
                 3.28-3.50(4 H, m), 3.51-3.72(6 H, m), 5.52-5.71(1 H, m), 5.95(1 H, s), 
               
               
                   
                   
                   
                 6.68-6.78(2 H, m), 6.80-6.89(2 H, m), 6.91(2 H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                 7.17(2 H, d, J = 8.4 Hz), 7.36(1 H, s), 7.89-8.01(2 H, m). 
               
               
                 601 
                 —OCH 3   
                 3 
                 1.85-2.08(2 H, m), 2.27-2.46(4 H, m), 2.55-2.71(2 H, m), 
               
               
                   
                   
                   
                 2.88-3.03(2 H, m), 3.30-3.46(6 H, m), 3.56(2 H, t, J = 6.3 Hz), 3.63(2 H, 
               
               
                   
                   
                   
                 t, J = 4.9 Hz), 3.71(3 H, s), 5.20-5.36(1 H, m), 5.95(2 H, s), 
               
               
                   
                   
                   
                 6.68-6.89(6 H, m), 7.00(1 H, d, J = 8.0 Hz), 7.15(1 H, s), 7.87(1 H, d, J = 
               
               
                   
                   
                   
                 2.4 Hz), 7.92(1 H, dd J = 2.8 Hz, 8.8 Hz). 
               
               
                 602 
                 —OCH 3   
                 2 
                 2.25-2.49(4 H, m), 2.58-2.72(2 H, m), 2.87-3.05(2 H, m), 
               
               
                   
                   
                   
                 3.30-3.71(10 H, m), 3.7.1(3 H, s), 5.40-5.52(1 H, m), 5.95(2 H, s), 
               
               
                   
                   
                   
                 6.66-6.91(6 H, m), 7.00(1 H, d, J = 8.0 Hz), 7.07(1 H, s), 7.85-7.99 
               
               
                   
                   
                   
                 (2 H, m). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
           
               
                 TABLE 87 
               
               
                   
               
               
                 Reference 
                   
                   
               
               
                 Example 
                   
                   
               
               
                 No. 
                 Chemical Structure 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
             
             
               
                 603 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (DMSO-d 6 ) 3.38(2 H, t, J = 6.1 Hz), 3.63(2 H, t, J = 6.1 Hz), 3.68(3 H, s), 6.27(1 H, t, J = 6.1 Hz), 6.76-6.84(2 H, m), 7.22-7.31(2 H, m), 8.41(1 H, s). 
               
               
                   
               
               
                 604 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 2.00-2.20(5 H, m), 3.27-3.47 (4 H, m), 3.48-3.60(2 H, m), 3.61-3.78 (2 H, m), 3.88(3 H, s), 3.89(3 H, s) 4 59 (2 H, s), 5.94-6.12(1 H, m), 6.66(1 H, d, J = 8.8 Hz), 6.83(1 H, d, J = 8.6 Hz), 6.80-6.92(3 H, m), 7.04(1 H, dd, J = 2.6 Hz, 8.6 Hz), 7.19(1 H, d, J = 2.6 Hz), 7.50(1 H, d, J = 2.8 Hz, 8.8 Hz), 7.73(1 H, s), 7.95(1 H, d, J = 2.8 Hz). 
               
               
                   
               
               
                 605 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 1.76-1.93(2 H, m), 2.00-2.20 (5 H, m), 3.11-3.28(2 H, m), 3.29-3.41 (2 H, m), 3.42-3.57(2 H, m), 3.60-3.78 (2 H, m), 3.87(3 H, s), 3.88(3 H, s), 4.57 (2 H, s), 5.70-5.88(1 H, m), 6.67(1 H, d, J = 8.8 Hz), 6.83(1 H, d, J = 8.6 Hz), 6.86(3 H, m), 7.04(1 H, dd, J = 2.6 Hz, 8.6 Hz), 7.17(1 H, d, J = 2.6 Hz), 7.56(1 H, dd, J = 2.8 Hz, 8.8 Hz), 7.68(1 H, s), 7.93(1 H, d, J =2.8 Hz). 
               
               
                   
               
             
          
         
       
     
       Reference Example 606 
     Production of methyl 3-(4-{5-[3-(4-trifluoromethyl-phenyl)ureido]pyridin-2-yloxy}phenyl)propionate 
       [0867]    Methyl 3-[4-(5-nitropyridin-2-yloxy)phenyl]propionate (1.00 g, 3.3 mmol) was dissolved in a mixed solvent consisting of THF (1 mL) and ethanol (120 mL). To the resulting solution was added 10% palladium-carbon (100 mg), and stirred for 23 hours at room temperature under a hydrogen atmosphere. The reaction solution was filtered and the filtrate was concentrated. To the residue were added THF (20 mL), triethylamine (0.917 mL, 6.6 mmol) and phenyl 4-trifluoromethylisocyanate (0.61 mL, 4.3 mmol), and the resulting solution was stirred for 20 hours at room temperature. The reaction solution was evaporated under reduced pressure. The residue was washed with ethyl acetate, to thereby yield 850 mg of the title compound. 
         [0868]    Appearance: White powder 
         [0869]      1 H NMR (DMSO-d 6 ) δ 2.62-2.68 (2H, m), 2.83-2.88 (2H, m), 3.60 (3H, s), 6.97-7.02 (3H, m), 7.24 (2H, d, J=8.4 Hz), 7.65-7.69 (4H, m), 7.99 (1H, dd, J=8.9 Hz, 2.8 Hz), 8.19 (1H, d, J=2.8 Hz), 8.88 (1H, s), 9.20 (1H, s). 
       Reference Example 607 
     Production of methyl 3-fluoro-4-{5-[(4-trifluoromethyl-benzylidene)amino]pyridin-2-yloxy}benzoate 
       [0870]    Methyl 4-(5-aminopyridin-2-yloxy)-3-fluorobenzoate (2.0 g, 7.63 mmol) was dissolved in methanol (50 mL). To the resulting solution was added 4-trifluoromethylbenzaldehyde (1.04 mL, 7.63 mmol), and refluxed for 6 hours. The reaction solution was cooled to room temperature, and the resulting precipitated crystals were collected by suction filtration. The collected crystals were washed with methanol, to thereby yield 2.81 g of the title compound. 
         [0871]    Appearance: Pale grey powder 
         [0872]      1 H NMR (DMSO-d 6 ) δ 3.89 (3H, s), 7.32 (1H, d, J=8.7 Hz), 7.48-7.54 (1H, m), 7.85-7.92 (4H, m), 8.01 (1H, dd, J=8.7 Hz, 2.6 Hz), 8.13-8.16 (3H, m), 8.86 (1H, s). 
         [0873]    The following compounds were produced in the same manner as in Reference Example 607. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 88 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 289   
                 R 290   
                 R 291   
                 R 292   
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
             
          
           
               
                 608 
                 —CF 3   
                 —H 
                 —H 
                 —CH 3   
                 (DMSO-d 6 ) 3.86 (3H, s), 7.24-7.30 (3H, m), 
               
               
                   
                   
                   
                   
                   
                 7.92 (2H, d, J = 8.1 Hz), 7.98-8.05 (3H, m), 
               
               
                   
                   
                   
                   
                   
                 8.16 (2H, d, J = 8.1 Hz), 8.24 (1H, d, J = 2.1 
               
               
                   
                   
                   
                   
                   
                 Hz), 8.88 (1H, s). 
               
               
                 609 
                 —CF 3   
                 —H 
                 —H 
                 —C 2 H 5   
                 (DMSO-d 6 ) 1.33 (3H, t, J = 7.1 Hz), 4.32 (2H, 
               
               
                   
                   
                   
                   
                   
                 q, J = 7.1 Hz), 7.24-7.30 (3H, m), 7.92 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.3 Hz), 8.00 (1H, dd, J = 8.7 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.02 (2H, d, J = 8.7 Hz), 8.16 (2H, d, J = 7.9 
               
               
                   
                   
                   
                   
                   
                 Hz), 8.24 (1H, d, J = 2.6 Hz), 8.88 (1H, s). 
               
               
                 610 
                 —Cl 
                 —Cl 
                 —F 
                 —CH 3   
                 (DMSO-d 6 ) 3.89 (3H, s), 7.21 (1H, d, J = 8.6 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.48-7.54 (1H, m), 7.80-7.94 (4H, m), 
               
               
                   
                   
                   
                   
                   
                 7.97 (1H, dd, J = 8.7 Hz, 2.8 Hz), 8.12- 
               
               
                   
                   
                   
                   
                   
                 8.15 (2H, m), 8.75 (1H, s). 
               
               
                 611 
                 —Cl 
                 —Cl 
                 —F 
                 —C 2 H 5   
                 (CDCl 3 ) 1.40 (3H, t, J = 7.1 Hz), 4.39 (2H, q, J = 
               
               
                   
                   
                   
                   
                   
                 7.1 Hz), 7.09 (1H, d, J = 8.6 Hz), 7.26- 
               
               
                   
                   
                   
                   
                   
                 7.35 (1H, m), 7.55-7.57 (1H, m), 7.66-7.73 (2H, 
               
               
                   
                   
                   
                   
                   
                 m), 7.86-7.92 (2H, m), 8.02-8.03 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 8.40 (1H, s). 
               
               
                   
               
             
          
         
       
     
       Reference Example 612 
     Production of ethyl 4-{5-[1-(4-trifluoromethylphenyl)-ethylideneamino]pyridin-2-yloxy}benzoate 
       [0874]    Ethyl 4-(5-aminopyridin-2-yloxy)benzoate (16.0 g, 62 mmol) was dissolved in toluene (300 mL). To the resulting solution were added 4-trifluoromethylacetophenone (11.7 g, 62 mmol) and (±)-camphor-10-sulfonic acid (1.08 g, 4.65 mmol), and refluxed overnight. The reaction solution was concentrated under reduced pressure, to thereby yield 26.5 g of the title compound. 
         [0875]    Appearance: Dark green oil 
         [0876]      1 H NMR (CDCl 3 ) δ 1.35-1.41 (3H, m), 2.34 (3H, s), 4.36 (2H, d, J=7.1 Hz), 7.01-7.31 (4H, m), 7.70-7.77 (3H, m), 8.01-8.11 (4H, m). 
       Reference Example 613 
     Production of methyl 4-[5-(4-trifluoromethylbenzyl-amino)pyridin-2-yloxy]benzoate 
       [0877]    Methyl 4-{5-[(4-trifluoromethylbenzylidene)-amino]pyridin-2-yloxy}benzoate (2.64 g, 6.59 mmol) was suspended in methanol (25 mL), and to the resulting suspension was slowly added sodium borohydride (1.25 g, 33.0 mmol). The resulting solution was stirred at room temperature for 3 days. The reaction solution was concentrated under reduced pressure. To the residue was added ethyl acetate, and washed with water and brine. The organic layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was washed with diethyl ether, to thereby yield 2.65 g of the title compound. 
         [0878]    Appearance: White powder 
         [0879]      1 H NMR (CDCl 3 ) δ 3.89 (3H, s), 4.16 (1H, brs), 4.42 (2H, s), 6.84 (1H, d, J=8.7 Hz), 7.01 (1H, dd, J=8.6 Hz, 3.0 Hz), 7.05 (2H, d, J=8.4 Hz), 7.49 (2H, d, J=8.4 Hz), 7.62 (2H, d, J=8.3 Hz), 7.67 (1H, d, J=3.1 Hz), 8.01 (2H, d, J=8.6 Hz). 
         [0880]    The following compounds were produced in the same manner as in Reference Example 613. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 89 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 293   
                 R 294   
                 R 295   
                 R 296   
                 R 297   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
             
          
           
               
                 614 
                 —CF 3   
                 —H 
                 —H 
                 —H 
                 —C 2 H 5   
                 1.37 (3H, t, J = 7.1 Hz), 4.19 (1H, brs), 
               
               
                   
                   
                   
                   
                   
                   
                 4.35 (2H, q, J = 7.1 Hz), 4.41 (2H, brs), 
               
               
                   
                   
                   
                   
                   
                   
                 6.83 (1H, d, J = 8.7 Hz), 7.01 (1H, dd, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.6 Hz, 3.0 Hz), 7.04 (2H, d, J = 8.6 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.48 (2H, d, J = 8.1 Hz), 7.61 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 8.3 Hz), 7.66 (1H, d, J = 3.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 8.02 (2H, d, J = 8.7 Hz). 
               
               
                 615 
                 —CF 
                 —H 
                 —CH 3   
                 —H 
                 —C 2 H 5   
                 1.37 (3H, t, J = 7.1 Hz), 1.56 (3H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 6.8 Hz), 4.06 (1H, brs), 4.34 (2H, q, J = 
               
               
                   
                   
                   
                   
                   
                   
                 7.1 Hz), 4.49 (1H, q, J = 6.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 6.75 (1H, d, J = 8.7 Hz), 6.87 (1H, dd, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.7 Hz, 3.0 Hz), 7.01 (2H, d, J = 8.6 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.47 (2H, d, J = 8.1 Hz), 7.53 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 3.0 Hz), 7.60 (2H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 8.00 (2H, d, J = 8.7 Hz). 
               
               
                 616 
                 —CF 3   
                 —H 
                 —H 
                 —F 
                 —CH 3   
                 3.90 (3H, s), 4.40 (2H, brs), 6.89 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.1 Hz), 7.03 (1H, dd, J = 8.7 Hz, 3.0 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.15-7.21 (1H, m), 7.47 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.1 Hz), 7.55 (1H, d, J = 3.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.61 (2H, d, J = 8.1 Hz), 7.80-7.84 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                 m). 
               
               
                 617 
                 —Cl 
                 —Cl 
                 —H 
                 —F 
                 —CH 3   
                 3.91 (3H, s), 4.29 (2H, brs), 6.88 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.7 Hz), 7.02 (1H, dd, J = 8.7 Hz, 3.0 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.15-7.21 (2H, m), 7.41 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.3 Hz), 7.46 (1H, d, J = 2.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.53 (1H, d, J = 3.0 Hz), 7.81-7.84 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                 m). 
               
               
                   
               
             
          
         
       
     
       Reference Example 618 
     Production of ethyl 3-{4-[5-(3,4-dichlorobenzylamino)-pyridin-2-yloxy]phenyl}propionate 
       [0881]    A solution of 3,4′-dichlorobenzaldehyde (1.28 g, 7.3 mmol) was added to a solution of ethyl 3-[4-(5-aminopyridin-2-yloxy)phenyl]propionate (2.1 g, 7.3 mmol) in ethanol (20 mL), and the resulting solution was stirred for 2 hours at 40° C. To the resulting reaction solution was added sodium borohydride (0.55 g, 15.7 mmol) under ice cooling, and stirred at the same temperature for 1 hour. To the solution was added water and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=4:1), to thereby yield 2.71 g of the title compound. 
         [0882]    Appearance: Colorless oil 
         [0883]      1 H NMR (CDCl 3 ) δ 1.24 (3H, t, J=7.1 Hz), 2.50-2.68 (2H, m), 2.81-3.01 (2H, m), 3.71-4.20 (3H, m), 4.28 (2H, s), 6.76 (1H, d, J=8.7 Hz), 6.88-7.02 (3H, m), 7.06-7.23 (3H, m), 7.41 (1H, d, J=8.2 Hz), 7.46 (1H, d, J=2.0 Hz), 7.60 (1H, d, J=3.0 Hz). 
         [0884]    The following compounds were produced in the same manner as in Reference Example 618. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 90 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 298   
                 R 299   
                 R 300   
                 Xa 21   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
             
          
           
               
                 619 
                 —CF 3   
                 —H 
                 —H 
                 —CH 2 — 
                 1.24 (3H, t, J = 7.3 Hz), 2.60 (2H, t, J = 8.1 Hz) 
               
               
                   
                   
                   
                   
                   
                 2.92 (2H, t, J = 8.1 Hz), 4.13 (2H, q, J = 7.3 Hz), 
               
               
                   
                   
                   
                   
                   
                 4.39 (2H, s), 6.76 (1H, d, J = 8.7 Hz), 6.97 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.4 Hz), 6.98 (1H, dd, J = 8.6 Hz, 3.1 Hz), 7.17 (2H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.4 Hz), 7.47 (2H, d, J = 8.1 Hz), 7.60 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                 7.9 Hz), 7.61 (1H, d, J = 3.1 Hz). 
               
               
                 620 
                 —Cl 
                 —Cl 
                 —OCH 3   
                 —CH 2 — 
                 1.25 (3H, t, J = 7.1 Hz), 2.65-2.74 (2H, m), 2.94 (2H, 
               
               
                   
                   
                   
                   
                   
                 t, J = 8.2 Hz), 3.76 (3H, s), 3.93 (1H, brs), 4.14 (2H 
               
               
                   
                   
                   
                   
                   
                 q, J =7.1 Hz), 4.22-4.34 (2H, m), 6.70-6.85 (3H, m), 
               
               
                   
                   
                   
                   
                   
                 6.85-7.02 (2H, m), 7.10-7.25 (1H m), 7.39 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.2 Hz), 7.44 (1H, d, J = 2.0 Hz), 7.53 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 2.7 Hz). 
               
               
                 621 
                 —CF 3   
                 —H 
                 —OCH 3   
                 —CH 2 — 
                 1.25 (3H, t, J = 7.1 Hz), 2.52-2.68 (2H, m), 2.81- 
               
               
                   
                   
                   
                   
                   
                 3.01 (2H, m) 3.76 (3H s), 3.93 (1H, brs), 4.14 (2H, 
               
               
                   
                   
                   
                   
                   
                 q, J = 7.1 Hz), 4.30-4.40 (2H, m), 6.72-6.84 (3H, m), 
               
               
                   
                   
                   
                   
                   
                 6.96 (1H, d, J = 8.0 Hz), 6.98 (1H, dd, J = 8.0 Hz, 
               
               
                   
                   
                   
                   
                   
                 3.0 Hz), 7.40 (2H, d, J = 8.0 Hz), 7.55 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 3.0 Hz), 7.59 (2H, d, J = 8.0 Hz). 
               
               
                 622 
                 —Cl 
                 —Cl 
                 —OC 2 H 5   
                 —CH 2 — 
                 1.18 (3H, t, J = 7.0 Hz), 1.25 (3H, t, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 2.52-2.69 (2H, m), 2.82-3.00 (2H, m), 3.81-4.02 (3H, 
               
               
                   
                   
                   
                   
                   
                 m), 4.14 (2H, q, J = 7.1 Hz), 4.27 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                 4.7 Hz), 6.72-6.82 (3H, m), 6.93-7.02 (2H, m), 7.18 
               
               
                   
                   
                   
                   
                   
                 (1H, dd, J = 8.2 Hz, 2.0 Hz), 7.39 (1H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.45 (1H, d, J = 2.0 Hz), 7.52 (1H, d, J = 3.0 Hz). 
               
               
                 623 
                 —CF 3   
                 —H 
                 —OC 2 H 5   
                 —CH 2 — 
                 1.18 (3H, t, J = 7.0 Hz), 1.25 (3H, t, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 2.51-2.72 (2H, m), 2.83-3.01 (2H, m), 3.87-4.06 (3H, 
               
               
                   
                   
                   
                   
                   
                 m), 4.16 (2H, q, J = 7.1 Hz), 4.30-4.42 (2H, m), 6.72- 
               
               
                   
                   
                   
                   
                   
                 6.83 (3H, m), 6.94-7.02 (2H, m), 7.46 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.1 Hz), 7.54 (1H, d, J = 3.0 Hz), 7.59 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.1 Hz). 
               
               
                 624 
                 —Cl 
                 —Cl 
                 —F 
                 —CH 2 — 
                 1.12-1.35 (3H, m), 2.50-2.74 (2H, m), 2.93 (2H, t, J = 
               
               
                   
                   
                   
                   
                   
                 7.7 Hz), 3.95 (1H, brs), 4.05-4.20 (2H, m), 4.27 
               
               
                   
                   
                   
                   
                   
                 (2H, s), 6.82 (1H, d, J = 8.4 Hz), 6.90-7.15 (4H, m), 
               
               
                   
                   
                   
                   
                   
                 7.18 (1H, dd, J = 8.4 Hz, 2.0 Hz), 7.35-7.60 (3H, m). 
               
               
                 625 
                 —CF 3   
                 —H 
                 —F 
                 —CH 2 — 
                 1.13-1.35 (3H, m), 2.65-2.70 (2H, m), 2.93 (2H, t, J = 
               
               
                   
                   
                   
                   
                   
                 7.7 Hz), 4.01 (1H, brs), 4.05-4.23 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 4.37 (2H, s), 6.82 (1H, d, J = 8.8Hz), 6.90-7.15 (4H, 
               
               
                   
                   
                   
                   
                   
                 m), 7.37-7.55 (3H, m) 7.55-7.70 (2H, m). 
               
               
                 626 
                 —Cl 
                 —Cl 
                 —H 
                 —N(Ac)— 
                 1.27 (3H, t, J = 7.1 Hz), 1.94 (3H, s), 4.10 (1H, brs), 
               
               
                   
                   
                   
                   
                   
                 4.19 (2H, q, J = 7.1 Hz), 4.31 (2H, s), 4.34 (2H, s), 
               
               
                   
                   
                   
                   
                   
                 6.84 (1H, d, J = 8.5 Hz), 7.00 (1H, dd, J = 8.5 Hz, 
               
               
                   
                   
                   
                   
                   
                 3.0 Hz), 7.06 (2H, d, J = 8.7 Hz), 7.20 (1H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 8.2 Hz, 2.2 Hz), 7.31 (2H, d, J = 8.7 Hz), 7.42 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.2 Hz), 7.47 (1H, d, J = 2.2 Hz), 7.62 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 3.0 Hz). 
               
               
                 627 
                 —CF 3   
                 —H 
                 —H 
                 —N(Ac)— 
                 1.27 (3H, t, J = 7.1 Hz), 1.93 (3H, s) 4.15 (1H, brs), 
               
               
                   
                   
                   
                   
                   
                 4.18 (2H, q, J = 7.1 Hz), 4.34 (2H, s), 4.35-4.50 (2H, 
               
               
                   
                   
                   
                   
                   
                 m), 6.83 (1H, d, J = 8.6 Hz), 7.01 (1H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 8.6 Hz, 3.0 Hz), 7.06 (2H, d, J = 8.9 Hz), 7.31 (2H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.9 Hz), 7.48 (2H, d, J = 8.1 Hz), 7.62 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.1 Hz), 7.64 (1H, d, J = 3.6 Hz). 
               
               
                   
               
             
          
         
       
     
       Reference Example 628 
     Production of ethyl 3-(4-{5-[benzyloxycarbonyl(2-methoxyethyl)amino]pyridin-2-yloxy}phenyl)propionate 
       [0885]    Under a nitrogen atmosphere, to a solution of ethyl 3-[4-(5-benzyloxycarbonylaminopyridin-2-yloxy)phenyl]propionate (1.7 g, 4.0 mmol) in DMF (50 mL) was added 60% sodium hydride (0.19 g, 4.9 mmol) under ice cooling, and the resulting solution was stirred for 35 minutes at the same temperature. 2-Bromoethylmethyl ether (0.4 mL, 4.2 mmol) was added dropwise to the solution. The reaction solution was stirred for 2 hours under ice cooling, and then stirred for 2 days at room temperature. To the reaction solution was added water, and extracted with ethyl acetate. The ethyl acetate layer was washed with water, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=4:1), to thereby yield 1.6 g of the title compound. 
         [0886]    Appearance: Pale yellow oil 
         [0887]      1 H NMR (CDCl 3 ) δ 1.25 (3H, t, J=7.1 Hz), 2.57-2.70 (2H, m), 2.89-3.02 (2H, m), 3.52 (2H, t, J=5.4 Hz), 3.79 (2H, t, J=5.4 Hz), 4.14 (2H, q, J=7.1 Hz), 5.14 (2H, brs), 6.87 (1H, d, J=8.7 Hz), 6.89-7.10 (2H, m), 7.11-7.41 (7H, m), 7.47-7.69 (1H, m), 8.10 (1H, brs). 
         [0888]    The following compounds were produced in the same manner as in Reference Example 628. 
       Reference Example 629 
     Ethyl[(4-{5-[(3,4-dichlorophenyl)methylamino]pyridin-2-yloxy}-2-trifluoromethylphenyl)ethylamino]acetate 
       [0889]    MS 541 (M + ) 
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 91 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 301   
                 R 302   
                   1 H NMR (CDCl 3 ) δ ppm or MS 
               
               
                   
               
             
          
           
               
                 630 
                 4-CF 3 PhCH 2 — 
                 –(CH 2 ) 2 OCH 3   
                   1 H NMR 1.24 (3H, t, J = 7.1 Hz), 2.54- 
               
               
                   
                   
                   
                 2.67 (2H, m), 2.76-2.98 (2H, m), 4.13 (2H, q, J = 
               
               
                   
                   
                   
                 7.1 Hz), 4.61 (2H, s), 6.76 (1H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                 6.93-7.01 (2H, m), 7.07 (1H, dd, J = 8.9 Hz, 3.3 
               
               
                   
                   
                   
                 Hz), 7.12-7.20 (2H, m), 7.33 (2H, d, J = 8.0 
               
               
                   
                   
                   
                 Hz), 7.56 (2H, d, J = 8.0 Hz), 7.65 (1H, d, J = 
               
               
                   
                   
                   
                 2.9 Hz). 
               
               
                 631 
                 4-CF 3 PhCH 2 — 
                 —C 2 H 5   
                   1 H NMR 1.09-1.32 (6H, m), 2.53-2.66 (2H, m), 
               
               
                   
                   
                   
                 2.84-2.98 (2H, m), 3.45 (2H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                 4.13 (2H, q, J = 7.1 Hz), 4.49 (2H, s), 6.77 (1H, 
               
               
                   
                   
                   
                 d, J = 8.5 Hz), 6.93-7.01 (2H, m), 7.02- 
               
               
                   
                   
                   
                 7.09 (1H, m), 7.12-7.20 (2H, m), 7.11-7.39 (2H, 
               
               
                   
                   
                   
                 m), 7.53-7.61 (2H, m), 7.66 (1H, d, J = 3.0 Hz). 
               
               
                 632 
                 PhCH 2 OCO— 
                 —C 2 H 5   
                   1 H NMR 1.15 (3H, t, J = 7.1 Hz), 1.25 (3H, t, J = 
               
               
                   
                   
                   
                 7.1 Hz), 2.54-2.71 (2H, m), 2.83-3.04 (2H, m), 
               
               
                   
                   
                   
                 3.69 (2H, q, J = 7.1 Hz), 4.14 (2H, q, J = 7.1 
               
               
                   
                   
                   
                 Hz), 5.14 (2H, brs), 6.88 (1H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                 7.02-7.11 (2H, m), 7.18-7.40 (7H, m), 7.44- 
               
               
                   
                   
                   
                 7.59 (1H, m), 7.98-8.08 (1H, m). 
               
               
                 633 
                 4-CF 3 PhCH 2 — 
                 —SO 2 CH 3   
                 MS 522(M + ) 
               
               
                 634 
                 3,4-Cl 2 PhCH 2 — 
                 —SO 2 CH 3   
                 MS 522(M + ) 
               
               
                 635 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 MS 444(M + ) 
               
               
                   
               
             
          
         
       
     
       Reference Example 636 
     Production of ethyl 3-{4-[5-(2-methoxyethylamino)-pyridin-2-yloxy]phenyl}propionate 
       [0890]    To a solution of ethyl 3-(4-{5[benzyloxycarbonyl(2-methoxyethyl)amino]pyridin-2-yloxy}phenyl}propionate (1.82 g, 3.8 mmol) in ethanol-ethyl acetate (10 mL-10 mL) was added under a nitrogen atmosphere 10% palladium-carbon (0.2 g), and the resulting solution was stirred for 3 hours under a hydrogen atmosphere at atmospheric pressure. The palladium-carbon was filtered off through Celite, and the filtrate was evaporated to yield 1.23 g of the title compound. 
         [0891]    Appearance: Blue oil 
         [0892]      1 H NMR (CDCl 3 ) δ 1.24 (3H, t, J=7.1 Hz), 2.55-2.68 (2H, m), 2.87-2.98 (2H, m), 3.20-3.31 (2H, m), 3.56-3.66 (2H, m), 4.13 (2H, q, J=7.1 Hz), 6.77 (1H, d, J=8.7 Hz), 6.93-7.01 (2H, m), 7.03 (1H, dd, J=8.7 Hz, 3.0 Hz), 7.13-7.22 (2H, m), 7.66 (1H, d, J=3.0 Hz). 
         [0893]    The following compound was produced in the same manner as in Reference Example 636. 
       Reference Example 637 
     Ethyl 3-[4-(5-ethylaminopyridin-2-yloxy)phenyl]-propionate 
       [0894]      1 H NMR (CDCl 3 ) δ 1.29-1.32 (6H, m), 2.55-2.67 (2H, m), 2.87-2.99 (2H, m), 3.14 (2H, q, J=7.1 Hz), 4.13 (2H, q, J=7.1 Hz), 6.77 (1H, d, J=8.7 Hz), 6.89-7.02 (3H, m), 7.09-7.25 (3H, m), 7.63 (1H, d, J=3.0 Hz). 
       Reference Example 638 
     Production of ethyl 3-(3-methoxy-4-{5-[methyl-(4-trifluoromethylbenzyl)amino]pyridin-2-yloxy}phenyl)-propionate 
       [0895]    To a solution of ethyl 3-{3-methoxy-4-[5-(4-trifluoromethylbenzylamino]pyridin-2-yloxy}phenyl}-propionate (0.8 g, 1.7 mmol) in methanol (15 mL) were added a 37% aqueous formaldehyde solution (0.38 mL, 5.1 mmol) and acetic acid (0.1 mL, 1.7 mmol). The reaction solution was stirred for 30 minutes at room temperature. After that, sodium cyanoborohydride (0.24 g, 3.4 mmol) was added to the reaction solution under ice cooling, and the mixture was stirred under ice cooling for 40 minutes. To the reaction solution was added water, and extracted with ethyl acetate. The ethyl acetate layer was washed with water, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=4:1), to thereby yield 0.62 g of the title compound. 
         [0896]    Appearance: Pale yellow oil 
         [0897]      1 H NMR (CDCl 3 ) δ 1.25 (3H, t, J=7.1 Hz), 2.52-2.70 (2H, m), 2.87-3.02 (5H, m), 3.77 (3H, s), 4.14 (2H, q, J=7.1 Hz), 4.40-4.50 (2H, m), 6.74-6.86 ((3H, m), 6.97 (1H, d, J=8.0 Hz), 7.11 (1H, dd, J=8.9 Hz, 3.2 Hz), 7.34 (2H, d, J=8.1 Hz), 7.57 (2H, d, J=8.1 Hz), 7.65 (1H, d, J=3.2 Hz). 
         [0898]    The following compounds were produced in the same manner as in Reference Example 638. 
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 92 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 303   
                 R 304   
                 R 305   
                   1 H NMR (CD Cl 3 ) δ ppm 
               
               
                   
               
               
                 639 
                 —H 
                 —CH 3   
                 —CH 3   
                 3.07(3 H, s), 3.89(3 H, s), 4.56(2 H, s), 6.87(1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.9 Hz), 7.06(2 H, d, J = 8.6 Hz), 7.13(1 H, dd, J = 8.9 
               
               
                   
                   
                   
                   
                 Hz, 3.3 Hz), 7.35(2 H, d, J = 8.1 Hz), 7.60(2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.3 Hz), 7.75(1 H, d, J = 3.1 Hz), 8.02(2 H, d, J = 8.6 
               
               
                   
                   
                   
                   
                 Hz). 
               
               
                 640 
                 —H 
                 —C 2 H 5   
                 —C 2 H 5   
                 1.24(3 H, t, J = 7.1 Hz), 1.37(3 H, t, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 3.49(2 H, q, J = 7.1 Hz), 4.35(2 H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 4 53(2 H, s), 6.84(1 H, d, J = 8.9 Hz), 7.05(2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.6 Hz), 7.06(1 H, dd, J = 8.9 Hz, 3.1 Hz), 7.36(2 H, d, 
               
               
                   
                   
                   
                   
                 J = 8.4 Hz), 7.58(2 H, d, J = 8.3 Hz), 7.69(1 H, d, J = 
               
               
                   
                   
                   
                   
                 3.1 Hz), 8.02(2 H, d, J = 8.6 Hz). 
               
               
                 641 
                 —CH 3   
                 —CH 3   
                 —C 2 H 5   
                 1.38(3 H, t, J = 7.1 Hz), 1.59(3 H, d, J = 6.9 Hz), 
               
               
                   
                   
                   
                   
                 2.74(3 H, s), 4.36(2 H, q, J = 7.1 Hz), 4.49(1 H, q, J = 
               
               
                   
                   
                   
                   
                 6.9 Hz), 6.89(1 H, d, J = 8.9 Hz), 7.08 (2 H, d, J = 8.9 
               
               
                   
                   
                   
                   
                 Hz), 7.24(1 H, dd, J = 8.9 Hz, 3.1 Hz), 7.43(2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.6 Hz), 7.61(2 H, d, J = 8.3 Hz), 7.84(1 H, d, J = 3.1 
               
               
                   
                   
                   
                   
                 Hz), 8.03(2 H, d, J = 8.9 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 93 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 306   
                 R 307   
                 Xa 22   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 642 
                 —CH 3   
                 —H 
                 —CH 2 — 
                 1.24(3 H, t, J = 7.1 Hz), 2.60(2 H, t, J = 7.8 Hz), 
               
               
                   
                   
                   
                   
                 2.92(2 H, t, J = 7.8 Hz), 3.02(3 H, s), 4.12(2 H, q, J = 
               
               
                   
                   
                   
                   
                 7.1 Hz), 4.51(2 H, s), 6.79(1 H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                 6.97(2 H, d, J = 8.4 Hz), 7.10(1 H, dd, J = 8.9 Hz, 3.3 
               
               
                   
                   
                   
                   
                 Hz), 7.17(2 H, d, J = 8.3 Hz), 7.34(2 H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                 7.58(2 H, d, J = 8.3 Hz), 7.69(1 H, d, J = 3.1 Hz). 
               
               
                 643 
                 −CH 3   
                 —H 
                 —N(Ac)- 
                 1.27(3 H, t, J = 7.1 Hz), 1.94(3 H, s), 3.06(3 H, s), 
               
               
                   
                   
                   
                   
                 4.18(2 H, q, J = 7.1 Hz), 4.34(2 H, s), 4.55(2 H, s), 
               
               
                   
                   
                   
                   
                 6.87(1 H, d, J = 8.9 Hz), 7.07(2 H, d, J = 83 Hz), 
               
               
                   
                   
                   
                   
                 7.13(1 H, dd, J = 8.9 Hz, 3.1 Hz), 7.31(2 H, d, J = 8.7 
               
               
                   
                   
                   
                   
                 Hz), 7.35(2 H, d, J = 8.0 Hz), 7.59(2 H, d, J = 8.0 Hz), 
               
               
                   
                   
                   
                   
                 7.72(1 H, d, J = 3.1 Hz). 
               
               
                 644 
                 —CH 3   
                 —F 
                 —CH 2 — 
                 1.25(3 H, t, J = 7.1 Hz), 2.55-2.70(2 H, m), 2.93(2 H, t, 
               
               
                   
                   
                   
                   
                 J = 7.9 Hz), 3.00(3 H, s), 4.13(2 H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 4.49(2 H, s), 6.86(1 H, d, J = 8.9 Hz), 6.90-7.16(4 H, 
               
               
                   
                   
                   
                   
                 m), 7.33(2 H, d, J = 8.1 Hz), 7.57(2 H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                 7.62(1 H, d, J = 3.2 Hz). 
               
               
                 645 
                 —CH 3   
                 —OC 2 H 5   
                 —CH 2 — 
                 1.19(3 H, t, J = 7.0 Hz), 1.25(3 H, t, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 2.50-2.69(2 H, m), 2.81-2.99(2 H, m), 2.98(3 H, s), 3.98(2 H, 
               
               
                   
                   
                   
                   
                 q, J = 7.0 Hz), 4.14(2 H, q, J = 7.1 Hz), 4.48(2 H, s), 
               
               
                   
                   
                   
                   
                 6.68-6.88(3 H, m), 7.00(1 H, d, J = 8.0 Hz), 7.11(1 H, 
               
               
                   
                   
                   
                   
                 dd, J = 8.0 Hz, 3.0 Hz), 7.33(2 H, d, J = 8.0 Hz), 
               
               
                   
                   
                   
                   
                 7.56(2 H, d, J = 8.0 Hz), 7.64(1 H, d, J = 3.0 Hz). 
               
               
                 646 
                 —C 2 H 5   
                 —F 
                 —CH 2 — 
                 1.19(3 H, t, J = 7.1 Hz), 1.10-1.35(3 H, m), 
               
               
                   
                   
                   
                   
                 2.50-2.70(2 H, m), 2.93 (2 H, t, J = 8.0 Hz), 3.43(2 H, q, J = 
               
               
                   
                   
                   
                   
                 7.1 Hz), 4.02-4.22(2 H, m), 4.47 (2 H, s), 6.83(1 H, d, J = 
               
               
                   
                   
                   
                   
                 9.0 Hz), 6.88-7.15(4 H, m), 7.34(2 H, d, J = 8.0 Hz), 
               
               
                   
                   
                   
                   
                 7.41-7.70(3 H, m). 
               
               
                 647 
                 —C 2 H 5   
                 —OCH 3   
                 —CH 2 — 
                 1.18(3 H, t, J = 7.0 Hz), 1.25(3 H, t, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 2.57-2.68(2 H, m), 2.88-2.99(2 H, m), 3.42(2 H, q, J = 7.0 
               
               
                   
                   
                   
                   
                 Hz), 3.77(3 H, s), 4.14(2 H, q, 4 7.1 Hz), 
               
               
                   
                   
                   
                   
                 4.42-4.50(2 H, m), 6.72-6.86((3 H, m), 6.97(1 H, d, J = 8.0 
               
               
                   
                   
                   
                   
                 Hz), 7.05(1 H, 4d, J = 9.0 Hz, 3.2 Hz), 7.30-7.38(2 H, 
               
               
                   
                   
                   
                   
                 m), 7.51-7.59 (2 H, m), 7.60(1 H, d, J = 3.2 Hz). 
               
               
                 648 
                 —C 2 H 5   
                 —OC 2 H 5   
                 —CH 2 — 
                 1.17(3 H, t, J = 7.0 Hz), 1.18(3 H, t, J = 7.0 Hz), 
               
               
                   
                   
                   
                   
                 1.25(3 H, t, J = 7.1 Hz), 2.55-2.69(2 H, m), 
               
               
                   
                   
                   
                   
                 2.84-2.98(2 H, m), 3.42(2 H, q, J = 7.1 Hz), 3.97(2 H, q, J = 
               
               
                   
                   
                   
                   
                 7.0 Hz), 4.13(2 H, q, J = 7.0 Hz), 4.46(2 H, s), 
               
               
                   
                   
                   
                   
                 6.71-6.82(3 H, m), 6.99(1 H, d, J = 8.0 Hz), 7.05(1 H, dd, J = 
               
               
                   
                   
                   
                   
                 8.9 Hz, 3.1 Hz), 7.34(2 H, d, J = 8.0 Hz), 7.55(2 H, 
               
               
                   
                   
                   
                   
                 d, J = 8.0 Hz), 7.59(1 H, d, J = 3.1 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 94 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 308   
                 R 309   
                 Xa 23   
                   1 H NMR (CD Cl 3 ) δ ppm 
               
               
                   
               
               
                 649 
                 —CH 3   
                 —H 
                 —N(Ac)- 
                 1.27(3 H, t, J = 7.1 Hz), 1.94(3 H, s); 3.03(3 H, s), 
               
               
                   
                   
                   
                   
                 4.19(2 H, q, J = 7.1 Hz), 4.34(2 H, s), 4.43(2 H, s), 
               
               
                   
                   
                   
                   
                 6 87(1 H, d, J = 9.0 Hz), 7.03-7.11(1 H, m), 
               
               
                   
                   
                   
                   
                 7.07(2 H d, J = 8.7 Hz), 7.13(1 H, dd, J = 9.0 Hz, 
               
               
                   
                   
                   
                   
                 3.1 Hz), 7.27-7.35(1 H, m), 7.31(2 H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                 7.40(1 H, d, J = 8.2 Hz), 7.71(1 H, d, J = 3.1 Hz). 
               
               
                 650 
                 —CH 3   
                 —F 
                 —CH 2 — 
                 1.15-1.30(3 H, m), 2.53-2.70(2 H, m), 2.93(2 H, t, J = 
               
               
                   
                   
                   
                   
                 7.9 Hz), 2.97(3 H, s), 4.02-4.20(2 H, m), 4.37(2 H, 
               
               
                   
                   
                   
                   
                 s), 6.86(1 H, d, J = 8.9 Hz), 6.91-7.18(5 H, m), 
               
               
                   
                   
                   
                   
                 7.32(1 H, d, J = 2.0 Hz), 7.38(1 H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                 7.61(1 H, d, J = 2.9 Hz). 
               
               
                 651 
                 —CH 3   
                 —OCH 3   
                 —CH 2 — 
                 1.25(3 H, t, J = 7.1 Hz), 2.55-2.75(2 H, m), 
               
               
                   
                   
                   
                   
                 2.85-3.05(2 H, m), 2.95(3 H, s), 3.77(3 H, s), 4.14(2 H, q, 
               
               
                   
                   
                   
                   
                 J = 7.1 Hz), 4.36(2 H, s), 6.71-6.88(3 H, m), 
               
               
                   
                   
                   
                   
                 6.98(1 H, d, J = 8.1 Hz), 7.00-7.15(2 H, m), 
               
               
                   
                   
                   
                   
                 7.32(1 H, d, J = 2.0 Hz), 7.38(1 H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                 7.64(1 H, d, J = 3.1 Hz). 
               
               
                 652 
                 —CH 3   
                 —OC 2 H 5   
                 —CH 2 — 
                 1.19(3 H, t, J = 7.0 Hz), 1.25(3 H, t, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 2.55-2.72(2 H, m), 2.84-3.01(5 H, m), 3.98(2 H, q, J = 
               
               
                   
                   
                   
                   
                 7.0 Hz), 4.14(2 H, q, 4 7.1 Hz), 4.29-4.40(2 H, 
               
               
                   
                   
                   
                   
                 m), 6.74-6.83(3 H, m), 7.00(1 H, d, J = 8.0 Hz), 
               
               
                   
                   
                   
                   
                 7.06(1 H, dd, J = 8.2 Hz, 2.0 Hz), 7.10(1 H, dd, J = 
               
               
                   
                   
                   
                   
                 9.0 Hz, 3.2 Hz), 7.31(1 H, d, J = 2.0 Hz), 7.37(1 H, 
               
               
                   
                   
                   
                   
                 d, J = 8.2 Hz), 7.63(1 H, d, J = 3.2 Hz). 
               
               
                 653 
                 —C 2 H 5   
                 —F 
                 —CH 2 — 
                 1.17(3 H, t, J = 7.1 Hz), 1.20-1.30(3 H, m), 
               
               
                   
                   
                   
                   
                 2.50-2.72(2 H, m), 2.93(2 H, t, J = 7.8 Hz), 3.40(2 H, q, J = 
               
               
                   
                   
                   
                   
                 7.1 Hz), 4.00-4.22(2 H, m), 4.36(2 H, s), 6.83(1 H, 
               
               
                   
                   
                   
                   
                 d, J = 8.9 Hz), 6.85-7.15(5 H, m), 7.28-7.32(1 H, m), 
               
               
                   
                   
                   
                   
                 7.37(1 H, d, J = 8.2 Hz), 7.56(1 H, d, J = 3.2 Hz). 
               
               
                 654 
                 —C 2 H 5   
                 —OCH 3   
                 —CH 2 — 
                 1.16(3 H, t, J = 7.1 Hz), 1.21-1.35(3 H, m), 
               
               
                   
                   
                   
                   
                 2.50-2.75(2 H, m), 2.82-3.05(2 H, m), 3.39(2 H, q, J = 7.1 
               
               
                   
                   
                   
                   
                 Hz), 3.77(3 H, s), 4.05-4.25 (2 H, m), 4.35(2 H, s), 
               
               
                   
                   
                   
                   
                 6.68-6.88(3 H, m), 6.90-7.00(1 H, m), 7.00-7.11(2 H, 
               
               
                   
                   
                   
                   
                 m), 7.31(1 H, d, J = 2.0 Hz), 7.37(1 H, d, J = 8.2 
               
               
                   
                   
                   
                   
                 Hz), 7.59(1 H, d, J = 3.0 Hz). 
               
               
                 655 
                 —C 2 H 5   
                 —OC 2 H 5   
                 —CH 2 — 
                 1.11-1.22(6 H, m), 1.25(3 H, t, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 2.56-2.67(2 H, m), 2.86-2.97(2 H, m), 3.39(2 H, q, J = 7.1 
               
               
                   
                   
                   
                   
                 Hz), 3.97(2 H, q, J = 7.0 Hz), 4.14(2 H, q, J = 7.1 
               
               
                   
                   
                   
                   
                 Hz), 4.34(2 H, s), 6.736.82(3 H, m), 6.99 (1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.0 Hz), 7.02-7.10(2 H, m), 7.32(1 H, d, J = 1.9 
               
               
                   
                   
                   
                   
                 Hz), 7.36(1 H, d, J = 8.2 Hz), 7.58(1 H, d, J = 3.1 
               
               
                   
                   
                   
                   
                 Hz). 
               
               
                   
               
             
          
         
       
     
       Reference Example 656 
     Production of ethyl 3-(4-(5-(3,4-dichlorophenylamino)pyridin-2-yloxy)phenyl)propionate 
       [0899]    Triethylamine (1.2 mL, 8.4 mmol) was added to a suspension of ethyl 3-(4-(5-aminopyridin-2-yloxy)phenyl)propionate (1.2 g, 4.2 mmol), 3,4-dichlorophenylboronic acid (1.6 g, 8.4 mmol), anhydrous copper acetate (0.762 g, 4.2 mmol) and molecular sieves 4A (5 g) in dichloromethane (24 mL), and the resulting reaction solution was stirred overnight at room temperature. After the resulting solution was filtered through Celite, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (n-hexane:ethyl acetate=4:1), to thereby yield 1.5 g of the title compound. 
         [0900]    Appearance: Slightly brown solid 
         [0901]      1 H NMR (CDCl 3 ) δ 1.25 (3H, t, J=7.1 Hz), 2.60-2.66 (2H, m), 2.93-2.99 (2H, m), 4.14 (2H, q, J=7.1 Hz), 5.52 (1H, brs), 6.71 (1H, dd, J=8.7 Hz, 2.7 Hz), 6.90 (1H, d, J=8.7 Hz), 6.97 (1H, d, J=2.7 Hz), 7.04-7.08 (2H, m), 7.21-7.26 (3H, m), 7.49 (1H, dd, J=8.7 Hz, 2.9 Hz), 8.01 (1H, d, J=2.8 Hz). 
         [0902]    The following compound was produced in the same manner as in Reference Example 656. 
       Reference Example 657 
     Ethyl({4-[5-(3,4-dichlorophenylamino)pyridin-2-yloxy]-2-trifluoromethylphenyl}ethylamino)acetate 
       [0903]    MS 527 (M + ) 
       Reference Example 658 
     Production of ethyl 4-[3-(4-benzyloxy-3-methyl)phenyl-2-oxotetrahydropyrimidin-1-yl]benzoate 
       [0904]    Under a nitrogen atmosphere, to a solution of 1-(4-benzyloxy-3-methyl)phenyltetrahydropyrimidin-2-one (0.5 g, 1.7 mmol) in dioxane (5 mL) were added copper (I) iodide (16 mg, 0.08 mmol) and N,N-dimethylglycine hydrochloride (47 mg, 0.34 mmol). The resulting solution was stirred for 5 minutes, and then ethyl 4-iodobenzoate (0.39 g, 1.4 mmol) and potassium (III) phosphate (1.04 g, 4.9 mmol) were added to the reaction mixture. The resulting solution was stirred for 20 hours at 100° C., after which the resulting solution was sprinkled with silica gel. The residue was purified by silica gel chromatography (n-hexane:ethyl acetate=3:1→dichloromethane:methanol=40:1), to thereby yield 0.43 g of the title compound. 
         [0905]    Appearance: White powder 
         [0906]      1 H NMR (DMSO-d 6 ) δ 1.30 (3H, t, J=7.1 Hz), 2.08-2.22 (5H, m), 3.66 (2H, t, J=5.9 Hz), 3.81 (2H, t, J=5.9 Hz), 4.28 (2H, q, J=7.1 Hz), 5.10 (2H, s), 6.86-7.14 (3H, m), 7.26-7.51 (7H, m), 7.82-7.92 (2H, m). 
       Reference Example 659 
     Production of ethyl(E)-3-(3-methoxy-4-{5-[2-(4-trifluoromethylphenyl)vinyl]pyridin-2-yloxy}phenyl)propionate 
       [0907]    To ethyl 3-[4-(5-bromopyridin-2-yloxy)-3-methoxyphenyl]propionate (610 mg, 1.6 mmol) were added 4-trifluoromethylstyrene (0.332 mL, 2.2 mmol), dichlorobis(benzonitrile)palladium(II) (33 mg, 0.082 mmol), N,N-dimethylglycine hydrochloride (17 mg, 0.16 mmol), sodium acetate (263 mg, 3.2 mmol) and N-methylpyrrolidone (5 mL) under an argon atmosphere. The resulting solution was stirred under an argon atmosphere for 17 hours at 130° C. To the reaction solution was added ethyl acetate and filtered. The filtrate was washed with water, and then dried over anhydrous sodium sulfate. The solvent was evaporated, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=3:1), to thereby yield 500 mg of the title compound. 
         [0908]    Appearance: Pale yellow oil 
         [0909]      1 H NMR (CDCl 3 ) δ 1.27 (3H, t, J=7.1 Hz), 2.64-2.69 (2H, m), 2.95-3.01 (2H, m), 3.76 (3H, s), 4.05 (2H, q, J=7.1 Hz), 6.71-6.88 (2H, m), 6.95 (1H, d, J=8.6 Hz), 6.98-7.08 (2H, m), 7.11 (1H, d, J=16.5 Hz), 7.56-7.63 (4H, m), 7.87-7.91 (1H, m), 8.23 (1H, d, J=2.3 Hz). 
         [0910]    The following compound was produced in the same manner as in Reference Example 659. 
       Reference Example 660 
     Ethyl 3-(4-{5-[(E)-2-(3,4-dichlorophenyl)vinyl]pyridin-2-yloxy}-3-methoxyphenyl)propionate 
       [0911]      1 H NMR (CDCl 3 ) δ 1.26 (3H, t, J=7.1 Hz), 2.63-2.69 (2H, m), 2.94-3.00 (2H, m), 3.76 (3H, s), 4.15 (2H, q, J=7.1 Hz), 6.81-6.90 (3H, m), 6.93 (1H, d, J=8.6 Hz), 6.99 (1H, d, J=15.3 Hz), 7.06 (1H, d, J=9.1 Hz), 7.27-7.31 (1H, m), 7.40 (1H, d, J=8.2 Hz), 7.55 (1H, d, J=2.0 Hz), 7.82-7.86 (1H, m), 8.19 (1H, d, J=2.5 Hz). 
       Reference Example 661 
     Production of ethyl{4-[4-(3,4-dichlorobenzoylamino)-2-fluorophenoxy]benzenesulfonyl}acetate 
       [0912]    To a solution of ethyl{4-[4-(3,4-dichlorobenzoylamino)-2-fluorophenoxy]phenylsulfanyl}-acetate (1.20 g, 2.43 mmol) in dichloromethane (20 mL) was added m-chloroperbenzoic acid (1.45 g, 6.06 mmol) at 0° C. The resulting solution was stirred for 2 hours at room temperature. To the reaction solution was added methanol and stirred for some time. To the resulting solution was then added water, and extracted with dichloromethane. The dichloromethane layer was washed with a saturated sodium bicarbonate solution and brine, dried over anhydrous sodium sulfate, and evaporated. The obtained residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=1:1), to thereby yield 1.28 g of the title compound. 
         [0913]    Appearance: Yellow amorphous powder 
         [0914]      1 H NMR (CDCl 3 ) δ 1.22 (3H, t, J=7.1 Hz), 4.11 (2H, s), 4.16 (2H, q, J=7.1 Hz), 7.06 (2H, d, J=8.9 Hz), 7.19 (1H, t, J=8.7 Hz), 7.30 (1H, d, J=8.7 Hz), 7.59 (1H, d, J=8.3 Hz), 7.71 (1H, dd, J=2.0 Hz, 8.3 Hz), 7.75-7.85 (1H, m), 7.86-7.95 (3H, m), 7.98 (1H, d, J=2.0 Hz). 
       Reference Example 662 
     Production of methyl 3-{4-[5-(3,4-dichlorobenzoyl-amino)pyridine-2-sulfinyl]phenyl}propionate 
       [0915]    To a solution of methyl 3-{4-[5-(3,4-=dichlorobenzoylamino)pyridin-2-ylsulfanyl]phenyl}propionate (1.00 g, 2.17 mmol) in dichloromethane (20 mL) was added m-chloroperbenzoic acid (0.620 g, 2.60 mmol) at 0° C. The resulting solution was stirred for 1 hour at 0° C. To the reaction solution was added methanol and stirred for some time. To the resulting solution was then added water, and extracted with dichloromethane. The dichloromethane layer was washed with water, a saturated sodium bicarbonate solution and brine, dried over anhydrous sodium sulfate, and evaporated. The obtained residue was recrystallized from ethanol 3 times, to thereby yield 0.790 g of the title compound. 
         [0916]    Appearance: White powder 
         [0917]    Melting point: 164-166° C. 
       Reference Example 663 
     Production of methyl 3-{4-[5-(3,4-dichlorobenzoyl-amino)pyridine-2-sulfonyl]phenyl}propionate 
       [0918]    To a solution of methyl 3-{4-[5-(3,4-dichlorobenzoylamino)pyridin-2-ylsulfanyl]phenyl}-propionate (1.00 g, 2.17 mmol) in dichloromethane (20 mL) was added m-chloroperbenzoic acid (1.29 g, 5.42 mmol) at 0° C. The resulting solution was stirred for 1.5 hours at 0° C. To the reaction solution was added methanol and stirred for some time. To the resulting solution was then added water, and extracted with dichloromethane. The dichloromethane layer was washed with brine, dried over anhydrous sodium sulfate, and evaporated. The obtained residue was recrystallized from ethanol, to thereby yield 0.890 g of the title compound. 
         [0919]    Appearance: White powder 
         [0920]    Melting point: 165-166° C. 
       Reference Example 664 
     Production of ethyl{4-[4-(3,4-dichlorobenzoylamino)-2-fluorophenoxy]benzenesulphenyl}acetate 
       [0921]    To a solution of ethyl{4-[4-(3,4-dichloro-benzoylamino)-2-fluorophenoxy]phenylsulfanyl}acetate (0.800 g, 1.61 mmol) in methanol (20 mL) was added a 31% hydrogen peroxide solution (2.08 mL, 18.5 mmol). The resulting solution was refluxed for 16 hours. The reaction solution was cooled with ice, and the resulting precipitated solid was collected by filtration, to thereby yield 0.651 g of the title compound. 
         [0922]    Appearance: White powder 
         [0923]      1 H NMR (DMSO-d 6 ) δ 1.13 (3H, t, J=7.1 Hz), 3.90-4.10 (4H, m), 7.14 (2H, d, J=8.8 Hz), 7.34 (1H, t, J=9.0 Hz), 7.55-7.65 (1H, m), 7.72 (2H, d, J=8.8 Hz), 7.84 (1H, d, J=8.4 Hz), 7.90-8.00 (2H, m), 8.22 (1H, d, J=2.0 Hz), 10.63 (1H, s). 
       Reference Example 665 
     Production of ethyl 3-(4-{5-[4-(trifluoromethyl)phenyl-carbomoyl]pyridin-2-yloxy}phenyl)butyrate 
       [0924]    To a suspension of 60% sodium hydride (0.133 g, 3.3 mmol) in THF (6 mL) was added dropwise triethylphosphono acetate (0.53 mL, 2.7 mmol) under ice cooling, and the resulting solution was stirred for 1 hour at room temperature. To the reaction solution was added a solution of 6-(4-acetylphenoxy)-N-[4-(trifluoromethyl]phenyl]nicotinamide (0.53 g, 1.3 mmol) in THF (6 mL), and the resulting solution was stirred for 10 hours at 60° C. To the reaction solution was added saturated aqueous ammonium chloride, and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by silica gel chromatography (n-hexane:ethyl acetate=4:1), to thereby yield 0.57 g of the intermediate product ethyl 3-(4-{5-[4-(trifluoromethyl)phenyl-carbamoyl]pyridin-2-yloxy}phenyl)-2-butenoate. 
         [0925]    10% palladium-carbon (0.057 g) was suspended in a mixed solvent consisting of ethanol (8 mL) and dioxane (2 mL), and to this suspension was added ethyl 3-(4-{5-[4-(trifluoromethyl)phenylcarbamoyl]pyridin-2-yloxy}phenyl)-2-butenoate (0.57 g, 1.2 mmol). The resulting product was subjected to catalytic reduction at atmospheric pressure and room temperature. Once the absorption of hydrogen had stopped, the catalyst was removed by filtration, and the filtrate was concentrated under reduced pressure, to thereby yield 0.56 g of the title compound. 
         [0926]    Appearance: White solid 
         [0927]      1 H NMR (CDCl 3 ) δ 1.21 (3H, t, J=7.1 Hz), 1.33 (3H, d, J=7.0 Hz), 2.51-2.67 (2H, m), 3.28-3.37 (1H, m), 4.10 (2H, q, J=7.1 Hz), 7.00 (1H, d, J=8.6 Hz), 7.07-7.12 (2H, m), 7.26-7.31 (2H, m), 7.60-7.65 (2H, m), 7.73-7.77 (2H, m), 7.81 (1H, brs), 8.21 (1H, dd, J=8.6, 2.6 Hz), 8.68 (1H, d, J=2.3 Hz). 
         [0928]    The following compound was produced in the same manner as in Reference Example 665. 
       Reference Example 666 
     Ethyl 2-methyl-3-{4-[5-(4-trifluoromethylphenyl-carbamoyl)pyridin-2-yloxy]phenyl}propionate 
       [0929]    MS 472 (M + ) 
       Reference Example 667 
     Production of 3,4-dichloro-N-{6-[4-(N-hydroxy-carbamimidoylmethyl)phenoxy]pyridin-3-yl}benzamide 
       [0930]    To a solution of 3,4-dichloro-N-[6-(4-cyanomethylphenoxy)pyridin-3-yl]benzamide (700 mg, 1.76 mmol) in ethanol (30 mL) were added water (2 mL), hydroxylamine (420 mg, 12.71 mmol) and potassium carbonate (1.76 g, 12.73 mmol). Under argon, the resulting solution was stirred under reflux for 4 hours. The resulting reaction solution was concentrated under reduced pressure. To the residue was added water, and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by silica gel column chromatography (dichloromethane:methanol=10:1), to thereby yield 510 mg of the title compound. 
         [0931]    Appearance: White powder 
         [0932]      1 H NMR (DMSO-d 6 ) δ 3.27 (2H, s), 5.41 (2H, brs), 7.03 (2H, d, J=8.4 Hz), 7.05 (1H, d, J=8.8 Hz), 7.31 (2H, d, J=8.4 Hz), 7.84 (1H, d, J=8.4 Hz), 7.94 (1H, dd, J=8.4 Hz, 2.0 Hz), 8.18 (1H, dd, J=8.8 Hz, 2.6 Hz), 8.22 (1H, d, J=2.0 Hz), 8.46 (1H, d, J=2.6 Hz), 8.88 (1H, s), 10.53 (1H, s). 
       Reference Example 668 
     Production of 3,4-dichloro-N-{6-[4-(N-acetoxy-carbamimidoylmethyl)phenoxy]pyridin-3-yl}benzamide 
       [0933]    To a solution of 3,4-dichloro-N-{6-[4-(N-hydroxycarbamimidoylmethyl)phenoxy]pyridin-3-yl}benzamide (510 mg, 1.18 mmol) in dioxane (8 mL) was added potassium carbonate (163 mg, 1.18 mmol). While stirring under ice cooling, to the resulting solution was added dropwise acetyl chloride (0.084 mL, 1.18 mmol), and the resulting solution was stirred for 15 minutes at room temperature. To the reaction solution was added THF (10 mL), and then water, and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, evaporated. The residue was washed with ethyl acetate to yield 340 mg of the title compound. 
         [0934]    Appearance: White powder 
         [0935]      1 H NMR (DMSO-d 6 ) δ 2.05 (3H, s), 3.35 (2H, s), 6.43 (2H, brs), 7.06 (1H, d, J=9.0 Hz), 7.06 (2H, d, J=8.6 Hz), 7.36 (2H, d, J=8.6 Hz), 7.84 (1H, d, J=8.3 Hz), 7.94 (1H, dd, J=8.3 Hz, 2.0 Hz), 8.18 (1H, dd, J=9.0 Hz, 2.5 Hz), 8.22 (1H, d, J=2.0 Hz), 8.47 (1H, d, J=2.5 Hz), 10.54 (1H, s). 
       Reference Example 66.9 
     Production of 4-{4-[4-(3,4-dichlorobenzoylamino)-2-fluorophenoxy]phenyl}-4-oxobutyric acid 
       [0936]    To a suspension consisting of 3,4-dichloro-3′-fluoro-4′-phenoxybenzanilide (5.05 g, 13.4 mmol) and succinic anhydride (1.48 g, 14.8 mmol) in 1,2-dichloroethane (25 mL) was added aluminum chloride (6.26 g, 47.0 mmol) under ice cooling, and the resulting mixture was stirred at the same temperature for 5 minutes, and then at room temperature for 1.5 hours. The resulting reaction solution was poured into ice water, and the resulting solid was collected by filtration. To the solid was added 50% aqueous acetone (200 mL), and the resulting solution was refluxed for 0.5 hours, then cooled. The obtained solid was collected by filtration, to thereby yield 6.30 g of the title compound. 
         [0937]    Appearance: White powder 
         [0938]    Melting point: 205-208° C. 
       Reference Example 670 
     Production of ethyl 3-{4-[hydroxy(5-nitro-2-pyridyl)-methyl]phenyl}propionate 
       [0939]    To a solution of ethyl 3-[4-(5-nitropyridine-2-carbonyl)phenyl]propionate (1.52 g, 4.63 mmol) in dichloromethane (15 mL) and ethanol (15 mL) was added sodium borohydride (0.175 g, 4.63 mmol) under ice cooling, and the resulting solution was stirred at the same temperature for 1 hour. The reaction solution was concentrated under reduced pressure. The residue was dissolved in water and ethyl acetate. To the solution was added acetic acid and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=3:1), to thereby yield 0.264 g of the title compound. 
         [0940]    Appearance: Brown powder 
         [0941]      1 H NMR (CDCl 3 ) δ 1.19 (3H, t, J=7.2 Hz), 2.56 (2H, t, J=7.8 Hz), 2.91 (2H, t, J=7.8 Hz), 4.09 (2H, q, J=7.2 Hz), 4.35 (1H, brs), 5.84 (1H, s), 7.17 (2H, d, J=8.1 Hz), 7.26 (2H, d, J=8.1 Hz), 7.46 (1H, d, J=8.7 Hz), 8.40 (1H, dd, J=8.7 Hz, 2.5 Hz), 9.36 (1H, d, J=2.5 Hz). 
         [0942]    The following compound was produced in the same manner as in Reference Example 670. 
       Reference Example 671 
     t-Butyl 4-[2-hydroxy-3-(4-hydroxyphenyl)propionyl]-piperazine-1-carboxylate 
       [0943]      1 H NMR (CDCl 3 ) δ 1.47 (9H, s), 1.62 (1H, brs), 2.85 (2H, d, J=6.0 Hz), 3.00-3.80 (8H, m), 4.56 (1H, t, J=6.0 Hz), 5.35 (1H, brs), 6.74 (2H, d, J 8.4 Hz), 7.06 (2H, d, J=8.4 Hz). 
       Reference Example 672 
     Production of ethyl 3-(4-{5-[bis(3,4-dichlorobenzoyl)-amino]-2-pyridylmethyl}phenyl)propionate 
       [0944]    To a suspension of 10% palladium-carbon (27 mg) in ethanol (5 mL) were added a solution of ethyl 3-{4-[hydroxy(5-nitro-2-pyridyl)-methyl]phenyl}propionate (0.264 g, 0.799 mmol) and 0.5 M hydrogen chloride in ethanol (2 mL), and the resulting solution was subjected to catalytic reduction at atmospheric pressure at 50° C. Once the absorption of hydrogen had stopped, the catalyst was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was suspended in THF (5 mL), and triethylamine (0.267 mL, 2.40 mmol) was added. To the solution was added dropwise a solution of 3,4-dichlorobenzoyl chloride (0.255 g, 0.879 mmol) in THF (1 mL) under ice cooling, and stirred for 1 hour at the same temperature. To the resulting solution was added water and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=5:1), to thereby yield 0.177 g of the title compound. 
         [0945]    Appearance: Pale yellow oil 
         [0946]      1 H NMR (CDCl 3 ) δ 1.20 (3H, t, J=7.2 Hz), 2.56 (2H, t, J=7.8 Hz), 2.89 (2H, t, J=7.8 Hz), 4.09 (2H, q, J=7.2 Hz), 6.99 (1H, s), 7.17 (2H, d, J=8.2 Hz), 7.35 (2H, d, J=8.2 Hz), 7.42 (1H, d, J=8.6 Hz), 7.43-7.56 (2H, m), 7.63 (1H, dd, J=8.6 Hz, 2.1 Hz), 7.85-7.94 (2H, m), 8.15 (1H, d, J=2.0 Hz), 8.20-8.32 (2H, m), 8.57 (1H, d, J=2.5 Hz). 
       Reference Example 673 
     Production of ethyl 3-(4-(5-(N-(4-(trifluoromethyl)-phenyl)sulfamoyl)pyridin-2-yloxy)phenyl)propionate 
       [0947]    To a solution of ethyl 3-(4-(3-bromo-5-(N-(4-(trifluoromethyl)phenyl)sulfamoyl)pyridin-2-yloxy)phenyl)propionate (0.41 g, 0.7 mmol) in ethanol (10 mL) were added 10% palladium-carbon (0.041 g) and ammonium formate (0.226 g, 3.6 mmol), and the resulting solution was heated to reflux for 2 hours. The catalyst was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was then purified by silica gel chromatography (n-hexane:ethyl acetate=4:1), to thereby yield 0.28 g of the title compound. 
         [0948]    Appearance: White solid 
         [0949]      1 H NMR (CDCl 3 ) δ 1.24 (3H, t, J=7.1 Hz), 2.60-2.66 (2H, m), 2.93-2.99 (2H, m), 4.14 (2H, q, J=7.1 Hz), 6.95 (1H, d, J=8.8 Hz), 7.01-7.05 (2H, m), 7.20-7.26 (3H, m), 7.50-7.54 (3H, m), 8.03 (1H, dd, J=8.8 Hz, 2.6 Hz), 8.59 (1H, d, J=2.6 Hz). 
       Reference Example 674 
     Production of 1-(4-methoxyphenyl)imidazolin-2-one 
       [0950]    To a suspension of 1-(2-chloroethyl)-3-(4-methoxyphenyl)urea (7.0 g, 30.6 mmol) in t-butanol (120 mL) was added potassium t-butoxide (6.4 g, 57.0 mmol) under a nitrogen atmosphere. The resulting solution was stirred for 10 minutes, and then potassium t-butoxide (3.0 g, 26.7 mmol) was added. This solution was stirred for 10 minutes, and then potassium t-butoxide (4.3 g, 38.3 mmol) was added. The resulting solution was stirred for 16 hours at room temperature. The pH was adjusted to between 2 and 3 with 10% hydrochloric acid, and the solvent was evaporated under reduced pressure. To the residue were added water (100 mL) and ethyl acetate (100 mL), and stirred for 1 hour at room temperature. Resulting precipitates were filtered, washed with diethyl ether, and then dried under reduced pressure, to thereby yield 5.1 g of the title compound. 
         [0951]    Appearance: White powder 
         [0952]      1 H NMR (DMSO-d 6 ) δ 3.29-3.44 (2H, m), 3.70 (3H, s), 3.71-3.88 (2H, m), 6.77 (1H, s), 6.81-6.95 (2H, m), 7.35-7.50 (2H, m). 
         [0953]    The following compounds were produced in the same manner as in Reference Example 674. 
       Reference Example 675 
     1-(4-Benzyloxy-3-methylphenyl)tetrahydropyrimidin-2-one 
       [0954]      1 H NMR (DMSO-d 6 ) δ 1.81-1.96 (2H, m), 2.16 (3H, s), 3.11-3.25 (2H, m), 3.51 (2H, t, J=5.6 Hz), 5.09 (2H, s), 6.42 (1H, s), 6.91 (1H, d, J=8.7 Hz), 6.98 (1H, dd, J=2.6 Hz, 8.7 Hz), 7.04 (1H, d, J=2.6 Hz), 7.28-7.34 (1H, m), 7.36-7.41 (2H, m), 7.42-7.48 (2H, m). 
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 95 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 310   
                 M 
                 mp (°C.) or  1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
             
          
           
               
                 676 
                 —H 
                 1 
                 mp 162.0-163.0 
               
               
                 677 
                 —H 
                 2 
                 mp 179.0-180.0 
               
               
                 678 
                 —OCH 3   
                 1 
                   1 H NMR 2.29-2.45 (4H, m), 2.59-2.69 (2H, m), 2.91-3.04 (2H, m), 
               
               
                   
                   
                   
                 3.34-3.47 (4H, m), 3.53-1.69 (4H, m), 3.75 (3H, s), 3.85-3.96 (2H, 
               
               
                   
                   
                   
                 m), 4.58 (1H, s), 5.95 (2H, s), 6.69-6.78 (2H, m), 6.79-6.89 (3H, 
               
               
                   
                   
                   
                 m), 6.91 (1H, d, J = 9.0 Hz), 7.02 (1H, d, J = 8.0 Hz), 7.99 (1H, d, 
               
               
                   
                   
                   
                 J = 2.9 Hz), 8.25 (1H, dd, J = 2.9 Hz, 9.0 Hz). 
               
               
                 679 
                 —OCH 3   
                 2 
                 mp 140.0-141.5 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
               
               
               
             
           
               
                 TABLE 96 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
               
               
                 Example 
               
               
                 No. 
                 M 
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
             
          
           
               
                 680 
                 1 
                 1.98-2.14 (2H, m), 2.18 (3H, s), 3.30 (2H, d, J = 6.0 Hz), 3.51-3.66 (2H, m), 3.67- 
               
               
                   
                   
                 3.78 (2H, m), 3.80-4.05 (8H, m), 4.57 (2H, s), 4.79 (1H, s), 6.78-6.94 (4H, m), 
               
               
                   
                   
                 6.99 (1H, d, J = 8.6 Hz), 7.13 (1H, dd, J = 2.6 Hz, 8.6 Hz), 7.22 (1H, d, J = 2.6 Hz), 
               
               
                   
                   
                 8.05 (1H, d, J = 2.9 Hz), 8.22 (1H, dd, J = 2.9 Hz, 9.0 Hz). 
               
               
                 681 
                 2 
                 1.91-2.15 (4H, m), 2.18 (3H, s), 3.18-3.36 (2H, m), 3.37-3.51 (2H, m), 3.58-3.78 (2H, 
               
               
                   
                   
                 m), 3.88 (3H, s), 3.88 (3H, s), 4.56 (2H, s), 4.89 (1H, s), 6.76-6.94 (4H, m), 7.00 (1H, 
               
               
                   
                   
                 d, J = 8.7 Hz), 7.13 (1H, dd, J = 2.6 Hz, 8.7 Hz), 7.23 (1H, d, J = 2.6 Hz), 
               
               
                   
                   
                 7.67 (1H, dd, J = 2.8 Hz, 8.8 Hz), 8.08 (1H, d, J = 2.8 Hz). 
               
               
                   
               
             
          
         
       
     
       Reference Example 682 
     Production of 3-{4-[4-(3,4-dichlorobenzoylamino)-phenoxy]phenyl}propionic acid 
       [0955]    To a solution of ethyl 3-{4-[4-(3,4-dichlorobenzoylamino)phenoxy]phenyl}propionate (6.00 g, 13.1 mmol) in THF (60 mL) and ethanol (30 mL) were added 5 M aqueous sodium hydroxide (3.14 mL, 15.7 mmol) and water (30 mL) and the resulting solution was refluxed for 1 hour. The reaction solution was cooled with ice. To the reaction solution were added 5 M hydrochloric acid (4.0 mL, 20.0 mmol) and water (100 mL). The obtained solid was collected by filtration, and recrystallized from water-containing acetone, to thereby yield 5.60 g of the title compound. 
         [0956]    Appearance: White powder 
         [0957]    Melting point: 188-190° C. 
         [0958]    The following compounds were produced in the same manner as in Reference Example 682. 
         [0000]    
       
         
               
             
               
               
               
             
               
               
               
             
           
               
                 TABLE 97 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 311   
                   1 H NMR (solvent) δ ppm or MS 
               
               
                   
               
             
          
           
               
                 683 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (CDCl 3 ) 1.51 (3H, d, J = 7.1 Hz), 2.12 (3H, s), 2.91 (3H, s), 4.49 (1H, q, J = 7.1 Hz), 6.71- 6.75 (2H, m), 6.95-7.00 (2H, m), 8.45 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.04 (1H, dd, J = 2.8 Hz, 0.5 Hz). 
               
               
                   
               
               
                 684 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 300 (M + ) 
               
               
                   
               
               
                 685 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (DMSO-d 6 ) 7.39 (1H, td, J = 2.0 Hz, 8.9 Hz), 7.50 (1H, d, J = 9.0 Hz), 7.78 (1H, td, J = 2.1 Hz, 8.9 Hz), 8.70 (1H, dd, J = 2.8 Hz, 9.0 Hz), 9.04 (1H, d, J = 2.8 Hz), 11.35-11.91 (1H, m). 
               
               
                   
               
               
                 686 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (CDCl 3 ) 2.72-2.77 (2H, m), 2.98-3.03 (2H, m), 3.74 (3H, s), 6.85-6.89 (2H, m), 7.03 (1H, d, J = 9.1 Hz), 7.06-7.09 (1H, m), 8.45 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.01. (1H, d, J = 2.8 Hz). 
               
               
                   
               
               
                 687 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (DMSO-d 6 ) 2.52 (2H, t, J = 7.6 Hz), 2.80 (2H, t, J = 7.6 Hz), 6.86 (1H, d, J = 9.4 Hz), 7.21 (2H, d, J = 8.5 Hz), 7.58 (2H, d, J = 8.5 Hz), 8.26 (1H, dd, J = 2.9 Hz, 9.4 Hz), 9.01 (1H, d, J = 2.9 Hz), 10.06 (1H, s). 
               
               
                   
               
               
                 688 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (DMSO-d 6 ) 2.96 (3H, s), 4.09 (2H, s), 6.44- 6.49 (2H, m), 6.56 (1H, dd, J = 8.3 Hz, 2.4 Hz), 7.15 (1H, d, J = 9.1 Hz), 7.20-7.26 (1H, m), 8.59 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.05 (1H, d, J = 2.8 Hz). 
               
               
                   
               
               
                 689 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (CDCl 3 ) 1.53 (3H, d, J = 7.1 Hz), 2.93 (3H, s), 4.51 (1H, q, J = 7.1 Hz); 6.87 (2H, d, J = 9.2 Hz), 6.98 (1H, d, J = 9.1 Hz), 7.05 (2H, d, J = 9.1 Hz), 8.44 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.05 (1H, d, J = 2.6 Hz). 
               
               
                   
               
               
                 690 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (CDCl 3 ) 2.63-2.69 (2H, m), 2.97 (3H, s), 3.68 (2H, t, J = 7.1 Hz), 6.81 (2H, d, J = 9.1 Hz), 6.98 (1H, d, J = 9.1 Hz), 7.05 (2H, d, J = 9.2 Hz), 8.44 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.06 (1H, d, J = 2.8 Hz). 
               
               
                   
               
               
                 691 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (DMSO-d 6 ) 3.55 (3H, s), 6.67 (1H, d, J = 9.5 Hz), 7.52 (2H, d, J = 8.5 Hz), 8.04 (2H, d, J = 8.5 Hz), 8.21 (1H, dd, J = 2.8 Hz, 9.5 Hz), 9.05 (1H, d, J = 2.8 Hz), 13.10 (1H, brs). 
               
               
                   
               
               
                 692 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (DMSO-d 6 ) 1.28-1.32 (2H, m), 1.75- 1.79 (3H, m), 2.01 (3H, s), 2.19 (2H, d, J = 6.8 Hz), 2.65 (2H, t, J = 12.0 Hz), 3.65 (2H, d, J = 12.4 Hz), 6.80-6.96 (3H, m), 7.15 (1H, d, J = 9.2 Hz), 8.58 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.01 (1H, d, J = 2.8 Hz), 10.71 (1H, brs). 
               
               
                   
               
               
                 693 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 306 (M + ) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 98 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
                   
               
               
                 Example 
                   
               
               
                 No. 
                 R 312   
                 R 313   
                 R 314   
                 R 315   
                 R 316   
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 694 
                 —F 
                 —H 
                 —H 
                 —H 
                 —CH 3   
                 (CDCl 3 ) 3.09 (3H, s), 4.12 (2H, s), 6.45- 
               
               
                   
                   
                   
                   
                   
                   
                 6.57 (2H, m), 7.05-7.12 (2H, m), 8.47 (1H, dd, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 9.1 Hz, 2.8 Hz), 9.02 (1H, dd, J = 2.8 Hz, 
               
               
                   
                   
                   
                   
                   
                   
                 0.7 Hz). 
               
               
                 695 
                 —F 
                 —H 
                 —H 
                 —H 
                 —C 2 H 5   
                 (CDCl 3 ) 1.25 (3H, t, J = 7.1 Hz), 3.47 (2H, q, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 7.1 Hz), 4.06 (2H, s), 6.42-6.53 (2H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.04-7.10 (2H, m), 8.47 (1H, dd, J = 9.1 Hz, 
               
               
                   
                   
                   
                   
                   
                   
                 2.8 Hz), 9.02 (1H, dd, J = 2.8 Hz, 0.5 Hz). 
               
               
                 696 
                 —F 
                 —H 
                 —H 
                 —H 
                 allyl 
                 (CDCl 3 ) 4.03 (2H, d, J = 5.0 Hz), 4.09 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                 s), 5.25-5.32 (2H, m), 5.82-5.96 (1H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 6.44-6.56 (2H, m), 7.04-7.10 (2H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 8.47 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.02 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 2.6 Hz). 
               
               
                 697 
                 —F 
                 —H 
                 —H 
                 —F 
                 —CH 3   
                 (DMSO-d 6 ) 2.94 (3H, s), 4.04 (3H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 6.92 (1H, dd, J = 8.5 Hz, 12.9 Hz), 7.30 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 dd, J = 7.5 Hz, 13.7 Hz), 7.35 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 9.1 Hz), 8.63 (1H, dd, d = 2.8 Hz, 9.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 9.04 (1H, d, J = 2.8 Hz), 12.41-12.82 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 m). 
               
               
                 698 
                 —F 
                 —H 
                 —H 
                 —F 
                 —C 2 H 5   
                 (DMSO-d 6 ) 1.10 (3H, t, J = 7.0 Hz), 3.12- 
               
               
                   
                   
                   
                   
                   
                   
                 3.48 (2H, m), 4.01 (2H, s), 6.90 (1H, dd, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.4 Hz, 13.1 Hz), 7.29 (1H, dd, J = 7.6 Hz, 
               
               
                   
                   
                   
                   
                   
                   
                 13.7 Hz), 7.35 (1H, d, J = 9.0 Hz), 8.63 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 dd, J = 2.8 Hz, 9.0 Hz), 9.04 (1H, d, J = 2.8 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 12.41-12.70 (1H, m). 
               
               
                 699 
                 —F 
                 —H 
                 —F 
                 —H 
                 —CH 3   
                 (DMSO-d 6 ) 2.96 (3H, s), 4.26 (2H, s), 6.41- 
               
               
                   
                   
                   
                   
                   
                   
                 6.61 (2H, m), 7.43 (1H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 8.65 (1H, dd, J = 2.8 Hz, 9.1 Hz), 9.05 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 2.8 Hz), 12.56-12.90 (1H, m). 
               
               
                 700 
                 —CH 3   
                 —CH 3   
                 —H 
                 —H 
                 —CH 3   
                 (CDCl 3 ) 2.07 (3H, s), 2.32 (3H, s), 2.85 (3H, 
               
               
                   
                   
                   
                   
                   
                   
                 s), 3.76 (2H, s), 6.91 (1H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.00 (1H, dd, J = 9.1 Hz, 0.6 Hz), 7.09 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 8.7 Hz), 8.46 (1H, dd, J = 9.1 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 9.04 (1H, dd, J = 2.8 Hz, 0.6 Hz). 
               
               
                 701 
                 —CH 3   
                 —H 
                 —H 
                 —CH 3   
                 —C 2 H 5   
                 (DMSO-d 6 ) 0.98 (3H, t, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 1.98 (3H, s), 2.20 (3H, s), 3.09 
               
               
                   
                   
                   
                   
                   
                   
                 (2H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 3.70 (2H, s), 6.91 (1H, s), 7.06 (1H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 7.18 (1H, d, J = 9.1 Hz), 8.59 (1H, dd, J = 9.1 Hz, 
               
               
                   
                   
                   
                   
                   
                   
                 2.9 Hz), 9.03 (1H, d, J = 2.9 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 12.30 (1H, brs). 
               
               
                 702 
                 —H 
                 —H 
                 —H 
                 —H 
                 —SO 2 CH 3   
                 (DMSO-d 6 ) 3.17 (3H, s), 4.43 (2H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 7.29 (2H, d, J = 8.7 Hz), 7.31 (1H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.55 (2H, d, J = 8.9 Hz), 8.64 (1H, dd, J = 
               
               
                   
                   
                   
                   
                   
                   
                 9.1 Hz, 2.8 Hz), 9.05 (1H, d, J = 2.8 Hz). 
               
               
                 703 
                 —CH 3   
                 —H 
                 —H 
                 —H 
                 —SO 2 CH 3   
                 (DMSO-d 6 ) 2.09 (3H, s), 3.11 (3H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 4.42 (2H, s), 7.20 (1H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.31 (1H, d, J = 9.1 Hz), 7.37 (1H, dd, J = 8.6 Hz, 
               
               
                   
                   
                   
                   
                   
                   
                 2.5 Hz), 7.44 (1H, d, J = 2.3 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 8.64 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.03 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 2.8 Hz), 12.88 (1H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 99 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
                   
                   
               
               
                 Example 
                   
               
               
                 No. 
                 R 317   
                 R 318   
                 R 319   
                 R 320   
                 R 321   
                 R 322   
                   1 H NMR (solvent) δ ppm or MS 
               
               
                   
               
               
                 704 
                 —NO 2   
                 —H 
                 —CH 3   
                 —H 
                 —CH 3   
                 —CH 3   
                 MS 331 (M + ) 
               
               
                 705 
                 —NO 2   
                 —H 
                 —CF 3   
                 —H 
                 —H 
                 —CH 3   
                 MS 371 (M + ) 
               
               
                 706 
                 —NO 2   
                 —H 
                 —CF 3   
                 —H 
                 —H 
                 —C 2 H 5   
                 MS 385 (M + ) 
               
               
                 707 
                 —NO 2   
                 —CH 3   
                 —H 
                 —CF 3   
                 —H 
                 —CH 3   
                 MS 385 (M + ) 
               
               
                 708 
                 —NO 2   
                 —H 
                 —F 
                 —F 
                 —H 
                 —CH 3   
                   1 H NMR (DMSO-d 6 ) 
               
               
                   
                   
                   
                   
                   
                   
                   
                 2.98 (3H, s), 4.05 (2H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.64-6.88 (1H, m), 6.96-7.20 
               
               
                   
                   
                   
                   
                   
                   
                   
                 (1H, m), 7.38 (1H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.64 (1H, dd, J = 2.7 Hz, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 9.1 Hz), 9.04 (1H, d, J = 2.7 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 12.24-12.95 (1H, m). 
               
               
                 709 
                 —NO 2   
                 —H 
                 —OCH 3   
                 —H 
                 —H 
                 —SO 2 CH 3   
                   1 H NMR (DMSO-d 6 ) 
               
               
                   
                   
                   
                   
                   
                   
                   
                 3.16 (3H, s), 3.70 (3H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 4.45 (2H, s), 7.10-7.30 (4H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 m), 8.61 (1H, dd, J = 9.1 Hz, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 2.8 Hz), 9.02 (1H, d, J = 2.8 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 12.97 (1H, brs). 
               
               
                 710 
                 —Br 
                 —H 
                 —F 
                 —H 
                 —F 
                 —CH 3   
                   1 H NMR (DMSO-d 6 ) 
               
               
                   
                   
                   
                   
                   
                   
                   
                 2.92 (3H, s), 4.01 (2H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.80-6.93 (1H, m), 7.11 (1H, d, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 J = 8.8 Hz), 7.14-7.26 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 m), 8.06 (1H, dd, J = 2.6 Hz, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.8 Hz), 8.25 (1H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 12.18-12.89 (1H, m). 
               
               
                 711 
                 4-CF 3 PhCH 2 — 
                 —H 
                 —H 
                 —H 
                 —H 
                 —CH 3   
                   1 H NMR (CDCl 3 ) 3.04 (3H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 3.93 (2H, s), 4.04 (2H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.69 (2H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.70 (1H, d, J = 8.5 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.97 (2H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.25 (2H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.39 (1H, dd, J = 8.5 Hz, 2.5 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.52 (2H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.09 (1H, d, J = 2.5 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 11.26 (1H, brs). 
               
               
                 712 
                 4-CF 3 PhOCH 2 — 
                 —H 
                 —H 
                 —H 
                 —H 
                 —SO 2 CH 3   
                   1 H NMR (DMSO-d 6 ) 
               
               
                   
                   
                   
                   
                   
                   
                   
                 3.11 (3H, s), 4.40 (2H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 5.18 (2H, s), 7.12 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.9 Hz), 7.15-7.23 (4H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.49 (2H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.67 (2H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.98 (1H, dd, J = 8.4 Hz, 2.5 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.28 (1H, d, J = 2.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 12.41 (1H, brs). 
               
               
                 713 
                 4-CF 3 PhOCH 2 — 
                 —H 
                 —CH 3   
                 —H 
                 —H 
                 —SO 2 CH 3   
                   1 H NMR (DMSO-d 6 ) 
               
               
                   
                   
                   
                   
                   
                   
                   
                 2.06 (3H, s), 3.18 (3H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 3.89 (2H, s), 5.15 (2H, s), 7.02 
               
               
                   
                   
                   
                   
                   
                   
                   
                 (1H, d, J = 8.4 Hz), 7.07 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 d, J = 8.6 Hz), 7.21 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.4 Hz), 7.44 (1H, dd, J = 8.6 Hz, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 2.6 Hz), 7.49 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 2.3 Hz), 7.67 (2H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.95 (1H, dd, J = 8.4 Hz, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 2.5 Hz), 8.24 (1H, d, J = 2.5 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 100 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
               
               
                 Example 
                   
               
               
                 No. 
                 R 323   
                 R 324   
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 714 
                 —H 
                 —H 
                 (DMSO-d 6 ) 3.35 (1H, brs), 3.84 (2H, s), 6.63 (2H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                 6.96 (2H, d, J = 8.9 Hz), 7.14 (1H, d, J = 9.1 Hz), 8.59 (1H, dd, J = 
               
               
                   
                   
                   
                 2.9 Hz, 9.1 Hz), 9.05 (1H, d, J = 2.9 Hz). 
               
               
                 715 
                 —H 
                 —CH 3   
                 (CDCl 3 ) 3.09 (3H, s), 4.11 (2H, s), 6.74 (2H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                 6.97 (1H, dd, J = 9.1 Hz, 0.5 Hz), 7.04 (2H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                 8.43 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.04 (1H, dd, J = 2.8 Hz, 0.5 Hz). 
               
               
                 716 
                 —H 
                 —C 2 H 5   
                 (CDCl 3 ) 1.24 (3H, t, J = 7.1 Hz), 3.48 (2H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                 4.07 (2H, s), 6.73 (2H, d, J = 9.2 Hz), 6.98 (1H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                 7.04 (2H, d, J = 9.2 Hz), 8.44 (1H, dd, J = 9.1 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                 9.05 (1H, d, J = 2.8 Hz). 
               
               
                 717 
                 —OCH 3   
                 —H 
                 (DMSO-d 6 ) 3.62 (3H, s), 3.83 (2H, s), 6.13 (1H, dd, J = 8.6 Hz, 
               
               
                   
                   
                   
                 2.5 Hz), 6.41 (1H, d, J = 2.5 Hz), 6.90 (1H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                 7.09 (1H, d, J = 8.6 Hz), 8.54 (1H, dd, J = 9.1 Hz, 3.0 Hz), 
               
               
                   
                   
                   
                 9.00 (1H, d, J =3.0 Hz). 
               
               
                 718 
                 —OCH 3   
                 —CH 3   
                 (DMSO-d 6 ) 3.00 (3H, s), 3.65 (3H, s), 4.12 (2H, s), 6.21 (1H, dd, 
               
               
                   
                   
                   
                 J = 8.8 Hz, 2.8 Hz), 6.39 (1H, d, J = 2.8 Hz), 6.96 (1H, d, J = 
               
               
                   
                   
                   
                 8.8 Hz), 7.11 (1H, d, J = 9.1 Hz), 8.54 (1H, dd, J = 9.1 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                 9.00 (1H, d, J = 2.8 Hz), 12.57 (1H, s). 
               
               
                 719 
                 —OCH 3   
                 —C 2 H 5   
                 (DMSO-d 6 ) 1.13 (3H, t, J = 7.0 Hz), 3.42 (2H, q, J = 7.0 Hz), 
               
               
                   
                   
                   
                 3.64 (3H, s), 4.05 (2H, s), 6.14 (1H, dd, J = 8.8 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                 6.31 (1H, d, J = 2.8 Hz), 6.95 (1H, d, J = 8.8 Hz), 7.12 (1H, d, J = 
               
               
                   
                   
                   
                 9.1 Hz), 8.53 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.00 (1H, d, J = 2.8 Hz), 
               
               
                   
                   
                   
                 12.59 (1H, brs). 
               
               
                 720 
                 —CH 3   
                 —Ac 
                 (DMSO-d 6 ) 1.86 (3H, s), 2.08 (3H, s), 4.26 (2H, s), 7.05-7.50 (4H, 
               
               
                   
                   
                   
                 m), 8.63 (1H, dd, J = 9.1 Hz, 2.9 Hz), 9.02 (1H, dd, J = 2.9 Hz, 
               
               
                   
                   
                   
                 0.4 Hz), 12.72 (1H, brs). 
               
               
                 721 
                 —CH 3   
                 —H 
                 (CDCl 3 ) 2.09 (3H, s), 3.98 (2H, s), 5.26 (1H, brs), 6.50-6.55 (2H, 
               
               
                   
                   
                   
                 m), 6.92 (1H, d, J = 8.4 Hz), 6.98 (1H, d, J = 8.1 Hz), 8.45 (1H, 
               
               
                   
                   
                   
                 dd, J = 8.1 Hz, 2.8 Hz), 9.04 (1H, d, J = 2.8 Hz). 
               
               
                 722 
                 —CH 3   
                 —CH 3   
                 (DMSO-d 6 ) 1.99 (3H, s), 2.97 (3H, s), 4.09 (2H, s), 6.52 (1H, dd, 
               
               
                   
                   
                   
                 J = 8.8 Hz, 3.0 Hz), 6.59 (1H, d, J = 3.0 Hz), 6.92 (1H, d, J = 
               
               
                   
                   
                   
                 8.8 Hz), 7.13 (1H, dd, J = 9.1 Hz, 0.3 Hz), 8.57 (1H, dd, J = 9.1 Hz, 
               
               
                   
                   
                   
                 2.9 Hz), 9.01 (1H, d, J = 2.9 Hz), 12.54 (1H, brs). 
               
               
                 723 
                 —CH 3   
                 —C 2 H 5   
                 (DMSO-d 6 ) 1.11 (3H, t, J = 7.0 Hz), 1.98 (3H, s), 3.89 (2H, q, J = 
               
               
                   
                   
                   
                 7.0 Hz), 4.02 (2H, s), 6.44 (1H, dd, J = 8.8 Hz, 2.9 Hz), 6.51 (1H, 
               
               
                   
                   
                   
                 d, J = 2.9 Hz), 6.90 (1H, d, J = 8.8 Hz), 7.13 (1H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                 8.56 (1H, dd, J = 9.1 Hz, 2.9 Hz), 9.0 1 (1H, d, J = 2.9 Hz), 
               
               
                   
                   
                   
                 12.53 (1H, brs). 
               
               
                   
               
               
                 724 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (DMSO-d 6 ) 0.54-0.59 (2H, m), 0.80-0.87 (2H, m), 2.02 (3H, s), 2.64-2.71 (1H, m), 4.11 (2H, s), 6.77-6.81 (1H, m), 6.85 (1H, d, J = 2.8 Hz), 6.96 (1H, d, J = 8.7 Hz), 7.17 (1H, dd, J = 9.2 Hz, 0.5 Hz), 8.59 (1H, dd, J = 9.1 Hz, 3.0 Hz), 9.04 (1H, dd, J = 3.0 Hz, 0.5 Hz), 12.56 (1H, brs). 
               
               
                   
               
               
                 725 
                 —F 
                 —H 
                 (DMSO-d 6 ) 3.82 (2H, s), 6.43 (1H, dd, J = 8.7 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                 6.53 (1H, dd, J = 13.4 Hz, 2.6 Hz), 7.07 (1H, t, J = 8.9 Hz), 
               
               
                   
                   
                   
                 7.28 (1H, dd, J = 9.1 Hz, 0.5 Hz), 8.61 (1H, dd, J = 9.1 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                 9.03 (1H, dd, J = 2.8 Hz, 0.5 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 101 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
               
               
                 Example 
                   
                   
                 mp (° C.) or  1 H NMR (solvent) 
               
               
                 No. 
                 R 325   
                 R 326   
                 δ ppm 
               
               
                   
               
               
                 726 
                 4-NO 2 Ph- 
                 4-N(CH 3 )CH 2 COOH 
                   1 H NMR (CDCl 3 ) 3.10 (3H, s), 
               
               
                   
                   
                   
                 4.13 (2H, s), 6.74 (2H, d, J = 9.2 Hz), 
               
               
                   
                   
                   
                 6.95 (2H, d, J = 9.2 Hz), 
               
               
                   
                   
                   
                 7.00 (2H, d, J = 9.2 Hz), 8.17 (2H, 
               
               
                   
                   
                   
                 d, J = 9.2 Hz). 
               
               
                   
               
               
                 727 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(CH 2 ) 2 COOH 
                 mp 157-159 
               
               
                   
               
               
                 728 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 3-(CH 2 ) 2 COOH 
                 mp 192-194 
               
               
                   
               
               
                 729 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 4-(CH 2 ) 2 COOH 
                   1 H NMR (CDCl 3 ) 2.67 (2H, t, J = 7.7 Hz), 2.94 (2H, t, J = 7.7 Hz), 6.78 (1H, dd, J = 8.2 Hz, 1.2 Hz), 6.97 (2H, d, J = 8.6 Hz), 7.02- 7.19 (2H, m), 7.20 (2H, d, J = 8.6 Hz), 7.48 (1H, d, J = 8.3 Hz), 7.56 (1H, dd, J = 8.3 Hz, 2.1 Hz), 7.84 (1H, d, J = 2.1 Hz), 8.38 (1H, brs), 8.49 (1H, dd, J = 8.3 Hz, 2.1 Hz), 10.46 (1H, brs). 
               
               
                   
               
               
                 730 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 4-(CH 2 ) 2 COOH 
                   1 H NMR (CDCl 3 ) 2.67 (2H, t, J = 7.6 Hz), 2.93 (2H, t, J = 7.6 Hz), 6.78 (1H, dt, J = 8.1 Hz, 1.2 Hz), 6.95 (2H, d, J = 8.5 Hz), 7.16 (2H, d, J = 8.5 Hz), 7.22-7.34 (3H, m), 7.53 (1H, d, J = 8.3 Hz), 7.64 (1H, dd, J = 8.3 Hz, 2.1 Hz), 7.73 (1H, brs), 7.90 (1H, d, J = 2.1 Hz), 10.23 (1H, brs). 
               
               
                   
               
               
                 731 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 4-(CH 2 ) 2 COOH 
                   1 H NMR (DMSO-d 6 ) 1.05 (3H, t, J = 7.1 Hz), 2.56 (2H, t, J = 7.6 Hz), 2.84 (2H, t, J = 7.6 Hz), 3.64 (2H q, J = 7.1 Hz), 7.05-7.10 (3H, m), 7.28 (2H, d, J = 8.6 Hz), 7.45 (2H, brs), 7.76-7.80 (2H, m), 8.08 (1H, dd J = 2.8 Hz, 0.5 Hz), 8.27 (1H, brs), 12.10 (1H, brs). 
               
               
                   
               
               
                 732 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 4-(CH 2 ) 2 COOH 
                   1 H NMR (DMSO-d 6 ) 1.06 (3H, t, J = 7.1 Hz), 2.53-2.59 (2H, m), 2.81-2.87 (2H, m), 3.67 (2H, q, J = 7.1 Hz), 7.05-7.10 (3H, m), 7.29 (2H, d, J = 8.7 Hz), 7.56 (2H, d, J = 8.7 Hz), 7.66 (2H, d, J = 8.7 Hz), 7.78 (1H, dd, J = 8.6 Hz, 2.8 Hz), 8.09 (1H, d, J = 2.8 Hz), 8.41 (1H, brs), 12.14 (1H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
               
             
           
               
                 TABLE 102 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
               
               
                 Example 
                   
               
               
                 No. 
                 R 327   
                 Xa 24   
                 M 
                 Form 
                 mp (° C.) or  1 H NMR (DMSO-d 6 ) δ ppm 
               
               
                   
               
               
                 733 
                 —H 
                 none 
                 0 
                 free 
                 mp 252-255 
               
               
                 734 
                 —F 
                 none 
                 0 
                 free 
                 mp 257-259 
               
               
                 735 
                 —F 
                 none 
                 1 
                 free 
                 mp 204-206 
               
               
                 736 
                 —F 
                 none 
                 2 
                 free 
                 mp 173-174 
               
               
                 737 
                 —F 
                 none 
                 3 
                 free 
                 mp 175-177 
               
               
                 738 
                 —F 
                 —S— 
                 1 
                 Na 
                   1 H NMR 3.86 (2H, s), 6.86 (2H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                 salt 
                 7.15 (1H, t, J = 9.0 Hz), 7.25 (2H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.55 (1H, d, J = 9.0 Hz), 7.80 (1H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.91 (1H, dd, J = 2.4 Hz, 13.3 Hz), 7.98 (1H, dd, 
               
               
                   
                   
                   
                   
                   
                 J = 2.0 Hz, 8.4 Hz), 8.25 (1H, d, J = 2.0 Hz). 
               
               
                 739 
                 —F 
                 —SO— 
                 1 
                 free 
                   1 H NMR 3.79 (1H, d, J = 14.3 Hz), 3.97 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 14.3 Hz), 7.12 (2H, d, J = 8.8 Hz), 7.33 (1H, t, 
               
               
                   
                   
                   
                   
                   
                 J = 9.1 Hz), 7.55-7.65 (1H, m), 7.71 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.8 Hz), 7.84 (1H, d, J = 8.4 Hz), 7.90-7.95 (2H, 
               
               
                   
                   
                   
                   
                   
                 m), 8.20 (1H, d, J = 2.0 Hz), 10.63 (1H, s), 
               
               
                   
                   
                   
                   
                   
                 13.20 (1H, brs). 
               
               
                 740 
                 —F 
                 —SO 2 — 
                 1 
                 free 
                 mp 214-216 
               
               
                 741 
                 —F 
                 —N(Ac)— 
                 1 
                 free 
                   1 H NMR 1.80 (3H, s), 4.22 (2H, s), 7.00 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.9 Hz), 7.25-7.30 (1H, m), 7.38 (2H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.50-7.60 (1H, m), 7.84 (1H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.90-7.96 (2H, m), 8.21 (1H, d, J = 2.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 10.61 (1H, s), 12.68 (1H, s). 
               
               
                 742 
                 —F 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 0 
                 free 
                 mp 241-243 
               
               
                   
               
             
          
           
               
                 (—SO— means a group of 
               
               
                                           
and —SO 2 — means a group of 
               
               
                                           
. 
               
               
                 Hereinafter —SO— and —SO 2 — indicate the same meanings.) 
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 103 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
               
               
                 Example 
                   
               
               
                 No. 
                 R 328   
                 R 329   
                 Xa 25   
                 M 
                 mp (° C.) or  1 H NMR (DMSO-d 6 ) δ ppm 
               
               
                   
               
               
                 743 
                 —Cl 
                 —Cl 
                 —CO— 
                 2 
                   1 H NMR 2.60 (2H, t, J = 7.6 Hz), 2.91 (2H, t, 
               
               
                   
                   
                   
                   
                   
                 J = 7.6 Hz), 7.39 (2H, d, J = 8.2 Hz), 7.82- 
               
               
                   
                   
                   
                   
                   
                 8.20 (4H, m), 8.07 (1H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.25 (1H, dd, J = 7.5 Hz, 2.1 Hz), 8.45 (1H, 
               
               
                   
                   
                   
                   
                   
                 dd, J = 8.6 Hz, 2.5 Hz), 9.03 (1H, d, J = 2.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 10.91 (1H, s), 12.16 (1H, brs). 
               
               
                 744 
                 —Cl 
                 —Cl 
                 —S— 
                 2 
                 mp 201-202 
               
               
                 745 
                 —Cl 
                 —Cl 
                 —SO— 
                 2 
                 mp 202-205 
               
               
                 746 
                 —Cl 
                 —Cl 
                 —SO 2 — 
                 2 
                 mp 172-173 
               
               
                 747 
                 —Cl 
                 —Cl 
                 —NH— 
                 2 
                   1 H NMR 2.76 (2H, t, J = 7.6 Hz), 3.20-3.40 
               
               
                   
                   
                   
                   
                   
                 (2H, m), 6.86 (1H, d, J = 8.8 Hz), 7.12 (2H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.3 Hz), 7.52 (2H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.83 (1H, d, J =8.4 Hz), 7.90-7.96 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 8.21 (1H, d, J =1.3 Hz), 8.45 (1H, d, J = 2.4 Hz), 
               
               
                   
                   
                   
                   
                   
                 9.03 (1H, brs), 10.37 (1H, s), 12.11 (1H, 
               
               
                   
                   
                   
                   
                   
                 brs). 
               
               
                 748 
                 —Cl 
                 —Cl 
                 —N(CH 3 )— 
                 2 
                 mp 158-160 
               
               
                 749 
                 —CF 3   
                 —H 
                 —N(CH 3 )— 
                 0 
                 mp 240-243 
               
               
                 750 
                 —CF 3   
                 —H 
                 —N(CH 3 )— 
                 2 
                   1 H NMR 2.57 (2H, t, J = 7.5 Hz), 2.84 (2H, t, 
               
               
                   
                   
                   
                   
                   
                 J = 7.5 Hz), 3.38 (3H, s), 6.61 (1H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.22 (2H, d, J = 8.3 Hz), 7.29 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.3 Hz), 7.80-7.85 (1H, m), 7.91 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.3 Hz), 8.15 (2H, d, J = 8.3 Hz), 8.51 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 2.5 Hz), 10.42 (1H, s), 12.10 (1H, brs). 
               
               
                 751 
                 —Cl 
                 —Cl 
                 —N(CH 2 Ph)- 
                 2 
                   1 H NMR 2.53 (2H, t, J = 7.9 Hz), 2.80 (2H, t, 
               
               
                   
                   
                   
                   
                   
                 J = 7.9 Hz), 5.21 (2H, s), 6.63 (1H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.15-7.30 (9 H, m), 7.75-7.95 (3H, m), 
               
               
                   
                   
                   
                   
                   
                 8.19 (1H, d, J = 2.1 Hz), 8.45 (1H, d, J = 2.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 10.34 (1H, s), 12.10 (1H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 104 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
               
               
                 Example 
                   
               
               
                 No. 
                 R 330   
                 R 331   
                 R 332   
                 M 
                 mp (° C.) or  1 H NMR (DMSO-d 6 ) δ ppm 
               
               
                   
               
               
                 752 
                 —H 
                 —CN 
                 —H 
                 0 
                   1 H NMR 7.18-7.21 (3H, m), 7.98 (2H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.05 (2H, d, J = 8.9 Hz), 8.13 (2H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.28 (1H, dd, J = 8.6 Hz, 2.6 Hz), 8.57 (1H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 10.70 (1H, s), 12.87 (1H, brs). 
               
               
                 753 
                 —Cl 
                 —Cl 
                 —H 
                 0 
                   1 H NMR 7.17-7.22 (3H, m), 7.85 (1H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.94-8.01 (3H, m), 8.23-8.29 (2H, m), 8.55 (1H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 10.01 (1H, s), 12.87 (1H, brs). 
               
               
                 754 
                 —H 
                 —Cl 
                 —H 
                 0 
                   1 H NMR 7.16-7.21 (3H, m), 7.63 (2H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.97-8.02 (4H, m), 8.28 (1H, dd, J = 8.6 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.57 (1H, d, J = 2.6 Hz), 10.53 (1H, s), 12.86 (1H, brs). 
               
               
                 755 
                 —H 
                 —CF 3   
                 —H 
                 0 
                   1 H NMR 7.18-7.22 (3H, m), 7.93-8.00 (4H, m), 8.18 (2H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.4 Hz), 8.30 (1H, dd, J = 8.9 Hz, 2.7 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.58 (1H, d, J = 2.7 Hz), 10.69 (1H, s), 12.91 (1H, brs). 
               
               
                 756 
                 —CH 3   
                 —CH 3   
                 —H 
                 0 
                   1 H NMR 2.30 (3H, s), 2.31 (3H, s), 7.16 (1H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.18 (2H, d, J = 8.7 Hz), 7.31 (1H, d, J = 7.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.72 (1H, d, J = 7.6 Hz), 7.77 (1H, s), 7.98 (2H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.28 (1H, dd, J = 8.9 Hz, 2.7 Hz), 8.58 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 2.7 Hz), 10.35 (1H, s), 12.88 (1H, brs). 
               
               
                 757 
                 —CF 3   
                 —H 
                 —F 
                 0 
                 mp 238-239 
               
               
                 758 
                 —OCF 3   
                 —H 
                 —H 
                 0 
                   1 H NMR 7.18-7.22 (3H, m), 7.61-7.81 (2H, m), 7.89- 
               
               
                   
                   
                   
                   
                   
                 8.06 (4H, m), 8.28 (1H, dd, J = 8.7 Hz, 2.6 Hz), 8.57 (1H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 2.3 Hz), 10.62 (1H, s), 12.95 (1H, brs). 
               
               
                 759 
                 —CF 3   
                 —H 
                 —H 
                 0 
                   1 H NMR 7.11-7.22 (3H, m), 7.70-7.85 (1H, m), 7.90- 
               
               
                   
                   
                   
                   
                   
                 8.05 (3H, m), 8.2-8.35 (3H, m), 8.56 (1H, d, J = 2.4 Hz), 
               
               
                   
                   
                   
                   
                   
                 10.70 (1H, s), 12.90 (1H, brs). 
               
               
                 760 
                 —H 
                 —CF 3   
                 —H 
                 1 
                   1 H NMR 3.59 (2H, s), 7.04-7.10 (3H, m), 7.27-7.33 (2H, 
               
               
                   
                   
                   
                   
                   
                 m), 7.94 (2H, d, J = 8.4 Hz), 8.17 (2H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.21-8.25 (1H, m), 8.51 (1H, d, J = 2.6 Hz), 10.64 (1H, s), 
               
               
                   
                   
                   
                   
                   
                 12.43 (1H, brs). 
               
               
                 761 
                 —Cl 
                 —Cl 
                 —H 
                 1 
                   1 H NMR 3.59 (2H, s), 7.04-7.09 (3H, m), 7.27-7.32 (2H, 
               
               
                   
                   
                   
                   
                   
                 m), 7.83 (1H, d, J = 8.4 Hz), 7.95 (1H, dd, J = 8.4 Hz, 2.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.18-8.23 (2H, m), 8.48 (1H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 10.55 (1H, s), 12.37 (1H, brs). 
               
               
                 762 
                 —Cl 
                 —Cl 
                 —H 
                 2 
                   1 H NMR 2.51-2.58 (2H, m), 2.81-2.86 (2H, m), 7.01- 
               
               
                   
                   
                   
                   
                   
                 7.06 (3H, m), 7.26 (2H, d, J = 8.6 Hz), 7.84 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.4 Hz), 7.93-7.97 (1H, m), 8.16-8.23 (2H, m), 8.47 (1H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 2.7 Hz), 10.54 (1H, s), 12.13 (1H, brs). 
               
               
                 763 
                 —H 
                 —CF 3   
                 —H 
                 2 
                   1 H NMR 2.56 (2H, t, J = 7.5 Hz), 2.84 (2H, t, J = 7.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.03 (2H, d, J = 8.6 Hz), 7.05 (1H, d, J = 8.8 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.27 (2H, d, J = 8.6 Hz), 7.93 (2H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.17 (2H, d, J = 8.2 Hz), 8.21 (1H, dd, J = 8.8 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.50 (1H, d, J = 2.6 Hz), 10.63 (1H, s), 12.16 (1H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 105 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
                   
               
               
                 No. 
                 R 333   
                 R 334   
                 M 
                   1 H NMR (DMSO-d 6 ) δ ppm 
               
               
                   
               
               
                 764 
                 —OCH 3   
                 —H 
                 0 
                 3.76 (3H, s), 7.09 (1H, d, J = 8.9 Hz), 7.23 (1H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                 7.59-7.63 (2H, m), 7.84 (1H, d, J = 8.4 Hz), 7.93- 
               
               
                   
                   
                   
                   
                 7.96 (1H, m), 8.16-8.22 (2H, m), 8.39 (1H, d, J = 2.7 Hz), 
               
               
                   
                   
                   
                   
                 10.53 (1H, s), 13.00 (1H, brs). 
               
               
                 765 
                 —H 
                 —OCH 3   
                 0 
                 3.80 (3H, s), 6.69 (1H, dd, J = 8.4 Hz, 2.2 Hz), 6.90 (1H, d, J = 
               
               
                   
                   
                   
                   
                 2.2 Hz), 7.17 (1H, d, J = 8.9 Hz), 7.73 (1H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                 7.85 (1H, d, J = 8.4 Hz), 7.97 (1H, dd, J = 8.4 Hz, 2.2 Hz), 
               
               
                   
                   
                   
                   
                 8.23-8.28 (2H, m), 8.56 (1H, d, J = 2.4 Hz), 10.62 (1H, s), 
               
               
                   
                   
                   
                   
                 12.56 (1H, brs). 
               
               
                 766 
                 —CH 3   
                 —H 
                 0 
                 2.18 (3H, s), 7.09-7.16 (2H, m), 7.79-7.97 (4H, m), 8.21- 
               
               
                   
                   
                   
                   
                 8.26 (2H, m), 8.47 (1H, d, J = 2.2 Hz), 10.57 (1H, s), 
               
               
                   
                   
                   
                   
                 12.86 (1H, brs). 
               
               
                 767 
                 —H 
                 —CH 3   
                 0 
                 2.53 (3H, s), 6.97-7.04 (2H, m), 7.16 (1H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                 7.77-7.98 (3H, m), 8.23-8.27 (2H, m), 8.54 (1H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                 10.62 (1H, s), 12.79 (1H, brs). 
               
               
                 768 
                 —F 
                 —H 
                 0 
                 7.24 (1H, d, J = 8.9 Hz), 7.39-7.45 (1H, m), 7.70-8.05 (4H, 
               
               
                   
                   
                   
                   
                 m), 8.23-8.28 (2H, m), 8.46 (1H, d, J = 2.6 Hz), 10.64 (1H, 
               
               
                   
                   
                   
                   
                 s), 13.55 (1H, brs). 
               
               
                 769 
                 —Cl 
                 —H 
                 0 
                 7.25 (1H, d, J = 8.9 Hz), 7.39 (1H, d, J = 8.6 Hz), 7.84 (1H, 
               
               
                   
                   
                   
                   
                 d, J = 8.4 Hz), 7.93-7.97 (2H, m), 8.06 (1H, d, J = 2.0 Hz), 
               
               
                   
                   
                   
                   
                 8.22 (1H, d, J = 2.0 Hz), 8.25-8.29 (1H, m), 8.47 (1H, d, J = 
               
               
                   
                   
                   
                   
                 2.6 Hz), 10.61 (1H, s), 13.31 (1H, brs). 
               
               
                 770 
                 —OCH 3   
                 —H 
                 2 
                 2.50-2.65 (2H, m), 2.71-2.92 (2H, m), 3.67 (3H, s), 6.81 (1H, 
               
               
                   
                   
                   
                   
                 dd, J = 8.1 Hz, 1.9 Hz), 6.95 (1H, d, J = 8.9 Hz), 6.99- 
               
               
                   
                   
                   
                   
                 7.05 (2H, m), 7.82 (1H, d, J = 8.4 Hz), 7.93 (1H, dd, J = 8.4 Hz, 
               
               
                   
                   
                   
                   
                 2.0 Hz), 8.10 (1H, dd, J = 8.9 Hz, 2.7 Hz), 8.20 (1H, d, J = 
               
               
                   
                   
                   
                   
                 2.0 Hz), 8.35 (1H, m), 10.47 (1H, s), 12.15 (1H, brs). 
               
               
                 771 
                 —OC 2 H 5   
                 —H 
                 2 
                 1.06 (3H, t, J = 7.0 Hz), 2.51-2.62 (2H, m), 2.74-2.88 (2H, 
               
               
                   
                   
                   
                   
                 m), 3.94 (2H, q, J = 7.0 Hz), 6.80 (1H, dd, J = 8.1 Hz, 1.8 Hz), 
               
               
                   
                   
                   
                   
                 6.92-7.04 (3H, m), 7.82 (1H, d, J = 8.4 Hz), 7.93 (1H, 
               
               
                   
                   
                   
                   
                 dd, J = 8.4 Hz, 2.0 Hz), 8.11 (1H, dd, J = 8.9 Hz, 2.7 Hz), 
               
               
                   
                   
                   
                   
                 8.20 (1H, d, J = 2.0 Hz), 8.36 (1H, d, J = 2.7 Hz), 10.47 (1H, 
               
               
                   
                   
                   
                   
                 s), 12.14 (1H, brs). 
               
               
                 772 
                 —F 
                 —H 
                 2 
                 2.50-2.67 (2H, m), 2.75-2.93 (2H, m), 7.03-7.29 (4H, m), 
               
               
                   
                   
                   
                   
                 7.82 (1H, d, J = 8.4 Hz), 7.93 (1H, dd, J = 8.4 Hz, 2.0 Hz), 
               
               
                   
                   
                   
                   
                 8.12-8.24 (2H, m), 8.39 (1H, d, J = 2.5 Hz), 10.53 (1H, s), 
               
               
                   
                   
                   
                   
                 12.18 (1H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 106 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
                   
               
               
                 No. 
                 R 335   
                 R 336    
                 M 
                   1 H NMR (DMSO-d 6 ) δ ppm 
               
               
                   
               
               
                 773 
                 —OCH 3   
                 —H 
                 0 
                 3.76 (3H, s), 7.10 (1H, d, J = 8.9 Hz), 7.23 (1H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                 7.59-7.64 (2H, m), 7.93 (2H, d, J = 8.1 Hz), 8.15- 
               
               
                   
                   
                   
                   
                 8.23 (3H, m), 8.42 (1H, d, J = 2.2 Hz), 10.60 (1H, s), 
               
               
                   
                   
                   
                   
                 13.00 (1H, brs). 
               
               
                 774 
                 —H 
                 —OCH 3   
                 0 
                 3.80 (3H, s), 6.69 (1H, dd, J = 8.6 Hz, 2.2 Hz), 6.90 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 2.2 Hz), 7.17 (1H, d, J = 8.6 Hz), 7.73 (1H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                 7.95 (2H, d, J = 8.4 Hz), 8.18 (2H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                 8.29 (1H, dd, J = 8.6 Hz, 2.7 Hz), 8.58 (1H, d, J = 2.7 Hz), 
               
               
                   
                   
                   
                   
                 10.69 (1H, s), 12.51 (1H, brs). 
               
               
                 775 
                 —CH 3   
                 —H 
                 0 
                 1.99 (3H, s), 7.09-7.17 (2H, m), 7.79-7.83 (1H, m), 7.91- 
               
               
                   
                   
                   
                   
                 7.95 (3H, m), 8.12-8.18 (2H, m), 8.27 (1H, dd, J = 8.9 Hz, 
               
               
                   
                   
                   
                   
                 2.7 Hz), 8.49 (1H, d, J = 2.7 Hz), 10.64 (1H, s), 12.87 (1H, 
               
               
                   
                   
                   
                   
                 brs). 
               
               
                 776 
                 —H 
                 —CH 3   
                 0 
                 2.54 (3H, s), 6.98-7.05 (2H, m), 7.17 (1H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                 7.87-7.97 (3H, m), 8.13-8.19 (2H, m), 8.26-8.30 (1H, m), 
               
               
                   
                   
                   
                   
                 8.57 (1H, d, J = 2.8 Hz), 10.70 (1H, s), 12.81 (1H, brs). 
               
               
                 777 
                 —F 
                 —H 
                 0 
                 7.26 (1H, d, J = 8.9 Hz), 7.40-7.46 (1H, m), 7.82-7.85 (2H, 
               
               
                   
                   
                   
                   
                 m), 7.94 (2H, d, J = 8.2 Hz), 8.17 (2H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                 8.30 (1H, dd, J = 8.9 Hz, 2.1 Hz), 8.49 (1H, d, J = 2.1 Hz), 
               
               
                   
                   
                   
                   
                 10.70 (1H, s), 13.39 (1H, brs). 
               
               
                 778 
                 —Cl 
                 —H 
                 0 
                 7.14 (1H, d, J = 8.9 Hz), 7.19 (1H, d, J = 8.2 Hz), 7.82- 
               
               
                   
                   
                   
                   
                 7.86 (1H, m), 7.92 (2H, d, J = 8.4 Hz), 7.96 (1H, d, J = 1.8 Hz), 
               
               
                   
                   
                   
                   
                 8.20 (2H, d, J = 8.2 Hz), 8.29 (1H, dd, J = 8.9 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                   
                 8.47 (1H, d, J = 2.6 Hz), 10.86 (1H, s). 
               
               
                 779 
                 —OCH 3   
                 —H 
                 2 
                 2.57-2.63 (2H, m), 2.83-2.89 (2H, m), 3.69 (3H, s), 6.84 (1H, 
               
               
                   
                   
                   
                   
                 dd, J = 8.1 Hz, 1.8 Hz), 6.97 (1H, d, J = 8.9 Hz), 7.01- 
               
               
                   
                   
                   
                   
                 7.04 (2H, m), 7.92 (2H, d, J = 8.4 Hz), 8.14-8.18 (3H, m), 
               
               
                   
                   
                   
                   
                 8.40 (1H, d, J = 2.5 Hz), 10.58 (1H, s). 
               
               
                 780 
                 —OC 2 H 5   
                 —H 
                 2 
                 1.06 (3H, t, J = 7.0 Hz), 2.47-2.67 (2H, m), 2.72-2.91 (2H, 
               
               
                   
                   
                   
                   
                 m), 3.94 (2H, q, J = 7.0 Hz), 6.80 (1H, dd, J = 8.0 Hz, 1.8 Hz), 
               
               
                   
                   
                   
                   
                 6.94-7.05 (3H, m), 7.91 (2H, d, J = 8.3 Hz), 8.09- 
               
               
                   
                   
                   
                   
                 8.19 (3H, m), 8.38 (1H, d, J = 2.6 Hz), 10.55 (1H, s), 
               
               
                   
                   
                   
                   
                 12.14 (1H, brs) 
               
               
                 781 
                 —F 
                 —H 
                 2 
                 2.49-2.63 (2H, m), 2.71-2.93 (2H, m), 7.09 (1H, dd, J = 8.3 Hz, 
               
               
                   
                   
                   
                   
                 1.5 Hz), 7.14 (1H, d, J = 8.9 Hz), 7.17-7.28 (2H, m), 
               
               
                   
                   
                   
                   
                 7.92 (2H, d, J = 8.2 Hz), 8.15 (2H, d, J = 8.2 Hz), 8.21 (1H, 
               
               
                   
                   
                   
                   
                 dd, J = 8.9 Hz, 2.7 Hz), 8.38-8.44 (1H, m), 10.60 (1H, s), 
               
               
                   
                   
                   
                   
                 12.17 (1H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 107 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
                   
               
               
                 No. 
                 R 337   
                 R 338   
                 R 339   
                   1 H NMR (DMSO-d 6 ) δ ppm 
               
               
                   
               
               
                 782 
                 —Cl 
                 —Cl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 7.20 (1H, d, J = 8.7 Hz), 7.40 (1H, dd, J = 8.7 Hz, 2.3 Hz), 7.60-7.67 (1H, m), 7.82- 8.03 (4H, m), 8.15 (1H, d, J = 8.9 Hz), 8.26- 8.32 (2H, m), 8.56-8.60 (2H, m), 10.78 (1H, s). 
               
               
                   
               
               
                 783 
                 —CF 3   
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 7.18 (1H, d, J = 8.7 Hz), 7.36 (1H, dd, J = 8.7 Hz, 2.3 Hz), 7.63 (1H, d, J = 2.0 Hz), 7.84-8.11 (5 H, m), 8.23 (2H, d, J = 8.1 Hz), 8.34 (1H, dd, J = 8.9 Hz, 2.5 Hz), 8.54- 8.60 (2H, m), 10.98 (1H, s). 
               
               
                   
               
               
                 784 
                 —Cl 
                 —Cl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 7.19 (1H, d, J = 8.7 Hz), 7.47 (1H, dd, J = 9.4 Hz, 2.5 Hz), 7.57-7.63 (1H, m), 7.73 (1H, d, J = 2.5 Hz), 7.85 (1H, d, J = 8.4 Hz), 7.96 (1H, dd, J = 8.4 Hz, 2.0 Hz), 8.10-8.14 (2H, m), 8.23-8.28 (2H, m), 8.52 (1H, d, J = 2.5 Hz), 8.92 (1H, d, J = 9.4 Hz), 10.60 (1H, s), 13.20 (1H, brs). 
               
               
                   
               
               
                 785 
                 —CF 3   
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 7.20 (1H, d, J = 8.7 Hz), 7.48 (1H, dd, J = 9.4 Hz, 2.6 Hz), 7.57-7.63 (1H, m), 7.73 (1H, d, J = 2.5 Hz), 7.94 (2H, d, J = 8.2 Hz), 8.11-8.19 (4H, m), 8.29 (1H, dd, J = 8.7 Hz, 2.6 Hz), 8.55 (1H, d, J = 2.5 Hz), 8.93 (1H, d, J = 9.4 Hz), 10.68 (1H, s), 13.21 (1H, brs). 
               
               
                   
               
               
                 786 
                 —Cl 
                 —Cl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 7.24 (1H, d, J = 8.1 Hz), 7.32 (1H, d, J = 8.7 Hz), 7.58-7.64 (1H, m), 7.69-7.77 (1H, m), 7.85 (1H, d, J = 8.4 Hz), 7.97 (1H, dd, J = 8.4 Hz, 2.1 Hz), 8.06-8.12 (1H, m), 8.20- 8.23 (2H, m), 8.30 (1H, dd, J = 8.7 Hz, 2.6 Hz), 8.48 (1H, d, J = 2.6 Hz), 9.02 (1H, d, J = 8.7 Hz), 10.63 (1H, s), 13.11 (1H, brs). 
               
               
                   
               
               
                 787 
                 —Cl 
                 —Cl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 7.17 (1H, d, J = 8.9 Hz), 7.38-7.43 (1H, m), 7.53-7.59 (2H, m), 7.76-7.86 (2H, m), 7.93- 7.97 (1H, m), 8.22-8.27 (2H, m), 8.51 (1H, d, J = 2.0 Hz), 10.60 (1H, s), 13.15 (1H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 108 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
               
               
                 Example 
                   
               
               
                 No. 
                 R 340   
                 R 341   
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 788 
                 —H 
                 —Ac 
                 (DMSO-d 6 ) 1.85 (3H, s), 4.26 (2H, s), 7.13 (1H, d, J = 8.8 Hz), 
               
               
                   
                   
                   
                 7.19 (2H, d, J = 8.7 Hz), 7.42 (2H, d, J = 8.7 Hz), 7.85 (1H, d, J = 
               
               
                   
                   
                   
                 8.4 Hz), 7.95 (1H, dd, J = 1.9 Hz, 8.4 Hz), 8.20-8.24 (2H, m), 
               
               
                   
                   
                   
                 8.51 (1H, d, J = 2.5 Hz), 12.77 (1H, brs). 
               
               
                 789 
                 —H 
                 —CH 3   
                 (DMSO-d 6 ) 2.98 (3H, s), 4.01 (2H, s), 6.65 (1H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                 6.90-6.95 (3H, m), 7.82 (1H, d, J = 8.4 Hz), 7.94 (1H, dd, J = 2.1 Hz, 
               
               
                   
                   
                   
                 8.4 Hz), 8.13 (1H, dd, J = 2.7 Hz, 8.9 Hz), 8.22 (1H, d, J = 2.1 Hz), 
               
               
                   
                   
                   
                 8.43 (1H, d, J = 2.7 Hz), 10.54 (1H, s). 
               
               
                 790 
                 —H 
                 —C 2 H 5   
                 (DMSO-d 6 ) 1.11 (3H, t, d = 7.1 Hz), 3.39 (2H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                 4.01 (2H, s), 6.58 (2H, d, J = 9.1 Hz), 6.90-6.95 (3H, m), 7.81 (1H, 
               
               
                   
                   
                   
                 d, J = 8.4 Hz), 7.92 (1H, dd, J = 2.0 Hz, 8.4 Hz), 8.11 (1H, dd, J = 
               
               
                   
                   
                   
                 2.7 Hz, 8.9 Hz), 8.19 (1H, d, J = 2.0 Hz), 8.41 (1H, d, J = 2.7 Hz), 
               
               
                   
                   
                   
                 10.48 (1H, s), 12.53 (1H, brs). 
               
               
                 791 
                 —OCH 3   
                 —CH 3   
                 (DMSO-d 6 ) 3.01 (3H, s), 3.67 (3H, s), 4.12 (2H, s), 6.20 (1H, dd, J = 
               
               
                   
                   
                   
                 8.7 Hz, 2.8 Hz), 6.39 (1H, d, J = 2.8 Hz), 6.85-6.94 (2H, m), 
               
               
                   
                   
                   
                 7.83 (1H, d, J = 8.4 Hz), 7.94 (1H, dd, J = 8.4 Hz, 2.1 Hz), 
               
               
                   
                   
                   
                 8.08 (1H, dd, J = 8.7 Hz, 2.6 Hz), 8.21 (1H, d, J = 2.0 Hz), 
               
               
                   
                   
                   
                 8.36 (1H, d, J = 2.5 Hz), 10.47 (1H, s), 12.58 (1H, brs). 
               
               
                 792 
                 —OCH 3   
                 —C 2 H 5   
                 (DMSO-d 6 ) 1.15 (3H, t, J = 7.1 Hz), 3.43 (2H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                 3.65 (3H, s), 4.06 (2H, s), 6.13 (1H, dd, J = 8.7 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                 6.30 (1H, d, J = 2.6 Hz), 6.87-6.91 (2H, m), 7.83 (1H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                 7.94 (1H, dd, J = 8.4 Hz, 2.0 Hz), 8.08 (1H, dd, J = 8.9 Hz, 
               
               
                   
                   
                   
                 2.6 Hz), 8.21 (1H, d, J = 2.0 Hz), 8.36 (1H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                 10.48 (1H, s), 12.58 (1H, brs). 
               
               
                 793 
                 —CH 3   
                 —Ac 
                 (DMSO-d 6 ) 1.84 (3H, s), 2.11 (3H, s), 4.23 (2H, s), 7.05-7.10 (2H, 
               
               
                   
                   
                   
                 m), 7.20-7.25 (1H, m), 7.32 (1H, d, J = 2.2 Hz), 7.75-7.85 (1H, m), 
               
               
                   
                   
                   
                 7.92 (1H, dd, J = 2.2 Hz, 8.4 Hz), 8.10-8.20 (2H, m), 8.43 (1H, d, J = 
               
               
                   
                   
                   
                 2.6 Hz), 10.53 (1H, s), 12.66 (1H, brs). 
               
               
                 794 
                 —CH 3   
                 —CH 3   
                 (DMSO-d 6 ) 2.01 (3H, s), 2.97 (3H, s), 4.07 (2H, s), 6.49 (1H, dd, J = 
               
               
                   
                   
                   
                 8.8 Hz, 3.0 Hz), 6.57 (1H, d, J = 3.0 Hz), 6.85 (1H, d, J = 8.8 Hz), 
               
               
                   
                   
                   
                 6.90 (1H, d, J = 8.9 Hz), 7.82 (1H, d, J = 8.4 Hz), 7.93 (1H, 
               
               
                   
                   
                   
                 dd, J = 8.4 Hz, 2.0 Hz), 8.11 (1H, dd, J = 8.9 Hz, 2.7 Hz), 
               
               
                   
                   
                   
                 8.20 (1H, d, J = 2.0 Hz), 8.39 (1H, d, J = 2.7 Hz), 10.47 (1H, s), 
               
               
                   
                   
                   
                 12.51 (1H, brs). 
               
               
                 795 
                 —F 
                 —Ac 
                 (CDCl 3  + DMSO-d 6 ) 1.99 (3H, s), 4.35 (2H, s), 7.03 (1H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                 7.21-7.31 (3H, m), 7.57 (1H, d, J = 8.4 Hz), 7.90 (1H, dd, J = 
               
               
                   
                   
                   
                 8.4 Hz, 2.1 Hz), 8.19 (1H, d, J = 2.0 Hz), 8.32 (1H, dd, J = 8.9 Hz, 
               
               
                   
                   
                   
                 2.6 Hz), 8.46 (1H, d, J = 2.5 Hz), 10.12 (1H, s). 
               
               
                 796 
                 —F 
                 —CH 3   
                 (CDCl 3  + DMSO-d 6 ) 3.04 (3H, s), 3.98 (2H, s), 6.40-6.49 (2H, m), 
               
               
                   
                   
                   
                 6.90 (1H, d, J = 8.9 Hz), 7.02 (1H, t, J = 8.7 Hz), 7.52 (1H, d, J = 
               
               
                   
                   
                   
                 8.4 Hz), 7.85 (1H, dd, J = 8.4 Hz, 2.1 Hz), 8.14 (1H, d, J = 2.0 Hz), 
               
               
                   
                   
                   
                 8.23 (1H, dd, J = 8.9 Hz, 2.6 Hz), 8.34 (1H, d, J = 2.5 Hz), 
               
               
                   
                   
                   
                 9.77 (1H, s). 
               
               
                 797 
                 —F 
                 —C 2 H 5   
                 (CDCl 3 ) 1.26 (3H, t, J = 7.1 Hz), 3.44 (2H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                 4.03 (2H, s), 6.39-6.52 (2H, m), 6.96 (1H, d, J = 9.7 Hz), 7.06 (1H, 
               
               
                   
                   
                   
                 t, J = 8.9 Hz), 7.55 (1H, d, J = 8.4 Hz), 7.69 (1H, dd, J = 8.6 Hz, 
               
               
                   
                   
                   
                 2.1 Hz), 7.96-7.97 (2H, m), 8.15-8.18 (2H, m). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 109 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
               
               
                 Example 
                   
               
               
                 No. 
                 R 342   
                 R 343   
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 798 
                 —H 
                 —Ac 
                 (DMSO-d 6 ) 1.85 (3H, s), 4.26 (2H, s), 7.13 (1H, d, J = 8.8 Hz), 
               
               
                   
                   
                   
                 7.18 (2H, d, J = 8.7 Hz), 7.42 (2H, d, J = 8.7 Hz), 7.94 (2H, d, 
               
               
                   
                   
                   
                 J = 8.2 Hz), 8.16 (2H, d, J = 8.2 Hz), 8.25 (1H, dd, J = 2.5 Hz, 
               
               
                   
                   
                   
                 8.8 Hz), 8.54 (1H, d, J = 2.5 Hz), 10.66 (1H, s), 
               
               
                   
                   
                   
                 12.70 (1H, brs). 
               
               
                 799 
                 —H 
                 —CH 3   
                 (DMSO-d 6 ) 2.99 (3H, s), 4.09 (2H, s), 6.67 (2H, d, J = 9.0 Hz), 
               
               
                   
                   
                   
                 6.96 (3H, d, J = 9.0 Hz), 7.93 (2H, d, J = 8.2 Hz), 8.16 (2H, d, 
               
               
                   
                   
                   
                 J = 8.2 Hz), 8.12-8.20 (1H, m), 8.46 (1H, d, J = 2.3 Hz), 
               
               
                   
                   
                   
                 10.59 (1H, s), 12.58 (1H, brs). 
               
               
                 800 
                 —H 
                 —C 2 H 5   
                 (DMSO-d 6 ) 1.13 (3H, t, J = 7.1 Hz) 3.38 (2H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                 4.00 (2H, s), 6.65 (1H, d, J = 8.9 Hz), 6.73 (1H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                 6.92-6.97 (3H, m), 7.93 (2H, d, J = 8.1 Hz), 8.15-8.18 (3H, 
               
               
                   
                   
                   
                 m), 8.46 (1H, s), 10.59 (1H, s). 
               
               
                 801 
                 —OCH 3   
                 —CH 3   
                 (DMSO-d 6 ) 3.01 (3H, s), 3.67 (3H, s), 4.12 (2H, s), 6.20 (1H, 
               
               
                   
                   
                   
                 dd, J = 8.7 Hz, 2.6 Hz), 6.39 (1H, d, J = 2.5 Hz), 6.83- 
               
               
                   
                   
                   
                 6.95 (2H, m), 7.93 (2H, d, J = 8.3 Hz), 8.09-8.17 (3H, m), 
               
               
                   
                   
                   
                 8.38 (1H, d, J = 2.6 Hz), 10.56 (1H, s), 12.58 (1H, brs). 
               
               
                 802 
                 —OCH 2   
                 —C 2 H 5   
                 (DMSO-d 6 ) 1.15 (3H, t, J = 7.1 Hz), 3.43 (2H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                 3.66 (3H, s), 4.06 (2H, s), 6.14 (1H, dd, J = 8.7 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                 6.31 (1H, d, J = 2.8 Hz), 6.88-6.92 (2H, m), 7.93 (2H, d, J = 
               
               
                   
                   
                   
                 8.4 Hz), 8.09-8.17 (3H, m), 8.39 (1H, d, J = 2.5 Hz), 
               
               
                   
                   
                   
                 10.55 (1H, s), 12.59 (1H, brs). 
               
               
                 803 
                 —CH 3   
                 —Ac 
                 (DMSO-d 6 ) 1.84 (3H, s), 2.11 (3H, s), 4.23 (2H, s), 7.05- 
               
               
                   
                   
                   
                 7.10 (2H, m), 7.23 (1H, dd, J = 2.4 Hz, 8.5 Hz), 7.33 (1H, d, J = 
               
               
                   
                   
                   
                 2.4 Hz), 7.86 (1H, d, J = 8.3 Hz), 7.91 (2H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                 8.14 (2H, d, J = 8.3 Hz), 8.20 (1H, dd, J = 2.7 Hz, 8.9 Hz), 
               
               
                   
                   
                   
                 8.45 (1H, d, J = 2.7 Hz), 10.61 (1H, s), 12.67 (1H, brs). 
               
               
                 804 
                 —CH 3   
                 —CH 3   
                 (DMSO-d 6 ) 2.01 (3H, s), 2.97 (3H, s), 4.06 (2H, s), 6.49 (1H, 
               
               
                   
                   
                   
                 dd, J = 8.8 Hz, 3.1 Hz), 6.57 (1H, d, J = 2.9 Hz), 6.85 (1H, d, 
               
               
                   
                   
                   
                 J = 8.8 Hz), 6.91 (1H, d, J = 8.9 Hz), 7.91 (2H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                 8.04-8.23 (3H, m), 8.41 (1H, d, J = 2.6 Hz), 10.56 (1H, s), 
               
               
                   
                   
                   
                 12.11-12.98 (1H, m). 
               
               
                 805 
                 —F 
                 —Ac 
                 (CDCl 3 ) 1.96 (3H, s), 4.32 (2H, s), 7.09-7.31 (4H, m), 7.75 (2H, 
               
               
                   
                   
                   
                 d, J = 8.4 Hz), 8.02 (2H, d, J = 8.3 Hz), 8.20 (1H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                 8.40 (1H, dd, J = 8.9 Hz, 2.6 Hz), 8.44 (1H, s). 
               
               
                 806 
                 —F 
                 —CH 3   
                 (CDCl 3  + DMSO-d 6 ) 3.08 (3H, s), 4.02 (2H, s), 6.47-6.52 (2H, 
               
               
                   
                   
                   
                 m), 6.92 (1H, d, J = 8.7 Hz), 7.06 (1H, t, J = 9.0 Hz), 
               
               
                   
                   
                   
                 7.73 (2H, d, J = 8.4 Hz), 8.11 (2H, d, J = 8.4 Hz), 8.26 (1H, 
               
               
                   
                   
                   
                 dd, J = 8.7 Hz, 2.5 Hz), 8.39 (1H, d, J = 2.5 Hz), 9.76 (1H, 
               
               
                   
                   
                   
                 s). 
               
               
                 807 
                 —F 
                 —C 2 H 5   
                 (CDCl 3  + DMSO-d 6 ) 1.23 (3H, t, J = 7.1 Hz), 3.45 (2H, q, J = 
               
               
                   
                   
                   
                 7.1 Hz), 3.97 (2H, s), 6.39-6.48 (2H, m), 6.91 (1H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                 7.04 (1H, t, J = 9.1 Hz), 7.73 (2H, d, J = 7.9 Hz), 
               
               
                   
                   
                   
                 8.12 (2H, d, J = 7.9 Hz), 8.25 (1H, d, J = 9.1 Hz), 8.42 (1H, d, 
               
               
                   
                   
                   
                 J = 2.5 Hz), 9.92 (1H, s). 
               
               
                 808 
                 —F 
                 —(CH 2 ) 2 CH 3   
                 (CDCl 3  + DMSO-d 6 ) 0.96 (3H, t, J = 7.2 Hz), 1.61-1.72 (2H, 
               
               
                   
                   
                   
                 m), 3.33 (2H, t, J = 7.6 Hz), 3.99 (2H, s), 6.37-6.48 (2H, m), 
               
               
                   
                   
                   
                 6.93 (1H, d, J = 8.8 Hz), 7.04 (1H, t, J = 9.1 Hz), 7.73 (2H, d, 
               
               
                   
                   
                   
                 J = 8.1 Hz), 8.09 (2H, d, J = 8.1 Hz), 8.26 (1H, dd, J = 8.9 Hz), 
               
               
                   
                   
                   
                 2.6 Hz), 8.36 (1H, d, J = 2.5 Hz), 9.45 (1H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 110 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
                   
               
               
                 No. 
                 R 344   
                 R 345   
                 R 346   
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 809 
                 —Cl 
                 —Cl 
                 —N(Ac)(CH 2 ) 2 COOH 
                 (DMSO-d 6 ) 1.71 (3H, s), 2.39 (2H, t, J = 
               
               
                   
                   
                   
                   
                 7.5 Hz), 3.78 (2H, t, J = 7.5 Hz), 7.08 (1H, 
               
               
                   
                   
                   
                   
                 d, J = 8.8 Hz), 7.14 (2H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                 7.31 (2H, d, J = 8.6 Hz), 7.80 (1H, d, J = 
               
               
                   
                   
                   
                   
                 8.4 Hz), 7.91 (1H, dd, J = 2.1 Hz, 8.4 Hz), 
               
               
                   
                   
                   
                   
                 8.15-8.21 (2H, m), 8.49 (1H, d, J = 2.5 Hz), 
               
               
                   
                   
                   
                   
                 10.55 (1H, s), 12.20 (1H, brs) 
               
               
                 810 
                 —CF 3   
                 —H 
                 —N(Ac)(CH 2 ) 2 COOH 
                 (DMSO-d 6 ) 1.71 (3H, s), 2.40 (2H, t, J = 
               
               
                   
                   
                   
                   
                 7.3 Hz), 3.78 (2H, t, J = 7.3 Hz), 7.09 (1H, 
               
               
                   
                   
                   
                   
                 d, J = 8.7 Hz), 7.14 (2H, d, S = 8.1 Hz), 
               
               
                   
                   
                   
                   
                 7.31 (2H, d, J = 8.1 Hz), 7.90 (2H, d, J = 
               
               
                   
                   
                   
                   
                 8.1 Hz), 8.12 (2H, d, J = 8.1 Hz), 8.21 (1H, 
               
               
                   
                   
                   
                   
                 d, J = 8.7 Hz), 8.52 (1H, s), 10.63 (1H, s), 
               
               
                   
                   
                   
                   
                 12.25 (1H, brs). 
               
               
                 811 
                 —Cl 
                 —Cl 
                 —CH(CH 3 )CH 2 COOH 
                 (CDCl 3 − CD 3 OD) 1.26 (3H, d, J = 7.0 Hz), 
               
               
                   
                   
                   
                   
                 2.42-2.61 (2H, m), 3.17-3.28 (1H, m), 
               
               
                   
                   
                   
                   
                 6.84 (1H, d, J = 8.9 Hz), 6.98 (2H, d, J = 
               
               
                   
                   
                   
                   
                 8.5 Hz), 7.20 (2H, d, J = 8.5 Hz), 7.50 (1H, 
               
               
                   
                   
                   
                   
                 d, J = 8.4 Hz), 7.73 (1H, dd, J = 8.5 Hz, 
               
               
                   
                   
                   
                   
                 2.1 Hz), 8.01 (1H, d, J = 2.1 Hz), 8.14 (1H, 
               
               
                   
                   
                   
                   
                 d, J = 2.7 Hz), 8.26 (1H, dd, J = 8.9 Hz, 
               
               
                   
                   
                   
                   
                 2.7 Hz). 
               
               
                 812 
                 —CF 3   
                 —H 
                 —CH(CH 3 )CH 2 COOH 
                 (CDCl 3 − CD 3 OD) 1.28 (3H, d, J = 7.0 Hz), 
               
               
                   
                   
                   
                   
                 2.44-2.61 (2H, m), 3.18-3.29 (1H, m), 
               
               
                   
                   
                   
                   
                 6.88 (1H, d, J = 8.9 Hz), 7.00 (2H, d, J = 
               
               
                   
                   
                   
                   
                 8.5 Hz), 7.20 (2H, d, J = 8.5 Hz), 7.70 (2H, 
               
               
                   
                   
                   
                   
                 d, J = 8.2 Hz), 7.99 (2H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                 8.17 (1H, d, J = 2.6 Hz), 8.28 (1H, dd, J = 
               
               
                   
                   
                   
                   
                 8.9 Hz, 2.6 Hz). 
               
               
                 813 
                 —CF 3   
                 —H 
                 —CH═CHCOOH 
                 (DMSO-d 6 ) 6.49 (1H, d, J = 16.0 Hz), 
               
               
                   
                   
                   
                 trans 
                 7.15 (3H, d, J = 8.8 Hz), 7.61 (1H, d, J = 
               
               
                   
                   
                   
                   
                 16.0 Hz), 7.74 (2H, d, J = 8.8 Hz), 
               
               
                   
                   
                   
                   
                 7.94 (2H, d, J = 8.3 Hz), 8.17 (2H, d, J = 
               
               
                   
                   
                   
                   
                 8.3 Hz), 8.26 (1H, dd, J = 8.8 Hz, 2.7 Hz), 
               
               
                   
                   
                   
                   
                 8.55 (1H, d, J = 2.7 Hz), 10.67 (1H, s), 
               
               
                   
                   
                   
                   
                 12.36 (1H, s). 
               
               
                   
               
               
                 814 
                 —CF 3   
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 1.34 (6 H, s), 2.79 (3H, s), 6.98 (1H, d, J = 8.9 Hz), 7.10 (2H, d, J = 8.9 Hz), 7.21 (2H, d, J = 9.1 Hz), 7.76 (2H, d, J = 8.2 Hz), 8.01 (2H, d, J = 8.1 Hz), 8.10 (1H, brs), 8.24 (1H, dd, J = 8.7 Hz, 2.6 Hz), 8.31 (1H, d, J = 2.3 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 111 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
                   
               
               
                 Example 
                   
               
               
                 No. 
                 R 347   
                 R 348   
                 R 349   
                 R 350   
                 M 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 815 
                 —Cl 
                 —Cl 
                 —H 
                 —F 
                 0 
                 (DMSO-d 6 ) 4.29 (2H, d, J = 5.6 Hz), 6.46 (1H, t, J = 
               
               
                   
                   
                   
                   
                   
                   
                 5.9 Hz), 6.94 (1H, d, J = 8.7 Hz), 7.15 (1H, dd, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.7 Hz, 3.0 Hz), 7.20 (1H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.36 (1H, dd, J = 8.3 Hz, 1.8 Hz), 7.47 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 2.8 Hz), 7.59 (1H, d, J = 8.3 Hz), 7.63 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 2.0 Hz), 7.72-7.77 (2H, m). 
               
               
                 816 
                 —CF 3   
                 —H 
                 —H 
                 —F 
                 0 
                 (DMSO-d 6 ) 4.37 (2H, d, J = 5.3 Hz), 6.47 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs), 6.89 (1H, d, J = 8.7 Hz), 7.06-7.12 (1H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.13 (1H, dd, J = 8.7 Hz, 3.0 Hz), 7.45 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 3.0 Hz), 7.58 (2H, d, J = 8.1 Hz), 7.65-7.69 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 7.70 (2H, d, J = 8.1 Hz). 
               
               
                 817 
                 —CF 3   
                 —H 
                 —CH 3   
                 —H 
                 0 
                 (DMSO-d 6 ) 3.03 (3H, s), 4.66 (2H, s), 6.82 (2H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.7 Hz), 6.87 (1H, d, J = 8.9 Hz), 7.29 (1H, dd, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.9 Hz, 3.3 Hz), 7.45 (2H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.68-7.72 (3H, m), 7.82 (2H, d, J = 8.7 Hz). 
               
               
                 818 
                 —CF 3   
                 —H 
                 —C 2 H 5   
                 —H 
                 0 
                 (DMSO-d 6 ) 1.13 (3H, t, J = 7.1 Hz), 3.49 (2H, q, J = 
               
               
                   
                   
                   
                   
                   
                   
                 7.1 Hz), 4.61 (2H, s), 6.81 (2H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 6.84 (1H, d, J = 8.9 Hz), 7.22 (1H, dd, J = 8.9 Hz, 
               
               
                   
                   
                   
                   
                   
                   
                 3.3 Hz), 7.47 (2H, d, J = 8.1 Hz), 7.62 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 3.3 Hz), 7.70 (2H, d, J = 8.3 Hz), 7.80 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.7 Hz). 
               
               
                 819 
                 —Cl 
                 —Cl 
                 —CH 3   
                 —OCH 3    
                 2 
                 (CDCl 3 ) 2.66 (2H, t, J = 7.7 Hz), 2.93 (2H, t, J = 
               
               
                   
                   
                   
                   
                   
                   
                 7.7 Hz), 2.95 (3H, s), 3.75 (3H, s), 4.35 (2H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 6.68-6.88 (3H, m), 6.90-7.00 (1H, m), 7.00- 
               
               
                   
                   
                   
                   
                   
                   
                 7.17 (2H, m), 7.31 (1H, d, J = 2.0 Hz), 7.37 (1H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.2 Hz), 7.65 (1H, d, J = 3.0 Hz), 8.21 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs). 
               
               
                 820 
                 —CF 3   
                 —H 
                 —CH 3   
                 —OCH 3   
                 2 
                 (DMSO-d 6 ) 2.41-2.62 (2H, m), 2.69-2.85 (2H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 2.96 (3H, s), 3.64 (3H, s), 4.58 (2H, s), 6.70- 
               
               
                   
                   
                   
                   
                   
                   
                 6.79 (2H, m), 6.88 (1H, d, J = 8.0 Hz), 6.95 (1H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 1.8 Hz), 7.25 (1H, dd, J = 9.2 Hz, 3.2 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.42 (2H, d, J = 8.0 Hz), 7.52 (1H, d, J = 3.2 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.67 (2H, d, J = 8.0 Hz), 11.64-12.51 (1H, m). 
               
               
                 821 
                 —Cl 
                 —Cl 
                 —CH 3   
                 —OC 2 H 5   
                 2 
                 (DMSO-d 6 ) 1.03 (3H, t, J = 7.0 Hz), 2.53 (2H, t, J = 
               
               
                   
                   
                   
                   
                   
                   
                 7.6 Hz), 2.78 (2H, t J = 7.6 Hz), 3.89 (2H, q, J = 
               
               
                   
                   
                   
                   
                   
                   
                 7.0 Hz), 4.49 (2H, s), 6.70-6.80 (2H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 6.88 (1H, d, J = 8.0 Hz), 6.92 (1H, d, J = 1.9 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.19 (1H, dd, J = 8.3 Hz, 2.0 Hz), 7.26 (1H, dd, J = 
               
               
                   
                   
                   
                   
                   
                   
                 9.0 Hz, 3.2 Hz), 7.45 (1H, dd, J = 2.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.52 (1H, d, J = 3.2 Hz), 7.56 (1H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 11.81-12.30 (1H, m). 
               
               
                 822 
                 —Cl 
                 —Cl 
                 —CH 3   
                 —F 
                 2 
                 (DMSO-d 6 ) 2.55 (2H, t, J = 7.6 Hz), 2.80 (2H, t, J = 
               
               
                   
                   
                   
                   
                   
                   
                 7.6 Hz), 2.96 (3H, s), 4.50 (2H, s), 6.92 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.9 Hz), 7.00-7.22 (4H, m), 7.22-7.38 (1H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.38-7.40 (1H, m), 7.40-7.55 (2H, m), 12.10 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs). 
               
               
                 823 
                 —Cl 
                 —Cl 
                 —C 2 H 5   
                 —F 
                 2 
                 (CDCl 3 ) 1.17 (3H, t, J = 7.0 Hz), 2.66 (2H, t, J = 
               
               
                   
                   
                   
                   
                   
                   
                 7.7 Hz), 2.93 (2H, t, J = 7.7 Hz), 3.40 (2H, q, J = 
               
               
                   
                   
                   
                   
                   
                   
                 7.0 Hz), 4.36 (2H, s), 6.72-6.86 (1H, m), 6.90- 
               
               
                   
                   
                   
                   
                   
                   
                 7.15 (5 H, m), 727-7.35 (1H, m), 7.36 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.2 Hz), 7.59 (1H, d, J = 3.2 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 112 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
               
               
                 Example 
                   
               
               
                 No. 
                 R 351   
                 R 352   
                 R 353   
                 R 354   
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
             
          
           
               
                 824 
                 —CF 3   
                 —H 
                 —CH 3   
                 —H 
                 (DMSO-d 6 ) 2.50-2.54 (2H, m), 2.79 (2H, t, J = 7.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 3.02 (3H, s), 4.64 (2H, s), 6.86 (1H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.89 (2H, d, J = 8.4 Hz), 7.19 (2H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.29 (1H, dd, J = 8.9 Hz, 3.3 Hz), 7.44 (2H, d, J = 7.9 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.69 (2H, d, J = 7.9 Hz), 7.64 (1H, d, J = 3.1 Hz). 
               
               
                 825 
                 —CF 3   
                 —H 
                 —CH 3   
                 —OC 2 H 5   
                 (DMSO-d 6 ) 1.03 (3H, t, J = 7.0 Hz), 2.47-2.59 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 2.71-2.83 (2H, m), 2.97 (3H, s), 3.89 (2H, q, J = 7.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 4.59 (2H, s), 6.69-6.79 (2H, m), 6.88 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.0 Hz), 6.91 (1H, d, J = 1.9 Hz), 7.26 (1H, dd, J = 9.0 Hz, 
               
               
                   
                   
                   
                   
                   
                 3.1 Hz), 7.41 (2H, d, J = 8.0 Hz), 7.52 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 3.1 Hz), 7.66 (2H, d, J = 8.0 Hz), 11.85-12.31 (1H, m), 
               
               
                 826 
                 —CF 3   
                 —H 
                 —CH 3   
                 —F 
                 (CDCl 3 ) 2.67 (2H, t, J = 7.7 Hz), 2.94 (2H, t, J = 7.7 Hz), 
               
               
                   
                   
                   
                   
                   
                 3.00 (3H, s), 4.49 (2H, s), 6.86 (1H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.90-7.16 (4H, m), 7.33 (2H, d, J = 8.1 Hz), 7.57 (2H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.1 Hz), 7.64 (1H, d, J = 3.1 Hz). 
               
               
                 827 
                 —CF 3   
                 —H 
                 —C 2 H 5   
                 —H 
                 (DMSO-d 6 ) 1.11 (3H, t, J = 7.0 Hz), 2.42-2.57 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 2.71-2.82 (2H, m), 3.47 (2H, q, J = 7.0 Hz), 4.58 (2H, 
               
               
                   
                   
                   
                   
                   
                 s), 6.82 (1H, d, J = 8.9 Hz), 6.84-6.91 (2H, m), 7.13- 
               
               
                   
                   
                   
                   
                   
                 7.21 (2H, m), 7.20 (1H, dd, J = 8.9 Hz, 3.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.45 (2H, d, J = 8.1 Hz), 7.57 (1H, d, J = 3.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.68 (2H, d, J = 8.1 Hz), 12.06 (1H, brs). 
               
               
                 828 
                 —Cl 
                 —Cl 
                 —C 2 H 5   
                 —OCH 3   
                 (CDCl 3 ) 1.16 (3H, t, J = 7.1 Hz), 2.55-2.78 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 2.94 (2H, t, J = 7.7 Hz), 3.39 (2H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 3.77 (3H, s), 4.35 (2H, s), 6.70-6.88 (3H, m), 6.92- 
               
               
                   
                   
                   
                   
                   
                 7.13 (3H, m), 7.32 (1H, d, J = 2.0 Hz), 7.36 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.2 Hz), 7.59 (1H, d, J = 3.1 Hz). 
               
               
                 829 
                 —CF 3   
                 —H 
                 —C 2 H 5   
                 —OCH 3   
                 (DMSO-d 6 ) 1.09 (3H, t, J = 7.0 Hz), 2.48-2.61 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 2.72-2.86 (2H, m), 3.40 (2H, q, J = 7.0 Hz), 3.64 (3H, 
               
               
                   
                   
                   
                   
                   
                 s), 4.54 (2H, s), 6.73 (1H, d, J = 9.0 Hz), 6.74 (1H, dd, 
               
               
                   
                   
                   
                   
                   
                 J = 8.0 Hz, 1.9 Hz), 6.87 (1H, d, J = 8.0 Hz), 6.95 (1H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 1.9 Hz), 7.18 (2H, dd, J = 9.0 Hz, 3.2 Hz), 7.39- 
               
               
                   
                   
                   
                   
                   
                 7.49 (3H, m), 7.62-7.71 (2H, m), 11.90-12.31 (1H, m). 
               
               
                 830 
                 —Cl 
                 —Cl 
                 —C 2 H 5   
                 —OC 2 H  5   
                 (DMSO-d 6 ) 0.95-1.11 (6 H, m), 2.41-2.57 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 2.77 (2H, t, J = 7.7 Hz), 3.29-3.47 (2H, m), 3.88 (2H, q, 
               
               
                   
                   
                   
                   
                   
                 J = 7.0 Hz), 4.44 (2H, s), 6.73 (1H, dd, J = 8.0 Hz, 1.9 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.74 (1H, d, J = 9.0 Hz), 6.88 (1H, d, J = 8.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.91 (1H, d, J = 1.9 Hz), 7.15-7.24 (2H, m), 7.41-7.48 
               
               
                   
                   
                   
                   
                   
                 (2H, m), 7.55 (1H, d, J = 8.2 Hz), 11.60-12.50 (1H, m). 
               
               
                 831 
                 —CF 3   
                 —H 
                 —C 2 H 5   
                 —OC 2 H 5   
                 (DMSO-d 6 ) 1.02 (3H, t, J = 7.0 Hz), 1.08 (3H, t, J = 
               
               
                   
                   
                   
                   
                   
                 7.0 Hz), 2.46-2.59 (2H, m), 2.71-2.83 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 3.43 (2H, q, J = 7.0 Hz), 3.89 (2H, q, J = 7.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.69-6.78 (2H, m), 6.87 (1H, d, J = 8.0 Hz), 6.91 (1H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 1.8 Hz), 7.19 (1H, dd, J = 9.0 Hz, 3.2 Hz), 7.39- 
               
               
                   
                   
                   
                   
                   
                 7.49 (3H, m), 7.61-7.69 (2H, m), 11.92-12.22 (1H, m). 
               
               
                 832 
                 —CF 3   
                 —H 
                 —C 2 H 5   
                 —F 
                 (CDCl 3 ) 1.19 (3H, t, J = 7.1 Hz), 2.67 (2H, t, J = 7.7 Hz), 
               
               
                   
                   
                   
                   
                   
                 2.93 (2H, t, J = 7.7 Hz), 3.43 (2H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 4.48 (2H, s), 6.83 (1H, d, J = 9.0 Hz), 6.90-7.20 (4H, 
               
               
                   
                   
                   
                   
                   
                 m), 7.34 (2H, d, J = 8.2 Hz), 7.50-7.65 (3H, m) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 113 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 355   
                 R 356   
                 R 357   
                 R 358   
                 R 359   
                 Form 
                   1 NMR (solvent) δ ppm 
               
               
                   
               
               
                 833 
                 —CF 3   
                 —H 
                 —CH 3   
                 —H 
                 —COOH 
                 free 
                 (DMSO-d 6 ) 1.45 (3H, d, J = 6.8 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 4.61 (1H, dt, J = 6.8 Hz, 6,8 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.85 (1H, d, J = 8.6 Hz), 6.97 (2H, d, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 J = 8,7 Hz), 7.04 (1H, dd, J = 8.7 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz, 3.0 Hz), 7.51 (1H, d, J = 3.0 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz), 7.62 (2H, d, J = 8.3 Hz), 7.70 
               
               
                   
                   
                   
                   
                   
                   
                   
                 (2H, d, J = 8.3 Hz), 7.89 (2H, d, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 J = 8.9 Hz), 12.79 (1H, brs). 
               
               
                 834 
                 —CF 3   
                 —H 
                 —CH 3   
                 —CH 3   
                 —COOH 
                 free 
                 (DMSO-d 6 ) 1.54 (3H, d, J = 6.8 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 2.73 (3H, s), 5.23 (1H, q, J = 6.8 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz), 7.00 (1H, d, J = 8.9 Hz), 7.05 
               
               
                   
                   
                   
                   
                   
                   
                   
                 (2H, d, J = 8.7 Hz), 7.46 (1H, dd, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 J = 9.1 Hz, 3.3 Hz), 7.54 (2H, d, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 J = 8.1 Hz), 7.72 (2H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.84 (1H, d, J = 3.3 Hz), 7.93 (2H, d, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 J = 8.6 Hz) 
               
               
                   
               
               
                 835 
                 —CF 3   
                 —H 
                 —H 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 dihydro- chloride 
                  (DMSO-d 6 ) 1.81 (3H, s), 3.05 (3H, s), 4.22 (2H, s), 4.67 (2H, s), 6.95 (1H, d, J = 8.7 Hz), 7.04 (2H, d, J = 8.6 Hz), 7.28-7.40 (1H, m), 7.35 (2H, d, J = 8.6 Hz), 7.45 (2H, d, J = 8.1 Hz), 7.62-7.80 (1H, m), 7.70 (2H, d, J = 8.1 Hz). 
               
               
                   
               
               
                 836 
                 —Cl 
                 —Cl 
                 —H 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 dihydro- chloride 
                  (CDCl 3 ) 1.81 (3H, s), 3.02 (3H, s), 4.23 (2H, s), 4.57 (2H, s), 6.95 (1H, d, J = 8.8 Hz), 7.04 (2H, d, J = 8.7 Hz), 7.22 (1H, dd, J = 8.2 Hz, 2.0 Hz), 7.32-7.40 (1H, m), 7.35 (2H, d, J = 8.7 Hz), 7.51 (1H, d, J = 2.0 Hz), 7.59 (1H, d, J = 8.2 Hz), 7.71 (1H, d, J = 3.0 Hz). 
               
               
                   
               
               
                 837 
                 —CF 3   
                 —H 
                 —H 
                 —(CH 2 ) 2 OCH 3   
                 —(CH 2 ) 2 COOH 
                 free 
                 (DMSO-d 6 ) 2.43-2.57 (2H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 2.71-2.82 (2H, m), 3.25 (3H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 3.48-3.58 (2H, m), 3.59-3.68 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 m), 4.66 (2H, s), 6.80 (1H, d, J = 8.9 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz), 6.83-6.90 (2H, m), 7.11-7.25 
               
               
                   
                   
                   
                   
                   
                   
                   
                 (3H, m), 7.44 (2H, d, J = 8.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.56 (1H, d, J = 3.1 Hz), 7.67 (2H, d, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 J = 8.0 Hz), 12.09 (1H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 114 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 360   
                 R 361   
                 R 362   
                 Xa 26   
                 Xa 27   
                   1 H NMR (solvent) δ ppm or MS 
               
               
                   
               
               
                 838 
                 —Cl 
                 —Cl 
                 —OCH 3   
                 —CH═CH— 
                 —CH 2 — 
                   1 H NMR (DMSO-d 6 ) 2.57-2.63 (2H, 
               
               
                   
                   
                   
                   
                 (trans) 
                   
                 m), 2.83-2.88 (2H, m), 3.68 (3H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 6.84 (1H, dd, J = 8.1 Hz, 1.7 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 6.98-7.05 (3H, m), 7.20 (1H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 16.5 Hz), 7.36 (1H, d, J = 16.5 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.54-7.65 (2H, m), 7.87 (1H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 1.8 Hz), 8.07-8.11 (1H, m), 8.22 
               
               
                   
                   
                   
                   
                   
                   
                 (1H, d, J = 2.1 Hz), 12.20 (1H, brs). 
               
               
                 839 
                 —CF 3   
                 —H 
                 —OCH 3   
                 —CH═CH— 
                 —CH 2 — 
                   1 H NMR (DMSO-d 6 ) 2.58-2.63 (2H, 
               
               
                   
                   
                   
                   
                 (trans) 
                   
                 m), 2.83-2.89 (2H, m), 3.68 (3H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 6.82-6.86 (1H, m), 6.99-7.06 (3H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 7.31 (1H, d, J = 16.5 Hz), 7.41 
               
               
                   
                   
                   
                   
                   
                   
                 (1H, d, J = 16.5 Hz), 7.71-7.81 (4H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 8.15 (1H, dd, J = 8.7 Hz, 2.5 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 8.27 (1H, d, J = 2.1 Hz), 12.18 
               
               
                   
                   
                   
                   
                   
                   
                 (1H, brs). 
               
               
                 840 
                 —CF 3   
                 —H 
                 —OCH 3   
                 —CO— 
                 —CH 2 — 
                   1 H NMR (DMSO-d 6 ) 2.57-2.63 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 2.83-2.89 (2H, m), 3.70 (3H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 6.86 (1H, dd, J = 8.1 Hz, 2.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.06-7.15 (3H, m), 7.90-7.97 (4H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 8.18-8.22 (1H, m), 8.50 (1H, dd, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 2.5 Hz, 0.7 Hz), 12.19 (1H, brs). 
               
               
                 841 
                 —CF 3   
                 —H 
                 —CH 3   
                 —CO— 
                 —N(C 2 H 5 )— 
                   1 H NMR (CDCl 3 ) 1.23 (3H, t, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 7.1 Hz), 2.12 (3H, s), 3.46 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                 q, J = 7.1 Hz), 4.04 (2H, s), 5.77 
               
               
                   
                   
                   
                   
                   
                   
                 (1H, brs), 6.55-6.59 (2H, m), 6.97 
               
               
                   
                   
                   
                   
                   
                   
                 (2H, d, J = 8.7 Hz), 7.73-7.89 (4H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 8.17-8.21 (1H, m), 8.58 (1H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 2.3 Hz). 
               
               
                 842 
                 —Cl 
                 —Cl 
                 —H 
                 —NHCONH— 
                 none 
                 MS 431 (M+) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 115 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 363   
                 R 364   
                 Form 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 843 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 hydro- chloride 
                  (DMSO-d 6 ) 2.94 (3H, s), 3.10-3.59 (7H, m), 4.02-4.39 (5H, m), 6.07 (2H, s), 6.68 (2H, d, J = 9.1 Hz), 6.74-7.06 (5H, m), 7.25 (1H, brs), 8.23 (1H, dd, J = 8.7 Hz, 2.3 Hz), 8.65 (1H, d, J = 2.3 Hz), 11.23 (1H, brs). 
               
               
                   
               
               
                 844 
                 —H 
                 —NO 2   
                 free 
                 (CDCl 3 ) 7.13 (1H, d, J = 8.5 Hz), 
               
               
                   
                   
                   
                   
                 7.35 (2H, d, J = 9.1 Hz), 8.33 (2H, d, 
               
               
                   
                   
                   
                   
                 J = 9.1 Hz), 8.41 (1H, dd, J = 8.5 
               
               
                   
                   
                   
                   
                 Hz, 2.5 Hz), 8.89 (1H, d, J = 2.5 
               
               
                   
                   
                   
                   
                 Hz). 
               
               
                   
               
               
                 845 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 (DMSO-d 6 ) 2.47 (4H, brs), 3.31-3.53 (6H, m), 7.16 (1H, d, J = 8.6 Hz), 7.23-7.34 (7H, m), 7.45-7.48 (2H, m), 8.31 (1H, dd, J = 8.6 Hz, 2.4 Hz), 8.68 (1H, d, J = 2.4 Hz), 13.20 (1H, brs). 
               
               
                   
               
               
                 846 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 (DMSO-d 6 ) 3.36-3.55 (8H, m), 3.58 (2H, s), 6.00 (2H, s), 6.78-6.92 (3H, m), 7.17 (1H, d, J = 8.6 Hz), 7.26 (2H, d, J = 8.6 Hz), 7.48 (2H, d, J = 8.4 Hz), 8.31 (1H, dd, J = 2.3 Hz, 8.6 Hz), 8.68 (1H, d, J = 2.2 Hz). 
               
               
                   
               
               
                 847 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 (DMSO-d 6 ) 2.50 (4H, brs), 2.63-2.68 (2H, m), 2.81-2.86 (2H, m), 3.48-3.61 (6H, m), 6.01 (2H, s), 6.81-6.90 (2H, m), 6.96 (1H, s), 7.06-7.10 (3H, m), 7.30 (2H, d, J = 8.6 Hz), 8.25-8.33 (1H, m), 8.66 (1H, d, J = 2.7 Hz), 12.58 (1H, brs). 
               
               
                   
               
               
                 848 
                 —CH 3   
                 —NO 2   
                 free 
                 (DMSO-d 6 ) 2.22 (3H, s), 7.28 (1H, 
               
               
                   
                   
                   
                   
                 dd, J = 8.6 Hz, 0.7 Hz), 7.40 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 8.9 Hz), 8.14 (1H, dd, J = 8.9 
               
               
                   
                   
                   
                   
                 Hz, 2.8 Hz), 8.28 (1H, d, J = 2.6 
               
               
                   
                   
                   
                   
                 Hz), 8.36 (1H, dd, J = 8.6 Hz, 2.3 
               
               
                   
                   
                   
                   
                 Hz), 8.65 (1H, dd, J = 2.3 Hz, 0.7 
               
               
                   
                   
                   
                   
                 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 116 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 365   
                 R 366   
                 R 367   
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 849 
                 —NO 2   
                 —CH 3   
                 —H 
                 (DMSO-d 6 ) 2.06 (3H, s), 7.14 (1H, 
               
               
                   
                   
                   
                   
                 d, J = 8.6 Hz), 7.26 (1H, d, J = 9.1 
               
               
                   
                   
                   
                   
                 Hz), 7.64 (1H, dd, J = 8.7 Hz, 2.5 
               
               
                   
                   
                   
                   
                 Hz), 7.74 (1H, d, J = 2.5 Hz), 8.62 
               
               
                   
                   
                   
                   
                 (1H, dd, J = 9.1 Hz, 3.0 Hz), 9.02 
               
               
                   
                   
                   
                   
                 (1H, d, J = 2.8 Hz), 10.75 (1H, brs). 
               
               
                 850 
                 —NO 2   
                 —CH 3   
                 —CH 3   
                 (DMSO-d 6 ) 2.09 (3H, s), 3.26 (3H, 
               
               
                   
                   
                   
                   
                 s), 7.20-7.36 (4H, m), 8.64 (1H, dd, 
               
               
                   
                   
                   
                   
                 J = 9.1 Hz, 2.8 Hz), 9.03 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 2.6 Hz). 
               
               
                 851 
                 4-CF 3 PhNHCO— 
                 —CH 3   
                 —H 
                 (DMSO-d 6 ) 2.08 (3H, s), 7.11 (1H, 
               
               
                   
                   
                   
                   
                 d, J = 8.7 Hz), 7.16 (1H, d, J = 8.7 
               
               
                   
                   
                   
                   
                 Hz), 7.64 (1H, dd, J = 8.7 Hz, 2.5 
               
               
                   
                   
                   
                   
                 Hz), 7.72-7.75 (3H, m), 7.98 (2H, d, 
               
               
                   
                   
                   
                   
                 J = 8.6 Hz), 8.37 (1H, dd, J = 8.7 
               
               
                   
                   
                   
                   
                 Hz, 2.5 Hz), 8.69 (1H, d, J = 2.5 
               
               
                   
                   
                   
                   
                 Hz), 10.62 (1H, brs), 10.74 (1H, brs). 
               
               
                 852 
                 4-CF 3 PhOCH 2 — 
                 —H 
                 —H 
                 (DMSO-d 6 ) 5.17 (2H, s), 7.06 (1H, 
               
               
                   
                   
                   
                   
                 d, J = 8.4 Hz), 7.13 (2H, d, J = 8.9 
               
               
                   
                   
                   
                   
                 Hz), 7.21 (2H, d, J = 8.6 Hz), 7.67 
               
               
                   
                   
                   
                   
                 (2H, d, J = 8.4 Hz), 7.79 (2H, d, 
               
               
                   
                   
                   
                   
                 J = 9.1 Hz), 7.95 (1H, dd, J = 8.4 
               
               
                   
                   
                   
                   
                 Hz, 2.5 Hz), 8.25 (1H, d, J = 2.0 
               
               
                   
                   
                   
                   
                 Hz), 10.78 (1H, brs). 
               
               
                 853 
                 4-CF 3 PhOCH 2 — 
                 —CH 3   
                 —H 
                 (CDCl 3 ) 2.18 (3H, s), 5.05 (2H, s), 
               
               
                   
                   
                   
                   
                 7.01-7.08 (5H, m), 7.51-7.58 (4H, 
               
               
                   
                   
                   
                   
                 m), 7.83-7.87 (1H, m), 8.20 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 2.1 Hz), 9.02 (1H, brs). 
               
               
                 854 
                 4-CF 3 PhOCH 2 — 
                 —CH 3   
                 —CH 3   
                 (DMSO-d 6 ) 2.09 (3H, s), 3.25 (3H, 
               
               
                   
                   
                   
                   
                 s), 5.17 (2H, s), 7.10 (1H, d, J = 8.4 
               
               
                   
                   
                   
                   
                 Hz), 7.11 (1H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                 7.17-7.23 (3H, m), 7.32 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 2.3 Hz), 7.67 (2H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                 7.98 (1H, dd, J = 8.4 Hz, 2.3 Hz), 
               
               
                   
                   
                   
                   
                 8.24 (1H, d, J = 2.3 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 117 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 368   
                 R 369   
                 R 370   
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 855 
                 3,4-Cl 2 PhSO 2 NH— 
                 —F 
                 —CH 3   
                 (DMSO-d 6 ) 2.96 (3H, s), 4.11 (2H, 
               
               
                   
                   
                   
                   
                 s), 6.43 (1H, dd, J = 8.9 Hz, 2.1 Hz), 
               
               
                   
                   
                   
                   
                 6.58 (1H, dd, J = 14.4 Hz, 3.0 Hz), 
               
               
                   
                   
                   
                   
                 6.97-7.02 (2H, m), 7.53 (1H, dd, 
               
               
                   
                   
                   
                   
                 J = 8.9 Hz, 2.8 Hz), 7.63 (1H, dd, 
               
               
                   
                   
                   
                   
                 J = 8.4 Hz, 2.1 Hz), 7.77 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 2.5 Hz), 7.86 (1H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                 7.88 (1H, d, J = 2.1 Hz), 10.40 (1H, 
               
               
                   
                   
                   
                   
                 s), 12.61 (1H, brs). 
               
               
                 856 
                 3,4-Cl 2 PhNHCO— 
                 —OCH 3   
                 —C 2 H 5   
                 (CDCl 3 ) 1.26 (3H, t, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 3.45 (2H, q, J = 7.1 Hz), 3.69 (3H, 
               
               
                   
                   
                   
                   
                 s), 4.08 (2H, s), 6.24 (1H, dd, J = 8.7 
               
               
                   
                   
                   
                   
                 Hz, 2.8 Hz), 6.31 (1H, d, J = 2.6 
               
               
                   
                   
                   
                   
                 Hz), 6.95 (1H, d, J = 8.7 Hz), 7.00 
               
               
                   
                   
                   
                   
                 (1H, d, J = 8.7 Hz), 7.29-7.50 (1H, 
               
               
                   
                   
                   
                   
                 m), 7.55 (1H, dd, J = 8.9 Hz, 2.5 
               
               
                   
                   
                   
                   
                 Hz), 7.88 (1H, d, J = 8.24 (1H, dd, 
               
               
                   
                   
                   
                   
                 J = 8.7 Hz, 2.5 Hz), 8.56 (1H, brs), 
               
               
                   
                   
                   
                   
                 8.73 (1H, d, J = 2.0 Hz). 
               
               
                   
               
             
          
         
       
     
       Reference Example 857 
     Production of 3-{4-[5-(3,4-dichlorobenzylmethylamino)-pyridin-2-yloxy]phenyl}propionic acid 
       [0959]    To a solution of ethyl 3-{4-[5-(3,4-dichlorobenzylamino)pyridin-2-yloxy]phenyl}propionate (1.63 g, 3.7 mmol) in ethanol (30 mL) were added 37% aqueous formaldehyde (2.0 mL, 22 mmol) and acetic acid (0.21 mL, 3.7 mmol), and the resulting solution was stirred at room temperature for 1 hour. To this solution was then added sodium cyanoborohydride (0.46 g, 7.3 mmol) at 0° C., and the resulting solution was stirred at the same temperature for 1 hour. To this solution was added water and extracted with ethyl acetate. The ethyl acetate layer was washed with water, and then dried over anhydrous magnesium sulfate. 
         [0960]    The solvent was evaporated, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=5:1), to thereby yield 1.55 g of ethyl 3-{4-[5-(3,4-dichlorobenzylmethylamino)-pyridin-2-yloxy]phenyl}propionate. This product was dissolved in ethanol (40 mL), and to the resulting solution was added 10% aqueous sodium hydroxide (2.7 mL, 6.7 mmol) and stirred at room temperature for 2 hours. The resulting solution was then acidified by adding 10% hydrochloric acid, and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate, and evaporated, to thereby yield 1.44 g of the title compound. 
         [0961]    Appearance: Colorless oil 
         [0962]      1 H NMR (DMSO-d 6 ) δ 2.38-2.60 (2H, m), 2.78 (2H, t, J=7.6 Hz), 4.52 (2H, s), 6.81-6.92 (3H, m), 7.12-7.23 (3H, m), 7.28 (1H, dd, J=8.9 Hz, 3.3 Hz), 7.48 (1H, d, J=1.9 Hz), 7.57 (1H, d, J=8.2 Hz), 7.63 (1H, d, J=3.3 Hz), 11.70-12.40 (1H, m). 
         [0963]    The following compound was produced in the same manner as in Reference Example 857. 
       Reference Example 858 
     3-(4-{5-[(3,4-Dichlorobenzyl)ethylamino]pyridin-2-yloxy}phenyl)propionic acid 
       [0964]      1 H NMR (DMSO-d 6 ) δ 1.09 (3H, t, J=6.9 Hz), 2.37-2.59 (2H, m), 2.64-2.83 (2H, m), 3.45 (2H, q, J=6.9 Hz), 4.48 (2H, s), 6.82 (1H, d, J=8.9 Hz), 6.85-6.92 (2H, m), 7.12-7.25 (4H, m), 7.48 (1H, d, J=1.8 Hz), 7.54-7.61 (2H, m), 11.77-12.38 (1H, m). 
       Reference Example 859 
     Production of N-[2-(4-formylphenoxy)-5-pyridyl]-3,4-dichlorobenzamide 
       [0965]    To a solution of 4-[(5-amino-2-pyridyl)oxy]benzaldehyde ethylene acetal (5.27 g, 20.4 mmol) and triethylamine (3.41 mL, 24.5 mmol) in THF (80 mL) was added dropwise a solution of 3,4-dichlorobenzoyl chloride (4.49 g, 21.4 mmol) in THF (30 mL) under ice cooling. The resulting solution was stirred for 2 hours at the same temperature. The reaction solution was concentrated under reduced pressure, to the residue, 80% acetic acid (55 mL) was added, and the mixture was heated at 80° C. with stirring for 1 hour. The reaction solution was concentrated under reduced pressure and to the residue was added water, and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, and evaporated. The obtained solid was recrystallized from isopropanol, to thereby yield 5.63 g of the title compound. 
         [0966]    Appearance: Pale yellow powder 
         [0967]      1 H NMR (CDCl 3 ) δ 7.05 (1H, d, J=8.7 Hz), 7.24 (2H, d, J=8.7 Hz), 7.57 (1H, d, J=8.4 Hz), 7.70 (1H, dd, J=8.4 Hz, 2.1 Hz), 7.82-7.93 (3H, m), 7.97 (1H, d, J=2.1 Hz), 8.25 (1H, dd, J=8.7 Hz, 2.7 Hz), 8.29 (1H, d, J=2.7 Hz), 9.96 (1H, s). 
       Reference Example 860 
     Production of ethyl{4-[5-(3,4-dichlorobenzoylamino)-pyridin-2-yloxy]benzylamino}acetate 
       [0968]    A solution of N-[2-(4-formylphenoxy)-5-pyridyl]-3,4-dichlorobenzamide (1.00 g, 2.58 mmol), glycine ethyl ester hydrochloride (0.400 g, 2.84 mmol) and sodium acetate (0.230 g, 2.84 mmol) in methanol (20 mL) was stirred for 30 minutes at 60° C. The reaction solution was cooled with ice, and then sodium cyanoborohydride (0.180 g, 2.84 mmol) was added. The resulting solution was stirred at the same temperature for 1 hour. To the reaction solution was added 5 M hydrochloric acid (2 mL) and concentrated under reduced pressure. To the residue was added a saturated sodium bicarbonate solution, and extracted with dichloromethane. The dichloromethane layer was washed with brine, dried over anhydrous sodium sulfate, and evaporated. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=1:2), to thereby yield 0.752 g of the title compound. 
         [0969]    Appearance: Yellow oil 
         [0970]      1 H NMR (CDCl 3 ) δ 1.27 (3H, t, J=7.1 Hz), 3.43 (2H, s), 3.81 (2H, s), 4.2.0 (2H, q, J=7.1 Hz), 6.95 (1H, d, J=8.8 Hz), 7.09 (2H, d, J=8.5 Hz), 7.36 (2H, d, J=8.5 Hz), 7.57 (1H, d, J=8.3 Hz), 7.71 (1H, dd, J=2.1 Hz, 8.3 Hz), 7.84 (1H, s), 7.98 (1H, d, J=2.1 Hz), 8.18 (1H, dd, J=2.7 Hz, 8.8 Hz), 8.24 (1H, d, J=2.7 Hz). 
       Reference Example 861 
     Production of (acetyl{4-[5-(3,4-dichlorobenzoylamino)-pyridin-2-yloxy]benzyl}amino)acetic acid 
       [0971]    To a solution of ethyl{4-[5-(3,4-dichloro-benzoylamino)pyridin-2-yloxy]benzylamino}acetate (0.811 g, 1.59 mmol) in dichloromethane (5 mL) were added triethylamine (0.332 mL, 2.39 mmol) and acetyl chloride (0.136 mL, 1.91 mmol) at room temperature. The resulting solution was stirred for 1 hour at the same temperature. To the reaction solution was added water, and extracted with dichloromethane. The dichloromethane layer was washed with brine, dried over anhydrous sodium sulfate, and evaporated, to thereby yield 0.785 g of residue. This residue was dissolved in ethanol (5 mL). To the resulting solution was added 5 M aqueous sodium hydroxide (0.350 mL, 1.75 mmol) at room temperature and stirred at the same temperature for 14 hours. To the resulting reaction solution were added 5 M hydrochloric acid (0.400 mL) and water, and extracted with dichloromethane. The dichloromethane layer was washed with brine, dried over anhydrous sodium sulfate, and evaporated, to thereby yield 0.776 g of the title compound. 
         [0972]    Appearance: White amorphous powder 
         [0973]      1 H NMR (DMSO-d 6  at 375 K) δ 2.10 (3H, s), 4.02 (2H, s), 4.60 (2H, s), 7.03 (1H, d, J=8.8 Hz), 7.11 (2H, d, J=8.2 Hz), 7.32 (2H, d, J=8.2 Hz), 7.7.8 (1H, d, J=8.4 Hz), 7.97 (1H, dd, J=2.1 Hz, 8.4 Hz), 8.10-8.30 (2H, m), 8.53 (1H, d, J=2.6 Hz), 10.23 (1H, s). 
       Reference Example 862 
     Production of 1-(4-piperonylpiperazin-1-yl)-2-{methyl-[3-methyl-4-(5-nitropyridin-2-yloxy)phenyl]amino}-ethanone 
       [0974]    To a solution of {methyl[3-methyl-4-(5-nitropyridin-2-yloxy)phenyl]amino}acetic acid (0.93 g, 2.9 mmol) in DMF (40 mL) were added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.67 g, 3.5 mmol), 1-hydroxybenzotriazole monohydrate (0.54 g, 3.5 mmol), and 1-piperonylpiperazine (0.68 g, 3.08 mmol). The reaction mixture was stirred for 15 hours at room temperature under a nitrogen atmosphere. To the resulting solution was added water and extracted with ethyl acetate. The ethyl acetate layer was washed with water and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=2:1→dichloromethane methanol=100:1), to thereby yield 1.2 g of the title compound. 
         [0975]    Appearance: Yellow powder 
         [0976]    Melting point: 142-143° C. 
         [0977]    The following compounds were produced in the same manner as in Reference Example 862. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 118 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 371   
                 R 372   
                 Xa 28   
                 Xa 29   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 863 
                 —CH 3   
                 —CH 3   
                 —CH 2 — 
                 —CO— 
                 2.09 (3H, s), 3.04 (3H, s), 3.22-3.39 
               
               
                   
                   
                   
                   
                   
                 (2H, m), 3.60-3.90 (2H, m), 4.11 
               
               
                   
                   
                   
                   
                   
                 (2H, s), 4.19-4.40 (2H, m), 4.53 (2H, 
               
               
                   
                   
                   
                   
                   
                 s), 5.95 (2H, s), 6.51-6.62 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 6.68-6.80 (3H, m), 6.92 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.6 Hz), 6.94 (1H, d, J = 9.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.42 (1H, dd, J = 9.0 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 9.04 (1H, d, J = 2.6 Hz). 
               
               
                 864 
                 —OCH 3   
                 —C 2 H 5   
                 —CH 2 — 
                 —CO— 
                 1.21 (3H, t, J = 6.7 Hz), 3.20-3.33 
               
               
                   
                   
                   
                   
                   
                 (2H, m), 3.46 (2H, q, J = 6.7 Hz), 
               
               
                   
                   
                   
                   
                   
                 3.71 (3H, s), 3.65-3.85 (2H, m), 4.07 
               
               
                   
                   
                   
                   
                   
                 (2H, s), 4.29 (2H, s), 4.52 (2H, s), 
               
               
                   
                   
                   
                   
                   
                 5.96 (2H, s), 6.23 (1H, dd, J = 8.7 
               
               
                   
                   
                   
                   
                   
                 Hz, 2.6 Hz), 6.39 (1H, d, J = 2.6 
               
               
                   
                   
                   
                   
                   
                 Hz), 6.65-6.85 (3H, m), 6.97 (2H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.7 Hz), 8.41 (1H, dd, J = 9.0 
               
               
                   
                   
                   
                   
                   
                 Hz, 2.8 Hz), 9.02 (1H, d, J = 2.8 
               
               
                   
                   
                   
                   
                   
                 Hz). 
               
               
                 865 
                 —H 
                 —CH 3   
                 —CH 2 — 
                 —CH(CH 3 )— 
                 1.12-1.16 (3H, m), 2.08-2.16 (1H, 
               
               
                   
                   
                   
                   
                   
                 m), 2.46-2.53 (1H, m), 2.71-2.73 
               
               
                   
                   
                   
                   
                   
                 (1H, m), 2.85-3.48 (6H, m), 
               
               
                   
                   
                   
                   
                   
                 3.54-3.59 (1H, m), 3.84-4.19 (4H, 
               
               
                   
                   
                   
                   
                   
                 m), 5.94 (2H, s), 6.68-6.74 (4H, m), 
               
               
                   
                   
                   
                   
                   
                 6.85 (1H, brs), 6.94 (1H, d, J = 9.1 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.01 (2H, d, J = 8.9 Hz), 8.41 
               
               
                   
                   
                   
                   
                   
                 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.05 
               
               
                   
                   
                   
                   
                   
                 (1H, d, J = 2.8 Hz). 
               
               
                 866 
                 —H 
                 —C 2 H 5   
                 —CH 2 — 
                 —CH(CH 3 )— 
                 1.13-1.28 (6H, m), 2.08-2.16 (1H, 
               
               
                   
                   
                   
                   
                   
                 m), 2.47-2.50 (1H, m), 2.71-2.75 
               
               
                   
                   
                   
                   
                   
                 (1H, m), 2.86-3.35 (3H, m), 
               
               
                   
                   
                   
                   
                   
                 3.41-3.49 (2H, m), 3.58-3.62 (1H, 
               
               
                   
                   
                   
                   
                   
                 m), 3.85-4.16 (4H, m), 5.94 (2H, s), 
               
               
                   
                   
                   
                   
                   
                 6.67 (2H, d, J = 9.1 Hz), 6.74 (2H, 
               
               
                   
                   
                   
                   
                   
                 brs), 6.85 (1H, brs), 6.94 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 9.1 Hz), 6.99 (2H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.41 (1H, dd, J = 9.1 Hz, 3.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 9.05 (1H, d, J = 2.5 Hz). 
               
               
                 867 
                 —H 
                 —CH 3   
                 —CH(CH 3 )— 
                 —CH 2 — 
                 1.29-1.40 (3H, m), 1.96-2.06 (1H, 
               
               
                   
                   
                   
                   
                   
                 m), 2.17 (1H, brs), 2.65-2.70 (1H, 
               
               
                   
                   
                   
                   
                   
                 m), 2.81-2.86 (1H, m), 2.96-3.06 
               
               
                   
                   
                   
                   
                   
                 (4H, m), 3.32-3.49 (3H, m), 
               
               
                   
                   
                   
                   
                   
                 3.97-4.71 (3H, m), 5.95 (2H, s), 6.70 
               
               
                   
                   
                   
                   
                   
                 (2H, d, J = 9.2 Hz), 6.74-6.75 (2H, 
               
               
                   
                   
                   
                   
                   
                 m), 6.87 (1H, brs), 6.94 (1H, dd, 
               
               
                   
                   
                   
                   
                   
                 J = 9.1 Hz, 0.5 Hz), 7.01 (2H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 9.2 Hz), 8.41 (1H, dd, J = 9.1 
               
               
                   
                   
                   
                   
                   
                 Hz, 2.8 Hz), 9.05 (1H, dd, J = 2.8 
               
               
                   
                   
                   
                   
                   
                 Hz, 0.5 Hz). 
               
               
                 868 
                 —H 
                 —C 2 H 5   
                 —CH(CH 3 )— 
                 —CH 2 — 
                 1.20 (3H, t, J = 7.1 Hz), 1.26-1.40 
               
               
                   
                   
                   
                   
                   
                 (3H, m), 1.98-2.05 (1H, m), 
               
               
                   
                   
                   
                   
                   
                 2.16-2.17 (1H, m), 2.65-2.69 (1H, 
               
               
                   
                   
                   
                   
                   
                 m), 2.81-2.85 (1H, m), 3.02-3.56 
               
               
                   
                   
                   
                   
                   
                 (6H, m), 4.03-4.71 (3H, m), 5.94 
               
               
                   
                   
                   
                   
                   
                 (2H, s), 6.66 (2H, d, J = 9.2 H), 
               
               
                   
                   
                   
                   
                   
                 6.74-6.75 (2H, m), 6.87 (1H, brs), 
               
               
                   
                   
                   
                   
                   
                 6.94 (1H, dd, J = 9.1 Hz, 0.7 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.99 (2H, d, J = 9.1 Hz), 8.41 (1H, 
               
               
                   
                   
                   
                   
                   
                 dd, J = 9.1 Hz, 2.8 Hz), 9.05 (1H, 
               
               
                   
                   
                   
                   
                   
                 dd, J = 2.8 Hz, 0.7 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 119 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
                   
                   
                   
                   1 H NMR (solvent) δ ppm 
               
               
                 No. 
                 R 373   
                 R 374   
                 R 375   
                 or MS 
               
               
                   
               
               
                 869 
                 —COOCH 3   
                 —H 
                 —C 2 H 5   
                 MS 577 (M + ). 
               
               
                 870 
                 —OCH 3   
                 —H 
                 —H 
                   1 H NMR (DMSO-d 6 ) 
               
               
                   
                   
                   
                   
                 2.32-2.40 (4H, m), 3.42 
               
               
                   
                   
                   
                   
                 (2H, s), 3.50 (4H, brs), 
               
               
                   
                   
                   
                   
                 3.63 (3H, s), 3.92 (2H, d, 
               
               
                   
                   
                   
                   
                 J = 4.6 Hz), 5.65 (1H, t, 
               
               
                   
                   
                   
                   
                 J = 4.8 Hz), 5.99 (2H, s), 
               
               
                   
                   
                   
                   
                 6.22 (1H, dd, J = 8.6 Hz, 
               
               
                   
                   
                   
                   
                 2.5 Hz), 6.51 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 2.5 Hz), 6.76 (1H, 
               
               
                   
                   
                   
                   
                 dd, J = 7.9 Hz, 1.5 Hz), 
               
               
                   
                   
                   
                   
                 6.84-6.91 (3H, m), 7.07 
               
               
                   
                   
                   
                   
                 (1H, dd, J = 9.1 Hz, 0.5 
               
               
                   
                   
                   
                   
                 Hz), 8.54 (1H, dd, 
               
               
                   
                   
                   
                   
                 J = 9.1 Hz, 2.8 Hz), 9.00 
               
               
                   
                   
                   
                   
                 (1H, dd, J = 2.8 Hz, 0.5 
               
               
                   
                   
                   
                   
                 Hz). 
               
               
                 871 
                 —OCH 3   
                 —H 
                 —CH 3   
                   1 H NMR (CDCl 3 ) 
               
               
                   
                   
                   
                   
                 2.35-2.52 (4H, m), 3.07 
               
               
                   
                   
                   
                   
                 (3H, s), 3.44 (2H, s), 
               
               
                   
                   
                   
                   
                 3.41-3.55 (2H, m), 
               
               
                   
                   
                   
                   
                 3.56-3.70 (2H, m), 3.73 
               
               
                   
                   
                   
                   
                 (3H, s), 5.95 (2H, s), 
               
               
                   
                   
                   
                   
                 6.24 (1H, dd, J = 8.8 Hz, 
               
               
                   
                   
                   
                   
                 2.8 Hz), 6.35 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 2.8 Hz), 6.64-6.79 
               
               
                   
                   
                   
                   
                 (2H, m), 6.85 (1H, s), 
               
               
                   
                   
                   
                   
                 6.89-7.04 (2H, m), 8.41 
               
               
                   
                   
                   
                   
                 (1H, dd, J = 9.1 Hz, 2.8 
               
               
                   
                   
                   
                   
                 Hz), 9.03 (1H, d, J = 2.8 
               
               
                   
                   
                   
                   
                 Hz). 
               
               
                 872 
                 —OCH 3   
                 —H 
                 —C 2 H 5   
                   1 H NMR (CDCl 3 ) 1.22 
               
               
                   
                   
                   
                   
                 (3H, t, J = 7.0 Hz), 
               
               
                   
                   
                   
                   
                 2.33-2.52 (4H, m), 
               
               
                   
                   
                   
                   
                 3.49-3.58 (6H, m), 
               
               
                   
                   
                   
                   
                 3.59-3.69 (2H, m), 3.72 
               
               
                   
                   
                   
                   
                 (3H, s), 4.06 (2H, s), 
               
               
                   
                   
                   
                   
                 5.95 (2H, s), 6.22 (1H, 
               
               
                   
                   
                   
                   
                 dd, J = 8.8 Hz, 2.7 Hz), 
               
               
                   
                   
                   
                   
                 6.33 (1H, d, J = 2.7 Hz), 
               
               
                   
                   
                   
                   
                 6.69-6.79 (2H, m), 6.85 
               
               
                   
                   
                   
                   
                 (1H, s), 6.95 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 9.1 Hz), 6.96 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 8.8 Hz), 8.41 (1H, 
               
               
                   
                   
                   
                   
                 dd, J = 9.1 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                   
                 9.04 (1H, d, J = 2.8 Hz). 
               
               
                 873 
                 —CH 3   
                 —H 
                 —H 
                   1 H NMR (CDCl 3 ) 2.08 
               
               
                   
                   
                   
                   
                 (3H, s), 2.43-2.48 (4H, 
               
               
                   
                   
                   
                   
                 m), 3.45-3.48 (4H, m), 
               
               
                   
                   
                   
                   
                 3.67-3.71 (2H, m), 3.86 
               
               
                   
                   
                   
                   
                 (2H, d, J = 4.1 Hz), 4.93 
               
               
                   
                   
                   
                   
                 (1H, t, J = 4.1 Hz), 5.96 
               
               
                   
                   
                   
                   
                 (2H, s), 6.47-6.52 (2H, 
               
               
                   
                   
                   
                   
                 m), 6.71-6.78 (2H, m), 
               
               
                   
                   
                   
                   
                 6.86-6.96 (3H, m), 8.44 
               
               
                   
                   
                   
                   
                 (1H, dd, J = 9.1 Hz, 2.8 
               
               
                   
                   
                   
                   
                 Hz), 9.05 (1H, d, J = 2.8 
               
               
                   
                   
                   
                   
                 Hz). 
               
               
                 874 
                 —CH 3   
                 —H 
                 —Ac 
                   1 H NMR (CDCl 3 ) 1.98 
               
               
                   
                   
                   
                   
                 (3H, s), 2.16 (3H, s), 
               
               
                   
                   
                   
                   
                 2.32-2.51 (4H, m), 
               
               
                   
                   
                   
                   
                 3.35-3.48 (4H, m), 
               
               
                   
                   
                   
                   
                 3.53-3.69 (2H, m), 4.46 
               
               
                   
                   
                   
                   
                 (2H, s), 5.95 (2H, s), 
               
               
                   
                   
                   
                   
                 6.65-6.79 (2H, m), 6.85 
               
               
                   
                   
                   
                   
                 (1H, s), 7.08 (2H, d, 
               
               
                   
                   
                   
                   
                 J = 8.7 Hz), 7.27-7.34 
               
               
                   
                   
                   
                   
                 (1H, m), 7.35-7.42 (1H, 
               
               
                   
                   
                   
                   
                 m), 8.51 (1H, dd, J = 9.0 
               
               
                   
                   
                   
                   
                 Hz, 2.8 Hz), 9.02 (1H, 
               
               
                   
                   
                   
                   
                 dd, J = 2.8 Hz, 0.3 Hz). 
               
               
                 875 
                 —CH 3   
                 —H 
                 —C 2 H 5   
                   1 H NMR (CDCl 3 ) 1.20 
               
               
                   
                   
                   
                   
                 (3H, t, J = 7.1 Hz), 2.08 
               
               
                   
                   
                   
                   
                 (3H, s), 2.37-2.55 (4H, 
               
               
                   
                   
                   
                   
                 m), 3.37-3.72 (8H, m), 
               
               
                   
                   
                   
                   
                 4.05 (2H, s), 5.95 (2H, 
               
               
                   
                   
                   
                   
                 s), 6.42-6.58 (2H, m), 
               
               
                   
                   
                   
                   
                 6.63-6.79 (2H, m), 
               
               
                   
                   
                   
                   
                 6.81-6.99 (3H, m), 8.42 
               
               
                   
                   
                   
                   
                 (1H, dd, J = 9.1 Hz, 2.8 
               
               
                   
                   
                   
                   
                 Hz), 9.05 (1H, d, J = 2.8 
               
               
                   
                   
                   
                   
                 Hz). 
               
               
                   
               
               
                 876 
                 —CH 3   
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (CDCl 3 ) 0.64-0.69 (2H, m), 0.80-0.87 (2H, m), 2.09 (3H, s), 2.41-2.49 (4H, m), 2.76-2.84 (1H, m), 3.44 (2H, s), 3.49-3.52 (2H, m), 3.60-3.64 (2H, m), 4.18 (2H, s), 5.95 (2H, s), 6.71-6.93 (7H, m), 8.39-8.44 (1H, m), 9.05-9.06 (1H, m). 
               
               
                   
               
               
                 877 
                 —CH 3   
                 —CH 3   
                 —CH 3   
                   1 H NMR (CDCl 3 ) 2.05 
               
               
                   
                   
                   
                   
                 (3H, s), 2.28 (3H, s), 
               
               
                   
                   
                   
                   
                 2.37-2.43 (4H, m), 2.72 
               
               
                   
                   
                   
                   
                 (3H, s), 3.42 (2H, s), 
               
               
                   
                   
                   
                   
                 3.52-3.56 (2H, m), 
               
               
                   
                   
                   
                   
                 3.62-3.65 (2H, m), 3.77 
               
               
                   
                   
                   
                   
                 (2H, s), 5.95 (2H, s), 
               
               
                   
                   
                   
                   
                 6.71-6.77 (2H, m), 
               
               
                   
                   
                   
                   
                 6.85-6.90 (2H, m), 
               
               
                   
                   
                   
                   
                 6.97-7.06 (2H, m), 8.45 
               
               
                   
                   
                   
                   
                 (1H, dd, J = 9.1 Hz, 3.0 
               
               
                   
                   
                   
                   
                 Hz), 9.04 (1H, dd, 
               
               
                   
                   
                   
                   
                 J = 3.0 Hz, 0.5 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 120 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
               
               
                 Example 
                   
                   
                   
                   
                   1 H NMR (solvent) δ ppm 
               
               
                 No. 
                 R 376   
                 R 377   
                 R 378   
                 R 379   
                 or MS 
               
               
                   
               
               
                 878 
                 —CH 3   
                 —H 
                 —CH 3   
                 —C 2 H 5   
                 MS 547 (M + ) 
               
               
                 879 
                 —F 
                 —H 
                 —H 
                 —H 
                   1 H NMR (CDCl 3 ) 
               
               
                   
                   
                   
                   
                   
                 2.44-2.49 (4H, m), 
               
               
                   
                   
                   
                   
                   
                 3.43-3.45 (2H, m), 3.45 
               
               
                   
                   
                   
                   
                   
                 (2H, s), 3.68-3.71 (2H, 
               
               
                   
                   
                   
                   
                   
                 m), 3.84 (2H, d, J = 4.1 
               
               
                   
                   
                   
                   
                   
                 Hz), 5.12 (1H, brs), 5.96 
               
               
                   
                   
                   
                   
                   
                 (2H, s), 6.40-6.45 (2H, 
               
               
                   
                   
                   
                   
                   
                 m), 6.71-6.80 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 6.85 (1H, brs), 7.02 (1H, 
               
               
                   
                   
                   
                   
                   
                 t, J = 8.5 Hz), 7.05 (1H, 
               
               
                   
                   
                   
                   
                   
                 dd, J = 9.1 Hz, 0.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.46 (1H, dd, J = 9.1 Hz, 
               
               
                   
                   
                   
                   
                   
                 2.8 Hz), 9.02 (1H, dd, 
               
               
                   
                   
                   
                   
                   
                 J = 2.8 Hz, 0.7 Hz). 
               
               
                 880 
                 —F 
                 —H 
                 —H 
                 —CH 3   
                   1 H NMR (CDCl 3 ) 2.44 
               
               
                   
                   
                   
                   
                   
                 (4H, brs), 3.06 (3H, s), 
               
               
                   
                   
                   
                   
                   
                 3.45 (2H, s), 3.45-3.47 
               
               
                   
                   
                   
                   
                   
                 (2H, m), 3.62-3.64 (2H, 
               
               
                   
                   
                   
                   
                   
                 m), 4.11 (2H, s), 5.95 
               
               
                   
                   
                   
                   
                   
                 (2H, s), 6.40-6.51 (2H, 
               
               
                   
                   
                   
                   
                   
                 m), 6.71-6.78 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 6.85 (1H, brs), 7.04 (1H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 9.1 Hz), 7.05 (1H, 
               
               
                   
                   
                   
                   
                   
                 t, J = 8.9 Hz), 8.46 (1H, 
               
               
                   
                   
                   
                   
                   
                 dd, J = 9.1 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                   
                   
                 9.02 (1H, d, J = 2.3 Hz) 
               
               
                 881 
                 —F 
                 —H 
                 —H 
                 —C 2 H 5   
                   1 H NMR (CDCl 3 ) 1.22 
               
               
                   
                   
                   
                   
                   
                 (3H, t, J = 7.2 Hz), 2.45 
               
               
                   
                   
                   
                   
                   
                 (4H, brs), 3.40-3.49 (4H, 
               
               
                   
                   
                   
                   
                   
                 m), 3.45 (2H, s), 3.65 
               
               
                   
                   
                   
                   
                   
                 (2H, brs), 4.05 (2H, s), 
               
               
                   
                   
                   
                   
                   
                 5.95 (2H, s), 6.37-6.46 
               
               
                   
                   
                   
                   
                   
                 (2H, m), 6.74-6.75 (2H, 
               
               
                   
                   
                   
                   
                   
                 m), 6.86 (1H, brs), 
               
               
                   
                   
                   
                   
                   
                 6.99-7.06 (2H, m), 8.45 
               
               
                   
                   
                   
                   
                   
                 (1H, dd, J = 9.1 Hz, 2.8 
               
               
                   
                   
                   
                   
                   
                 Hz), 9.03 (1H, d, J = 2.5 
               
               
                   
                   
                   
                   
                   
                 Hz). 
               
               
                 882 
                 —F 
                 —H 
                 —H 
                 allyl 
                   1 H NMR (CDCl 3 ) 2.46 
               
               
                   
                   
                   
                   
                   
                 (4H, brs), 3.45 (2H, s), 
               
               
                   
                   
                   
                   
                   
                 3.48 (2H, brs), 3.65 (2H, 
               
               
                   
                   
                   
                   
                   
                 brs), 4.00 (2H, d, J = 5.0 
               
               
                   
                   
                   
                   
                   
                 Hz), 4.07 (2H, s), 
               
               
                   
                   
                   
                   
                   
                 5.19-5.29 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 5.82-5.94 (1H, m), 5.95 
               
               
                   
                   
                   
                   
                   
                 (2H, s), 6.37-6.47 (2H, 
               
               
                   
                   
                   
                   
                   
                 m), 6.71-6.78 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 6.86-6.87 (1H, m), 
               
               
                   
                   
                   
                   
                   
                 6.98-7.05 (2H, m), 8.45 
               
               
                   
                   
                   
                   
                   
                 (1H, dd, J = 9.1 Hz, 2.8 
               
               
                   
                   
                   
                   
                   
                 Hz), 9.02 (1H, dd, 
               
               
                   
                   
                   
                   
                   
                 J = 2.8 Hz, 0.5 Hz) 
               
               
                 883 
                 —F 
                 —H 
                 —F 
                 —CH 3   
                   1 H NMR (CDCl 3 ) 
               
               
                   
                   
                   
                   
                   
                 2.33-2.49 (4H, m), 2.99 
               
               
                   
                   
                   
                   
                   
                 (3H, s), 3.43 (2H, s), 
               
               
                   
                   
                   
                   
                   
                 3.37-3.50 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 3.51-3.68 (2H, m), 4.10 
               
               
                   
                   
                   
                   
                   
                 (2H, s), 5.95 (2H, s), 
               
               
                   
                   
                   
                   
                   
                 6.69-6.78 (2H, m), 6.81 
               
               
                   
                   
                   
                   
                   
                 (1H, dd, J = 8.2 Hz, 12.1 
               
               
                   
                   
                   
                   
                   
                 Hz), 6.85 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 0.96 Hz), 6.90 (1H, 
               
               
                   
                   
                   
                   
                   
                 dd, J = 7.1 Hz, 12.8 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.09 (1H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.49 (1H, dd, J = 2.8 Hz, 
               
               
                   
                   
                   
                   
                   
                 9.0 Hz), 9.01 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 2.8 Hz). 
               
               
                 884 
                 —F 
                 —H 
                 —F 
                 —C 2 H 5   
                   1 H NMR (CDCl 3 ) 1.17 
               
               
                   
                   
                   
                   
                   
                 (3H, t, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 2.30-2.52 (4H, m), 3.35 
               
               
                   
                   
                   
                   
                   
                 (2H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 3.37-3.70 (6H, m), 4.04 
               
               
                   
                   
                   
                   
                   
                 (2H, s), 5.95 (2H, s), 
               
               
                   
                   
                   
                   
                   
                 6.68-6.78 (2H, m), 6.82 
               
               
                   
                   
                   
                   
                   
                 (1H, dd, J = 8.0 Hz, 12.1 
               
               
                   
                   
                   
                   
                   
                 Hz), 6.83-6.88 (1H, m), 
               
               
                   
                   
                   
                   
                   
                 6.91 (1H, dd, J = 7.2 
               
               
                   
                   
                   
                   
                   
                 Hz, 12.5 Hz), 7.09 (1H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 9.0 Hz), 8.49 (1H, 
               
               
                   
                   
                   
                   
                   
                 dd, J = 2.8 Hz, 9.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 9.02 (1H, d, J = 2.8 Hz). 
               
               
                 885 
                 —F 
                 —F 
                 —H 
                 —CH 3   
                   1 H NMR (CDCl 3 ) 
               
               
                   
                   
                   
                   
                   
                 2.20-2.45 (4H, m), 2.91 
               
               
                   
                   
                   
                   
                   
                 (3H, s), 3.34-3.53 (6H, 
               
               
                   
                   
                   
                   
                   
                 m), 4.31 (2H, s), 5.98 
               
               
                   
                   
                   
                   
                   
                 (2H, s), 6.47 (2H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 11.8 Hz), 6.70-6.79 
               
               
                   
                   
                   
                   
                   
                 (1H, m), 6.80-6.91 (2H, 
               
               
                   
                   
                   
                   
                   
                 m), 7.42 (1H, d, J = 9.1 
               
               
                   
                   
                   
                   
                   
                 Hz), 8.64 (1H, dd, 
               
               
                   
                   
                   
                   
                   
                 J = 2.8 Hz, 9.1 Hz), 9.05 
               
               
                   
                   
                   
                   
                   
                 (1H, d, J = 2.8 Hz). 
               
               
                 886 
                 —CH 3   
                 —H 
                 —CH 3   
                 —CH 3   
                 MS 533 (M + ) 
               
               
                 887 
                 —CF 3   
                 —H 
                 —H 
                 —C 2 H 5   
                 MS 587 (M + ) 
               
               
                 888 
                 —CF 3   
                 —H 
                 —H 
                 —CH 3   
                 MS 573 (M + ) 
               
               
                 889 
                 —H 
                 —F 
                 —F 
                 —CH 3   
                   1 H NMR (CDCl 3 ) 
               
               
                   
                   
                   
                   
                   
                 2.30-2.52 (4H, m), 3.01 
               
               
                   
                   
                   
                   
                   
                 (3H, s), 3.43 (2H, s), 
               
               
                   
                   
                   
                   
                   
                 3.38-3.71 (4H, m), 4.10 
               
               
                   
                   
                   
                   
                   
                 (2H, s), 5.95 (2H, s), 
               
               
                   
                   
                   
                   
                   
                 6.65-6.81 (3H, m), 
               
               
                   
                   
                   
                   
                   
                 6.82-6.96 (2H, m), 7.10 
               
               
                   
                   
                   
                   
                   
                 (1H, d, J = 9.1 Hz), 8.49 
               
               
                   
                   
                   
                   
                   
                 (1H, dd, J = 2.8 Hz, 9.1 
               
               
                   
                   
                   
                   
                   
                 Hz), 9.01 (1H, d, J = 2.8 
               
               
                   
                   
                   
                   
                   
                 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 121 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
               
               
                 Example 
                   
                   
                   
                   
                 mp (° C.) or  1 H NMR (CDCl 3 ) 
               
               
                 No. 
                 R 380   
                 R 381   
                 Xa 30   
                 R 382   
                 δ ppm 
               
               
                   
               
               
                 890 
                 —CH 3   
                 —CH 3   
                 —CH 2 — 
                 benzyl 
                   1 H NMR 2.12 (3H, s), 2.40-2.55 (4H, 
               
               
                   
                   
                   
                   
                   
                 m), 3.04 (3H, s), 3.45-3.55 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 3.54 (2H, s), 3.60-3.70 (2H, m), 4.10 
               
               
                   
                   
                   
                   
                   
                 (2H, s), 6.50-6.61 (2H, m), 6.91 (1H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.5 Hz), 6.92 (1H, d, J = 9.1 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.22-7.40 (5H, m), 8.42 (1H, 
               
               
                   
                   
                   
                   
                   
                 dd, J = 9.1 Hz, 2.8 Hz), 9.05 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 2.8 Hz). 
               
               
                 891 
                 —CH 3   
                 —C 2 H 5   
                 —CH 2 — 
                 benzyl 
                 mp 134-136 
               
               
                 892 
                 —H 
                 —CH 3   
                 —CH 2 CH 2 — 
                 piperonyl 
                   1 H NMR 2.23-2.41 (4H, m), 
               
               
                   
                   
                   
                   
                   
                 2.56-2.61 (2H, m), 2.97 (3H, s), 
               
               
                   
                   
                   
                   
                   
                 3.39-3.42 (4H, m), 3.60-3.64 (2H, 
               
               
                   
                   
                   
                   
                   
                 m), 3.71-3.76 (2H, m), 5.94 (2H, s), 
               
               
                   
                   
                   
                   
                   
                 6.72-6.76 (5H, m), 6.83 (1H, brs), 
               
               
                   
                   
                   
                   
                   
                 6.97 (1H, d, J = 9.1 Hz), 7.02 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 9.1 Hz), 8.43 (1H, dd, J = 9.1 
               
               
                   
                   
                   
                   
                   
                 Hz, 2.8 Hz), 9.04 (1H, d, J = 2.8 
               
               
                   
                   
                   
                   
                   
                 Hz). 
               
               
                 893 
                 —CH 3   
                 —CH 3   
                 —CH(CH 3 )— 
                 piperonyl 
                   1 H NMR 1.31 (3H, d, J = 6.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 2.11 (3H, s), 2.17-2.49 (4H, m), 2.78 
               
               
                   
                   
                   
                   
                   
                 (3H, s), 3.31-3.56 (3H, m), 3.39 (2H, 
               
               
                   
                   
                   
                   
                   
                 s), 3.77(1H, brs), 4.57 (1H, q, J = 6.6 
               
               
                   
                   
                   
                   
                   
                 Hz), 5.94 (2H, s), 6.60-6.63 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 6.68-6.75 (2H, m), 6.83 (1H, brs), 
               
               
                   
                   
                   
                   
                   
                 6.93-6.98 (2H, m), 8.44 (1H, dd, 
               
               
                   
                   
                   
                   
                   
                 J = 9.1 Hz, 2.8 Hz), 9.05 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 2.8 Hz). 
               
               
                 894 
                 —H 
                 —CH 3   
                 —CH(CH 3 )— 
                 piperonyl 
                   1 H NMR 1.32 (3H, d, J = 6.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 2.19-2.50 (4H, m), 2.80 (3H, s), 
               
               
                   
                   
                   
                   
                   
                 3.30-3.56 (3H, m), 3.32 (2H, s), 3.78 
               
               
                   
                   
                   
                   
                   
                 (1H, brs), 4.58 (1H, q, J = 6.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 5.93 (2H, s), 6.68-6.82 (3H, m), 6.77 
               
               
                   
                   
                   
                   
                   
                 (2H, d, J &#39;2 9.1 Hz), 6.98 (1H, dd, 
               
               
                   
                   
                   
                   
                   
                 J = 8.6 Hz, 0.5 Hz), 7.04 (2H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 9.2 Hz), 8.44 (1H, dd, J = 9.1 
               
               
                   
                   
                   
                   
                   
                 Hz, 2.8 Hz), 9.05 (1H, dd, J = 2.8 
               
               
                   
                   
                   
                   
                   
                 Hz, 0.5 Hz). 
               
               
                 895 
                 —CH 3   
                 —H 
                 —CO— 
                 piperonyl 
                   1 H NMR 2.15 (3H, s), 2.49-2.55 (4H, 
               
               
                   
                   
                   
                   
                   
                 m), 3.45 (2H, s), 3.71-3.75 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 4.25-4.28 (2H, m), 5.96 (2H, s), 6.75 
               
               
                   
                   
                   
                   
                   
                 (2H, brs), 6.86 (1H, brs), 7.04 (1H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 9.1 Hz), 7.06 (1H, d, J = 8.6 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.49 (1H, dd, J = 8.7 Hz, 2.6 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.61 (1H, d, J = 2.5 Hz), 8.48 
               
               
                   
                   
                   
                   
                   
                 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.02 
               
               
                   
                   
                   
                   
                   
                 (1H, d, J = 2.8 Hz), 9.23 (1H, brs). 
               
               
                 896 
                 —CH 3   
                 —CH 3   
                 —CO— 
                 piperonyl 
                   1 H NMR 2.15 (3H, s), 2.25-2.33 (4H, 
               
               
                   
                   
                   
                   
                   
                 m), 3.33-3.42 (9H, m), 5.93 (2H, s), 
               
               
                   
                   
                   
                   
                   
                 6.66-6.79 (3H, m,) 7.04-7.21 (4H, 
               
               
                   
                   
                   
                   
                   
                 m), 8.51 (1H, dd, J = 9.1 Hz, 2.8 
               
               
                   
                   
                   
                   
                   
                 Hz), 8.99 (1H, dd, J = 2.8 Hz, 0.5 
               
               
                   
                   
                   
                   
                   
                 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 122 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 383   
                   1 H NMR (CDCl 3 ) δ ppm or MS 
               
               
                   
               
               
                 897 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 502 (M + ) 
               
               
                   
               
               
                 898 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 2.44 (4H, brs), 3.07 (3H, s), 3.44 (2H, s), 3.47-3.51 (2H, m), 3.62-3.66 (2H, m), 4.12 (2H, s), 5.95 (2H, s), 6.67-6.75 (4H, m), 6.86 (1H, s), 6.93-6.99 (4H, m), 8.16 (2H, d, J = 9.2 Hz). 
               
               
                   
               
               
                 899 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 2.42 (4H, t, J = 4.9 Hz), 3.04 (3H, s), 3.42 (2H, s), 3.44 (2H, t, J = 4.9 Hz), 3.62 (2H, t, J = 4.9 Hz), 4.11 (2H, s), 5.95 (2H, s), 6.42-6.44 (1H, m), 6.50-6.51 (1H, m), 6.54-6.58 (1H, m), 6.70-6.77 (2H, m), 6.84 (1H, m), 6.96 (1H, d, J = 9.1 Hz), 7.24-7.30 (1H, m), 8.43 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.08 (1H, d, J = 2.8 Hz). 
               
               
                   
               
               
                 900 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 2.44 (4H, brs), 3.44 (2H, s), 3.55 (2H, brs), 3.73 (2H, brs), 5.95 (2H, s), 6.74 (2H, s), 6.85 (1H, s), 6.86 (1H, d, J = 8.6 Hz), 7.14 (2H, d, J = 8.6 Hz), 7.46 (2H, d, J = 8.6 Hz), 7.79 (1H, dd, J = 8.7 Hz, 2.5 Hz), 8.22 (1H, d, J = 2.5 Hz). 
               
               
                   
               
               
                 901 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 508 (M + ) 
               
               
                   
               
               
                 902 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 587 (M + ) 
               
               
                   
               
               
                 903 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 2.31-2.50 (4H, m), 2.96 (3H, s), 3.42 (2H, s), 3.40-3.52 (2H, m), 3.53-3.67 (2H, m), 4.05 (2H, s), 5.95 (2H, s), 6.65-6.95 (6H, m), 7.77 (1H, dd, J = 2.5 Hz, 8.7 Hz), 8.16 (1H, dd, J = 0.5 Hz, 2.5 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 123 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 384   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 904 
                 —H 
                 2.29-2.34 (4H, m), 3.15 (3H, s), 3.34-3.43 (6H, 
               
               
                   
                   
                 m), 4.63 (2H, s), 5.98 (2H, s), 6.72-6.76 (1H, m), 
               
               
                   
                   
                 6.83-6.86 (2H, m), 7.27 (2H, d, J = 8.9 Hz), 7.31 
               
               
                   
                   
                 (1H, d, J = 9.3 Hz), 7.54 (2H, d, J = 8.9 Hz), 
               
               
                   
                   
                 8.64 (1H, dd, J = 9.2 Hz, 2.8 Hz), 9.05 (1H, d, 
               
               
                   
                   
                 J = 2.8 Hz). 
               
               
                 905 
                 —CH 3   
                 2.15 (3H, s), 2.42-2.43 (4H, m), 3.22 (3H, s), 
               
               
                   
                   
                 3.39-3.41 (2H, m), 3.43 (2H, s), 3.61-3.63 (2H, 
               
               
                   
                   
                 m), 4.56 (2H, s), 5.94 (2H, s), 6.70-6.77 (2H, m), 
               
               
                   
                   
                 6.84 (1H, brs), 7.06 (1H, d, J = 8.2 Hz), 7.07 
               
               
                   
                   
                 (1H, d, J = 9.1 Hz), 7.48-7.52 (2H, m), 8.49 (1H, 
               
               
                   
                   
                 dd, J = 9.1 Hz, 2.8 Hz), 9.01 (1H, d, J = 2.8 Hz). 
               
               
                 906 
                 —OCH 3   
                 2.42-2.46 (4H, m), 3.24 (3H, s), 3.40 (2H, brs), 
               
               
                   
                   
                 3.43 (2H, s), 3.63 (2H, brs), 3.74 (3H, s), 4.58 
               
               
                   
                   
                 (2H, s), 5.94 (2H, s), 6.70-6.77 (2H, m), 6.84 
               
               
                   
                   
                 (1H, s), 7.06-7.14 (2H, m), 7.23-7.28 (1H, m), 
               
               
                   
                   
                 7.32 (1H, d, J = 2.3 Hz), 8.47 (1H, dd, J = 9.1 
               
               
                   
                   
                 Hz, 2.8 Hz), 8.98 (1H, d, J = 2.8 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 124 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 385   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 907 
                 piperonyl 
                 1.33-1.46 (2H, m), 1.86-2.00 (3H, m), 2.10 (3H, 
               
               
                   
                   
                 s), 2.29 (2H, d, J = 6.8 Hz), 2.39-2.43 (4H, m), 
               
               
                   
                   
                 2.75 (2H, t, J = 12.2 Hz), 3.40-3.48 (4H, m), 
               
               
                   
                   
                 3.62-3.66 (4H, m), 5.94 (2H, s), 6.73-6.85 (5H, 
               
               
                   
                   
                 m), 6.91-6.96 (2H, m), 8.43 (1H, dd, J = 9.1 Hz, 
               
               
                   
                   
                 3.0 Hz), 9.04 (1H, d, J = 2.8 Hz). 
               
               
                 908 
                 benzyl 
                 1.35-1.46 (2H, m), 1.86-2.00 (3H, m), 2.10 (3H, 
               
               
                   
                   
                 s), 2.29 (2H, d, J = 6.8 Hz), 2.41-2.45 (4H, m), 
               
               
                   
                   
                 2.75 (2H, t, J = 12.2 Hz), 3.47-3.53 (4H, m), 
               
               
                   
                   
                 3.61-3.65 (4H, m), 6.79-6.96 (4H, m), 7.24-7.33 
               
               
                   
                   
                 (5H, m), 8.43 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.05 
               
               
                   
                   
                 (1H, d, J = 2.8 Hz). 
               
               
                   
               
             
          
         
       
     
       Reference Example 909 
     Production of (4-benzylpiperazin-1-yl){4-[methyl(5-nitropyridin-2-yl)amino]phenyl}methanone 
       [0978]    To a solution of 4-[methyl-(5-nitropyridin-2-yl)amino]benzoic acid (0.800 g, 2.93 mmol) and 1-benzylpiperazine (0.542 g, 3.08 mmol) in. DMF (15 mL) were added triethylamine (1.02 mL, 7.32 mmol) and diethyl cyanophosphonate (0.593 mL, 3.52 mmol), and the resulting solution was stirred for 3 hours. To the resulting reaction solution was added water and extracted with ethyl-acetate. The ethyl acetate layer was washed with brine, dried over anhydrous sodium sulfate, evaporated, and the residue was purified by silica gel column chromatography (ethyl acetate), to thereby yield 1.25 g of the title compound. 
         [0979]    Appearance: Yellow amorphous powder 
         [0980]      1 H NMR (CDCl 3 ) δ 2.25-2.65 (4H, m), 3.49 (2H, brs), 3.56 (2H, s), 3.57 (3H, s), 3.81 (2H, brs), 6.43 (1H, d, J=9.5 Hz), 7.25-7.35 (7H, m), 7.53 (2H, d, J=8.4 Hz), 8.06 (1H, dd, J=2.8 Hz, 9.5 Hz), 9.12 (1H, d, J=2.8 Hz). 
         [0981]    The following compounds were produced in the same manner as in Reference Example 909. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 125 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 Xa 31   
                 R 386   
                 Xa 32   
                 M 
                   1 H NMR (DMSO-d 6 ) δ ppm 
               
               
                   
               
             
          
           
               
                 910 
                 —NH— 
                 —H 
                 —CH 2 — 
                 1 
                 2.20-2.30 (4H, m), 2.59 (2H, t, J = 7.3 Hz), 
               
               
                   
                   
                   
                   
                   
                 2.78 (2H, t, J = 7.3 Hz), 3.35 (2H, s), 3.36- 
               
               
                   
                   
                   
                   
                   
                 3.45 (4H, m), 5.98 (2H, s), 6.72 (1H, dd, J = 1.3 
               
               
                   
                   
                   
                   
                   
                 Hz, 7.9 Hz), 6.80-6.90 (3H, m), 7.21 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.4 Hz), 7.57 (2H, d, J = 8.4 Hz), 8.26 (1H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 2.9 Hz, 9.3 Hz), 9.01 (1H, d, J = 2.9 Hz), 
               
               
                   
                   
                   
                   
                   
                 10.06 (1H, s). 
               
               
                 911 
                 —O— 
                 —H 
                 —NH— 
                 1 
                 2.32 (2H, brs), 2.39 (2H, brs), 3.41 (2H, s), 
               
               
                   
                   
                   
                   
                   
                 3.50 (4H, brs), 3.91 (2H, d, J = 5.2 Hz); 5.68 (1H, 
               
               
                   
                   
                   
                   
                   
                 t, J = 5.2 Hz), 5.99 (2H, s), 6.70 (2H, d, J = 8.9 
               
               
                   
                   
                   
                   
                   
                 Hz), 6.74-6.77 (1H, m), 6.83-6.88 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 6.94 (2H, d, J = 8.9 Hz), 7.11 (1H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.56 (1H, dd, J = 2.9 Hz, 9.1 Hz), 9.02 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 2.9 Hz). 
               
               
                 912 
                 —O— 
                 —OCH 3   
                 —NH— 
                 2 
                 2.48 (2H, brs), 2.49 (2H, brs), 3.39 (2H, s), 
               
               
                   
                   
                   
                   
                   
                 3.50 (4H, brs), 3.63 (3H, s), 3.92 (2H, d, J = 4.8 
               
               
                   
                   
                   
                   
                   
                 Hz), 4.22 (4H, s), 5.65 (1H, brt), 6.22 (1H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 8.6 Hz, 2.5 Hz), 6.51 (1H, d, J = 2.5 Hz), 6.73- 
               
               
                   
                   
                   
                   
                   
                 6.81 (3H, m), 6.89 (1H, d, J = 8.6 Hz), 7.07 (1H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 9.1 Hz), 8.54 (1H, dd, J = 9.1 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                   
                   
                 9.00 (1H, d, J = 2.8 Hz). 
               
               
                   
               
             
          
         
       
     
       Reference Example 913 
     Production of N-[4-(5-nitropyridin-2-yloxy)phenyl]-N-[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]acetamide 
       [0982]    To a solution of ethyl{acetyl[4-(5-nitropyridin-2-yloxy)phenyl]amino}acetate (2.30 g, 6.40 mmol) in ethanol (50 mL) was added 5 M aqueous sodium hydroxide (1.92 mL, 9.60 mmol), and the resulting solution was stirred at room temperature for 30 minutes. To this reaction solution were added 5 M hydrochloric acid (2 mL) and water, and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous sodium sulfate, evaporated, and the obtained residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=1:1), to thereby yield 1.68 g of an oil. 
         [0983]    To a solution of this oil in DMF (10 mL) were added 1-piperonylpiperazine (1.29 g, 5.86 mmol), triethylamine (1.85 mL, 13.3 mmol) and diethyl cyanophosphonate (1.07 mL, 6.36 mmol), and the resulting solution was stirred for 1 hour at room temperature. To this reaction solution was added water and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous sodium sulfate, evaporated, and the residue was purified by silica gel column chromatography (dichloromethane:methanol=30:1), to thereby yield 2.21 g of the title compound. 
         [0984]    Appearance: Yellow amorphous powder 
         [0985]      1 H NMR (CDCl 3 ) δ 1.98 (3H, s), 2.40-2.50 (4H, m), 3.40-3.45 (4H, m), 3.62 (2H, brs), 4.48 (2H, s), 5.94 (2H, s), 6.70-6.76 (2H, m), 6.85 (1H, s), 7.09 (1H, d, J=9.1 Hz), 7.20 (2H, d, J=8.7 Hz), 7.51 (2H, d, J=8.7 Hz), 8.51 (1H, dd, J=2.8 Hz, 9.1 Hz), 9.04 (1H, d, J=2.8 Hz). 
         [0986]    The following compounds were produced in the same manner as in Reference Example 913. 
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 126 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 387   
                 R 388   
                 MS (M + ) 
               
               
                   
               
             
          
           
               
                 914 
                 —CH 3   
                 —CH 3   
                 587 
               
               
                 915 
                 —H 
                 —C 2 H 5   
                 587 
               
               
                   
               
             
          
         
       
     
       Reference Example 916 
     Production of 3-[3-methoxy-4-(5-nitropyridin-2-yloxy)phenyl]-1-(4-piperonylpiperazin-1-yl)propan-1-one 
       [0987]    3-[3-methoxy-4-(5-nitropyridin-2-yloxy)phenyl]propionic acid (3.18 g, 10 mmol) was dissolved in dichloromethane (30 mL). To the resulting solution were added thionyl chloride (0.88 mL, 12 mmol) and DMF (1 drop), and refluxed for 2 hours. The reaction solution was concentrated under reduced pressure, and the residue was dissolved in dichloromethane (20 mL). To the resulting solution were added triethylamine (1.67 mL, 12 mmol) and a solution of 1-piperonylpiperazine (2.20 g, 10 mmol) in dichloromethane (30 mL) under ice cooling, and the resulting solution was stirred for 1 hour at 0° C. The resulting reaction solution was washed with water and brine. The organic layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was recrystallized from ethyl acetate, to thereby yield 4.95 g of the title compound. 
         [0988]    Appearance: Pale yellow powder 
         [0989]      1 H NMR (CDCl 3 ) δ 2.33-2.42 (4H, m), 2.63-2.69 (2H, m), 2.97-3.03 (2H, m), 3.42 (4H, brs), 3.62-3.66 (2H, m), 3.74 (3H, s), 5.95 (2H, s), 6.73-6.75 (2H, m), 6.85-6.90 (3H, m), 7.04 (1H, d, J=9.1 Hz), 7.06 (1H, d, J=7.9 Hz), 8.45 (1H, dd, J=9.1 Hz, 2.8 Hz), 9.01 (1H, d, J=2.8 Hz). 
         [0990]    The following compound was produced in the same manner as in Reference Example 916. 
       Reference Example 917 
     6-Chloro-N-(4-trifluoromethylphenyl)nicotinamide 
       [0991]      1 H NMR (DMSO-d 6 ) δ7.74 (1H, d, J=8.4 Hz), 7.76 (2H, d, J=8.7 Hz), 8.00 (2H, d, J=8.7 Hz), 8.38 (1H, dd, J=8.7 Hz, 2.5 Hz), 8.97 (1H, d, J=2.5 Hz), 10.80 (1H, brs). 
       Reference Example 918 
     Production of 3-{3-methoxy-4-[methyl(5-nitropyridin-2-yl)amino]phenyl}-1-(4-piperonylpiperazin-1-yl)propan-1-one 
       [0992]    To a solution of ethyl 3-{3-methoxy-4-[methyl-(5-nitropyridin-2-yl)amino]phenyl}propionate (3.85 g, 11 mmol) in ethanol (80 mL) was added 2 N aqueous sodium hydroxide (6.4 mL, 13 mmol), and the resulting solution was stirred at room temperature for 2.5 hours. To the resulting reaction solution was added 6 N hydrochloric acid (2.2 mL, 13 mmol), and the solvent was removed under reduced pressure. To the residue were added THF (80 mL) and N,N′carbonyldiimidazole (2.08 g, 13 mmol), and the resulting solution was stirred at room temperature for 3 hours. To the resulting reaction solution were added 1-piperonylpiperazine (2.60 g, 12 mmol) and DMF (40 mL), and stirred at room temperature for 21 hours. The solvent was evaporated under reduced pressure, and the residue was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution, dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by silica gel column chromatography (ethyl acetate), to thereby yield 4.59 g of the title compound. 
         [0993]    Appearance: Yellow powder 
         [0994]      1 H NMR (CDCl 3 ) δ 2.36-2.43 (4H, m), 2.64-2.70 (2H, m), 2.99-3.05 (2H, m), 3.42-3.46 (7H, m), 3.63-3.67 (2H, m), 3.77 (3H, s), 5.95 (2H, s), 6.12 (1H, brd, J=9.1 Hz), 6.70-6.77 (2H, m), 6.85-6.90 (3H, m), 7.12 (1H, d, J=8.1 Hz), 7.97-8.01 (1H, m), 9.11 (1H, d, J=2.6 Hz). 
       Reference Example 919 
     Production of 5-{methyl[2-oxo-2-(4-piperonylpiperazin-1-yl)ethyl]amino}-2-(5-nitropyridin-2-yloxy)-benzonitrile 
       [0995]    To a solution of t-butyl 2-((3-cyano-4-(5-nitropyridin-2-yloxy)phenyl)(methyl)amino)acetate (1.2 g, 3.1 mmol) in dichloromethane (12 mL) was added trifluoroacetic acid (12 mL), and the resulting reaction solution was stirred at room temperature for 5 hours. The solvent was evaporated, and water was added to the residue, and extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and evaporated, to thereby yield crude 2-((3-cyano-4-(5-nitropyridin-2-yloxy)phenyl)(methyl)amino)-acetic acid. To a solution of this compound in DMF (24 mL) were added 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (659 mg, 3.4 mmol), 1-hydroxybenzotriazole monohydrate (526 mg, 3.4 mmol) and 1-piperonylpiperazine (757 mg, 3.4 mmol), and the resulting reaction solution was stirred for 8 hours at room temperature. Water was added to the reaction solution and extracted with ethyl acetate. The ethyl acetate layer was then washed with, in order, saturated aqueous sodium bicarbonate solution, water and brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel chromatography (ethyl acetate), to thereby yield 412 g of the title compound. 
         [0996]    Appearance: Yellow amorphous powder 
         [0997]      1 H NMR (CDCl 3 ) δ 2.40-2.55 (4H, m), 3.09 (3H, s), 3.45-3.50 (4H, m), 3.55-3.70 (2H, m), 4.14 (2H, s), 5.95 (2H, s), 6.70-6.80 (2H, m), 6.80-6.95 (3H, m), 7.10-7.20 (2H, m), 8.50 (1H, dd, J=9.1 Hz, 2.8 Hz), 8.99 (1H, d, J=2.8 Hz). 
       Reference Example 920 
     Production of 2-{(2,3-difluoro-4-t-butoxycarbonyl-amino)phenoxy}-5-nitropyridine 
       [0998]    To a solution of {2,3-difluoro-4-(5-nitropyridin-2-yloxy)}benzoic acid (1.22 g, 4.1 mmol) in t-butanol (50 mL) were added diphenylphosphorylazide (0.98 mL, 4.5 mmol) and triethylamine (0.63 mL, 4.5 mmol), and the resulting solution was refluxed for 4 hours under a nitrogen atmosphere. After cooling, water was added to the reaction solution and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=6:1), to thereby yield 1.2 g of the title compound. 
         [0999]    Appearance: White powder 
         [1000]      1 H NMR (CDCl 3 ) δ 1.54 (9H, s), 6.59-6.78 (1H, m), 6.90-7.04 (1H, m), 7.13 (1H, d, J=9.0 Hz), 7.84-8.02 (1H, m), 8.51 (1H, dd, J=2.8 Hz, 9.0 Hz), 8.99 (1H, d, J=2.8 Hz). 
       Reference Example 921 
     Production of 3,4-dichloro-N-[3-fluoro-4-(4-formylphenoxy)phenyl]benzamide 
       [1001]    3,4-Dichloro-N-[4-(4-[1,3]dioxsolane-2-ylphenoxy)-3-fluorophenyl]benzamide (17.4 g, 38.9 mmol) was added to 80% acetic acid, and the resulting solution was stirred for 1.5 hours at 80° C. The reaction solution was concentrated under reduced pressure, wherein the obtained residue was recrystallized from 80% ethanol to thereby yield 12.8 g of the title compound. 
         [1002]    Appearance: Pale yellow powder added triethylamine (1.1 mL, 7.89 mmol). To the resulting solution was then added dropwise phenyl chlorocarbonate (0.39 mL, 3.14 mmol) under ice cooling. The resulting reaction solution was stirred for 1 hour at room temperature. Water was added to the residue, and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and evaporated, whereupon the residue solidified into a powder. The powder was filtered, and washed with diethyl ether, to thereby yield 470 mg of the title compound. 
         [1003]    Appearance: White powder 
         [1004]      1 H NMR (DMSO-d 6 ) δ 7.04 (1H, d, J=8.9 Hz), 7.11 (2H, d, J=8.9 Hz), 7.19-7.31 (3H, m), 7.38-7.49 (2H, m), 7.53 (2H, d, J=8.0 Hz), 7.84 (1H, d, J=8.4 Hz), 7.95 (1H, dd, J=8.4 Hz, 2.0 Hz), 8.18 (1H, dd, J=8.9 Hz, 2.2 Hz), 8.22 (1H, d, J=2.0 Hz), 8.47 (1H, d, J=2.2 Hz), 10.26 (1H, s), 10.54 (1H, s). 
         [1005]    The following compounds were produced in the same manner as in Reference Example 928. 
         [1006]      1 H NMR (DMSO-d 6 ) δ 7.13 (2H, d, J=8.6 Hz), 3.40 (1H, t, J=9.0 Hz), 7.63 (1H, d, J=9.0 Hz), 7.85 (1H, d, J=8.4 Hz), 7.90-8.00 (4H, m), 8.22 (1H, d, J=1.9 Hz), 9.93 (1H, s), 10.67 (1H, s). 
       Reference Example 922 
     Production of N-[6-(4-aminophenoxy)pyridin-3-yl]-3,4-dichlorobenzamide dihydrochloride 
       [1007]    t-Butyl{4-[5-(3,4-dichlorobenzoylamino)-pyridin-2-yloxy]phenyl}carbamate (4.31 g, 9.09 mmol) was dissolved in a mixed solution of chloroform-methanol-ethyl acetate. The resulting solution was concentrated to a volume of about 20 mL. To the residue solution was added a solution of 4 N hydrogen chloride in ethyl acetate (70 mL), and left to cool for 2 hours at room temperature. The precipitated white powder was filtered, and washed with ethyl acetate, to thereby yield 4.04 g of the title compound. 
         [1008]    Appearance: White powder 
         [1009]      1 H NMR (DMSO-d 6 ) δ 5.20 (2H, brs), 7.14 (1H, d, J=8.5 Hz), 7.25 (2H, d, J=8.9 Hz), 7.42 (2H, d, J=8.9 Hz), 7.84 (1H, d, J=8.5 Hz), 7.97 (1H, dd, J=8.5 Hz, 2.0 Hz), 8.24 (1H, dd, J=8.5 Hz, 2.6 Hz), 8.25 (1H, d, J=2.0 Hz), 8.51 (1H, d, J=2.6 Hz), 10.65 (1H, s). 
         [1010]    The following compounds were produced in the same manner as in Reference Example 922. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 127 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
                   
               
               
                 Example 
                   
                   
                   
                   
                   
                   1 H NMR (CDCl 3 ) δ ppm or 
               
               
                 No. 
                 R 389   
                 R 390   
                 R 391   
                 R 392   
                 R 393   
                 MS 
               
               
                   
               
             
          
           
               
                 923 
                 —F 
                 —H 
                 —F 
                 —H 
                 —CH 3   
                   1 H NMR 2.83 (3H, d, J = 5.2 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 3.90-4.05 (1H, m), 6.18- 
               
               
                   
                   
                   
                   
                   
                   
                 6.27 (2H, m), 7.15 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 9.0 Hz), 8.49 (1H, dd, J = 2.8 
               
               
                   
                   
                   
                   
                   
                   
                 Hz, 9.0 Hz), 9.02 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 2.8 Hz). 
               
               
                 924 
                 —F 
                 —F 
                 —H 
                 —H 
                 —CH 3   
                   1 H NMR 2.92 (3H, d, J = 3.8 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 3.90-4.16 (1H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 6.46 (1H, td, J = 22 Hz, 8.8 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 6.89 (1H, td, J = 2.4 Hz, 
               
               
                   
                   
                   
                   
                   
                   
                 7.8 Hz), 7.08 (1H, d, J = 9.0 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 8.49 (1H, dd, J = 2.8 Hz, 
               
               
                   
                   
                   
                   
                   
                   
                 9.0 Hz), 9.02 (1H, d, J = 28 
               
               
                   
                   
                   
                   
                   
                   
                 Hz). 
               
               
                 925 
                 —COOCH 3   
                 —H 
                 —H 
                 —CH 2 COOH 
                 —C 2 H 5   
                 MS 375(M + ) 
               
               
                   
               
             
          
         
       
     
       Reference Example 926 
     Production of 4-(tetrahydropyran-2-yloxy)benzylamine 
       [1011]    To a solution of lithium aluminum hydride (2.66 g, 70 mmol) in THF (2.00 mL) was added dropwise under ice cooling a solution of 4-(tetrahydropyran-2-yloxy)benzonitrile in THF (70 mL). The resulting solution was then refluxed for 1 hour. The resulting reaction solution was again cooled with ice, and then to the solution was added dropwise, in order, water (2.66 mL), 1 N aqueous sodium hydroxide (2.66 mL) and water (7.98 mL). Insoluble matter was removed by filtration. The filtrate was concentrated under reduced pressure, after which the residue was purified by silica gel column chromatography (chloroform methanol 7:1), to thereby yield 11.41 g of the title compound. 
         [1012]    Appearance: Colorless oil 
         [1013]      1 H NMR (CDCl 3 ) δ 1.56 (2H, s), 1.45-1.78 (3H, m), 1.78-2.12 (3H, m), 3.53-3.66 (1H, m), 3.80 (2H, s), 3.84-3.99 (1H, m), 5.41 (1H, t, J=3.2 Hz), 7.02 (2H, d, J=8.7 Hz), 7.22 (2H, d, J=8.7 Hz). 
       Reference Example 927 
     Production of 4-(2-fluoro-4-nitrophenoxy)phenylamine hydrochloride 
       [1014]    N-[4-(2-fluoro-4-nitrophenoxy)phenyl]-acetamide (1.00 g, 3.45 mmol) was added to 6 M hydrochloric acid (10 mL), and the resulting solution was refluxed for 2 hours. The resulting reaction solution was concentrated under reduced pressure, to thereby yield 0.910 g of the title compound. 
         [1015]    Appearance: Pale yellow powder 
         [1016]      1 H-NMR (DMSO-d 6 ) δ 3.40-4.00 (2H, m), 7.18 (1H, t, J=8.7 Hz), 7.24 (2H, d, J=8.9 Hz), 7.32 (2H, d, J=8.9 Hz), 8.10 (1H, ddd, J=1.4 Hz, 2.6 Hz, 8.9 Hz), 8.35 (1H, dd, J=2.6 Hz, 10.8 Hz). 
       Reference Example 928 
     Production of {4-[5-(3,4-dichlorobenzoylamino)pyridin-2-yloxy]phenyl}carbamate phenyl ester 
       [1017]    To a suspension of N-[6-(4-aminophenoxy)pyridin-3-yl]-3,4-dichlorobenzamide dihydrochloride (700 mg, 1.57 mmol) in THF (20 mL) was 
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 128 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 394   
                 M 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
             
          
           
               
                 929 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 0 
                 (DMSO-d 6 ) 7.08 (1H, t, J = 8.7 Hz), 7.15-7.30 (5H, m), 7.35-7.50 (2H, m), 7.60 (2H, d, J = 8.9 Hz), 8.07 (1H, dd, J = 1.1 Hz, 9.0 Hz), 8.31 (1H, dd, J = 2.6 Hz, 10.9 Hz), 10.36 (1H, s). 
               
               
                   
               
               
                 930 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 0 
                 (CDCl 3 ) 1.50-1.80 (3H, m), 1.80-2.15 (3H, m), 3.55- 3.67 (1H, m), 3.85-4.00 (1H, m), 5.37 (1H, t, J = 3.3 Hz), 6.83 (1H, brs), 7.03 (2H, d, J = 9.1 Hz) 7.14-7.30 (3H, m); 7.30-7.47 (4H, m). 
               
               
                   
               
               
                 931 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1 
                 (CDCl 3 ) 1.50-1.79 (3H, m), 1.79-2.15 (3H, m), 3.55- 3.60 (1H, m), 3.82-4.00 (1H, m), 3.39 (2H, d, J = 6.0 Hz), 5.26 (1H, brs), 5.42 (1H, t, J = 3.1 Hz), 7.05 (2H, d, J = 8.7 Hz), 7.27 (2H, d, J = 8.7 Hz), 7.10-7.40 (5H, m). 
               
               
                   
               
             
          
         
       
     
       Reference Example 932 
     Production of 4-piperonylpiperazine-1-carboxylic acid 4-(2-fluoro-4-nitrophenoxy)phenyl]amide 
       [1018]    To a solution of [4-(2-fluoro-4-nitrophenoxy)phenyl]carbamate phenyl ester (0.700 g, 1.90 mmol) in DMF (15 mL) was added 1-piperonylpiperazine (0.460 g, 2.09 mmol), and the resulting solution was stirred for 2 hours at room temperature water was added to the resulting reaction solution, and extracted with ethyl acetate. The ethyl acetate layer was washed with brine. The ethyl acetate layer was dried over anhydrous sodium sulfate, and evaporated, to thereby yield 0.939 g of the title compound. 
         [1019]    Appearance: Yellow oil 
         [1020]      1 H NMR (DMSO-d 6 ) δ 2.30-2.40 (4H, m), 3.35-3.50 (6H, m), 6.00 (2H, s), 6.70-6.90 (2H, m), 7.00-7.15 (2H, m), 7.55 (2H, d, J=9.1 Hz), 8.05-8.10 (1H, m), 8.30 (1H, dd, J=2.8 Hz, 10.9 Hz), 9.31 (1H, s). 
         [1021]    The following compounds were produced in the same manner as in Reference Example 932. 
       Reference Example 933 
     Ethyl 3-(4-{5-[3-(3,4-dichlorophenyl)-3-ethylureido]-pyridin-2-yloxy}phenyl)propionate 
       [1022]    MS 501 (M + ). 
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 129 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 395   
                 M 
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
             
          
           
               
                 934 
                 benzyl 
                 0 
                 1.50-1.87 (3H, m), 1.87-2.15 (3H, m), 2.48 (4H, t, J = 5.1 Hz), 
               
               
                   
                   
                   
                 3.48 (4H, t, J = 5.1 Hz), 3.54 (2H, s), 3.50-3.65 (1H, m), 3.85- 
               
               
                   
                   
                   
                 4.00 (1H, m), 5.34 (1H, t, J = 3.2 Hz), 6.21 (1H, brs), 6.98 (2H, 
               
               
                   
                   
                   
                 d, J = 8.9 Hz), 7.22 (2H, d, J = 8.9 Hz), 7.25-7.38 (5H, m). 
               
               
                 935 
                 piperonyl 
                 1 
                 1.48-1.77 (3H, m), 1.77-2.11 (3H, m), 2.40 (4H, t, J = 5.0 Hz), 
               
               
                   
                   
                   
                 3.36 (4H, t, J = 5.0 Hz), 3.41 (2H, s), 3.50-1.67 (1H, m), 3.81- 
               
               
                   
                   
                   
                 3.96 (1H, m), 4.34 (2H, d, J = 5.1 Hz), 4.61 (1H, t, J =5.1 Hz), 
               
               
                   
                   
                   
                 5.40 (1H, t, J = 3.2 Hz), 5.94 (2H, s), 6.74 (2H, s), 6.84 (1H, s), 
               
               
                   
                   
                   
                 7.00 (2H, d, J = 8.6 Hz), 7.22 (2H, d, J = 8.6 Hz). 
               
               
                   
               
             
          
         
       
     
       Reference Example 936 
     Production of 4-piperonylpiperazine-1-carboxylic acid 4-hydroxybenzylamide 
       [1023]    To a solution of 4-piperonylpiperazine-1-carboxylic acid 4-(tetrahydropyran-2-yloxy)benzylamide (1.1 g, 2.43 mmol) in methanol (50 mL) was added p-toluenesulfonic acid monohydrate (1.0 g, 5.26 mmol), and the resulting solution was stirred for 1 hour at room temperature. The resulting reaction solution was concentrated under reduced pressure. Water was added to the residue, and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and evaporated, to thereby yield 330 mg of the title compound. 
         [1024]    Appearance: White powder 
         [1025]      1 H NMR (CDCl 3 ) δ 2.41 (4H, t, J=5.0 Hz), 3.37 (4H, t, J=5.0 Hz), 3.42 (2H, s), 4.32 (2H, d, J=5.2 Hz), 4.68 (1H, t, J=5.2 Hz), 5.94 (2H, s), 6.15 (1H, brs), 6.70-6.80 (2H, m), 6.75 (2H, d, J=8.6 Hz), 6.84 (1H, s), 7.13 (2H, d, J=8.6 Hz). 
         [1026]    The following compound was produced in the same manner as in Reference Example 936. 
       Reference Example 937 
     4-Benzylpiperazine-1-carboxylic acid (4-hydroxyphenyl)methylamide hydrochloride 
       [1027]      1 H NMR (DMSO-d 6 ) δ 2.69-2.91 (2H, m), 3.03 (3H, s), 2.92-3.23 (4H, m), 3.68 (2H, d, J=13.7 Hz), 4.26 (2H, s), 6.75 (2H, d, J=8.7 Hz), 6.98 (2H, d, J=8.7 Hz), 7.45 (3H, brs), 7.54 (2H, brs), 9.52 (1H, s). 
       Reference Example 938 
     Production of 3,4-dichloro-N-{6-[4-(3-hydroxypropyl)-phenoxy]pyridin-3-yl}benzamide 
       [1028]    To 2-{4-[3-(t-butyldimethylsilanyloxy)propyl]phenoxy}-5-nitropyridine (950 mg, 1.8 mmol) were added acetic acid (10 mL) and water (5 mL), and the resulting solution was stirred for 1 hour at room temperature. The resulting reaction solution was concentrated under reduced pressure. Water was added to the residue, and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was recrystallized from ethyl acetate, to thereby yield 520 mg of the title compound. 
         [1029]    Appearance: White prisms 
         [1030]      1 H NMR (DMSO-d 6 ) δ 1.70-1.78 (2H, m), 2.59-2.65 (2H, m), 3.32-3.47 (2H, m), 4.46-4.49 (1H, m), 7.00-7.05 (3H, m), 7.23 (2H, d, J=8.2 Hz), 7.84 (1H, d, J=8.2 Hz), 7.95 (1H, dd, J=8.3 Hz, 2.0 Hz), 8.16-8.22 (2H, m), 8.48 (1H, d, J=2.6 Hz), 10.54 (1H, s). 
         [1031]    The following compound was produced in the same manner as in Reference Example 938. 
       Reference Example 939 
     3,4-Dichloro-N-{6-[4-(2-hydroxyethyl)phenoxy]pyridin-3-yl}benzamide 
       [1032]      1 H NMR (DMSO-d 6 ) δ 2.73 (2H, t, J=6.9 Hz), 3.59-3.66 (2H, m), 4.65 (1H, t, J=5.3 Hz), 7.00-7.06 (3H, m), 7.25 (2H, d, J=8.3 Hz), 7.84 (1H, d, J=8.3 Hz), 7.95 (1H, dd, J=8.3 Hz, 2.0 Hz), 8.16-8.23 (2H, m), 8.47 (1H, d, J=2.6 Hz), 10.54 (1H, s). 
       Reference Example 940 
     Production of 3,4-dichloro-N-{6-[4-(5-hydroxypentyl)-phenoxy]pyridin-3-yl}benzamide 
       [1033]    To a solution of ethyl 5-{4-[5-(3,4-dichloro-benzoylamino)pyridin-2-yloxy]phenyl}pentanoate (8.79 g, 18.0 mmol) in THF (140 mL) was added sodium borohydride (3.14 g, 144 mmol), and the resulting solution was refluxed for 3 hours under a nitrogen atmosphere. The resulting reaction solution was cooled with ice, and treated with 1 N hydrochloric acid. The resulting solution was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=1:2), to thereby yield 7.07 g of the title compound. 
         [1034]    Appearance: White powder 
         [1035]      1 H NMR (CDCl 3 ) δ 1.25-1.75 (7H, m), 2.62 (2H, t, J=7.6 Hz), 3.65 (2H, t, J=6.6 Hz), 6.92 (1H, d, J=8.5 Hz), 7.02 (2H, d, J=8.5 Hz), 7.19 (2H, d, J=8.5 Hz), 7.56 (1H, d, J=8.5 Hz), 7.69 (1H, dd, J=8.5 Hz, 2.0 Hz), 7.93 (1H, s), 7.97 (1H, d, J=2.0 Hz), 8.15 (1H, dd, J=8.5 Hz, 2.5 Hz), 8.22 (1H, d, J=2.5 Hz). 
         [1036]    The following compounds were produced in the same manner as in Reference Example 940. 
         [0000]    
       
         
               
             
               
               
               
             
               
               
               
             
           
               
                 TABLE 130 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
               
               
                 Example 
               
               
                 No. 
                 M 
                 mp (° C.) 
               
               
                   
               
             
          
           
               
                 941 
                 1 
                 162-163 
               
               
                 942 
                 2 
                 104-105 
               
               
                 943 
                 3 
                 111-113 
               
               
                 944 
                 4 
                 102-104 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 131 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 396   
                 R 397   
                 M 
                   1 H NMR (DMSO-d 6 ) δ ppm 
               
               
                   
               
             
          
           
               
                 945 
                 —Cl 
                 —Cl 
                 1 
                 4.49 (2H, d, J = 5.6 Hz), 5.17 (1H, brs), 7.03-7.08 (3H, m), 
               
               
                   
                   
                   
                   
                 7.35 (2H, d, J = 8.6 Hz), 7.84 (1H, d, J = 8.6 Hz), 7.93- 
               
               
                   
                   
                   
                   
                 7.97 (1H, m), 8.17-8.22 (2H, m), 8.47 (1H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                 10.53 (1H, s). 
               
               
                 946 
                 —CF 3   
                 —H 
                 1 
                 4.50 (2H, d, J = 5.7 Hz), 5.18 (1H, t, J = 5.7 Hz), 7.04- 
               
               
                   
                   
                   
                   
                 7.09 (3H, m), 7.35 (2H, d, J = 8.4 Hz), 7.93 (2H, d, J = 8.4 
               
               
                   
                   
                   
                   
                 Hz), 8.15-8.24 (3H, m), 8.50 (1H, d, J = 2.7 Hz), 10.61 (1H, 
               
               
                   
                   
                   
                   
                 s). 
               
               
                 947 
                 —Cl 
                 —Cl 
                 4 
                 1.35-1.70 (4H, m), 2.59 (2H, t, J = 7.5 Hz), 3.42 (2H, q, J = 
               
               
                   
                   
                   
                   
                 6.0 Hz), 4.37 (1H, t, J = 5.5 Hz), 7.02 (2H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                 7.04 (1H, d, J = 8.6 Hz), 7.22 (2H, d, J = 8.2 Hz), 7.84 (1H, 
               
               
                   
                   
                   
                   
                 d, J = 8.2 Hz), 7.94 (1H, dd, J = 8.2 Hz, 2.0 Hz), 8.18 (1H, 
               
               
                   
                   
                   
                   
                 dd, J = 8.9 Hz, 2.6 Hz), 8.22 (1H, d, J = 2.0 Hz), 8.47 (1H, 
               
               
                   
                   
                   
                   
                 d, J = 2.6 Hz), 10.53 (1H, s). 
               
               
                   
               
             
          
         
       
     
       Reference Example 948 
     Production of 4-cyano-N-[6-(4-hydroxymethylphenoxy)-pyridin-3-yl]benzamide 
       [1037]    A suspension of 4-[5-(4-cyanobenzoylamino)-pyridin-2-yloxy]benzoic acid (1.80 g, 5.01 mmol) in THF (20 mL) was cooled with ice-common salt, and to the solution was added triethylamine (0.77 mL, 5.51 mmol), and then ethyl chlorformate (0.53 mL, 5.51 mmol). The resulting solution was stirred at room temperature. Thirty minutes later, the reaction solution was filtered and insoluble matter was removed. The resulting filtrate was poured while stirring under ice cooling into an aqueous solution of sodium borohydride (0.95 g, 25.05 mmol) in 80% methanol (40 mL). After stirring for 30 minutes at room temperature, water (200 mL) was added to the reaction solution. The obtained mixture was extracted with ethyl acetate (200 mL). The ethyl acetate layer was washed with brine, dried over anhydrous sodium sulfate, and evaporated under reduced pressure. The residue was recrystallized from a mixed solution of ethyl acetate-n-hexane, to thereby yield 1.26 g of the title compound. 
         [1038]    Appearance: Slightly yellow powder 
         [1039]      1 H NMR (DMSO-d 6 ) δ 4.50 (2H, d, J=5.3 Hz), 5.19 (1H, t, J=5.6 Hz), 7.04-7.09 (3H, m), 7.35 (2H, d, J=8.6 Hz), 8.04 (2H, d, J=8.9 Hz), 8.12 (2H, d, J=8.6 Hz), 8.21 (1H, dd, J=8.9 Hz, 2.6 Hz), 8.49 (1H, d, J=2.3 Hz), 11.63 (1H, s). 
         [1040]    The following compounds were produced in the same manner as in Reference Example 948. 
       Reference Example 949 
     4-Chloro-N-[6-(4-hydroxymethylphenoxy)pyridin-3-yl]benzamide 
       [1041]      1 H NMR (DMSO-d 6 ) δ 4.50 (2H, d, J=5.3 Hz), 5.18 (1H, t, J=5.6 Hz), 7.03-7.08 (3H, m), 7.35 (2H, d, J=8.6 Hz), 7.63 (2H, d, J=8.6 Hz), 8.00 (2H, d, J=8.6 Hz), 8.20 (1H, dd, J=8.9 Hz, 2.6 Hz), 8.48 (1H, d, J=2.3 Hz), 10.46 (1H, s). 
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 132 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
               
               
                 Example 
               
               
                 No. 
                 R 398   
                 R 399   
                   1 H NMR (CDC1 3 ) δ ppm 
               
               
                   
               
             
          
           
               
                 950 
                 —H 
                 —NO 2   
                 4.71 (2H, s), 7.05 (1H, d, J = 8.4 Hz), 7.25 (2H, d, J = 8.9 Hz), 7.83 (1H, dd, J = 8.3 Hz, 2.3 Hz), 8.19 (1H, d, J = 2.5 Hz), 8.27 (2H, d, J = 8.9 Hz). 
               
               
                   
               
               
                 951 
                 —CH 3   
                 —NO 2   
                 2.30 (4H, brs), 4.67 (2H, s), 7.02 (1H, d, J = 8.41 Hz,), 7.12 (1H, d, J = 8.90 Hz), 7.80 (1H, dd, J = 8.41 Hz, 2.47 Hz), 8.05-8.17 (3H, m). 
               
               
                   
               
               
                 952 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2.45 (4H, brs), 3.45 (2H, s), 3.57 (2H, brs), 3.69 (2H, brs), 4.67 (2H, s), 5.95 (2H, s), 6.74-6.77 (2H, m), 6.85 (1H, s), 6.94 (1H, d, J = 8.4 Hz), 7.14 (2H, d, J  8.4 Hz), 7.44 (2H, d, J = 8.4 Hz), 7.76 (1H, dd, J = 2.5 Hz, 8.4 Hz), 8.16 (1H, d, J = 2.5 Hz). 
               
               
                   
               
               
                 953 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.96 (1H, brs), 2.40-2.44 (4H, m), 3.02 (3H, s), 3.43 (2H, brs), 3.47- 3.49 (2H, m), 3.62 (2H, brs), 4.07 (2H, s), 4.62 (2H, s), 5.94 (2H, s), 6.68- 6.77 (4H, m), 6.81 (1H, d, J = 8.6 Hz), 6.85 (1H, brs), 6.99 (2H, d, J = 9.2 Hz), 7.66 (1H, dd, J = 8.4 Hz, 2.5 Hz), 8.13 (1H, d, J = 2.5 Hz). 
               
               
                   
               
               
                 954 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.75-2.01 (1H, m), 2.22-2.50 (4H, m), 2.51-2.70 (2H, m), 2.88-3.07 (2H, m), 3.30-3.51 (4H, m), 3.52-3.78 (2H, m), 4.67 (2H, s), 5.96 (2H, s), 6.69- 6.81 (2H, m), 6.83-6.88 (1H, m), 6.91 (1H, d, J = 8.4 Hz), 7.01-7.11 (2H, m), 7.19-7.29 (2H, m), 7.74 (1H, dd, J = 2.5 Hz, 8.4 Hz), 8.16 (1H, dd, J = 0.5 Hz, 2.5 Hz). 
               
               
                   
               
             
          
         
       
     
       Reference Example 955 
     Production of 2-[4-(1-bromoethyl)phenoxy]-5-nitropyridine 
       [1042]    2-(4-ethylphenoxy)-5-nitropyridine (7.33 g, 30 mmol) was dissolved in carbon tetrachloride (100 mL), and to the resulting solution were added N-bromosuccimide (5.34 g, 30 mmol) and benzoyl peroxide (0.73 g, 3 mmol). This solution was refluxed overnight under a nitrogen atmosphere. The reaction solution was allowed to cool, after which insoluble matter was removed by filtration. The resulting filtrate was washed with a saturated sodium bicarbonate solution and brine. The organic layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=10:1), to thereby yield 1.34 g of the title compound. 
         [1043]    Appearance: White powder 
         [1044]      1 H NMR (CDCl 3 ) δ 2.08 (3H, d, J=6.9 Hz), 5.26 (1H, q, J=6.9 Hz), 7.05 (1H, d, J=9.1 Hz), 7.15 (2H, d, J=8.6 Hz), 7.53 (2H, d, J=8.7 Hz), 8.49 (1H, dd, J=9.1 Hz, 2.8 Hz), 9.04 (1H, d, J=2.8 Hz). 
       Reference Example 956 
     Production of N-[6-(4-chloromethylphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide 
       [1045]    To a solution of N-[6-(4-hydroxymethylphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide (3.06 g, 7.9 mmol) in dichloromethane (90 mL) was added thionyl chloride (1.7 mL, 23.3 mmol), and the resulting solution was stirred for 4 hours at room temperature. To the residue was added a saturated sodium bicarbonate solution, and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was washed with diethyl ether, to thereby yield 2.95 g of the title compound. 
         [1046]    Appearance: White powder 
         [1047]      1 H NMR (CDCl 3 ) δ 4.61 (2H, s), 7.00 (1H, d, J=8.9 Hz), 7.11-7.14 (2H, m), 7.41-7.44 (2H, m), 7.77 (2H, d, J=8.4 Hz), 7.89 (1H, brs), 8.00 (2H, d, J=8.4 Hz), 8.22-8.28 (2H, m). 
         [1048]    The following compounds were produced in the same manner as in Reference Example 956. 
       Reference Example 957 
     3,4-Dichloro-N-[4-(4-chloromethylphenoxy)-3-fluorophenyl]benzamide 
       [1049]      1 H NMR (CDCl 3 ) δ 4.58 (2H, s), 6.95 (2H, d, J=8.6 Hz), 7.10 (1H, t, J=8.6 Hz), 7.20-7.30 (1H, m), 7.30-7.40 (3H, m), 7.59 (1H, d, J=8.3 Hz), 7.65-7.78 (2H, m), 7.96 (1H, d, J=2.1 Hz). 
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 133 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
               
               
                 Example No. 
                 R 400   
                 R 401   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 958 
                 —NO 2   
                 CH 2 Cl 
                 4.63 (2H, s), 7.06 (1H, d, J = 8.9 
               
               
                   
                   
                   
                 Hz), 7.16 (2H, dd, J = 6.6 Hz, 2.0 
               
               
                   
                   
                   
                 Hz), 7.47 (2H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                 8.47-8.51 (1H, m), 9.04 (1H, d, J = 
               
               
                   
                   
                   
                 2.6 Hz) 
               
               
                 959 
                 3,4- 
                 —CH 2 Cl 
                 4.59 (2H, s), 6.95 (1H, d, J = 8.9 
               
               
                   
                 Cl 2 PhCONH— 
                   
                 Hz), 7.10 (2H, d, J = 8.6 Hz), 7.40 
               
               
                   
                   
                   
                 (2H, d, J = 8.6 Hz), 7.54 (1H, d, J = 
               
               
                   
                   
                   
                 8.2 Hz), 7.71-7.75 (1H, m), 7.99 
               
               
                   
                   
                   
                 (1H, d, J = 2.3 Hz), 8.18-8.22 
               
               
                   
                   
                   
                 (2H, m), 8.30 (1H, d, J = 2.6 Hz). 
               
               
                 960 
                 4-CNPhCONH— 
                 —CH 2 Cl 
                 4.60 (2H, s), 6.99 (1H, d, J = 8.9 
               
               
                   
                   
                   
                 Hz), 7.12 (2H, d, J = 8.6 Hz), 7.42 
               
               
                   
                   
                   
                 (2H, d, J = 8.6 Hz), 7.79 (2H, d, J = 
               
               
                   
                   
                   
                 8.3 Hz), 7.97-8.00 (3H, m), 8.21 
               
               
                   
                   
                   
                 (1H, dd, J = 8.9 Hz, 2.6 Hz), 8.27 
               
               
                   
                   
                   
                 (1H, d, J = 2.6 Hz). 
               
               
                 961 
                 4-ClPhCONH— 
                 —CH 2 Cl 
                 4.61 (2H, s), 6.99 (1H, d, J = 9.6 
               
               
                   
                   
                   
                 Hz), 7.12 (2H, d, J = 8.3 Hz), 7.42 
               
               
                   
                   
                   
                 (2H, d, J = 8.3 Hz), 7.48 (2H, d, J = 
               
               
                   
                   
                   
                 8.3 Hz), 7.75 (1H, brs), 7.85 (2H, d, 
               
               
                   
                   
                   
                 J = 8.3 Hz), 8.20-8.25 (2H, m). 
               
               
                   
               
               
                 962 
                 —CH 2 Cl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2.41-2.45 (4H, m), 3.03 (3H, s), 3.43 (2H, brs), 3.49 (2H, brs), 3.63 (2H, brs), 4.08 (2H, s), 4.54 (2H, s), 5.94 (2H, s), 6.70 (2H, d, J = 9.2 Hz), 6.73-6.77 (2H, m), 6.82 (1H, d, J = 8.6 Hz), 6.85 (1H, brs), 7.00 (2H, d, J = 9.2 Hz), 7.67 (1H, dd, J = 8.6 Hz, 2.5 Hz), 8.15 (1H, d, J = 2.5 Hz). 
               
               
                   
               
               
                 (CNPh means a cyanophenyl group. Hereinafter CNPh indicates the same meaning.) 
               
             
          
         
       
     
       Reference Example 963 
     Production of 3,4-dichloro-N-{6-[4-(5-chloropentyl)-phenoxy]pyridin-3-yl}benzamide hydrochloride 
       [1050]    To 3,4-dichloro-N-{6-[4-(5-hydroxypentyl)-phenoxy]pyridin-3-yl}benzamide (6.83 g, 15.34 mmol) was added thionyl chloride (35 mL). The resulting solution was stirred for 20 minutes at room temperature, followed by stirring for 1 hour at 50° C. Excess thionyl chloride was evaporated, after which to the resulting residue was added ethyl acetate (100 mL). The obtained white powder was filtered, and washed with ethyl acetate, to thereby yield 6.98 g of the title compound. 
         [1051]    Appearance: White powder 
         [1052]      1 H NMR (DMSO-d 6 ) δ 1.33-1.50 (2H, m), 1.50-1.68 (2H, m), 1.68-1.85 (2H, m), 2.59 (2H, t, J=7.6 Hz), 3.64 (2H, t, J=6.6 Hz), 7.02 (2H, d, J=8.5 Hz), 7.03 (1H, d, J=9.0 Hz), 7.23 (2H, d, J=8.5 Hz), 7.83 (1H, d, J=8.5 Hz), 7.97 (1H, dd, J=8.5 Hz, 2.0 Hz), 8.20 (1H, dd, J=9.0 Hz, 2.5 Hz), 8.25 (1H, d, J=2.0 Hz), 8.50 (1H, d, J=2.5 Hz), 10.63 (1H, s). 
         [1053]    The following compounds were produced in the same manner as in Reference Example 963. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 134 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
                   
                   
               
               
                 Example No. 
                 R 402   
                 R 403   
                 M 
                 Form 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 964 
                 —Cl 
                 —Cl 
                 2 
                 free 
                 (CDCl 3 ) 3.04-3.10 (2H, m), 3.69-3.75 (2H, 
               
               
                   
                   
                   
                   
                   
                 m), 6.95 (1H, d, J = 8.6 Hz), 7.06-7.09 (2H, 
               
               
                   
                   
                   
                   
                   
                 m), 7.24 (2H, d, J = 8.2 Hz), 7.56 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.2 Hz), 7.69 (1H, dd, J = 8.2 Hz, 2.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.93 (1H, brs), 7.97 (1H, d, J = 2.0 Hz), 8.15- 
               
               
                   
                   
                   
                   
                   
                 8.19 (1H, m), 8.24 (1H, d, J = 2.6 Hz). 
               
               
                 965 
                 —Cl 
                 —Cl 
                 3 
                 free 
                 (CDCl 3 ) 2.04-2.12 (2H, m), 2.76-2.81 (2H, 
               
               
                   
                   
                   
                   
                   
                 m), 3.53-3.58 (2H, m), 6.94 (1H, d, J = 8.9 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.04-7.07 (2H, m), 7.20-7.26 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 7.56 (1H, d, J = 8.1 Hz), 7.70 (1H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 8.4 Hz, 2.2 Hz), 7.90 (1H, brs), 7.97 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 2.2 Hz), 8.14-8.18 (1H, m), 8.24 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 2.7 Hz). 
               
               
                 966 
                 —CF 3   
                 —H 
                 3 
                 free 
                 (CDCl 3 ) 2.04-2.14 (2H, m), 2.75-2.81 (2H, 
               
               
                   
                   
                   
                   
                   
                 m), 3.53-3.57 (2H, m), 6.93 (1H, d, J = 8.7 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.03-7.07 (2H, m), 7.20-7.23 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 7.73 (2H, d, J = 8.2 Hz), 7.97 (2H, d, J = 8.2 
               
               
                   
                   
                   
                   
                   
                 Hz), 8.09 (1H, brs), 8.16-8.21 (1H, m), 
               
               
                   
                   
                   
                   
                   
                 8.25 (1H, d, J = 2.6 Hz). 
               
               
                 967 
                 —Cl 
                 —Cl 
                 4 
                 hydrochloride 
                 (DMSO-d 6 ) 1.60-1.85 (4H, m), 2.62 (2H, t, J = 
               
               
                   
                   
                   
                   
                   
                 6.3 Hz), 3.68 (2H, t, J = 6.3 Hz), 7.03 (2H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.5 Hz), 7.04 (1H, d, J = 9.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.24 (2H, d, J = 8.5 Hz), 7.83 (1H, d, J = 8.6 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.97 (1H, dd, J = 8.6 Hz, 2.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.20 (1H, dd, J = 9.0 Hz, 2.7 Hz), 8.25 (1H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 2.2 Hz), 8.50 (1H, d, J = 2.7 Hz), 
               
               
                   
                   
                   
                   
                   
                 10.64 (1H, s). 
               
               
                   
               
             
          
         
       
     
       Reference Example 968 
     Production of N-{6-[4-(2-bromoacetyl)phenoxy]pyridin-3-yl}-3,4-dichlorobenzamide 
       [1054]    N-[6-(4-acetylphenoxy)pyridin-3-yl}-3,4-dichlorobenzamide (4.0 g, 10 mmol) was dissolved in chloroform (200 mL). To the resulting solution was added copper bromide (5.76 g, 25 mmol), and refluxed overnight. The resulting reaction solution was filtered, and the filtrate was washed with saturated sodium thiosulfate solution and brine. The organic layer was dried over anhydrous magnesium sulfate, and evaporated. To the filtered product from the earlier step was added ethyl acetate, and washed with saturated sodium thiosulfate water and brine. The organic layer was dried over anhydrous magnesium sulfate, and evaporated. The residues were combined for purification by silica gel column chromatography (n-hexane:ethyl acetate=3:1), to thereby yield 1.86 g of the title compound. 
         [1055]    Appearance: White powder 
         [1056]      1 H NMR (CDCl 3 ) δ 4.43 (2H, s), 7.06 (1H, d, J=8.7 Hz), 7.21 (2H, d, J=8.9 Hz), 7.57 (1H, d, J=8.4 Hz), 7.72 (1H, dd, J=8.4 Hz, 2.0 Hz), 7.99 (1H, d, J=2.0 Hz), 8.03 (2H, d, J=8.9 Hz), 8.09 (1H, brs), 8.27 (1H, dd, J=8.7 Hz, 2.8 Hz), 8.32 (1H, d, J=2.2 Hz). 
         [1057]    The following compound was produced in the same manner as in Reference Example 968. 
       Reference Example 969 
     N-{4-[4-(2-Bromoacetyl)phenoxy]-3-fluorophenyl}-3,4-dichlorobenzamide 
       [1058]      1 H NMR (DMSO-D 6 ) δ 4.88 (2H, s), 7.06 (2H, d, J=8.9 Hz), 7.30-7.50 (1H, m), 7.60-7.70 (1H, m), 7.80-8.20 (5H, m), 8.22 (1H, d, J=2.0 Hz), 10.67 (1H, brs). 
       Reference Example 970 
     Production of 4′-[4-(3-bromopropyl)phenoxy]-3,4-dichloro-3′-fluorobenzanilide 
       [1059]    To a suspension of 3,4-dichloro-3′-fluoro-4′-[4-(3-hydroxypropyl)phenoxy]benzanilide (2.32 g, 5.34 mmol) in dichloromethane (46 mL) were added carbon tetrabromide (2.13 g, 6.41 mmol) and triphenylphosphine (1.54 g, 5.88 mmol), and the resulting solution was stirred for 12 hours at room temperature. The reaction solution was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=5:1), to thereby yield 2.41 g of the title compound. 
         [1060]    Appearance: White powder 
         [1061]      1 H NMR (CDCl 3 ) δ 2.08-2.11 (2H, m), 2.73 (2H, t, J=7.3 Hz), 3.38 (2H, t, J=6.5 Hz), 6.88 (2H, d, J=8.5 Hz), 7.02 (1H, dd, J=9.0 Hz, 8.0 Hz), 7.13 (2H, d, J=8.5 Hz), 7.17-7.28 (1H, m), 7.54 (1H, d, J=8.3 Hz), 7.60-7.74 (2H, m), 7.85 (1H, brs), 7.93 (1H, d, J=2.0 Hz). 
         [1062]    The following compounds were produced in the same manner as in Reference Example 970. 
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 135 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
               
               
                 Example No. 
                 M 
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 971 
                 2 
                 3.13 (2H, t, J = 7.5 Hz), 3.55 (2H, t, J = 7.5 Hz), 
               
               
                   
                   
                 6.91 (2H, d, J = 6.6 Hz), 7.08 (1H, t, J = 8.7 Hz), 
               
               
                   
                   
                 7.15 (2H, d, J = 6.6 Hz), 7.18-7.25 (1H, m), 7.56 (1H, 
               
               
                   
                   
                 d, J = 8.3 Hz), 7.65-7.75 (2H, m), 7.90-8.00 (2H, m). 
               
               
                 972 
                 4 
                 1.67-1.79 (2H, m), 1.81-1.94 (2H, m), 2.60 (2H, t, J = 
               
               
                   
                   
                 7.5 Hz), 3.40 (2H, t, J = 6.6 Hz), 6.88 (2H, d, J = 8.6 
               
               
                   
                   
                 Hz), 7.02 (1H, dd, J = 9.0 Hz, 8.0 Hz), 7.11 (2H, d, 
               
               
                   
                   
                 J = 8.6 Hz), 7.14-7.21 (1H, m), 7.55 (1H, d, J = 8.3 
               
               
                   
                   
                 Hz), 7.60-7.73 (2H, m), 7.78 (1H, brs), 7.93 (1H, d, 
               
               
                   
                   
                 J = 1.9 Hz). 
               
               
                   
               
             
          
         
       
     
       Reference Example 973 
     Production of t-butyl 4-[4-(5-nitropyridin-2-yloxy)benzyl]piperazine-1-carboxylate 
       [1063]    To a solution of 2-(4-chloromethylphenoxy)-5-nitropyridine (12.32 g, 47 mmol) in DMF (120 mL) were added triethylamine (19.4 mL, 140 mmol) and t-butyl piperazine-1-carboxylate 11.27 g, 61 mmol), and the resulting solution was stirred for 3 hours at 50° C. Water was added to the residue, and extracted with ethyl acetate. The ethyl acetate layer was washed with water and brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=1:1), to thereby yield 11.26 g of the title compound. 
         [1064]    Appearance: Yellow powder 
         [1065]      1 H NMR (CDCl 3 ) δ 1.46 (9H, s), 2.40-2.44 (4H, m), 3.43-3.46 (4H, m), 3.54 (2H, s), 7.04 (1H, d, J=8.9 Hz), 7.09-7.14 (2H, m), 7.38-7.44 (2H, m), 8.48 (1H, dd, J=8.9 Hz, 2.8 Hz), 9.05 (1H, d, J=2.8 Hz). 
         [1066]    The following compound was produced in the same manner as in Reference Example 973. 
       Reference Example 974 
     4-{1-[4-(5-Nitropyridin-2-yloxy)phenyl]ethyl}morpholine 
       [1067]      1 H NMR (CDCl 3 ) δ 1.38 (3H, d, J=6.8 Hz), 2.36-2.54 (4H, m), 3.37 (1H, q, J=6.8 Hz), 3.69-3.72 (4H, m), 7.02 (1H, dd, J=9.1 Hz, 0.5 Hz), 7.11 (2H, d, J=8.6 Hz), 7.40 (2H, d, J=8.5 Hz), 8.47 (1H, dd, J=9.1 Hz, 2.8 Hz), 9.06 (1H, dd, J=2.8 Hz, 0.5 Hz). 
       Reference Example 975 
     Production of methanesulfonic acid 6-(4-nitrophenoxy)-pyridin-3-ylmethyl ester 
       [1068]    [6-(4-nitrophenoxy)pyridin-3-yl]methanol (6.1 g, 24.8 mmol) was dissolved in dichloromethane (150 mL), and to the resulting solution was added triethylamine (4.15 mL, 29.8 mmol) under ice cooling. To the resulting solution was added dropwise methanesulfonic acid chloride (2.11 mL, 27.3 mmol), and then stirred under a nitrogen atmosphere for 30 minutes at 0° C. The reaction solution was washed with a saturated sodium bicarbonate solution and brine. The organic layer was dried over anhydrous magnesium sulfate, and evaporated. To the residue was added a mixed solvent (50 mL) of n-hexane ethyl acetate=1:1. The precipitated crystals were removed by suction filtration, to thereby yield 7.9 g of the title compound. 
         [1069]    Appearance: White powder 
         [1070]      1 H NMR (CDCl 3 ) δ 3.04 (3H, s), 5.23 (2H, s), 7.09 (1H, d, J=8.4 Hz), 7.29 (2H, d, J=9.1 Hz), 7.88 (1H, dd, J=8.4 Hz, 2.5 Hz), 8.23 (1H, d, J=2.3 Hz), 8.28 (2H, d, J=9.1 Hz). 
         [1071]    The following compounds were produced in the same manner as in Reference Example 975. 
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 136 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Reference 
                   
                   
                   
               
               
                 Example No. 
                 R 404   
                 R 405   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 976 
                 —CH 3   
                 —NO 2   
                 2.29 (3H, s), 3.03 (3H, s), 5.22 (2H, s), 
               
               
                   
                   
                   
                 7.08 (1H, dd, J = 8.4 Hz, 0.5 Hz), 7.18 (1H, 
               
               
                   
                   
                   
                 d, J = 8.9 Hz), 7.86 (1H, dd, J = 8.4 Hz, 2.5 
               
               
                   
                   
                   
                 Hz), 8.11 (1H, dd, J = 8.9 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                 8.17 (1H, dd, J = 2.5 Hz, 0.5 Hz), 8.19 (1H, 
               
               
                   
                   
                   
                 d, J = 2.8 Hz). 
               
               
                   
               
               
                 977 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2.65 (4H, brs), 3.01 (3H, s), 3.65-3.75 (6H, m), 5.22 (2H, s), 5.97 (2H, s), 6.79 (2H, s), 6.92 (1H, s), 7.00 (1H, d, J = 8.4 Hz), 7.18 (2H, d, J = 8.6 Hz), 7.47 (2H, d, J = 8.7 Hz), 7.81 (1H, dd, J = 2.5 Hz, 8.4 Hz), 8.20 (1H, d, J = 2.0 Hz). 
               
               
                   
               
             
          
         
       
     
       Reference Example 978 
     Production of 2-(4-nitrophenoxy)-5-(4-trifluoromethyl-phenoxymethyl)pyridine 
       [1072]    Methanesulfonic acid 6-(4-nitrophenoxy)-pyridin-3-ylmethyl ester (4.86 g, 15 mmol) was dissolved in DMF (250 mL), and to the resulting solution were added 4-hydroxybenzotrifluoride (2.92 g, 18 mmol) and potassium carbonate (3.11 g, 22.5 mmol). The resulting solution was stirred under a nitrogen atmosphere for 1 hour at 50° C. The reaction solution was concentrated under reduced pressure. To the residue was added ethyl acetate, and washed with a saturated sodium bicarbonate solution and brine. The organic layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatography (dichloromethane methanol=80:1), to thereby yield 5.8 g of the title compound. 
         [1073]    Appearance: Pale yellow powder 
         [1074]      1 H NMR (CDCl 3 ) δ 5.09 (2H, s), 7.02-7.10 (3H, m), 7.26-7.31 (2H, m), 7.56-7.59 (2H, m), 7.88 (1H, dd, J=8.4 Hz, 2.5 Hz), 8.25-8.31 (3H, m). 
         [1075]    The following compound was produced in the same manner as in Reference Example 978. 
       Reference Example 979 
     2-(2-Methyl-4-nitrophenoxy)-5-(4-trifluoromethyl-phenoxymethyl)pyridine 
       [1076]      1 H NMR (CDCl 3 ) δ 2.31 (3H, s), 5.07 (2H, s), 7.03 (2H, d, J=8.6 Hz), 7.08 (1H, d, J=8.4 Hz), 7.17 (1H, d, J=8.9 Hz), 7.57 (2H, d, J=8.4 Hz), 7.87 (1H, dd, J=8.4 Hz, 2.5 Hz), 8.10 (1H, dd, J=8.9 Hz, 2.8 Hz), 8.18 (1H, d, J=2.6 Hz), 8.21 (1H, d, J=2.5 Hz). 
       Example 1 
     Production of N-{6-[4-(4-benzylpiperazine-1-carbonyl)-phenoxy]pyridin-3-yl}-4-trifluoromethylbenzamide 
       [1077]    To a solution of 4-[5-(4-trifluoromethyl-benzoylamino)pyridin-2-yloxy]benzoic acid (1.19 g, 2.3 mmol) in DMF (30 mL) were added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (530 mg, 2.8 mmol), 1-hydroxybenzotriazole monohydrate (370 mg, 2.7 mmol) and benzylpiperazine (0.475 mL, 2.7 mmol) under ice cooling. The resulting solution was stirred for 1 day gradually warming up to room temperature. To the residue was added a saturated sodium bicarbonate solution and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatography (methanol:chloroform=1:19), to thereby yield 800 mg of the title compound. 
         [1078]    Appearance: White needles 
         [1079]      1 H NMR (CDCl 3 ) δ 2.46 (4H, brs), 3.55 (2H, s), 3.72 (4H, brs), 6.96 (1H, d, J=8.9 Hz), 7.10-7.13 (2H, m), 7.28-7.40 (7H, m), 7.74 (2H, d, J=8.3 Hz), 8.02 (2H, d, J=8.3 Hz), 8.16-8.21 (1H, m), 8.32 (1H, d, J=2.6 Hz), 8.53 (1H, brs). 
         [1080]    The following compounds were produced in the same manner as in Example 1. 
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 137 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 501   
                 R 502   
                 Form 
                 mp (° C.) 
               
               
                   
               
               
                 2 
                 —H 
                 —CH 3   
                 hydrochloride 
                 175-176 
               
               
                 3 
                 —H 
                 benzyl 
                 hydrochloride 
                 187-189 
               
               
                 4 
                 —H 
                 piperonyl 
                 free 
                 182-183 
               
               
                 5 
                 —H 
                 —COOC(CH 3 ) 3   
                 free 
                 217-220 
               
               
                 6 
                 —H 
                 -Ac 
                 free 
                 152-154 
               
               
                 7 
                 —H 
                 —(CH 2 ) 2 OH 
                 hydrochloride 
                 153-155 
               
               
                 8 
                 —F 
                 benzyl 
                 free 
                 172-173 
               
               
                 9 
                 —F 
                 piperonyl 
                 free 
                 170-171 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 138 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 503   
                 R 504   
                 Form 
                 mp (° C.) 
               
               
                   
               
               
                 10 
                 —H 
                 morpholino 
                 free 
                 189-192 
               
               
                 11 
                 —F 
                 morpholino 
                 free 
                 203-204 
               
               
                   
               
               
                 12 
                 —F 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 210-211 
               
               
                   
               
               
                 13 
                 —F 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 hydrochloride 
                 233-235 
               
               
                   
               
               
                 14 
                 —F 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 hydrochloride 
                 247-249 
               
               
                   
               
               
                 15 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 174-175 
               
               
                   
               
               
                 16 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 hydrochloride 
                 213-216 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 139 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 505   
                 R 506   
                   1 H NMR (DMSO-d 6 ) δ ppm 
               
               
                   
               
               
                 17 
                 —CH 3   
                 —NHAc 
                 1.92 (3H, s), 2.17 (3H, s), 7.13 
               
               
                   
                   
                   
                 (1H, d, J = 8.2 Hz), 7.14 (1H, d, 
               
               
                   
                   
                   
                 J = 8.9 Hz), 7.74 (1H, dd, 
               
               
                   
                   
                   
                 J = 8.2 Hz, 2.2 Hz), 7.84 (1H, d, 
               
               
                   
                   
                   
                 J = 8.2 Hz), 7.84 (1H, d, J = 2.2 
               
               
                   
                   
                   
                 Hz), 7.95 (1H, dd, J = 8.2 Hz, 
               
               
                   
                   
                   
                 2.2 Hz), 8.22 (1H, d, J = 2.2 
               
               
                   
                   
                   
                 Hz), 8.23 (1H, dd, J = 8.9 Hz, 
               
               
                   
                   
                   
                 2.6 Hz), 8.46 (1H, d, J = 2.6 
               
               
                   
                   
                   
                 Hz), 9.89 (1H, s), 10.24 (1H, s), 
               
               
                   
                   
                   
                 10.57 (1H, s). 
               
               
                 18 
                 —H 
                 cyclopropyl 
                 0.51-0.60 (2H, m), 0.66-0.74 
               
               
                   
                   
                   
                 (2H, m), 2.80-2.89 (1H, m), 
               
               
                   
                   
                   
                 7.10-7.20 (3H, m), 7.81-7.89 
               
               
                   
                   
                   
                 (3H, m), 7.95 (1H, dd, J = 8.4 
               
               
                   
                   
                   
                 Hz, 2.1 Hz), 8.19-8.28 (2H, m), 
               
               
                   
                   
                   
                 8.42 (1H, brd), 8.52 (1H, d, 
               
               
                   
                   
                   
                 J = 2.7 Hz), 10.59 (1H, s). 
               
               
                 19 
                 —H 
                 cyclohexyl 
                 1.06-1.19 (1H, m), 1.21-1.36 
               
               
                   
                   
                   
                 (4H, m), 1.55-1.65 (1H, m), 
               
               
                   
                   
                   
                 1.69-1.78 (2H, m), 1.78-1.87 
               
               
                   
                   
                   
                 (2H, m), 3.69-3.80 (1H, m), 
               
               
                   
                   
                   
                 7.10-7.20 (3H, m), 7.85 (1H, d, 
               
               
                   
                   
                   
                 J = 8.4 Hz), 7.86-7.92 (2H, m), 
               
               
                   
                   
                   
                 7.95 (1H, dd, J = 8.4 Hz, 2.1 
               
               
                   
                   
                   
                 Hz), 8.17 (1H, brd), 8.20-8.29 
               
               
                   
                   
                   
                 (2H, m), 8.52 (1H, d, J = 2.7 
               
               
                   
                   
                   
                 Hz), 10.58 (1H, s). 
               
               
                 20 
                 —H 
                 cyclopentyl 
                 1.46-1.60 (4H, m), 1.63-1.76 
               
               
                   
                   
                   
                 (2H, m), 1.82-1.94 (2H, m), 
               
               
                   
                   
                   
                 4.17-4.28 (1H, m), 7.10-7.20 
               
               
                   
                   
                   
                 (3H, m), 7.85 (1H, d, J = 8.4 
               
               
                   
                   
                   
                 Hz), 7.87-7.92 (2H, m), 7.95 
               
               
                   
                   
                   
                 (1H, dd, J = 8.4 Hz, 2.1 Hz), 
               
               
                   
                   
                   
                 8.19-8.28 (3H, m), 8.52 (1H, d, 
               
               
                   
                   
                   
                 J = 2.6 Hz), 10.58 (1H, s). 
               
               
                 21 
                 —H 
                 cycloheptyl 
                 1.36-1.71 (10H, m), 1.80-1.90 
               
               
                   
                   
                   
                 (2H, m), 3.88-4.00 (1H, m), 
               
               
                   
                   
                   
                 7.10-7.20 (3H, m), 7.85 (1H, d, 
               
               
                   
                   
                   
                 J = 8.4 Hz), 7.86-7.92 (2H, m), 
               
               
                   
                   
                   
                 7.95 (1H, dd, J = 8.4 Hz, 2.1 
               
               
                   
                   
                   
                 Hz), 8.17-8.28 (3H, m), 8.51 
               
               
                   
                   
                   
                 (1H, d, J = 2.6 Hz), 10.58 (1H, 
               
               
                   
                   
                   
                 s). 
               
               
                 22 
                 —H 
                 cyclododecanyl 
                 1.20-1.57 (20H, m), 1.61-1.63 
               
               
                   
                   
                   
                 (2H, m), 4.08-4.21 (1H, m), 
               
               
                   
                   
                   
                 7.10-7.21 (3H, m), 7.85 (1H, d, 
               
               
                   
                   
                   
                 J = 8.4 Hz), 7.88-7.92 (2H, m), 
               
               
                   
                   
                   
                 7.95 (1H, dd, J = 8.4 Hz, 2.1 
               
               
                   
                   
                   
                 Hz), 8.09 (1H, brd), 8.20-8.29 
               
               
                   
                   
                   
                 (2H, m), 8.51 (1H, d, J = 2.7 
               
               
                   
                   
                   
                 Hz), 10.58 (1H, s). 
               
               
                 23 
                 —H 
                 cyclooctyl 
                 1.44-1.65 (8H, m), 1.65-1.80 
               
               
                   
                   
                   
                 (6H, m), 3.98-4.09 (1H, m), 
               
               
                   
                   
                   
                 7.10-7.20 (3H, m), 7.85 (1H, d, 
               
               
                   
                   
                   
                 J = 8.4 Hz), 7.88-7.92 (2H, m), 
               
               
                   
                   
                   
                 7.95 (1H, dd, J = 8.4 Hz, 2.1 
               
               
                   
                   
                   
                 Hz), 8.17-8.27 (3H, m), 8.51 
               
               
                   
                   
                   
                 (1H, d, J = 2.7 Hz), 10.58 (1H, 
               
               
                   
                   
                   
                 s). 
               
               
                 24 
                 —H 
                 cyclopropyl-methyl 
                 0.19-0.26 (2H, m), 0.38-0.47 
               
               
                   
                   
                   
                 (2H, m), 0.99-1.09 (1H, m), 
               
               
                   
                   
                   
                 3.12-3.19 (2H, m), 7.12-7.21 
               
               
                   
                   
                   
                 (3H, m), 7.85 (1H, d, J = 8.4 
               
               
                   
                   
                   
                 Hz), 7.89-7.94 (2H, m), 7.95 
               
               
                   
                   
                   
                 (1H, dd, J = 8.4 Hz, 2.1 Hz), 
               
               
                   
                   
                   
                 8.21-8.29 (2H, m), 8.53 (1H, d, 
               
               
                   
                   
                   
                 J = 2.8 Hz), 8.54 (1H, brt), 
               
               
                   
                   
                   
                 10.60 (1H, s). 
               
               
                 25 
                 —H 
                 —(CH 2 ) 2 NHAc 
                 1.81 (3H, s), 3.15-3.24 (2H, m), 
               
               
                   
                   
                   
                 3.24-3.33 (2H, m), 7.10-7.20 
               
               
                   
                   
                   
                 (3H, m), 7.80-8.00 (5H, m), 
               
               
                   
                   
                   
                 8.20-8.26 (2H, m), 8.48 (1H, 
               
               
                   
                   
                   
                 brt), 8.52 (1H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                 10.59 (1H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 140 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 507   
                 Form 
                   1 H NMR (solvent) δ ppm or MS 
               
               
                   
               
               
                 26 
                 morpholino 
                 hydro- 
                   1 H NMR (DMSO-d 6 ) 3.50-3.65 (8 H, m), 7.13- 
               
               
                   
                   
                 chloride 
                 7.19 (3 H, m), 7.47 (2 H, d, J = 8.6 Hz), 7.84 (1 H, d, J = 
               
               
                   
                   
                   
                 8.2 Hz), 7.97 (1 H, dd, J = 8.3 Hz, 2.0 Hz), 8.23- 
               
               
                   
                   
                   
                 8.27 (2 H, m), 8.54 (1 H, d, J = 2.6 Hz), 10.63 (1 H, s). 
               
               
                   
               
               
                 27 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                   1 H NMR (CDCl 3 ) 1.81-1.95 (2 H, m), 2.59-2.77 (4 H, m), 3.51-3.57 (4 H, m), 3.75 (2 H, brs), 5.94 (2 H, s), 6.71-6.75 (2 H, m), 6.83-6.93 (2 H, m), 7.05-7.10 (2 H, m), 7.32-7.37 (2 H, m), 7.54 (1 H, d, J = 8.2 Hz), 7.79 (1 H, dd, J = 8.3 Hz, 2.0 Hz), 8.06-8.10 (2 H, m), 8.30 (1 H, s), 8.96 (1 H, s). 
               
               
                   
               
               
                 28 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 MS 574 (M + ) 
               
               
                   
               
               
                 29 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 MS 611 (M + ) 
               
               
                   
               
               
                 30 
                 —NH(CH 2 ) 2 OCH 3   
                 free 
                   1 H NMR (DMSO-d 6 ) 3.32 (3 H, s), 3.39-3.48 (4 H, m), 
               
               
                   
                   
                   
                 7.15-7.20 (3 H, m), 7.85 (1 H, d, J = 8.3 Hz), 7.86- 
               
               
                   
                   
                   
                 7.92 (2 H, m), 7.95 (1 H, dd, J = 8.4 Hz, 2.1 Hz), 8.20- 
               
               
                   
                   
                   
                 8.26 (2 H, m), 8.50 (1 H, brt), 8.52 (1 H, d, J = 2.5 Hz), 
               
               
                   
                   
                   
                 10.59 (1 H, s). 
               
               
                   
               
               
                 31 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 MS 601 (M +  − 1) 
               
               
                   
               
               
                 32 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                   1 H NMR (DMSO-d 6 ) 0.86-0.99 (2 H, m), 1.10- 1.27 (3 H, m), 1.50-1.65 (2 H, m), 1.65-1.78 (4 H, m), 3.06-3.15 (2 H, m), 7.11-7.22 (3 H, m), 7.85 (1 H, d, J = 8.4 Hz), 7.88-7.92 (2 H, m), 7.95 (1 H, dd, J = 8.4 Hz, 2.1 Hz), 8.20-8.28 (2 H, m), 8.40 (1 H, brt), 8.52 (1 H, d, J = 2.7 Hz), 10.58 (1 H, s). 
               
               
                   
               
               
                 33 
                 —NH(CH 2 ) 2 OPh 
                 free 
                   1 H NMR (DMSO-d 6 ) 3.63 (2 H, t, J = 5.8 Hz), 
               
               
                   
                   
                   
                 4.12 (2 H, t, J = 5.9 Hz), 6.90-7.01 (3 H, m), 7.13- 
               
               
                   
                   
                   
                 7.24 (3 H, m), 7.26-7.35 (2 H, m), 7.85 (1 H, d, J = 8.4 
               
               
                   
                   
                   
                 Hz), 7.90-8.00 (3 H, m), 8.20-8.30 (2 H, m), 8.52 (1 H, 
               
               
                   
                   
                   
                 d, J = 2.6 Hz), 8.69 (1 H, brt), 10.59 (1 H, s). 
               
               
                   
               
               
                 34 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 MS 574 (M + ) 
               
               
                   
               
               
                 35 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                   1 H NMR (CDCl 3 ) 1.80-1.96 (2 H, m), 2.61-2.79 (4 H, m), 3.45-3.57 (2 H, m), 3.62-3.67 (2 H, m), 3.75- 3.77 (2 H, m), 6.94 (1 H, d, J = 8.6 Hz), 7.08-7.13 (2 H, m), 7.24-7.41 (7 H, m), 7.56 (1 H, d, J = 8.6 Hz), 7.76 (1 H, dd, J = 8.6 Hz, 2.0 Hz), 8.04 (1 H, d, J = 2.0 Hz), 8.07-8.14 (1 H, m), 8.29 (1 H, d, J = 2.0 Hz), 8.39 (1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 141 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 508   
                 Property 
               
               
                   
               
               
                 36 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 mp 221-224° C. 
               
               
                   
               
               
                 37 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 mp 228-230° C. 
               
               
                   
               
               
                 38 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 mp 193-194° C. 
               
               
                   
               
               
                 39 
                 —N(CH 3 )COOC(CH 3 ) 3   
                   1 H NMR (CDCl 3 ) δ 1.47 (9 H, s), 1.45-1.81 (4 H, m), 
               
               
                   
                   
                 2.73 (3 H, s), 2.90 (2 H, brs), 4.10 (2 H, brs), 4.75 (1 H, 
               
               
                   
                   
                 brs), 6.95 (1 H, d, J = 8.7 Hz), 7.11 (2 H, d, J = 8.7 
               
               
                   
                   
                 Hz), 7.39 (2 H, d, J = 8.7 Hz), 7.55 (1 H, d, J = 8.2 
               
               
                   
                   
                 Hz), 7.77 (1 H, dd, J = 8.2 Hz, 2.0 Hz), 8.05 (1 H, d, J = 
               
               
                   
                   
                 2.0 Hz), 8.14 (1 H, dd, J = 8.7 Hz, 2.6 Hz), 
               
               
                   
                   
                 8.30 (1 H, d, J = 2.6 Hz), 8.77 (1 H, s). 
               
               
                 40 
                 —OPh 
                 MS 560 (M +  − 1) 
               
               
                 41 
                 4-CF 3 OPhO— 
                 MS 629 (M + ) 
               
               
                 42 
                 4-CF 3 OPhO— 
                 MS 644 (M +  − 1) 
               
               
                 43 
                 4-CNPhO— 
                 MS 586 (M + ) 
               
               
                 44 
                 —C 2 H 5   
                 MS 496 (M +  − 1) 
               
               
                 45 
                 —COOC 2 H 5   
                   1 H NMR (CDCl 3 ) δ 1.27 (3 H, t, J = 7.0 Hz), 
               
               
                   
                   
                 1.73 (2 H, brs), 1.95 (2 H, brs), 2.58 (1 H, m), 3.08 (2 H, 
               
               
                   
                   
                 brs), 3.86 (1 H, brs), 4.16 (2 H, q, J = 7.0 Hz), 
               
               
                   
                   
                 4.50 (1 H, brs), 6.97 (1 H, d, J = 9.0 Hz), 7.12 (2 H, d, 
               
               
                   
                   
                 J = 8.5 Hz), 7.40 (2 H, d, J = 8.5 Hz), 7.57 (1 H, d, J = 
               
               
                   
                   
                 8.5 Hz), 7.75 (1 H, dd, J = 8.5 Hz, 2.0 Hz), 
               
               
                   
                   
                 8.03 (1 H, d, J = 2.0 Hz), 8.16 (1 H, dd, J = 9.0 Hz, 
               
               
                   
                   
                 3.0 Hz), 8.30 (1 H, d, J = 3.0 Hz), 8.34 (1 H, brs). 
               
               
                 46 
                 —(CH 2 ) 2 N(CH 3 )Ph 
                 MS 602 (M + ) 
               
               
                 47 
                 2-FPhCH 2 O— 
                 MS 592 (M +  − 1) 
               
               
                 48 
                 PhCH 2 O— 
                 MS 574 (M +  − 1) 
               
               
                 49 
                 cyclohexyl 
                 MS 550 (M +  − 1) 
               
               
                 50 
                 4-ClPh- 
                 MS 580 (M +  + 1) 
               
               
                 51 
                 -Ph 
                 MS 544 (M +  − 1) 
               
               
                 52 
                 —CHPh 2   
                 MS 635 (M + ) 
               
               
                 53 
                 2-NH 2 PhCO— 
                 MS 587 (M +  − 1) 
               
               
                 54 
                 4-CH 3 OPhCONH— 
                 MS 617 (M +  − 1) 
               
               
                 55 
                 —NHCOPh 
                 MS 587 (M +  − 1) 
               
               
                 56 
                 4-CF 3 PhCH 2 O— 
                 mp 186-187° C. 
               
               
                 57 
                 4-ClPhCH 2 O— 
                 mp 176-177° C. 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 142 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 509   
                 MS 
               
               
                   
               
               
                 58 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 580 (M +  − 1) 
               
               
                   
               
               
                 59 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 610 (M +  − 1) 
               
               
                   
               
               
                 60 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 580 (M +  − 1) 
               
               
                   
               
               
                 61 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 598 (M +  − 1) 
               
               
                   
               
               
                 62 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 592 (M +  − 1) 
               
               
                   
               
               
                 63 
                 Ph(CH 2 ) 2 N(CH 3 )— 
                 600 (M +  − 2) 
               
               
                 64 
                 Ph 2 CH(CH 2 ) 2 N(CH 3 )— 
                 691 (M +  − 1) 
               
               
                 65 
                 4-CH 3 SPh(CH 2 ) 2 N(CH 3 )— 
                 648 (M + ) 
               
               
                   
               
               
                 66 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 678 (M +  + H) 
               
               
                   
               
               
                 67 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 613 (M +  + H) 
               
               
                   
               
               
                 68 
                 4-CH 3 OPh(CH 2 ) 4 N(CH 3 )— 
                 660 (M + ) 
               
               
                 69 
                 4-CH 3 Ph(CH 2 ) 2 N(CH 3 )— 
                 617 (M +  + H) 
               
               
                 70 
                 PhO(CH 2 ) 2 N(CH 3 )— 
                 618 (M + ) 
               
               
                 71 
                 PhN(CH 3 )(CH 2 ) 2 N(CH 3 )— 
                 631 (M + ) 
               
               
                 72 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 608 (M + ) 
               
               
                 73 
                 —O(CH 2 ) 2 Ph 
                 588 (M +  − 1) 
               
               
                   
               
               
                 74 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 575 (M +  − 1) 
               
               
                   
               
               
                 75 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 576 (M + ) 
               
               
                   
               
               
                 76 
                 4-ClPhCH 2 — 
                 594 (M +  + 1) 
               
               
                   
               
               
                 77 
                 4-CF 3 PhNH— 
                 644 (M + ) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 143 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                   
                 Example 
                   
                   
               
               
                   
                 No. 
                 R 510   
                 MS 
               
               
                   
                   
               
             
          
           
               
                   
                 78 
                 4-CH3PhO(CH 2 ) 2 N(CH 3 )— 
                 633 (M +  + H) 
               
               
                   
                 79 
                 Ph(CH 2 ) 3 N(CH 3 )— 
                 616 (M + ) 
               
               
                   
                 80 
                 2-phenylmorpholino 
                 630 (M + ) 
               
               
                   
                 81 
                 4-CH 3 PhCH 2 — 
                 572 (M +  − 1) 
               
               
                   
                 82 
                 morpholino 
                 554 (M + ) 
               
               
                   
                 83 
                 4-CH 3 OPhCH 2 O— 
                 606 (M +  + H) 
               
               
                   
                 84 
                 3-ClPhCH 2 O— 
                 608 (M +  − 1) 
               
               
                   
                 85 
                 2-ClPhCH 2 O— 
                 608 (M +  − 1) 
               
               
                   
                 86 
                 3,4-Cl 2 PhCH 2 O— 
                 644 (M +  + 1) 
               
               
                   
                 87 
                 3-CH 3 OPhCH 2 O— 
                 604 (M +  − 1) 
               
               
                   
                 88 
                 3,5-(CH 3 O) 2 PhCH 2 O— 
                 634 (M +  − 1) 
               
               
                   
                 89 
                 4-CH 3 PhCH 2 O— 
                 588 (M +  − 1) 
               
               
                   
                 90 
                 3-CH 3 PhCH 2 O— 
                 588 (M +  − 1) 
               
               
                   
                 91 
                 2-CH 3 PhCH 2 O— 
                 588 (M +  − 1) 
               
               
                   
                 92 
                 3,4-(CH 3 ) 2 PhCH 2 O— 
                 602 (M +  − 1) 
               
               
                   
                 93 
                 4-FPhCH 2 O— 
                 592 (M +  − 1) 
               
               
                   
                 94 
                 3-FPhCH 2 O— 
                 592 (M +  − 1) 
               
               
                   
                 95 
                 3,5-F 2 PhCH 2 O— 
                 610 (M +  − 1) 
               
               
                   
                 96 
                 2-CF 3 PhCH 2 O— 
                 642 (M +  − 1) 
               
               
                   
                 97 
                 4-CF 3 OPhCH 2 O— 
                 658 (M +  − 1) 
               
               
                   
                 98 
                 3-CF 3 OPhCH 2 O— 
                 658 (M +  − 1) 
               
               
                   
                 99 
                 2-CF 3 OPhCH 2 O— 
                 658 (M +  − 1) 
               
               
                   
                   
               
               
                   
                 100 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 638 (M +  − 1) 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 144 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 511    
                 mp (° C.) or  1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 101 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 mp 218-220 
               
               
                   
               
               
                 102 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 mp 227-231 
               
               
                   
               
               
                 103 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.09-1.30 (1 H, m), 1.60- 1.87 (4 H, m), 2.55-2.95 (4 H, m), 3.80 (1 H, brs), 4.59 (1 H, brs), 6.92 (1 H, d, J = 8.7 Hz), 7.05-7.35 (9 H, m), 7.71 (2 H, d, J = 8.6 Hz), 8.04 (2 H, d, J = 8.1 Hz), 8.14 (1 H, dd, J = 8.9 Hz, 2.6 Hz), 8.34 (1 H, d, J = 2.6 Hz), 8.99 (1 H, s). 
               
               
                   
               
               
                 104 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.27 (3 H, t, J = 7.0 Hz), 1.74 (2 H, brs), 1.95 (2 H, brs), 2.58 (1 H, m), 3.08 (2 H, brs), 3.92 (1 H, brs), 4.17 (2 H, q, J = 7.0 Hz), 4.51 (1 H, brs), 7.01 (1 H, d, J = 9.0 Hz), 7.16 (2 H, d, J = 8.5 Hz), 7.44 (2 H, d, J = 8.5 Hz), 7.78 (2 H, d, J = 8.0 Hz), 7.88 (1 H, brs), 8.01 (2 H, d, J = 8.0 Hz), 8.24 (1 H, dd, J = 9.0 Hz, 3.0 Hz), 8.32 (1 H, d, J = 3.0 Hz) 
               
               
                   
               
               
                 105 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.46 (9 H, s), 1.50-1.90 (4 H, m), 2.35-3.00 (2 H, m), 2.89 (3 H, s), 4.10- 4.70 (3 H, m), 6.99 (1 H, d, J = 8.7 Hz), 7.14 (2 H, d, J = 8.3 Hz), 7.40 (2 H, d, J = 8.3 Hz), 7.76 (2 H, d, J = 8.1 Hz), 8.03 (2 H, d, J = 8.1 Hz), 8.22 (1 H, dd, J = 8.7 Hz, 2.6 Hz), 8.33 (1 H, d, J = 2.6 Hz), 8.34 (1 H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 145 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 512   
                   1 H NMR (CDCl 3 ) δ ppm or MS 
               
               
                   
               
               
                 106 
                 4-CH 3 OPhCH(Ph)- 
                 MS 665 (M +  − 1) 
               
               
                 107 
                 4-CH 3 OPhCOCH 2 — 
                   1 H NMR 2.63 (4 H, brs), 3.65 (4 H, brs), 3.82 (2 H, 
               
               
                   
                   
                 s), 3.88 (3 H, s), 6.92-6.98 (3 H, m), 7.12 (2 H, d, J = 
               
               
                   
                   
                 8.7 Hz), 7.41 (2 H, d, J = 8.7 Hz), 7.56 (1 H, d, J = 
               
               
                   
                   
                 8.2 Hz), 7.75 (1 H, dd, J = 8.2 Hz, 2.1 Hz), 
               
               
                   
                   
                 7.97 (2 H, d, J = 8.9 Hz), 8.03 (1 H, d, J = 2.0 Hz), 
               
               
                   
                   
                 8.16 (1 H, dd, J = 8.9 Hz, 2.8 Hz), 8.30 (1 H, d, J = 
               
               
                   
                   
                 2.8 Hz), 8.39 (1 H, s). 
               
               
                 108 
                 4-ClPhCOCH 2 — 
                   1 H NMR 2.63 (4 H, brs), 3.66 (4 H, brs), 3.83 (2 H, 
               
               
                   
                   
                 s), 6.97 (1 H, d, J = 8.7 Hz), 7.13 (2 H, d, J = 8.6 
               
               
                   
                   
                 Hz), 7.39-7.47 (4 H, m), 7.56 (1 H, d, J = 8.4 Hz), 
               
               
                   
                   
                 7.74 (1 H, dd, J = 8.2 Hz, 2.1 Hz), 7.94 (2 H, d, J = 
               
               
                   
                   
                 8.6 Hz), 8.02 (1 H, d, J = 2.0 Hz), 8.16 (1 H, dd, J = 
               
               
                   
                   
                 8.7 Hz, 2.8 Hz), 8.30 (1 H, d, J = 2.8 Hz), 8.37 (1 H 
               
               
                   
                   
                 s). 
               
               
                 109 
                 3-pyridyl 
                   1 H NMR 3.20 (4 H, brs), 3.78 (4 H, brs), 6.93 (1 H, d, 
               
               
                   
                   
                 J = 8.7 Hz), 7.11 (2 H, d, J = 8.6 Hz), 7.19- 
               
               
                   
                   
                 7.21 (2 H, m), 7.39 (2 H, d, J = 8.6 Hz), 7.46 (1 H, d, 
               
               
                   
                   
                 J = 8.4 Hz), 7.76 (1 H, dd, J = 8.4 Hz, 2.0 Hz), 
               
               
                   
                   
                 8.03 (1 H, d, J = 2.0 Hz), 8.11-8.25 (3 H, m), 
               
               
                   
                   
                 8.36 (1 H, d, J = 2.5 Hz), 9.81 (1 H, s). 
               
               
                 110 
                 —CH 2 CONHPh 
                 MS 603 (M + ) 
               
               
                 111 
                 2-pyridyl 
                 MS 547 (M + ) 
               
               
                 112 
                 4-pyridyl 
                 MS 547 (M + ) 
               
               
                   
               
               
                 113 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 548 (M + ) 
               
               
                   
               
               
                 114 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 548 (M + ) 
               
               
                   
               
               
                 115 
                 —(CH 2 ) 4 Ph 
                 MS 603 (M +  + H) 
               
               
                 116 
                 —CH(C 2 H 5 ) 2   
                 MS 540 (M + ) 
               
               
                 117 
                 —CH(CH 3 ) 2   
                 MS 511 (M +  − 1) 
               
               
                 118 
                 —(CH 2 ) 2 N(CH 3 ) 2   
                 MS 540 (M +  − 1) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 146 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 513   
                 R 514   
                 R 515   
                 R 516   
                 MS (M + ) 
               
               
                   
               
               
                 119 
                 —F 
                 —H 
                 —H 
                 —H 
                 564 
               
               
                 120 
                 —Cl 
                 —H 
                 —H 
                 —H 
                 582 
               
               
                 121 
                 —CF 3   
                 —H 
                 —H 
                 —H 
                 614 
               
               
                 122 
                 —OCH 3   
                 —H 
                 —H 
                 —H 
                 576 
               
               
                 123 
                 —CH 3   
                 —H 
                 —H 
                 —H 
                 560 
               
               
                 124 
                 —H 
                 —CF 3   
                 —H 
                 —H 
                 614 
               
               
                 125 
                 —H 
                 —Cl 
                 —H 
                 —H 
                 582 
               
               
                 126 
                 —H 
                 —OCH 3   
                 —H 
                 —H 
                 576 
               
               
                 127 
                 —H 
                 —CH 3   
                 —H 
                 —H 
                 560 
               
               
                 128 
                 —H 
                 —H 
                 —CN 
                 —H 
                 571 
               
               
                 129 
                 —H 
                 —H 
                 —OCF 3   
                 —H 
                 630 
               
               
                 130 
                 —H 
                 —H 
                 —CO 2 C(CH 3 ) 3   
                 —H 
                 646 
               
               
                 131 
                 —H 
                 —H 
                 —F 
                 —H 
                 564 
               
               
                 132 
                 —H 
                 —H 
                 —Cl 
                 —H 
                 580 
               
               
                 133 
                 —H 
                 —H 
                 —OCH 3   
                 —H 
                 576 
               
               
                 134 
                 —H 
                 —H 
                 —CH 3   
                 —H 
                 560 
               
               
                 135 
                 —H 
                 —H 
                 —CF 3   
                 —H 
                 614 
               
               
                 136 
                 —H 
                 —H 
                 -Ph 
                 —H 
                 622 
               
               
                 137 
                 —Cl 
                 —Cl 
                 —H 
                 —H 
                 616 
               
               
                 138 
                 —CH 3   
                 —CH 3   
                 —H 
                 —H 
                 574 
               
               
                 139 
                 —H 
                 —CH 3   
                 —CH 3   
                 —H 
                 574 
               
               
                 140 
                 —F 
                 —H 
                 —F 
                 —H 
                 582 
               
               
                 141 
                 —OCH 3   
                 —H 
                 —H 
                 —Cl 
                 612 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 147 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 517   
                 R 518   
                 R 519   
                 mp (° C.) or  1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 142 
                 —H 
                 —H 
                 —H 
                   1 H NMR 3.20 (4 H, brs), 3.79 (4 H, brs), 6.89- 
               
               
                   
                   
                   
                   
                 6.96 (3 H, m), 7.00 (1 H, d, J = 8.9 Hz), 7.14-7.19 (2 H, 
               
               
                   
                   
                   
                   
                 m), 7.27-7.33 (2 H, m), 7.43-7.48 (2 H, m), 7.76 (2 H, 
               
               
                   
                   
                   
                   
                 d, J = 8.1 Hz), 8.02 (2 H, d, J = 8.1 Hz), 8.23 (1 H, dd, 
               
               
                   
                   
                   
                   
                 J = 8.9 Hz, 2.7 Hz), 8.31-8.34 (2 H, m). 
               
               
                 143 
                 —F 
                 —H 
                 —H 
                 mp 193-194 
               
               
                 144 
                 —Cl 
                 —H 
                 —H 
                   1 H NMR 3.07 (4 H, brs), 3.82 (4 H, brs), 7.00- 
               
               
                   
                   
                   
                   
                 7.06 (3 H, m), 7.18 (2 H, d, J = 8.4 Hz), 7.22-7.26 (1 H, 
               
               
                   
                   
                   
                   
                 m), 7.38-7.41 (1 H, m), 7.48 (2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                 7.77 (2 H, d, J = 8.1 Hz), 8.04 (2 H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                 8.24 (1 H, dd, J = 8.9 Hz, 2.4 Hz), 8.30 (1 H, brs), 
               
               
                   
                   
                   
                   
                 8.35 (1 H, d, J = 2.4 Hz). 
               
               
                 145 
                 —H 
                 —Cl 
                 —H 
                   1 H NMR 3.19 (4 H, brs), 3.76 (4 H, brs), 6.77- 
               
               
                   
                   
                   
                   
                 6.81 (1 H, m), 6.86-6.88 (2 H, m), 6.99 (1 H, d, J = 8.9 
               
               
                   
                   
                   
                   
                 Hz), 7.13-7.22 (3 H, m), 7.40-7.45 (2 H, m), 7.73 (2 H, 
               
               
                   
                   
                   
                   
                 d, J = 8.4 Hz), 8.02 (2 H, d, J = 8.4 Hz), 8.21 (1 H, dd, 
               
               
                   
                   
                   
                   
                 J = 8.9 Hz, 2.7 Hz), 8.34 (1 H, d, J = 2.7 Hz), 
               
               
                   
                   
                   
                   
                 8.56 (1 H, s). 
               
               
                 146 
                 —H 
                 —CH 3   
                 —H 
                   1 H NMR 2.31 (3 H, s), 3.15 (4 H, brs), 3.74 (4 H, brs), 
               
               
                   
                   
                   
                   
                 6.71-6.73 (3 H, m), 6.97 (1 H, d, J = 8.9 Hz), 7.11- 
               
               
                   
                   
                   
                   
                 7.18 (3 H, m), 7.42 (2 H, d, J = 8.1 Hz), 7.72 (2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.1 Hz), 8.01 (2 H, d, J = 8.1 Hz), 8.18-8.21 (1 H, 
               
               
                   
                   
                   
                   
                 m), 8.34 (1 H, brs), 8.54 (1 H, brs). 
               
               
                 147 
                 —H 
                 —OCH 3   
                 —H 
                   1 H NMR 3.07 (4 H, brs), 3.73 (4 H, brs), 3.88 (3 H, s), 
               
               
                   
                   
                   
                   
                 6.88-7.08 (5 H, m), 7.13-7.17 (2 H, m), 7.42-7.47 (2 H, 
               
               
                   
                   
                   
                   
                 m), 7.75 (2 H, d, J = 8.4 Hz), 8.03 (2 H, d, J = 7.8 
               
               
                   
                   
                   
                   
                 Hz), 8.21 (1 H, dd, J = 8.9 Hz, 2.4 Hz), 8.34 (1 H, d, J = 
               
               
                   
                   
                   
                   
                 2.4 Hz), 8.45 (1 H, brs). 
               
               
                 148 
                 —H 
                 —CF 3   
                 —H 
                 mp 174-177 
               
               
                 149 
                 —H 
                 —H 
                 —OH 
                 mp 241-242 
               
               
                 150 
                 —H 
                 —H 
                 —OCH 3   
                   1 H NMR 3.06 (4 H, brs), 3.63-3.91 (7 H, m), 6.83- 
               
               
                   
                   
                   
                   
                 6.93 (4 H, m), 6.99 (1 H, d, J = 8.6 Hz), 7.15 (2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.4 Hz), 7.44 (2 H, d, J = 8.4 Hz), 7.75 (2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.4 Hz), 8.02 (2 H, d, J = 8.1 Hz), 8.22 (1 H, dd, J = 
               
               
                   
                   
                   
                   
                 8.9 Hz, 2.4 Hz), 8.33 (1 H, d, J = 2.4 Hz), 8.40 (1 H, 
               
               
                   
                   
                   
                   
                 brs). 
               
               
                 151 
                 —H 
                 —H 
                 —CN 
                   1 H NMR 3.23 (4 H, brs), 3.79 (4 H, brs), 7.01 (1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.9 Hz), 7.12-7.19 (5 H, m), 7.33-7.39 (1 H, m), 
               
               
                   
                   
                   
                   
                 7.43-7.48 (2 H, m), 7.74 (2 H, d, J = 8.4 Hz), 8.02 (2 H, 
               
               
                   
                   
                   
                   
                 d, J = 8.4 Hz), 8.23 (1 H, dd, J = 8.9 Hz, 2.7 Hz), 
               
               
                   
                   
                   
                   
                 8.35 (1 H, d, J = 2.7 Hz), 8.47 (1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 148 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 520   
                 R 521   
                   1 H NMR (solvent) δ ppm or MS 
               
               
                   
               
               
                 152 
                 —H 
                 piperonyl 
                   1 H NMR (CDCl 3 ) 2.38-2.45 (4 H, m), 
               
               
                   
                   
                   
                 3.45 (2 H, s), 3.49-3.74 (4 H, m), 5.95 (2 H, 
               
               
                   
                   
                   
                 s), 6.74 (2 H, s), 6.85 (1 H, s), 6.97 (1 H, d, J = 
               
               
                   
                   
                   
                 8.6 Hz), 7.10 (2 H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                 7.41 (2 H, d, J = 8.9 Hz), 7.58 (1 H, d, J = 
               
               
                   
                   
                   
                 8.3 Hz), 7.74 (1 H, dd, J = 8.3 Hz, 2.0 Hz), 
               
               
                   
                   
                   
                 8.02 (1 H, d, J = 2.3 Hz), 8.13-8.20 (2 H, m), 
               
               
                   
                   
                   
                 8.29 (1 H, d, J = 2.6 Hz). 
               
               
                 153 
                 —H 
                 —COOCH(CH 3 ) 3   
                   1 H NMR (DMSO-d 6 ) 1.41 (9 H, s), 3.39- 
               
               
                   
                   
                   
                 3.50 (8 H, m), 7.13-7.19 (3 H, m), 7.45- 
               
               
                   
                   
                   
                 7.48 (2 H, m), 7.84 (1 H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                 7.95 (1 H, dd, J = 8.4 Hz, 2.1 Hz), 8.21- 
               
               
                   
                   
                   
                 8.26 (2 H, m), 8.52 (1 H, d, J = 2.3 Hz), 
               
               
                   
                   
                   
                 10.58 (1 H, s). 
               
               
                 154 
                 —H 
                 2-naphthylmethyl 
                 MS 611 (M +  + 1) 
               
               
                   
               
               
                 155 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 671 (M +  + 1) 
               
               
                   
               
               
                 156 
                 —H 
                 1-naphthylmethyl 
                 MS 611 (M +  + 1) 
               
               
                 157 
                 —CH 3   
                 3,4-(CH 3 O) 2 PhCH 2 — 
                 MS 633 (M +  + 1) 
               
               
                   
               
               
                 158 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 631 (M +  − 1) 
               
               
                   
               
               
                 159 
                 —H 
                 —CH(CH 3 )Ph 
                 MS 573 (M +  − 1) 
               
               
                   
               
               
                 160 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 637 (M + ) 
               
               
                 161 
                 —H 
                 (4-FPh) 2 CH— 
                 MS 671 (M +  − 1) 
               
               
                 162 
                 —H 
                 —(CH 2 ) 3 CH 3   
                 MS 526 (M + ) 
               
               
                 163 
                 —H 
                 —(CH 2 ) 3 Ph 
                 MS 588 (M + ) 
               
               
                 164 
                 —H 
                 cyclopentyl 
                 MS 538 (M + ) 
               
               
                 165 
                 —H 
                 cycloheptyl 
                 MS 565 (M +  − 1) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 149 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                   
                 Example 
                   
                   
               
               
                   
                 No. 
                 R 522   
                 MS 
               
               
                   
                   
               
               
                   
                 166 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 567 (M + ) 
               
               
                   
                   
               
               
                   
                 167 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 581 (M + ) 
               
               
                   
                   
               
               
                   
                 168 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 583 (M + ) 
               
               
                   
                   
               
               
                   
                 169 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 567 (M + ) 
               
               
                   
                   
               
               
                   
                 170 
                 4-pyridylmethyl 
                 561 (M + ) 
               
               
                   
                 171 
                 2-pyridylmethyl 
                 562 (M +  + H) 
               
               
                   
                   
               
               
                   
                 172 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 643 (M +  + H) 
               
               
                   
                   
               
               
                   
                 173 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 580 (M + ) 
               
               
                   
                   
               
               
                   
                 174 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 643 (M + ) 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 150 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 523   
                 R 524   
                 mp (° C.) or  1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 175 
                 —H 
                 3-pyridyl 
                   1 H NMR (CDCl 3 ) 3.21 (4 H, brs), 3.78 (4 H, brs), 
               
               
                   
                   
                   
                 6.98 (1 H, d, J = 8.7 Hz), 7.13-7.21 (4 H, m), 7.41- 
               
               
                   
                   
                   
                 7.44 (2 H, m), 7.70 (2 H, d, J = 8.1 Hz), 8.02 (2 H, d, J = 
               
               
                   
                   
                   
                 8.1 Hz), 8.12-8.14 (1 H, m), 8.20-8.27 (2 H, m), 
               
               
                   
                   
                   
                 8.35 (1 H, d, J = 2.6 Hz), 8.99 (1 H, s). 
               
               
                 176 
                 —H 
                 2-pyridyl 
                 mp 222-224 
               
               
                 177 
                 —F 
                 3-pyridyl 
                   1 H NMR (CDCl 3 ) 3.21 (4 H, brs), 3.79 (4 H, brs), 
               
               
                   
                   
                   
                 7.05 (1 H, d, J = 8.4 Hz), 7.20-7.30 (5 H, m), 7.71 (2 H, 
               
               
                   
                   
                   
                 d, J = 8.2 Hz), 8.00 (2 H, d, J = 8.2 Hz), 8.14 (1 H, 
               
               
                   
                   
                   
                 brs), 8.21-8.25 (3 H, m), 8.78 (1 H, s). 
               
               
                   
               
               
                 178 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 mp 205-206 
               
               
                   
               
               
                 179 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (DMSO-d 6 ) 2.38 (4 H, brs), 2.43 (2 H, t, J = 7.5 Hz), 2.86 (2 H, t, J = 7.5 Hz), 3.41 (2 H, s), 3.45 (4 H, brs), 6.80 (1 H, d, J = 7.9 Hz), 7.06 (1 H, d, J = 7.9 Hz), 7.10 (1 H, s), 7.15 (1 H, d, J = 8.8 Hz), 7.17 (2 H, d, J = 8.4 Hz), 7.44 (2 H, d, J = 8.4 Hz), 7.94 (2 H, d, J = 8.0 Hz), 8.17 (2 H, d, J = 8.0 Hz), 8.26 (1 H, dd, J = 8.8 Hz, 2.6 Hz), 8.54 (1 H, d, J = 2.6 Hz), 10.06 (1 H, s), 10.68 (1 H, s). 
               
               
                   
               
               
                 180 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (CDCl 3 ) 1.71-2.05 (4 H, m), 2.58 (4 H, brs), 3.16 (2 H, s), 3.36-3.53 (4 H, m), 3.55 (2 H, brs), 3.74 (2 H, brs), 7.00 (1 H, d, J = 8.9 Hz), 7.14 (2 H, d, J = 8.6 Hz), 7.42 (2 H, d, J = 8.6 Hz), 7.76 (2 H, d, J = 8.1 Hz), 8.04 (2 H, d, J = 8.1 Hz), 8.26 (1 H, dd, J = 8.9 Hz, 2.6 Hz), 8.34 (1 H, d, J = 2.6 Hz), 8.50 (1 H, s). 
               
               
                   
               
               
                 181 
                 —H 
                 —COOC(CH 3 ) 3   
                   1 H NMR (CDCl 3 ) 1.48 (9 H, s), 3.45 (4 H, brs), 
               
               
                   
                   
                   
                 3.58 (4 H, brs), 6.99 (1 H, d, J = 8.7 Hz), 7.15 (2 H, d, J = 
               
               
                   
                   
                   
                 8.7 Hz), 7.41 (2 H, d, J = 8.7 Hz), 7.74 (2 H, d, J = 
               
               
                   
                   
                   
                 8.2 Hz), 8.02 (2 H, d, J = 8.2 Hz), 8.21 (1 H, dd, J = 
               
               
                   
                   
                   
                 8.7 Hz, 2.6 Hz), 8.33 (1 H, d, J = 2.6 Hz), 8.43 (1 H, 
               
               
                   
                   
                   
                 brs). 
               
               
                 182 
                 —H 
                 —CH 2 COOC 2 H 5   
                   1 H NMR (CDCl 3 ) 1.28 (3 H, t, J = 7.1 Hz), 2.61 (4 H, 
               
               
                   
                   
                   
                 brs), 3.26 (2 H, s), 3.57 (2 H, brs), 3.78 (2 H, brs), 
               
               
                   
                   
                   
                 4.19 (2 H, q, J = 7.1 Hz), 6.97 (1 H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                 7.12 (2 H, d, J = 8.7 Hz), 7.40 (2 H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                 7.74 (2 H, d, J = 8.1 Hz), 8.03 (2 H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                 8.19 (1 H, dd, J = 8.7 Hz, 2.6 Hz), 8.33 (1 H, d, J = 2.6 
               
               
                   
                   
                   
                 Hz), 8.61 (1 H, brs). 
               
               
                 183 
                 —H 
                 —CH 2 CONHNHCOOC(CH 3 ) 3   
                   1 H NMR (CDCl 3 ) 1.46 (9 H, s), 2.60 (4 H, brs), 
               
               
                   
                   
                   
                 3.17 (2 H, s), 3.67 (4 H, brs), 6.48 (1 H, brs), 7.00 (1 H, 
               
               
                   
                   
                   
                 d, J = 8.7 Hz), 7.14 (2 H, d, J = 8.5 Hz), 7.41 (2 H, d, J = 
               
               
                   
                   
                   
                 8.5 Hz), 7.75 (2 H, d, J = 8.1 Hz), 8.02 (2 H, d, J = 
               
               
                   
                   
                   
                 8.1 Hz), 8.24 (1 H, dd, J = 8.7 Hz, 2.6 Hz), 8.33 (1 H, 
               
               
                   
                   
                   
                 d, J = 2.6 Hz), 8.53 (2 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 151 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
                 mp (° C.) or  1 H NMR 
               
               
                 No. 
                 R 525   
                 R 526   
                 R 527   
                 R 528   
                 R 529   
                 Form 
                 (solvent) δ ppm 
               
               
                   
               
               
                 184 
                 —Cl 
                 —Cl 
                 —H 
                 —F 
                 3-pyridyl 
                 free 
                   1 H NMR (CDCl) 3.21 (4 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 brs), 3.79 (4 H, brs), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.02 (1 H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.18-7.28 (5 H, m), 7.49 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 d, J = 8.2 Hz), 7.74 (1 H, dd, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 J = 8.2 Hz, 1.7 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.00 (1 H, d, J = 1.7 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.13 (1 H, brs), 8.17-8.21 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 m), 8.26 (2 H, d, J = 2.3 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 9.33 (1 H, brs). 
               
               
                 185 
                 —H 
                 —Cl 
                 —H 
                 —H 
                 4-CNPhCH 2 — 
                 free 
                 mp 199-201 
               
               
                 186 
                 —OCF 3   
                 —H 
                 —H 
                 —H 
                 3-pyridyl- 
                 free 
                   1 H NMR (CDCl 3 ) 2.43- 
               
               
                   
                   
                   
                   
                   
                 methyl 
                   
                 2.55 (4 H, m), 3.43-3.71 (6 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 m), 6.90 (1 H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.05-7.08 (2 H, m), 7.25- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.46 (5 H, m), 7.66-7.69 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 m), 7.82-7.88 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.15 (1 H, dd, J = 8.9 Hz, 2.8 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz), 8.36 (1 H, d, J = 2.5 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.48 (1 H, dd, J = 4.8 Hz, 1.7 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz), 8.51 (1 H, d, J = 1.7 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 9.84 (1 H, s). 
               
               
                 187 
                 —CF 3   
                 —H 
                 —H 
                 —H 
                 4-CNPhCH 2 — 
                 free 
                 mp 193-197 
               
               
                 188 
                 —F 
                 —H 
                 —CF 3   
                 —H 
                 4-CNPhCH 2 — 
                 oxalate 
                 mp 136-139 
               
               
                 189 
                 —CH 3   
                 —CH 3   
                 —H 
                 —H 
                 —COOC(CH 3 ) 3   
                 free 
                   1 H NMR (CDCl 3 ) 1.48 (9 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 s), 2.34 (6 H, s), 3.46 (4 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 brs), 3.60 (4 H, brs), 6.99 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 d, J = 8.7 Hz), 7.14-7.17 
               
               
                   
                   
                   
                   
                   
                   
                   
                 (2 H, m), 7.23-7.26 (1 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.42-7.47 (2 H, m), 7.61 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dd, J = 7.8 Hz, 2.0 Hz), 7.67 
               
               
                   
                   
                   
                   
                   
                   
                   
                 (1 H, d, J = 2.0 Hz), 7.93 
               
               
                   
                   
                   
                   
                   
                   
                   
                 (1 H, brs), 8.25-8.31 (2 H, m). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 152 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 530   
                 R 531   
                 R 532   
                 R 533   
                 R 534   
                 MS 
               
               
                   
               
               
                 190 
                 —Cl 
                 —H 
                 —H 
                 —H 
                 —H 
                 594 (M + ) 
               
               
                 191 
                 —OCH 3   
                 —H 
                 —H 
                 —H 
                 —H 
                 590 (M + ) 
               
               
                 192 
                 —CH 3   
                 —H 
                 —H 
                 —H 
                 —H 
                 574 (M + ) 
               
               
                 193 
                 —F 
                 —H 
                 —H 
                 —H 
                 —H 
                 578 (M + ) 
               
               
                 194 
                 —NO 2   
                 —H 
                 —H 
                 —H 
                 —H 
                 603 (M +  − 2) 
               
               
                 195 
                 —CF 3   
                 —H 
                 —H 
                 —H 
                 —H 
                 628 (M + ) 
               
               
                 196 
                 —OCF 3   
                 —H 
                 —H 
                 —H 
                 —H 
                 645 (M +  + 1) 
               
               
                 197 
                 —H 
                 —Cl 
                 —H 
                 —H 
                 —H 
                 595 (M +  + 1) 
               
               
                 198 
                 —H 
                 —F 
                 —H 
                 —H 
                 —H 
                 579 (M +  + 1) 
               
               
                 199 
                 —H 
                 —NO 2   
                 —H 
                 —H 
                 —H 
                 605 (M + ) 
               
               
                 200 
                 —H 
                 —CF 3   
                 —H 
                 —H 
                 —H 
                 628 (M + ) 
               
               
                 201 
                 —H 
                 —OCF 3   
                 —H 
                 —H 
                 —H 
                 644 (M + ) 
               
               
                 202 
                 —H 
                 —COOCH 3   
                 —H 
                 —H 
                 —H 
                 618 (M + ) 
               
               
                 203 
                 —H 
                 —H 
                 —Cl 
                 —H 
                 —H 
                 594 (M + ) 
               
               
                 204 
                 —H 
                 —H 
                 —F 
                 —H 
                 —H 
                 578 (M + ) 
               
               
                 205 
                 —H 
                 —H 
                 —NO 2   
                 —H 
                 —H 
                 605 (M + ) 
               
               
                 206 
                 —H 
                 —H 
                 —COOCH 3   
                 —H 
                 —H 
                 618 (M + ) 
               
               
                 207 
                 —H 
                 —H 
                 -Ph 
                 —H 
                 —H 
                 636 (M + ) 
               
               
                 208 
                 —H 
                 —H 
                 —C 2 H 5   
                 —H 
                 —H 
                 588 (M + ) 
               
               
                 209 
                 —Cl 
                 —Cl 
                 —H 
                 —H 
                 —H 
                 630 (M + ) 
               
               
                 210 
                 —Cl 
                 —H 
                 —Cl 
                 —H 
                 —H 
                 630 (M + ) 
               
               
                 211 
                 —H 
                 —F 
                 —H 
                 —F 
                 —H 
                 596 (M + ) 
               
               
                 212 
                 —H 
                 —OCH 3   
                 —H 
                 —OCH 3   
                 —H 
                 622 (M +  + 2) 
               
               
                 213 
                 —F 
                 —H 
                 —F 
                 —H 
                 —H 
                 596 (M + ) 
               
               
                 214 
                 —H 
                 —Cl 
                 —Cl 
                 —H 
                 —H 
                 630 (M + ) 
               
               
                 215 
                 —F 
                 —H 
                 —H 
                 —H 
                 —F 
                 596 (M + ) 
               
               
                 216 
                 —Cl 
                 —H 
                 —H 
                 —H 
                 —Cl 
                 630 (M + ) 
               
               
                 217 
                 —F 
                 —H 
                 —H 
                 —F 
                 —H 
                 596 (M + ) 
               
               
                 218 
                 —Cl 
                 —H 
                 —H 
                 —Cl 
                 —H 
                 629 (M +  + 1) 
               
               
                 219 
                 —H 
                 —Cl 
                 —OCH 3   
                 —H 
                 —H 
                 624 (M + ) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 153 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 535   
                 R 536   
                 R 537   
                 R 538   
                 mp (° C.) or  1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 220 
                 —Cl 
                 —Cl 
                 —H 
                 —H 
                 mp 164-166 
               
               
                 221 
                 —Cl 
                 —Cl 
                 —F 
                 —H 
                   1 H NMR 2.46 (4 H, brs), 3.39-3.82 (6 H, m), 7.00 (1 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.9 Hz), 7.13-7.33 (8 H, m), 7.52 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.4 Hz), 7.72 (1 H, dd, J = 8.4 Hz, 2.0 Hz), 8.00 (1 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 2.0 Hz), 8.15 (1 H, dd, J = 8.9 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.23 (1 H, d, J = 2.6 Hz), 8.61 (1 H, brs). 
               
               
                 222 
                 —CF 3   
                 —H 
                 —F 
                 —H 
                   1 H NMR 2.44 (4 H, brs), 3.42-3.78 (6 H, m), 6.97 (1 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.7 Hz), 7.09-7.36 (8 H, m), 7.66 (2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.1 Hz), 7.96 (2 H, d, J = 8.1 Hz), 8.16 (1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 8.7 Hz, 2.5 Hz), 8.26 (1 H, d, J = 2.5 Hz), 9.04 (1 H, 
               
               
                   
                   
                   
                   
                   
                 brs). 
               
               
                 223 
                 —Cl 
                 —Cl 
                 —Cl 
                 —H 
                   1 H NMR 2.47 (4 H, brs), 3.42-3.83 (6 H, m), 7.00 (1 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.9 Hz), 7.17 (1 H, d, J = 8.2 Hz), 7.25- 
               
               
                   
                   
                   
                   
                   
                 7.33 (6 H, m), 7.46 (1 H, d, J = 1.8 Hz), 7.53 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.4 Hz), 7.74 (1 H, dd, J = 8.4 Hz, 2.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.01 (1 H, d, J = 2.1 Hz), 8.17 (1 H, dd, J = 8.9 Hz, 
               
               
                   
                   
                   
                   
                   
                 2.6 Hz), 8.25 (1 H, d, J = 2.6 Hz), 8.64 (1 H, brs). 
               
               
                 224 
                 —CF 3   
                 —H 
                 —Cl 
                 —H 
                   1 H NMR 2.47 (4 H, brs), 3.42-3.82 (6 H, m), 7.02 (1 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.9 Hz), 7.19 (1 H, d, J = 8.4 Hz), 7.27- 
               
               
                   
                   
                   
                   
                   
                 7.33 (6 H, m), 7.47 (1 H, d, J = 1.8 Hz), 7.73 (2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.4 Hz), 8.00 (2 H, d, J = 7.9 Hz), 8.20-8.26 (2 H, 
               
               
                   
                   
                   
                   
                   
                 m), 8.46 (1 H, brs). 
               
               
                 225 
                 —Cl 
                 —Cl 
                 —CH 3   
                 —H 
                   1 H NMR 2.15 (3 H, s), 2.45 (4 H, brs), 3.46-3.75 (6 H, 
               
               
                   
                   
                   
                   
                   
                 m), 6.85 (1 H, d, J = 8.9 Hz), 6.95 (1 H, d, J = 8.4 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.13-7.33 (7 H, m), 7.50 (1 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.75 (1 H, dd, J = 8.4 Hz, 2.2 Hz), 8.03 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 2.2 Hz), 8.08 (1 H, dd, J = 8.9 Hz, 3.0 Hz), 8.27 (1 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 3.0 Hz), 9.06 (1 H, s). 
               
               
                 226 
                 —CF 3   
                 —H 
                 —CH 3   
                 —H 
                   1 H NMR 2.17 (3 H, s), 2.44 (4 H, brs), 3.40-3.82 (6 H, 
               
               
                   
                   
                   
                   
                   
                 m), 6.88 (1 H, d, J = 8.9 Hz), 6.98 (1 H, d, J = 8.1 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.14-7.18 (1 H, m), 7.23-7.33 (6 H, m), 7.70 (2 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.4 Hz), 8.01 (2 H, d, J = 8.1 Hz), 8.15 (1 H, 
               
               
                   
                   
                   
                   
                   
                 dd, J = 8.9 Hz, 2.7 Hz), 8.30 (1 H, d, J = 2.7 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.90 (1 H, brs). 
               
               
                 227 
                 —Cl 
                 —Cl 
                 —OCH 3   
                 —H 
                 mp 197-199 
               
               
                 228 
                 —CF 3   
                 —H 
                 —OCH 3   
                 —H 
                 mp 152-154 
               
               
                 229 
                 —Cl 
                 —Cl 
                 —H 
                 —CH 3   
                 mp 182-183 
               
               
                 230 
                 —CF 3   
                 —H 
                 —H 
                 —CH 3   
                 mp 188-190 
               
               
                 231 
                 —Cl 
                 —Cl 
                 —H 
                 —OCH 3   
                 mp 196-198 
               
               
                 232 
                 —CF 3   
                 —H 
                 —H 
                 —OCH 3   
                   1 H NMR 2.32-2.50 (4 H, m), 3.30 (2 H, brs), 3.53 (2 H, 
               
               
                   
                   
                   
                   
                   
                 s), 3.70-3.81 (5 H, m), 6.61-6.65 (2 H, m), 6.91 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.9 Hz), 7.11-7.15 (1 H, m), 7.26-7.36 (5 H, m), 
               
               
                   
                   
                   
                   
                   
                 7.72 (2 H, d, J = 8.4 Hz), 8.05-8.13 (3 H, m), 
               
               
                   
                   
                   
                   
                   
                 8.36 (1 H, d, J = 2.4 Hz), 9.07 (1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 154 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 539   
                 R 540   
                 R 541   
                 R 542   
                 Form 
                 mp (° C.) or  1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 233 
                 —CF 3   
                 —H 
                 —H 
                 —H 
                 hydro- 
                   1 H NMR (DMSO-d 6 ) 2.90-3.70 (6 H, m), 3.80- 
               
               
                   
                   
                   
                   
                   
                 chloride 
                 4.60 (2 H, m), 4.24 (2 H, brs), 6.07 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 6.98 (1 H, d, J = 8.0 Hz), 7.05 (1 H, dd, J = 8.0 
               
               
                   
                   
                   
                   
                   
                   
                 Hz, 1.5 Hz), 7.16 (1 H, d, J = 8.7 Hz), 7.20 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 8.6 Hz), 7.27 (1 H, s), 7.52 (2 H, d, J = 8.6 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.93 (2 H, d, J = 8.3 Hz), 8.21 (2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.3 Hz), 8.30 (1 H, dd, J = 8.7 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 8.60 (1 H, d, J = 2.6 Hz), 10.80 (1 H, s). 
               
               
                 234 
                 —Cl 
                 —Cl 
                 —F 
                 —H 
                 free 
                   1 H NMR (CDCl 3 ) 2.42 (4 H, brs), 3.37-3.79 (6 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 5.94 (2 H, s), 6.70-6.77 (2 H, m), 6.84 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs), 6.96 (1 H, d, J = 8.7 Hz), 7.10-7.22 (3 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 7.47 (1 H, d, J = 8.2 Hz), 7.72 (1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.2 Hz, 2.0 Hz), 7.99 (1 H, d, J = 2.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 8.12 (1 H, dd, J = 8.9 Hz, 2.6 Hz), 8.25 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 2.6 Hz), 9.14 (1 H, brs). 
               
               
                 235 
                 —CF 3   
                 —H 
                 —F 
                 —H 
                 free 
                   1 H NMR (CDCl 3 ) 2.41 (4 H, brs), 3.37-3.79 (6 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 5.94 (2 H, s), 6.69-6.76 (2 H, m), 6.84 (1 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 6.99 (1 H, d, J = 8.9 Hz), 7.10-7.26 (3 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.67 (2 H, d, J = 8.1 Hz), 7.97 (2 H, d, J = 8.1 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 8.17 (1 H, dd, J = 8.9 Hz, 2.5 Hz), 8.26 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 2.5 Hz), 8.89 (1 H, brs). 
               
               
                 236 
                 —Cl 
                 —Cl 
                 —Cl 
                 —H 
                 free 
                   1 H NMR (CDCl 3 ) 2.45 (4 H, brs), 3.38-3.81 (6 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 5.95 (2 H, s), 6.71-6.78 (2 H, m), 6.85 (1 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 7.01 (1 H, d, J = 8.7 Hz), 7.17-7.30 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.45-7.47 (1 H, m), 7.54 (1 H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.70-7.74 (1 H, m), 8.00 (1 H, d, J = 1.8 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 8.17 (1 H, dd, J = 8.9 Hz, 2.6 Hz), 8.24 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 2.6 Hz), 8.48 (1 H, s). 
               
               
                 237 
                 —CF 3   
                 —H 
                 —Cl 
                 —H 
                 free 
                   1 H NMR (CDCl 3 ) 2.45 (4 H, brs), 3.40-3.81 (6 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 5.95 (2 H, s), 6.71-6.77 (2 H, m), 6.85 (1 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 7.03 (1 H, d, J = 8.6 Hz), 7.20 (1 H, d, J = 8.2 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.28-7.31 (1 H, m), 7.48 (1 H, d, J = 2.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.74 (2 H, d, J = 8.4 Hz), 8.00 (2 H, d, J = 8.2 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 8.21-8.26 (2 H, m), 8.34 (1 H, brs). 
               
               
                 238 
                 —CF 3   
                 —H 
                 —CH 3   
                 —H 
                 free 
                   1 H NMR (CDCl 3 ) 2.16 (3 H, s), 2.42 (4 H, brs), 
               
               
                   
                   
                   
                   
                   
                   
                 3.44-3.70 (6 H, m), 5.94 (2 H, s), 6.70-6.77 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 6.85-6.89 (2 H, m), 6.97 (1 H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.14-7.23 (2 H, m), 7.69 (2 H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 8.01 (2 H, d, J = 8.1 Hz), 8.13-8.17 (1 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 8.30 (1 H, d, J = 2.7 Hz), 8.97 (1 H, brs). 
               
               
                 239 
                 —Cl 
                 —Cl 
                 —OCH 3   
                 —H 
                 free 
                 mp 194-196 
               
               
                 240 
                 —CF 3   
                 —H 
                 —OCH 3   
                 —H 
                 free 
                 mp 134-136 
               
               
                 241 
                 —CF 3   
                 —H 
                 —H 
                 —Ch 3   
                 free 
                 mp 199-201 
               
               
                 242 
                 —CF 3   
                 —H 
                 —H 
                 —OCH 3   
                 free 
                 mp 192-193 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 155 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 543   
                 R 544   
                 R 545   
                   1 H NMR (CDCl 3 ) δppm 
               
               
                   
               
               
                 243 
                 —Cl 
                 —Cl 
                 benzyl 
                 2.39-2.62(4 H, m), 3.42-3.91(6 H, m), 6.94(1 H, 
               
               
                   
                   
                   
                   
                 d, J = 8.9 Hz), 7.28-7.33(6 H, m), 7.41(1 H, dd, 
               
               
                   
                   
                   
                   
                 J = 8.4 Hz, 1.6 Hz), 7.50-7.53(2 H, m), 7.72- 
               
               
                   
                   
                   
                   
                 7.75(2 H, m), 7.81-7.84(2 H, m), 8.02(1 H, d, J = 
               
               
                   
                   
                   
                   
                 2.1 Hz), 8.14(1 H, dd, J = 8.9 Hz, 2.7 Hz), 
               
               
                   
                   
                   
                   
                 8.28(1 H, d, J = 2.7 Hz), 8.66(1 H, s). 
               
               
                 244 
                 —Cl 
                 —Cl 
                 piperonyl 
                 2.41-2.74(4 H, m), 3.42-3.91(6 H, m), 5.94(2 H, 
               
               
                   
                   
                   
                   
                 s), 6.73(2 H, brs), 6.84(1 H, brs), 6.97(1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.9 Hz), 7.29-7.33(1 H, m), 7.42(1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.2 Hz), 7.52-7.57(2 H, m), 7.71-7.85(4 H, m), 
               
               
                   
                   
                   
                   
                 8.02(1 H, d, J = 2.0 Hz), 8.18(1 H, dd, J = 8.9 
               
               
                   
                   
                   
                   
                 Hz, 2.8 Hz), 8.28(1 H, d, J = 2.8 Hz), 8.48(1 H, 
               
               
                   
                   
                   
                   
                 brs). 
               
               
                 245 
                 —Cl 
                 —Cl 
                 3-pyridyl 
                 3.25(4 H, brs), 3.82(4 H, brs), 7.01(1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.7 Hz), 7.21-7.22(2 H, m), 7.35(1 H, dd, J = 
               
               
                   
                   
                   
                   
                 8.9 Hz, 2.3 Hz), 7.47-7.50(1 H, m), 7.52- 
               
               
                   
                   
                   
                   
                 7.56(2 H, m), 7.74(1 H, dd, J = 8.2 Hz, 2.0 Hz), 
               
               
                   
                   
                   
                   
                 7.80(1 H, d, J = 8.6 Hz), 7.86-7.91(2 H, m), 
               
               
                   
                   
                   
                   
                 8.01(1 H, d, J = 2.0 Hz), 8.13-8.15(1 H, m), 
               
               
                   
                   
                   
                   
                 8.18-8.22(1 H, m), 8.29-8.31(2 H, m), 8.42(1 H, 
               
               
                   
                   
                   
                   
                 brs). 
               
               
                 246 
                 —CF 3   
                 —H 
                 benzyl 
                 2.35-2.58(4 H, m), 3.37-3.87(6 H, m), 6.96(1 H, 
               
               
                   
                   
                   
                   
                 d, J = 8.9 Hz), 7.28-7.34(6 H, m), 7.41(1 H, dd, 
               
               
                   
                   
                   
                   
                 J = 8.4 Hz, 1.5 Hz), 7.52(1 H, d, J = 2.0 Hz), 
               
               
                   
                   
                   
                   
                 7.64-7.76(3 H, m), 7.83(2 H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                   
                 8.00(2 H, d, J = 8.2 Hz), 8.19(1 H, dd, J = 8.9 
               
               
                   
                   
                   
                   
                 Hz, 2.6 Hz), 8.30(1 H, d, J = 2.6 Hz), 8.68(1 H, 
               
               
                   
                   
                   
                   
                 brs). 
               
               
                 247 
                 —CF 3   
                 —H 
                 piperonyl 
                 2.30-2.58(4 H, m), 3.35-3.87(6 H, m), 5.94(2 H, 
               
               
                   
                   
                   
                   
                 s), 6.70-6.l77(2 H, m), 6.85(1 H, brs), 6.95(1 H, 
               
               
                   
                   
                   
                   
                 d, J = 8.7 Hz), 7.31(1 H, dd, J = 8.9 Hz, 2.1 
               
               
                   
                   
                   
                   
                 Hz), 7.39(1 H, d, J = 8.4 Hz), 7.51(1 H, brs), 
               
               
                   
                   
                   
                   
                 7.66-7.83(5 H, m), 7.99(2 H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                 8.17(1 H, dd, J = 8.7 Hz, 2.3 Hz), 8.30(1 H, 
               
               
                   
                   
                   
                   
                 brs), 8.89(1 H, brs). 
               
               
                 248 
                 —CF 3   
                 —H 
                 3-pyridyl 
                 3.22(4 H, brs), 3.79(4 H, brs), 6.99(1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.7 Hz), 7.17-7.23(2 H, m), 7.33(1 H, dd, J = 
               
               
                   
                   
                   
                   
                 8.9 Hz, 2.3 Hz), 7.45(1 H, dd, J = 8.4 Hz, 1.5 
               
               
                   
                   
                   
                   
                 Hz), 7.54(1 H, d, J = 2.3 Hz), 7.66(2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.4 Hz), 7.76-7.86(3 H, m), 7.99(2 H, d, J = 8.1 
               
               
                   
                   
                   
                   
                 Hz), 8.13(1 H, brs), 8.21-8.25(1 H, m), 8.28(1 H, 
               
               
                   
                   
                   
                   
                 brs), 8.33(1 H, d, J = 2.5 Hz), 9.13(1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 156 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 546    
                 R 547   
                 R 548   
                   1 H NMR (CDCl 3 ) δppm 
               
               
                   
               
               
                 249 
                 —Cl 
                 —Cl 
                 benzyl 
                 2.27-2.34(2 H, m), 2.58-2.61(2 H, m), 3.20- 
               
               
                   
                   
                   
                   
                 3.29(2 H, m), 3.53(2 H, s), 3.90-3.99(2 H, m), 
               
               
                   
                   
                   
                   
                 6.91(1 H, d, J = 8.7 Hz), 7.29-7.32(7 H, m), 7.39- 
               
               
                   
                   
                   
                   
                 7.45(1 H, m), 7.53-7.56(2 H, m), 7.71-7.81(3 H, 
               
               
                   
                   
                   
                   
                 m), 8.00-8.04(2 H, m), 8.25(1 H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                 8.47(1 H, s). 
               
               
                 250 
                 —Cl 
                 —Cl 
                 piperonyl 
                 2.25-2.31(2 H, m), 2.55-2.59(2 H, m), 3.22(2 H, 
               
               
                   
                   
                   
                   
                 brs), 3.44(2 H, s), 3.86-4.01(2 H, m), 5.94(2 H, s), 
               
               
                   
                   
                   
                   
                 6.69-6.76(2 H, m), 6.84-6.91(2 H, m), 7.25- 
               
               
                   
                   
                   
                   
                 7.29(2 H, m), 7.38-7.44(1 H, m), 7.52-7.55(2 H, 
               
               
                   
                   
                   
                   
                 m), 7.71-7.80(3 H, m), 7.97-8.03(2 H, m), 
               
               
                   
                   
                   
                   
                 8.24(1 H, d, J = 2.8 Hz), 8.60(1 H, s). 
               
               
                 251 
                 —CF 3   
                 —H 
                 benzyl 
                 2.27-2.34(2 H, m), 2.57-2.61(2 H, m), 3.23- 
               
               
                   
                   
                   
                   
                 3.25(2 H, m), 3.53(2 H, s), 3.89-3.98(2 H, m), 
               
               
                   
                   
                   
                   
                 6.96(1 H, d, J = 8.7 Hz), 7.27-7.31(7 H, m), 7.40- 
               
               
                   
                   
                   
                   
                 7.45(1 H, m), 7.55(1 H, d, J = 2.3 Hz), 7.72-7.83 
               
               
                   
                   
                   
                   
                 (4 H, m), 8.00(2 H, d, J = 8.1 Hz), 8.12(1 H, dd, J = 
               
               
                   
                   
                   
                   
                 8.9 Hz, 2.8 Hz), 8.30(1 H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                 8.40(1 H, brs). 
               
               
                 252 
                 —CF 3   
                 —H 
                 piperonyl 
                 2.25-2.31(2 H, m), 2.55-2.58(2 H, m), 3.23(2 H, 
               
               
                   
                   
                   
                   
                 m), 3.43(2 H, s), 3.85-4.00(4 H, m), 5.94(2 H, s), 
               
               
                   
                   
                   
                   
                 6.70-6.76(2 H, m), 6.84(1 H, s), 6.96(1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.9 Hz), 7.28-7.31(2 H, m), 7.40-7.46(1 H, m), 
               
               
                   
                   
                   
                   
                 7.55(1 H, d, J = 2.5 Hz), 7.72-7.83(4 H, m), 
               
               
                   
                   
                   
                   
                 8.00(2 H, d, J = 7.9 Hz), 8.12(1 H, dd, J = 8.9 
               
               
                   
                   
                   
                   
                 Hz, 2.6 Hz), 8.30(1 H, d, J = 2.6 Hz), 8.44(1 H, 
               
               
                   
                   
                   
                   
                 brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 157 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 549   
                 R 550   
                 R 551   
                 R 552   
                 R 553   
                 Form 
                   1 H NMR (solvent) δppm 
               
               
                   
               
               
                 253 
                 —CF 3   
                 —H 
                 —CH 3   
                 —H 
                 3-pyridyl 
                 free 
                 (CDCl 3 ) 3.06(3 H, s), 3.22(4 H, brs), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 3.81(4 H, brs), 4.55(2 H, s), 6.87(1 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 d, J = 8.9 Hz), 7.09(2 H, d, J = 8.7 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz), 7.14(1 H, dd, J = 8.9 Hz, 3.3 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz), 7.19-7.21(2 H, m), 7.35(2 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 J = 7.9 Hz), 7.44(2 H, d, J = 8.7 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz), 7.60(2 H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.74(1 H, d, J = 3.0 Hz), 8.14- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.17(1 H, m), 8.31-8.33(1 H, m). 
               
               
                 254 
                 —CF 3   
                 —H 
                 —H 
                 —F 
                 benzyl 
                 free 
                 (CDCl 3 ) 2.46(4 H, brs), 3.54(6 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 brs), 4.11(1 H, brs), 4.38(2 H, brs), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.85(1 H, d, J = 8.7 Hz), 7.01(1 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dd, J = 8.7 Hz, 3.1 Hz), 7.16- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.25(3 H, m), 7.28-7.33(5 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.46(2 H, d, J = 8.1 Hz), 7.52(1 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 J = 2.6 Hz), 7.60(2 H, d, J = 8.1 Hz). 
               
               
                 255 
                 —CF 3   
                 —H 
                 —CH 3   
                 —H 
                 piperonyl 
                 hydro- 
                 (DMSO-d 6 ) 2.49-2.52(2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 chloride 
                 3.06(5 H, brs), 3.35(4 H, brs), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 4.22(2 H, brs), 4.68(2 H, brs), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.07(2 H, s), 6.94-7.05(5 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.23(1 H, brs), 7.32(1 H, dd, J = 8.9 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz, 3.3 Hz), 7.43-7.46(4 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.69-7.72(3 H, m), 11.23(1 H, brs). 
               
               
                 256 
                 —Cl 
                 —Cl 
                 —H 
                 —F 
                 benzyl 
                 free 
                 (CDCl 3 ) 2.47(4 H, brs), 3.49- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 3.68(6 H, m), 4.29(2 H, s), 6.86(1 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 d, J = 8.7 Hz), 7.01(1 H, dd, J = 8.7 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz, 3.0 Hz), 7.17-7.22(4 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.32(5 H, brs), 7.41(1 H, d, J = 8.3 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz), 7.45(1 H, d, J = 1.8 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.51(1 H, d, J = 3.0 Hz). 
               
               
                 257 
                 —CF 3   
                 —H 
                 —CH 3   
                 —H 
                 4-CH 3 OPhCH 2 — 
                 hydro- 
                 (DMSO-d 6 ) 2.49-2.52(2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 chloride 
                 3.06(5 H, brs), 3.32-3.38(4 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 3.78(3 H, s), 4.27(2 H, d, J = 4.1 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz), 4.68(2 H, brs), 6.96(1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.9 Hz), 7.00-7.05(4 H, m), 7.32(1 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dd, J = 8.9 Hz, 3.3 Hz), 7.43- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.49(6 H, m), 7.68-7.72(3 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 10.72(1 H, brs). 
               
               
                 258 
                 —CF 3   
                 —H 
                 —CH 3   
                 —H 
                 4-pyridyl- 
                 hydro- 
                 (DMSO-d 6 ) 2.49-2.52(2 H, m), 3.05- 
               
               
                   
                   
                   
                   
                   
                 methyl 
                 chloride 
                 3.44(9H, m), 4.26(2 H, brs), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 4.68(2 H, brs), 6.96(1 H, d, J = 8.9 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz), 7.03(2 H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.32(1 H, dd, J = 8.9 Hz, 3.3 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.42-7.47(4 H, m), 7.68-7.72(5 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 m), 8.71(2 H, dd, J = 4.6 Hz, 1.5 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 158 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 554   
                 R 555   
                 R 556   
                 Form 
                   1 H NMR (solvent) δppm 
               
               
                   
               
               
                 259 
                 —CH 3   
                 —H 
                 benzyl 
                 hydro- 
                 (DMSO-d 6 ) 1.44(3 H, d, J = 6.8 Hz), 2.44- 
               
               
                   
                   
                   
                   
                 chloride 
                 2.52(2 H, m), 3.08-3.15(2 H, m), 3.30-3.38(4 H, 
               
               
                   
                   
                   
                   
                   
                 m), 4.33(2 H, brs), 4.55-4.62(1 H, m), 6.51(1 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 6.3 Hz), 6.82(1 H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.97(2 H, d, J = 8.7 Hz), 7.04(1 H, dd, J = 8.7 
               
               
                   
                   
                   
                   
                   
                 Hz, 3.0 Hz), 7.41(2 H, d, J = 8.6 Hz), 7.45- 
               
               
                   
                   
                   
                   
                   
                 7.47(4 H, m), 7.57(2 H, brs), 7.61(2 H, d, J = 8.3 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.69(2 H, d, J = 8.4 Hz), 10.99(1 H, brs). 
               
               
                 260 
                 —CH 3   
                 —CH 3   
                 benzyl 
                 free 
                 (CDCl 3 ) 1.58(3 H, d, J = 6.9 Hz), 2.46(4 H, brs), 
               
               
                   
                   
                   
                   
                   
                 2.72(3 H, s), 3.46-3.53(6 H, m), 4.97(1 H, q, J = 
               
               
                   
                   
                   
                   
                   
                 6.9 Hz), 6.86(1 H, d, J = 8.9 Hz), 7.07(2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.6 Hz), 7.23(1 H, dd, J = 8.9 Hz, 3.3 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.27-7.36(5 H, m), 7.40(2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.43(2 H, d, J = 7.3 Hz), 7.60(2 H, d, J = 8.3 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.82(1 H, d, J = 3.3 Hz). 
               
               
                 261 
                 —CH 3   
                 —CH 3   
                 piperonyl 
                 free 
                 (CDCl 3 ) 1.58(3 H, d, J = 6.9 Hz), 2.43(4 H, brs), 
               
               
                   
                   
                   
                   
                   
                 2.72(3 H, s), 3.44(2 H, s), 3.48-3.68(4 H, m), 
               
               
                   
                   
                   
                   
                   
                 4.97(1 H, q, J = 6.9 Hz), 5.95(2 H, s), 6.74(2 H, 
               
               
                   
                   
                   
                   
                   
                 brs), 6.85(1 H, brs), 6.87(1 H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.07(2 H, d, J = 8.7 Hz), 7.23(1 H, dd, J = 8.9 
               
               
                   
                   
                   
                   
                   
                 Hz, 3.3 Hz), 7.40(2 H, d, J = 8.6 Hz), 7.43(2 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 7.9 Hz), 7.60(2 H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.82(1 H, d, J = 3.1 Hz). 
               
               
                 262 
                 —CH 3   
                 —H 
                 piperonyl 
                 hydro- 
                 (DMSO-d 6 ) 1.44(3 H, d, J = 6.8 Hz), 2.49- 
               
               
                   
                   
                   
                   
                 chloride 
                 2.52(2 H, m), 3.01-3.06(2 H, m), 3.29-3.45(4 H, 
               
               
                   
                   
                   
                   
                   
                 m), 4.23(2 H, brs), 4.58-4.62(1 H, m), 6.07(2 H, 
               
               
                   
                   
                   
                   
                   
                 s), 6.51(1 H, d, J = 6.6 Hz), 6.82(1 H, d, J = 8.7 
               
               
                   
                   
                   
                   
                   
                 Hz), 6.96-6.99(4 H, m), 7.04(1 H, dd, J = 8.7 
               
               
                   
                   
                   
                   
                   
                 Hz, 3.0 Hz), 7.20(1 H, brs), 7.41(2 H, d, J = 8.6 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.46(1 H, d, J = 3.0 Hz), 7.61(2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.3 Hz), 7.69(2 H, d, J = 8.4 Hz), 10.99(1 H, 
               
               
                   
                   
                   
                   
                   
                 brs). 
               
               
                 263 
                 —H 
                 —C 2 H 5   
                 benzyl 
                 hydro- 
                 (DMSO-d 6 ) 1.14(3 H, d, J = 6.9 Hz), 2.50- 
               
               
                   
                   
                   
                   
                 chloride 
                 2.51(2 H, m), 3.11(2 H, brs), 3.35(4 H, brs), 
               
               
                   
                   
                   
                   
                   
                 3.51(2 H, q, J = 6.9 Hz), 4.33(2 H, brs), 
               
               
                   
                   
                   
                   
                   
                 4.63(2 H, brs), 6.94(1 H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.03(2 H, d, J = 8.6 Hz), 7.25(1 H, dd, J = 8.9 
               
               
                   
                   
                   
                   
                   
                 Hz, 3.3 Hz), 7.42-7.48(7 H, m), 7.57(2 H, brs), 
               
               
                   
                   
                   
                   
                   
                 7.62(1 H, d, J = 3.1 Hz), 7.70(2 H, d, J = 8.1 
               
               
                   
                   
                   
                   
                   
                 Hz), 11.03(1 H, brs). 
               
               
                 264 
                 —H 
                 —C 2 H 5   
                 piperonyl 
                 hydro- 
                 (DMSO-d 6 ) 1.14(3 H, d, J = 6.9 Hz), 2.50- 
               
               
                   
                   
                   
                   
                 chloride 
                 2.51(2 H, m), 3.06(2 H, brs), 3.36(4 H, brs), 
               
               
                   
                   
                   
                   
                   
                 3.52(2 H, q, J = 6.9 Hz), 4.22(2 H,brs), 
               
               
                   
                   
                   
                   
                   
                 4.64(2 H, brs), 6.07(2 H, s), 6.94(1 H, d, J = 8.9 
               
               
                   
                   
                   
                   
                   
                 Hz), 6.99(2 H, brs), 7.03(2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.23(1 H, brs), 7.25(1 H, dd, J = 8.9 Hz, 3.3 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.42-7.49(4 H, m), 7.62(1 H, d, J = 3.1 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.71(2 H, d, J = 8.1 Hz), 11.29(1 H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 159 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 557   
                 R 558   
                   1 H NMR (solvent) δppm 
               
               
                   
               
               
                 265 
                 3,4-Cl 2 PhCONH— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 2.39-2.49(4 H, m), 3.39- 3.79(6 H, m), 6.87(1 H, d, J = 8.9 Hz), 7.06-7.15(3 H, m), 7.27- 7.37(6 H, m), 7.51(1 H, d, J = 8.4 Hz), 7.74-7.78(1 H, m), 8.01- 8.05(2 H, m), 8.28(1 H, d, J = 2.6 Hz), 9.10(1 H, brs). 
               
               
                   
               
               
                 266 
                 3,4-Cl 2 PhCONH— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 2.37-2.48(4 H, m), 3.43- 3.75(6 H, m), 5.94(2 H, s), 6.70- 6.77(2 H, m), 6.84(1 H, brs), 6.92(1 H, d, J = 8.9 Hz), 7.09- 7.17(3 H, m), 7.34-7.40(1 H, m), 7.55(1 H, d, J = 8.4 Hz), 7.73- 7.77(1 H, m), 8.04(1 H, d, J = 2.1 Hz), 8.09(1 H, dd, J = 8.9 Hz, 2.8 Hz), 8.28(1 H, d, J = 2.8 Hz), 8.63(1 H, brs). 
               
               
                   
               
               
                 267 
                 4-CF 3 PhCH 2 N(CH 3 )— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (DMSO-d 6 ) 3.03-3.13(5 H, m), 4.69-4.75(3 H, m), 6.88-6.98(3 H, m), 7.06(2 H, d, J = 8.6 Hz), 7.16- 7.23(2 H, m), 7.33(1 H, dd, J = 9.1 Hz, 3.1 Hz), 7.46(2 H, d, J = 8.3 Hz), 7.69-7.73(3 H, m), 7.91(2 H, d, J = 8.7 Hz), 8.61(1 H, d, J = 8.1 Hz), 10.35(1 H, brs). 
               
               
                   
               
               
                 268 
                 4-CF 3 PhCH 2 N(CH 3 )— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (DMSO-d 6 ) 2.89-3.06(2 H, m), 3.06(3 H, s), 4.61-4.72(3 H, m), 5.96(2 H, s), 6.50(1 H, s), 6.84(1 H, s), 6.97(1 H, d, J = 8.9 Hz), 7.06(2 H, d, J = 8.7 Hz), 7.33(1 H, dd, J = 8.9 Hz, 3.3 Hz), 7.46(2 H, d, J = 8.1 Hz), 7.69-7.73(3 H, m), 7.89(2 H, d, J = 8.7 Hz), 8.56(1 H, d, J = 8.3 Hz), 10.15(1 H, brs). 
               
               
                   
               
               
                 269 
                 3,4-Cl 2 PhCONH— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 2.28-2.30(2 H, m), 2.58- 2.60(2 H, m), 3.25-3.29(2 H, m), 3.44(2 H, s), 3.92-3.98(2 H, m), 5.94(2 H, s), 6.73(2 H, s), 6.84(1 H, s), 6.96(1 H, d, J = 8.7 Hz), 7.14(1 H, d, J ==0 7.8 Hz), 7.37(1 H d, J = 7.8 Hz), 7.50-7.59(3 H, m), 7.73(1 H, dd, J = 8.2 Hz, 2.1 Hz), 7.83(1 H, dd, J = 7.6 Hz, 3.0 Hz), 8.03(1 H, d, J = 2.1 Hz), 8.06- 8.13(2 H, m), 8.17(1 H, s), 8.24(1 H, d, J = 3.0 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 160 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
                 mp (° C.) or  1 H NMR 
               
               
                 No. 
                 R 559   
                 R 560   
                 Xb 1   
                 Xb 2   
                 R 561   
                 Form 
                 (DMSO-d 6 ) δppm 
               
               
                   
               
               
                 270 
                 —Cl 
                 —Cl 
                 —O— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 piperonyl 
                 free 
                   1 H NMR (at 375 K) 2.00(3 H, brs), 2.30- 2.38(4 H, m), 3.34-3.43(6 H, m), 4.12(2 H, s), 4.51(2 H, brs), 5.91(2 H, s), 6.73(1 H, d, J = 7.9 Hz), 6.77(1 H, d, J = 7.9 Hz), 6.81(1 H, s), 6.98(1 H, d, J = 8.8 Hz), 7.05(2 H, d, J = 8.2 Hz), 7.26(2 H, d, J = 8.2 Hz), 7.73(1 H, d, J = 8.4 Hz), 7.91(1 H, dd, J = 2.1 Hz, 8.4 Hz), 8.12- 8.18(3 H, m), 8.48(1 H, d, J = 2.6 Hz), 10.17(1 H, s). 
               
               
                   
               
               
                 271 
                 —Cl 
                 —Cl 
                 —O— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 benzyl 
                 free 
                   1 H NMR (at 375 K) 2.00(3 H, brs), 2.33- 2.40(4 H, m), 3.38-3.42(4 H, m), 3.49- 3.53(2 H, m), 4.13(2 H, s), 4.51(2 H, brs), 698(1 H, d, J = 8.8 Hz), 7.02-7.10(2 H, m), 7.16-7.30(7 H, m), 7.73(1 H, d, J = 8.4 Hz), 7.91(1 H, dd, J = 8.4 Hz, 2.1 Hz), 8.11-8.17(2 H, m), 8.48(1 H, d, J = 2.5 Hz), 10.17(1 H, s). 
               
               
                   
               
               
                 272 
                 —CF 3   
                 —H 
                 —O— 
                 —CH═CH— 
                 benzyl 
                 free 
                   1 H NMR 2.39(4 H, brs), 3.52(2 H, s), 
               
               
                   
                   
                   
                   
                 (trans) 
                   
                   
                 3.58(2 H, brs), 3.71(2 H, brs), 7.13(1 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 J = 8.9 Hz), 7.14(2 H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.24(1 H, d, J = 15.3 Hz), 7.18-7.41(5 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 m), 7.50(1 H, d, J = 15.3 Hz), 7.76(2 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 J = 8.7 Hz), 7.94(2 H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.17(2 H, d, J = 8.3 Hz), 8.25(1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.9 Hz, 2.7 Hz), 8.54(1 H, d, J = 2.7 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 10.66(1 H, s). 
               
               
                 273 
                 —CF 3   
                 —H 
                 —O— 
                 —CH═CH— 
                 piperonyl 
                 free 
                   1 H NMR 2.37(4 H, brs), 3.42(2 H, s), 
               
               
                   
                   
                   
                   
                 (trans) 
                   
                   
                 3.58(2 H, brs), 3.70(2 H, brs), 5.99(2 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.76(1 H, dd,J = 8.0 Hz, 2.4Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.85(1 H, d, J = 8.0 Hz), 6.88(1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 1.5 Hz), 7.13(1 H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.14(2 H, d, J = 8.7 Hz), 7.20(1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 15.4 Hz), 7.50(1 H, d, J = 15.4 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.76(2 H, d, J = 8.7 Hz), 7.94(2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.2 Hz), 8.17(2 H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.25(1 H, dd, J = 8.9 Hz, 2.6 Hz), 8.54 
               
               
                   
                   
                   
                   
                   
                   
                   
                 (1 H, d, J = 2.6 Hz), 10.65(1 H, s). 
               
               
                 274 
                 —CF 3   
                 —H 
                 —N(CH 3 )— 
                 none 
                 piperonyl 
                 dihydro- 
                   1 H NMR 2.98-3.12(2 H, m), 3.12- 
               
               
                   
                   
                   
                   
                   
                   
                 chloride 
                 3.36(2 H, m), 3.50(3 H, s), 3.71-4.68(6 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 m), 6.06(2 H, s), 6.93-7.06(3 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.26(1 H, s), 7.42(2 H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.53(2 H, d, J = 8.3 Hz), 7.92(2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.3 Hz), 8.12(1 H, d, J = 9.2 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.20(2 H, d, J = 8.3 Hz), 8.67(1 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 10.79(1 H, s), 11.47(1 H, brs). 
               
               
                 275 
                 —CF 3   
                 —H 
                 —N(CH 3 )— 
                 none 
                 benzyl 
                 free 
                 mp 213-214 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 161 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                 mp (° C.) or  1 H NMR (CDCl 3 ) 
               
               
                 No. 
                 R 562   
                 R 563   
                 R 564   
                 δppm 
               
               
                   
               
               
                 276 
                 —Cl 
                 —Cl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.62-1.80(2 H, m), 1.82- 1.87(2 H, m), 2.71(1 H, dt, J = 3 Hz, 11.0 Hz), 2.84(1 H, brs), 2.94(1 H, t, J = 11.0 Hz), 3.55- 3.70(10 H, m), 6.89(1 H, d, J = 9.0 Hz), 6.93(2 H, dd, J = 7.0 Hz, 2.0 Hz), 7.02(2 H, dd, J = 7.0 Hz, 2.0 Hz), 7.56(1 H, d, J = 8.0 Hz), 7.71(1 H, dd, J = 9.0 Hz, 2.0 Hz), 7.99(1 H, d, J = 2.0 Hz), 2.0 Hz), 7.99(1 H, d, J = 2.0 Hz), 8.10(1 H, s), 8.15(1 H, dd, J = 9.0 Hz, 2.5 Hz), 8.25(1 H, d, J = 2.5 Hz). 
               
               
                   
               
               
                 277 
                 —Cl 
                 —Cl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 2.38-2.42(4 H, m), 2.62- 2.67(4 H, m), 3.14-3.17(4 H, m), 3.22(2 H, s), 3.42(2 H, s), 3.61- 3.63(4 H, m), 5.95(2 H, s), 6.70- 6.75(2 H, m), 7.03(2 H, d, J = 8.0 Hz), 7.55(1 H, d, J = 8.0 Hz), 7.70(1 H, brs), 7.73(2 H, d, J = 8.0 Hz), 8.01(1 H, s), 8.15(1 H, brd, J = 9.0 Hz), 8.27(1 H, d, J = 2.5 Hz). 
               
               
                   
               
               
                 278 
                 —Cl 
                 —Cl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 2.40-2.45(4 H, m), 2.60- 2.64(4 H, m), 3.13(4 H, brs), 3.20(2 H, brs), 3.48(2 H, brs), 3.62(4 H, brs), 6.85-6.91(3 H, m), 7.01(2 H, d, J = 8.0 Hz), 7.26- 7.32(5 H, m), 7.52(1 H, d, J = 8.5 Hz), 7.70(1 H, brs), 7.74(1 H, dd, J = 8.5 Hz, 2.0 Hz), 8.03(1 H, d, J = 2.0 Hz), 8.15(1 H, brd, J = 9.0, Hz), 8.29(1 H, d, J = 2.5 Hz). 
               
               
                   
               
               
                 279 
                 —H 
                 —CF 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 mp 180-183 
               
               
                   
               
               
                 280 
                 —H 
                 —CF 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 mp 197-199 
               
               
                   
               
               
                 281 
                 —H 
                 —CF 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 mp 133-135 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 162 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 565   
                 Form 
                 mp (° C.) 
               
               
                   
               
               
                 282 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 108-110 
               
               
                   
               
               
                 283 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 136-138 
               
               
                   
               
               
                 284 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 133-136 
               
               
                   
               
               
                 285 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 147-151 
               
               
                   
               
               
                 286 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 dihydrochloride 
                 180-183 
               
               
                   
               
               
                 287 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 111-113 
               
               
                   
               
               
                 288 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 111-113 
               
               
                   
               
               
                 289 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 246-249 
               
               
                   
               
               
                 290 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 148-151 
               
               
                   
               
               
                 291 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 120-121 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 163 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 566   
                 Form 
                 mp (° C.) 
               
               
                   
               
               
                 292 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                  83-86 
               
               
                   
               
               
                 293 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 130-133 
               
               
                   
               
               
                 294 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 145-146 
               
               
                   
               
               
                 295 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 trihydro- chloride 
                 180-185 
               
               
                   
               
               
                 296 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 184-186 
               
               
                   
               
               
                 297 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 173-176 
               
               
                   
               
               
                 298 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 181-183 
               
               
                   
               
               
                 299 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 166-170 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 164 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 567   
                 mp (° C.) 
               
               
                   
               
               
                 300 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 102-104 
               
               
                   
               
               
                 301 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 106-109 
               
               
                   
               
               
                 302 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 261-264 
               
               
                   
               
               
                 303 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 173-175 
               
               
                   
               
               
                 304 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 164-166 
               
               
                   
               
               
                 305 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 158-160 
               
               
                   
               
               
                 306 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 174-176 
               
               
                   
               
               
                 307 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 206-207 
               
               
                   
               
               
                 308 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 165-166 
               
               
                   
               
               
                 309 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 164-167 
               
               
                   
               
               
                 310 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 188-190 
               
               
                   
               
               
                 311 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 130-132 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 165 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 568   
                 R 569   
                 mp (° C.) or  1 H NMR (CDCl 3 ) δppm 
               
               
                   
               
               
                 312 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 mp 166-167 
               
               
                   
               
               
                 313 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 mp 157-158 
               
               
                   
               
               
                 314 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 mp 218-219 
               
               
                   
               
               
                 315 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 benzyl 
                   1 H NMR 0.25-0.31(2 H, m), 0.61- 0.69(2 H, m), 2.67-2.73(1 H, m), 2.86(4 H, brs), 3.18(4 H, brs), 3.83(2 H, s), 6.80-6.92(3 H, m), 7.16-7.62(8 H, m), 8.11(2 H, d, J = 8.1 Hz), 8.39(1 H, dd, J = 8.9 Hz, 2.6 Hz), 8.45(1 H, d, J = 2.5 Hz), 10.23(1 H, s), 10.93(1 H, brs). 
               
               
                   
               
               
                 316 
                 —CONHPh 
                 benzyl 
                   1 H NMR 3.07(4 H, brs), 3.26(4 H, 
               
               
                   
                   
                   
                 brs), 3.98(2 H, s), 6.83-7.59(14 H, 
               
               
                   
                   
                   
                 m), 7.65(2 H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                 8.06(2 H, d, J = 8.1 Hz), 8.37(1 H, 
               
               
                   
                   
                   
                 d, J = 2.6 Hz), 8.49(1 H, dd, J = 
               
               
                   
                   
                   
                 8.9 Hz, 2.6 Hz), 9.30(1 H, s), 
               
               
                   
                   
                   
                 9.71(1 H, brs). 
               
               
                   
               
               
                 317 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 benzyl 
                   1 H NMR 1.87(4 H, brs), 2.72(4 H, brs), 3.19(4 H, brs), 3.40(4 H, brs), 3.69(2 H, s), 6.58(1 H, d, J = 8.7 Hz), 6.80(1 H, s), 6.92(1 H, d, J = 9.2 Hz), 7.02(1 H, d, J = 8.9 Hz), 7.26-7.34(5 H, m), 7.57(2 H, d, J = 7.9 Hz), 7.90(1 H, d, J = 7.1 Hz), 8.05(2 H, d, J = 8.1 Hz), 8.40(1 H, s), 9.73(1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 166 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 Xb 3   
                 Xb 4   
                 Xb 5   
                 R 570   
                 mp (° C.) or  1 H NMR (CDCl 3 ) δppm 
               
               
                   
               
               
                 318 
                 —O— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 benzyl 
                 mp 162-163 
               
               
                   
               
               
                 319 
                 —O— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 piperonyl 
                 mp 136-137 
               
               
                   
               
               
                 320 
                 —O— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —O— 
                 none 
                 mp 176-177 
               
               
                   
               
               
                 321 
                 —N(CH 3 )— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 2.43(4 H, brs), 2.67(4 H, t, J = 4.8 Hz), 3.22(4 H, t, J = 4.8 Hz), 3.24(2 H, s), 3.42(3 H, s), 3.52(2 H, s), 3.63(4 H, brs), 6.46 (1 H, d, J = 9.1 Hz), 6.95(2 H, d, J = 8.9 Hz), 7.15(2 H, d, J = 8.9 Hz), 7.20-7.40(5 H, m), 7.65-7.80(2 H, m), 7.74(2 H, d, J = 8.2 Hz), 7.98(2 H, d, J = 8.2 Hz), 8.26(1 H, d, J = 2.5 Hz). 
               
               
                   
               
               
                 322 
                 —N(CH 3 )— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 piperonyl 
                   1 H NMR 2.41(4 H, brs), 2.67(4 H, t, J = 4.8 Hz), 3.22(4 H, t, J = 5.1 Hz), 3.24(2 H, s), 3.42(5 H, s), 3.62(4 H, t, J = 4.5 Hz), 5.94(2 H, s), 6.46(1 H, d, J = 9.1 Hz), 6.74(2 H, s), 6.85(1 H, s), 6.95(2 H, d, J = 8.9 Hz), 7.15(2 H, d, J = 8.9 Hz), 7.65-7.75(1 H, m), 7.74(2 H, d, J = 8.1 Hz), 7.83(1 H, brs), 7.99(2 H, d, J = 8.1 Hz), 8.26(1 H,d, J = 2.5 Hz). 
               
               
                   
               
               
                 323 
                 —N(CH 3 )— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 benzyl 
                   1 H NMR 1.31-1.52(2 H, m), 1.88(2 H, d, J = 12.3 Hz), 1.88-2.15(1 H, m), 2.29(2 H, d, J = 6.7 Hz), 2.44(4 H, t, J = 5.1 Hz), 2.76(2 H, t, J = 11.2 Hz), 3.42(3 H, s), 3.49(2 H, t, J = 4.9 Hz), 3.53(2 H, s), 3.59-3.78(4 H, m), 6.47(1 H, d, J = 9.1 Hz), 6.96(2 H, d, J = 8.9 Hz), 7.13 (2 H, d, J = 8.9 Hz), 7.20-7.41(5 H, m), 7.61- 7.78(2 H, m), 7.75(2 H, d, J = 8.1 Hz), 7.98 (2 H, d, J = 8.1 Hz), 8.25(1 H, d, J = 2.3 Hz). 
               
               
                   
               
               
                 324 
                 —N(CH 3 )— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 piperonyl 
                   1 H NMR 1.30-1.51(2 H, m), 1.88(2 H, d, J = 2.9 Hz), 1.98-2.11(1 H, m), 2.29(2 H, d, J = 6.7 Hz), 2.41(4 H, m), 2.76(2 H, t, J = 11.2 Hz), 3.42(3 H, s), 3.43(2 H, s), 3.49(2 H, t, J = 4.8 Hz), 3.55-3.78(4 H, m), 5.95(2 H, s), 6.47(1 H, d, J = 9.0 Hz), 6.74(2 H, s), 6.86(1 H, s), 6.96(2 H, d, J = 8.9 Hz), 7.13(2 H, d, J = 8.9 Hz), 7.70(1 H, brs), 7.71(1 H, dd, J = 9.0 Hz, 2.7 Hz), 7.75(2 H, d, J = 8.2 Hz), 7.99(2 H, d, J = 8.2 Hz), 8.26(1 H, d, J = 2.7 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 167 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 Xb 6   
                 M 
                 R 571   
                 Form 
                 δmp (° C.) or  1 H NMR 
               
               
                   
               
               
                 325 
                 —N(Ac)— 
                 1 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 hydro- chloride 
                 mp 214-216 
               
               
                   
               
               
                 326 
                 —N(Ac)— 
                 1 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                   1 H NMR (DMSO-d 6 ) δ 1.77(3 H,s), 2.25-2.34(4 H, m), 3.30-3.50(6 H, m), 4.40 (2 H, s), 6.97(2 H, d, J = 8.8 Hz), 7.22-7.35(6 H, m), 7.36(2 H, d, J = 8.8 Hz), 7.53- 7.59(1 H, m), 7.84(1 H, d, J = 8.3 Hz), 7.89-7.95(2 H, m), 8.20(1 H, d, J = 2.2 Hz), 10.61(1 H, s). 
               
               
                   
               
               
                 327 
                 none 
                 1 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 mp 178-179 
               
               
                   
               
               
                 328 
                 none 
                 1 
                 morpholino 
                 free 
                 mp 196-198 
               
               
                   
               
               
                 329 
                 none 
                 1 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 mp 197-198 
               
               
                   
               
               
                 330 
                 none 
                 3 
                 morpholino 
                 free 
                 mp 144-146 
               
               
                   
               
               
                 331 
                 none 
                 3 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 hydro- chloride 
                 mp 194-196 
               
               
                   
               
               
                 332 
                 none 
                 3 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 hydro- chloride 
                 mp 205-206 
               
               
                   
               
               
                 333 
                 —S— 
                 1 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                   1 H NMR (CDCl 3 ) δ 2.35- 2.45(4 H, m), 3.42(2 H, s), 3.42-3.48(2 H, m), 3.58(2 H, brs), 3.65(2 H, s), 5.94(2 H, s), 6.72-6.75(2 H, m), 6.84(1 H, d, J = 1.1 Hz), 6.89(2 H, d, J = 8.8 Hz), 7.00-7.10(1 H, m), 7.19-7.25(1 H, m), 7.42(2 H, d, J = 8.8 Hz), 7.58(1 H, d, J = 8.3 Hz), 7.65-7.76(2 H, m), 7.98(1 H, s), 7.99(1 H, s). 
               
               
                   
               
               
                 334 
                 —SO— 
                 1 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 mp 133-135 
               
               
                   
               
               
                 335 
                 —SO 2 — 
                 1 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 mp 125-128 
               
               
                   
               
               
                 336 
                 CH═CH— (trans) 
                 0 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 mp 169-171 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 168 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 572   
                 R 573   
                   1 H NMR (solvent) δppm 
               
               
                   
               
               
                 337 
                 4-CF 3 Ph- 
                 benzyl 
                 (CDCl 3 ) 2.30-2.34(2 H, m), 2.39-2.43(2 H, m), 
               
               
                   
                   
                   
                 3.46-3.49(4 H, m), 3.62-3.66(2 H, m), 3.69(2 H, 
               
               
                   
                   
                   
                 s), 6.94(1 H, d, J = 8.7 Hz), 7.03-7.08(2 H, m), 
               
               
                   
                   
                   
                 7.19-7.35(7 H, m), 7.75(2 H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                 8.00(2 H, d, J = 8.2 Hz), 8.21(1 H, dd, J = 8.7 
               
               
                   
                   
                   
                 Hz, 2.8 Hz), 8.26(1 H, s), 8.29(1 H, d, J = 2.8 
               
               
                   
                   
                   
                 Hz). 
               
               
                 338 
                 4-CF 3 Ph- 
                 piperonyl 
                 (CDCl 3 ) 2.28-2.32(2 H, m), 2.36-2.39(2 H, m), 
               
               
                   
                   
                   
                 3.39(2 H, s), 3.45-3.49(2 H, m), 3.60-3.64(2 H, 
               
               
                   
                   
                   
                 m), 3.68(2 H, s), 5.94(2 H, s), 6.69-6.76(2 H, m), 
               
               
                   
                   
                   
                 6.83(1 H, brs), 6.92(1 H, d, J = 8.7 Hz), 7.01- 
               
               
                   
                   
                   
                 7.06(2 H, m), 7.17-7.22(2 H, m), 7.72(2 H, d, J = 
               
               
                   
                   
                   
                 8.4 Hz), 8.00(2 H, d, J = 8.1 Hz), 8.17-8.21(1 H, 
               
               
                   
                   
                   
                 m), 8.29(1 H, d, J = 2.6 Hz), 8.49(1 H, brs). 
               
               
                 339 
                 3,4-Cl 2 Ph- 
                 benzyl 
                 (CDCl 3 ) 2.31-2.34(2 H, m), 2.38-2.42(2 H, m), 
               
               
                   
                   
                   
                 3.46-3.50(4 H, m), 3.62-3.65(2 H, m), 3.69(2 H, 
               
               
                   
                   
                   
                 s), 6.90(1 H, d, J = 8.9 Hz), 7.00-7.05(2 H, m), 
               
               
                   
                   
                   
                 7.17-7.23(2 H, m), 7.28-7.35(5 H, m), 7.54(1 H, d, 
               
               
                   
                   
                   
                 J = 8.2 Hz), 7.73(1 H, dd, J = 8.4 Hz, 2.1 Hz), 
               
               
                   
                   
                   
                 7.99(1 H, d, J = 2.1 Hz), 8.12-8.17(1 H, m), 
               
               
                   
                   
                   
                 8.28(1 H, d, J = 2.8 Hz), 8.44(1 H, brs). 
               
               
                 340 
                 3,4-Cl 2 Ph- 
                 3-pyridyl 
                 (CDCl 3 ) 3.02-3.06(2 H, m), 3.13-3.17(2 H, m), 
               
               
                   
                   
                   
                 3.63-3.67(2 H, m), 3.76-3.82(4 H, m), 6.91(1 H, d, 
               
               
                   
                   
                   
                 J = 8.9 Hz), 7.02-7.07(2 H, m), 7.17-7.24(4 H, 
               
               
                   
                   
                   
                 m), 7.52(1 H, d, J = 8.4 Hz), 7.73-7.76(1 H, m), 
               
               
                   
                   
                   
                 8.01(1 H, d, J = 2.0 Hz), 8.11-8.13(1 H, m), 
               
               
                   
                   
                   
                 8.18(1 H,dd, J = 8.9 Hz, 2.8 Hz), 8.23-8.25(2 H, 
               
               
                   
                   
                   
                 m), 8.95(1 H, brs). 
               
               
                 341 
                 3,4-Cl 2 Ph- 
                 piperonyl 
                 (CDCl 3 ) 2.28-2.39(4 H, m), 3.39(2 H, s), 3.46- 
               
               
                   
                   
                   
                 3.49(2 H, m), 3.60-3.64(2 H, m), 3.69(2 H, s) 
               
               
                   
                   
                   
                 5.94(2 H, s), 6.69-6.76(2 H, m), 6.82-6.83(1 H, 
               
               
                   
                   
                   
                 m), 6.89(1 H, d, J = 8.9 Hz), 6.99-7.04(2 H, m), 
               
               
                   
                   
                   
                 7.15-7.21(2 H, m), 7.53(1 H, d, J = 8.4 Hz), 7.71- 
               
               
                   
                   
                   
                 7.75(1 H, m), 7.99(1 H, d, J = 2.1 Hz), 8.14(1 H, 
               
               
                   
                   
                   
                 dd, J = 8.9 Hz, 2.6 Hz), 8.28(1 H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                 8.56(1 H, s). 
               
               
                 342 
                 3,4-Cl 2 PhNH— 
                 piperonyl 
                 (DMSO-d 6 ) 2.20-2.35(4 H, m), 3.38(2 H, s), 3.40- 
               
               
                   
                   
                   
                 3.55(4 H, m), 3.69(2 H, s), 5.98(2 H, s), 6.70- 
               
               
                   
                   
                   
                 6.76(1 H, m), 6.76-6.86(2 H, m), 6.97-7.00(3 H, 
               
               
                   
                   
                   
                 m), 7.02-7.24(2 H, m), 7.35(1 H, dd, J = 8.8 Hz, 
               
               
                   
                   
                   
                 2.5 Hz), 7.52(1 H, d, J = 8.8 Hz), 7.86(1 H, d, J = 
               
               
                   
                   
                   
                 2.5 Hz), 7.98(1 H, dd, J = 8.8 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                 8.19(1 H, d, J = 2.6 Hz), 8.89(1 H, s), 9.08(1 H, 
               
               
                   
                   
                   
                 s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 169 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 574   
                   1 H NMR (DMSO-d 6 ) δppm or MS 
               
               
                   
               
               
                 343 
                 —H 
                   1 H NMR 2.33(2 H, t, J = 7.7 Hz), 2.77(2 H, t, J = 7.7 Hz), 
               
               
                   
                   
                 6.75(1 H, brs), 6.87(2 H, d, J = 8.6 Hz), 7.15-7.23(3 H, m), 
               
               
                   
                   
                 7.28(1 H, brs), 7.54(1 H, d, J = 8.7 Hz), 7.85(1 H, d, J = 8.4 
               
               
                   
                   
                 Hz), 7.89(1 H, dd, J = 13.2 Hz, 2.4 Hz), 7.94(1 H, dd, J = 8.4 
               
               
                   
                   
                 Hz, 2.0 Hz), 8.21(1 H, d, J = 2.0 Hz), 10.57(1 H, s). 
               
               
                 344 
                 —CH 3   
                 MS 460(M + ) 
               
               
                 345 
                 —C 2 H 5   
                   1 H NMR 0.97(3 H, t, J = 7.2 Hz), 2.32(2 H, t, J = 7.8 Hz), 
               
               
                   
                   
                 2.77(2 H, t, J = 7.8 Hz), 3.00-3.08(2 H, m), 6.87(2 H, d, J = 8.6 
               
               
                   
                   
                 Hz), 7.14-7.21(3 H, m), 7.54(1 H, d, J = 9.8 Hz), 7.78(1 H, brt), 
               
               
                   
                   
                 7.85(1 H, d, J = 8.4 Hz), 7.89(1 H, dd, J = 13.2 Hz, 2.3 Hz), 
               
               
                   
                   
                 7.94(1 H, dd, J = 8.4 Hz, 2.1 Hz), 8.21(1 H, d, J = 2.1 Hz), 
               
               
                   
                   
                 10.57(1 H, s). 
               
               
                 346 
                 —CH(CH 3 ) 2   
                   1 H NMR 1.00(6 H, d, J = 6.6 Hz), 2.30(2 H, t, J = 7.7 Hz), 
               
               
                   
                   
                 2.77(2 H, t, J = 7.7 Hz), 3.75-3.86(1 H, m), 6.87(2 H, d, J = 8.6 
               
               
                   
                   
                 Hz), 7.13-7.20(3 H, m), 7.54(1 H, d, J = 8.9 Hz), 7.65(1 H, 
               
               
                   
                   
                 brd), 7.85(1 H, d, J = 8.4 Hz), 7.89(1 H, dd, J = 13.1 Hz, 2.5 
               
               
                   
                   
                 Hz), 7.94(1 H, dd, J = 8.4 Hz, 2.1 Hz), 8.22(1 H, d, J = 2.1 
               
               
                   
                   
                 Hz), 10.58(1 H, s). 
               
               
                 347 
                 —CH 2 CH(CH 3 ) 2   
                   1 H NMR 0.78(6 H, d, J = 6.7 Hz), 1.56-1.68(1 H, m), 2.36(2 H, 
               
               
                   
                   
                 t, J = 7.6 Hz), 2.78(2 H, t, J = 7.6 Hz), 2.81-2.87(2 H, m), 
               
               
                   
                   
                 6.87(2 H, d, J = 8.6 Hz), 7.10-7.22(3 H, m), 7.54(1 H, d, J = 
               
               
                   
                   
                 8.9 Hz), 7.77(1 H, brt), 7.85(1 H, d, J = 8.4 Hz), 7.89(1 H, dd, J = 
               
               
                   
                   
                 13.2 Hz, 2.4 Hz), 7.94(1 H, dd, J = 8.4 Hz, 2.1 Hz), 
               
               
                   
                   
                 8.21(1 H, d, J = 2.1 Hz), 10.57(1 H, s). 
               
               
                 348 
                 —(CH 2 ) 3 CH 3   
                   1 H NMR 0.84(3 H, t, J = 7.3 Hz), 1.15-1.27(2 H, m), 1.27- 
               
               
                   
                   
                 1.38(2 H, m), 2.33(2 H, t, J = 7.7 Hz), 2.77(2 H, t, J = 7.7 Hz), 
               
               
                   
                   
                 2.97-3.05(2 H, m), 6.87(2 H, d, J = 8.6 Hz), 7.11-7.21(3 H, m), 
               
               
                   
                   
                 7.50-7.58(1 H, m), 7.74(1 H, brt), 7.85(1 H, d, J = 8.4 Hz), 7.89 
               
               
                   
                   
                 (1 H, dd, J = 13.2 Hz, 2.4Hz), 7.94(1 H, dd, J = 8.4 Hz, 2.1 
               
               
                   
                   
                 Hz), 8.21(1 H, d, J = 2.1 Hz), 10.57(1 H, s). 
               
               
                 349 
                 cyclopropyl 
                   1 H NMR 0.26-0.37(2 H, m), 0.51-0.63(2 H, m), 2.29(2 H, t, J = 
               
               
                   
                   
                 7.7 Hz), 2.53-2.61(1 H, m), 2.76(2 H, t, J = 7.7 Hz), 6.87(2 H, 
               
               
                   
                   
                 d, J = 8.6 Hz), 7.10-7.23(3 H, m), 7.54(1 H, d, J = 8.6 Hz), 
               
               
                   
                   
                 7.80-8.00(4 H, m), 8.21(1 H, d, J = 2.1 Hz), 10.57(1 H, s). 
               
               
                 350 
                 cyclopentyl 
                   1 H NMR 1.21-1.34(2 H, m), 1.41-1.51(2 H, m), 1.51-1.63(2 H, 
               
               
                   
                   
                 m), 1.68-1.80(2 H, m), 2.31(2 H, t, J = 7.7 Hz), 2.76(2 H, t, J = 
               
               
                   
                   
                 7.7 Hz), 3.90-3.99(1 H, m), 6.87(2 H, d, J = 8.6 Hz), 7.14- 
               
               
                   
                   
                 7.21(3 H, m), 7.50-7.57(1 H, m), 7.72(1 H, brd), 7.85(1 H, d, J = 
               
               
                   
                   
                 8.4 Hz), 7.89(1 H, dd, J = 13.2 Hz, 2.4 Hz), 7.94(1 H, dd, J = 
               
               
                   
                   
                 8.4 Hz, 2.1 Hz), 8.22(1 H, d, J = 2.1 Hz), 10.58(1 H, s). 
               
               
                 351 
                 cyclohexyl 
                   1 H NMR 1.00-1.15(3 H, m), 1.15-1.28(2 H, m), 1.48-1.58(1 H, 
               
               
                   
                   
                 m), 1.58-1.70(4 H, m), 2.31(2 H, t, J = 7.6 Hz), 2.77(2 H, t, J = 
               
               
                   
                   
                 7.6 Hz), 3.44-3.53(1 H, m), 6.87(2 H, d, J = 8.6 Hz), 7.11- 
               
               
                   
                   
                 7.23(3 H, m), 7.50-7.57(1 H, m), 7.62(1 H, brd), 7.85(1 H, d, J = 
               
               
                   
                   
                 8.4 Hz), 7.89(1 H, dd, J = 13.2 Hz, 2.4 Hz), 7.94(1 H, dd, J = 
               
               
                   
                   
                 8.4 Hz, 2.1 Hz), 8.21(1 H, d, J = 2.1 Hz), 10.57(1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 170 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 575   
                   1 H NMR (DMSO-d 6 ) δ ppm 
               
               
                   
               
               
                 352 
                 cycloheptyl 
                 1.28-1.40 (4 H, m), 1.40-1.61 (6 H, m), 1.63-1.77 (2 H, m), 
               
               
                   
                   
                 2.31 (2 H, t, J = 7.6 Hz), 2.76 (2 H, t, J = 7.6 Hz), 3.64- 
               
               
                   
                   
                 3.74 (1 H, m), 6.87 (2 H, d, J = 8.6 Hz), 7.11-7.23 (3 H, m), 
               
               
                   
                   
                 7.54 (1 H, d, J = 9.1 Hz), 7.67 (1 H, brd), 7.85 (1 H, d, J = 8.4 Hz), 
               
               
                   
                   
                 7.89 (1 H, dd, J = 13.2 Hz, 2.4 Hz), 7.94 (1 H, dd, 
               
               
                   
                   
                 J = 8.4 Hz, 2.1 Hz), 8.21 (1 H, d, J = 2.1 Hz), 10.57 (1 H, s). 
               
               
                 353 
                 cyclooctyl 
                 1.30-1.65 (14 H, m), 2.31 (2 H, t, J = 7.6 Hz), 2.76 (2 H, t, 
               
               
                   
                   
                 J = 7.6 Hz), 3.69-3.80 (1 H, m), 6.87 (2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                 7.10-7.22 (3 H, m), 7.54 (1 H, d, J = 8.9 Hz), 7.65 (1 H, brd), 
               
               
                   
                   
                 7.85 (1 H, d, J = 8.4 Hz), 7.89 (1 H, dd, J = 13.2 Hz, 2.3 Hz), 
               
               
                   
                   
                 7.94 (1 H, dd, J = 8.4 Hz, 2.0 Hz), 8.21 (1 H, d, J = 2.0 Hz), 
               
               
                   
                   
                 10.57 (1 H, s). 
               
               
                 354 
                 cyclododecanyl 
                 1.10-1.41 (20 H, m), 1.41-1.54 (2 H, m), 2.32 (2 H, t, J = 7.5 Hz), 
               
               
                   
                   
                 2.77 (2 H, t, J = 7.5 Hz), 3.79-3.88 (1 H, m), 6.86 (2 H, 
               
               
                   
                   
                 d, J = 8.6 Hz), 7.10-7.21 (3 H, m), 7.48-7.57 (2 H, m), 
               
               
                   
                   
                 7.85 (1 H, d, J = 8.4 Hz), 7.89 (1 H, dd, J = 13.1 Hz, 
               
               
                   
                   
                 2.5 Hz), 7.94 (1 H, dd, J = 8.4 Hz, 2.1 Hz), 8.21 (1 H, d, 
               
               
                   
                   
                 J = 2.1 Hz), 10.58 (1 H, s). 
               
               
                 355 
                 cyclopropylmethyl 
                 0.06-0.16 (2 H, m), 0.28-0.42 (2 H, m), 0.78-0.90 (1 H, m), 
               
               
                   
                   
                 2.35 (2 H, t, J = 7.7 Hz), 2.78 (2 H, t, J = 7.7 Hz), 2.84- 
               
               
                   
                   
                 2.97 (2 H, m), 6.87 (2 H, d, J = 8.5 Hz), 7.12-7.27 (3 H, m), 
               
               
                   
                   
                 7.54 (1 H, d, J = 8.8 Hz), 7.85 (1 H, d, J = 8.4 Hz), 7.87 (1 H, 
               
               
                   
                   
                 brt), 7.89 (1 H, dd, J = 13.2 Hz, 2.3 Hz), 7.94 (1 H, dd, 
               
               
                   
                   
                 J = 8.4 Hz, 2.0 Hz), 8.21 (1 H, d, J = 2.0 Hz), 10.57 (1 H, s). 
               
               
                 356 
                 cyclohexylmethyl 
                 0.71-0.86 (2 H, m), 1.03-1.20 (3 H, m), 1.22-1.34 (1 H, m), 
               
               
                   
                   
                 1.50-1.69 (5 H, m), 2.35 (2 H, t, J = 7.6 Hz), 2.78 (2 H, t, 
               
               
                   
                   
                 J = 7.6 Hz), 2.80-2.90 (2 H, m), 6.86 (2 H, d, J = 8.6 Hz), 7.12- 
               
               
                   
                   
                 7.23 (3 H, m), 7.54 (1 H, d, J = 8.9 Hz), 7.73 (1 H, brt), 
               
               
                   
                   
                 7.85 (1 H, d, J = 8.4 Hz), 7.89 (1 H, dd, J = 13.2 Hz, 
               
               
                   
                   
                 2.4 Hz), 7.94 (1 H, dd, J = 8.4 Hz, 2.1 Hz), 8.21 (1 H, d, 
               
               
                   
                   
                 J = 2.1 Hz), 10.57 (1 H, s). 
               
               
                 357 
                 piperonyl 
                 2.41 (2 H, t, J = 7.6 Hz), 2.81 (2 H, t, J = 7.6 Hz), 4.15 (2 H, 
               
               
                   
                   
                 d, J = 5.9 Hz), 5.96 (2 H, s), 6.63 (1 H, d, J = 8.0 Hz), 
               
               
                   
                   
                 6.74 (1 H, d, J = 1.4 Hz), 6.80 (1 H, d, J = 8.0 Hz), 6.87 (2 H, 
               
               
                   
                   
                 d, J = 8.8 Hz), 7.14-7.23 (3 H, m), 7.54 (1 H, d, J = 9.8 Hz), 
               
               
                   
                   
                 7.85 (1 H, d, J = 8.4 Hz), 7.89 (1 H, dd, J = 13.2 Hz, 2.4 Hz), 
               
               
                   
                   
                 7.94 (1 H, dd, J = 8.4 Hz, 2.1 Hz), 8.22 (1 H, d, J = 2.1 Hz), 
               
               
                   
                   
                 8.25 (1 H, brt), 8.40-8.46 (2 H, m), 10.58 (1 H, s). 
               
               
                 358 
                 —CH(CH 3 )Ph 
                 1.30 (3 H, d, J = 7.0 Hz), 2.40 (2 H, t, J = 7.5 Hz), 2.78 (2 H, 
               
               
                   
                   
                 t, J = 7.5 Hz), 3.86-3.96 (1 H, m), 6.82-6.99 (2 H, m), 7.12- 
               
               
                   
                   
                 7.24 (6 H, m), 7.24-7.31 (2 H, m), 7.55 (1 H, dd, J = 8.9 Hz, 
               
               
                   
                   
                 1.2 Hz), 7.85 (1 H, d, J = 8.4 Hz), 7.90 (1 H, dd, J = 13.2 Hz, 
               
               
                   
                   
                 2.5 Hz), 7.94 (1 H, dd, J = 8.4 Hz, 2.1 Hz), 8.22 (1 H, d, 
               
               
                   
                   
                 J = 2.1 Hz), 8.24 (1 H, brd), 10.59 (1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 171 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 576   
                   1 H NMR (DMSO-d 6 ) δ ppm or MS 
               
               
                   
               
               
                 359 
                 2-pyridylmethyl 
                 MS 537(M + ) 
               
               
                 360 
                 3-pyridylmethyl 
                   1 H NMR 2.44 (2 H, t, J = 7.6 Hz), 2.82 (2 H, t, J = 7.6 Hz), 
               
               
                   
                   
                 4.27 (2 H, d, J = 5.9 Hz), 6.86 (2 H, dd, J = 6.7 Hz, 
               
               
                   
                   
                 1.9 Hz), 7.14-7.22 (3 H, m), 7.25-7.32 (1 H, m), 7.46- 
               
               
                   
                   
                 7.58 (2 H, m), 7.85 (1 H, d, J = 8.4 Hz), 7.90 (1 H, dd, 
               
               
                   
                   
                 J = 13.2 Hz, 2.5 Hz), 7.94 (1 H, dd, J = 8.4 Hz, 2.1 Hz), 
               
               
                   
                   
                 8.22 (1 H, d, J = 2.1 Hz), 8.38 (1 H, brt), 8.40-8.46 (2 H, 
               
               
                   
                   
                 m), 10.58 (1 H, s). 
               
               
                 361 
                 4-pyridylmethyl 
                 MS 537(M + ) 
               
               
                 362 
                 —(CH 2 ) 2 NHAc 
                   1 H NMR 1.78 (3 H, s), 2.34 (2 H, t, J = 7.8 Hz), 
               
               
                   
                   
                 2.78 (2 H, t, J = 7.8 Hz), 2.96-3.10 (4 H, m), 6.83- 
               
               
                   
                   
                 6.91 (2 H, m), 7.14-7.23 (3 H, m), 7.54 (1 H, dd, J = 8.9 Hz, 
               
               
                   
                   
                 1.3 Hz), 7.80-7.98 (5 H, m), 8.21 (1 H, d, J = 2.1 Hz), 
               
               
                   
                   
                 10.58 (1 H, s). 
               
               
                 363 
                 —CH(CH 3 )(CH 2 ) 4 CH 3   
                   1 H NMR 0.84 (3 H, t, J = 7.0 Hz), 0.96 (3 H, d, J = 6.6 Hz), 
               
               
                   
                   
                 1.08-1.34 (8 H, m), 2.32 (2 H, t, J = 7.2 Hz), 
               
               
                   
                   
                 2.77 (2 H, t, J = 7.2 Hz), 3.65-3.76 (1 H, m), 6.82- 
               
               
                   
                   
                 6.89 (2 H, m), 7.12-7.21 (3 H, m), 7.50-7.60 (2 H, m), 
               
               
                   
                   
                 7.85 (1 H, d, J = 8.4 Hz), 7.89 (1 H, dd, J = 13.2 Hz, 
               
               
                   
                   
                 2.5 Hz), 7.94 (1 H, dd, J = 8.3 Hz, 2.1 Hz), 8.21 (1 H, d, 
               
               
                   
                   
                 J = 2.1 Hz), 10.58 (1 H, s). 
               
               
                 364 
                 —(CH 2 ) 2 OCH 3   
                   1 H NMR 2.35 (2 H, t, J = 7.7 Hz), 2.77 (2 H, t, J = 7.7 Hz), 
               
               
                   
                   
                 3.13-3.22 (2 H, m), 3.22 (3 H, s), 3.29 (2 H, t, 
               
               
                   
                   
                 J = 5.8 Hz), 6.82-6.92 (2 H, m), 7.13-7.23 (3 H, m), 
               
               
                   
                   
                 7.54 (1 H, d, J = 8.9 Hz), 7.85 (1 H, d, J = 8.4 Hz), 7.85- 
               
               
                   
                   
                 7.92 (2 H, m), 7.94 (1 H, dd, J = 8.4 Hz, 2.0 Hz), 
               
               
                   
                   
                 8.21 (1 H, d, J = 2.0 Hz), 10.57 (1 H, s). 
               
               
                   
               
               
                 365 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 554(M + ) 
               
               
                   
               
               
                 366 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 619(M + ) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 172 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                 mp (° C.) 
               
               
                 No. 
                 R 577   
                 R 578   
                 or MS 
               
               
                   
               
               
                 367 
                 —H 
                 morpholino 
                 mp 160-162 
               
               
                 368 
                 —F 
                 morpholino 
                 mp 150-151 
               
               
                   
               
               
                 369 
                 —F 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 657 (M  +  + H) 
               
               
                   
               
               
                 370 
                 —F 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 646 (M  +  − 1) 
               
               
                   
               
               
                 371 
                 —F 
                 4-CH 3 OPh(CH 2 ) 2 N(C 2 H 5 )— 
                 MS 608 (M  + ) 
               
               
                 372 
                 —F 
                 4-CH 3 OPhCH 2 N(C 2 H 5 )— 
                 MS 594 (M  + ) 
               
               
                 373 
                 —F 
                 3,4- 
                 MS 638 (M  + ) 
               
               
                   
                   
                 (CH 3 O) 2 PhCH 2 N(CH 2 CH 2 CH 3 )— 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 173 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 579   
                   1 H NMR (DMSO-d 6 ) δ ppm 
               
               
                   
               
               
                 374 
                 Ph- 
                 2.39-2.49 (2 H, m), 2.78-2.88 (2 H, m), 4.18-4.30 (2 H, m), 
               
               
                   
                   
                 6.87 (2 H, d, J = 8.6 Hz), 7.02-7.33 (8 H, m), 7.55 (1 H, d, J = 8.9 Hz), 
               
               
                   
                   
                 7.85 (1 H, d, J = 8.4 Hz), 7.90 (1 H, dd, J = 13.2 Hz, 2.4 Hz), 
               
               
                   
                   
                 7.94 (1 H, dd, J = 8.4 Hz, 2.0 Hz), 8.22 (1 H, d, J = 2.0 Hz), 
               
               
                   
                   
                 8.32 (1 H, brt), 10.58 (1 H, s). 
               
               
                 375 
                 4-FPh- 
                 2.43 (2 H, t, J = 7.6 Hz), 2.82 (2 H, t, J = 7.6 Hz), 4.22 (2 H, d, 
               
               
                   
                   
                 J = 5.9 Hz), 6.87 (2 H, d, J = 8.6 Hz), 7.04-7.12 (2 H, m), 7.12- 
               
               
                   
                   
                 7.24 (5 H, m), 7.55 (1 H, d, J = 9.0 Hz), 7.85 (1 H, d, J = 8.4 Hz), 
               
               
                   
                   
                 7.90 (1 H, dd, J = 13.2 Hz, 2.4 Hz), 7.94 (1 H, dd, J = 8.4 Hz, 2.1 Hz), 
               
               
                   
                   
                 8.22 (1 H, d, J = 2.1 Hz), 8.32 (1 H, brt), 10.58 (1 H, s). 
               
               
                 376 
                 3,4-(CH 3 O) 2 Ph- 
                 2.42 (2 H, t, J = 7.6 Hz), 2.82 (2 H, t, J = 7.6 Hz), 3.70 (3 H, s), 
               
               
                   
                   
                 3.71 (3 H, s), 4.18 (2 H, d, J = 5.8 Hz), 6.67 (1 H, d, J = 8.4 Hz), 
               
               
                   
                   
                 6.77-6.90 (4 H, m), 7.15-7.23 (3 H, m), 7.55 (1 H, d, J = 9.0 Hz), 
               
               
                   
                   
                 7.85 (1 H, d, J = 8.4 Hz), 7.89 (1 H, dd, J = 13.2 Hz, 2.4 Hz), 
               
               
                   
                   
                 7.94 (1 H, dd, J = 8.4 Hz, 2.1 Hz), 8.21 (1 H, d, J = 2.0 Hz), 
               
               
                   
                   
                 8.25 (1 H, brt), 10.58 (1 H, s). 
               
               
                 377 
                 2-ClPh- 
                 2.48 (2 H, t, J = 7.5 Hz), 2.83 (2 H, t, J = 7.5 Hz), 4.30 (2 H, d, 
               
               
                   
                   
                 J = 5.9 Hz), 6.88 (2 H, d, J = 8.6 Hz), 7.08-7.15 (1 H, m), 7.15- 
               
               
                   
                   
                 7.32 (5 H, m), 7.38-7.46 (1 H, m), 7.51-7.59 (1 H, m), 7.85 (1 H, d, 
               
               
                   
                   
                 J = 8.4 Hz), 7.90 (1 H, dd, J = 13.2 Hz, 2.4 Hz), 7.94 (1 H, dd, 
               
               
                   
                   
                 J = 8.4 Hz, 2.1 Hz), 8.22 (1 H, d, J = 2.0 Hz), 8.34 (1 H, brt), 10.58 
               
               
                   
                   
                 (1 H, s). 
               
               
                 378 
                 3-ClPh- 
                 2.45 (2 H, t, J = 7.5 Hz), 2.83 (2 H, t, J = 7.5 Hz), 4.25 (2 H, d, 
               
               
                   
                   
                 J = 6.0 Hz), 6.87 (2 H, d, J = 8.6 Hz), 7.07-7.12 (1 H, m), 7.12- 
               
               
                   
                   
                 7.21 (3 H, m), 7.21-7.25 (1 H, m), 7.25-7.33 (2 H, m), 7.55 (1 H, d, 
               
               
                   
                   
                 J = 9.0 Hz), 7.85 (1 H, d, J = 8.4 Hz), 7.90 (1 H, dd, J = 13.2 Hz, 
               
               
                   
                   
                 2.4 Hz), 7.94 (1 H, dd, J = 8.4 Hz, 2.1 Hz), 8.22 (1 H, d, J = 2.1 Hz), 
               
               
                   
                   
                 8.37 (1 H, brt), 10.58 (1 H, s). 
               
               
                 379 
                 4-ClPh- 
                 2.44 (2 H, t, J = 7.5 Hz), 2.82 (2 H, t, J = 7.5 Hz), 4.22 (2 H, d, 
               
               
                   
                   
                 J = 6.0 Hz), 6.87 (2 H, d, J = 8.6 Hz), 7.14 (2 H, d, J = 8.4 Hz), 
               
               
                   
                   
                 7.16-7.22 (3 H, m), 7.29-7.34 (2 H, m), 7.55 (1 H, d, J = 8.1 Hz), 
               
               
                   
                   
                 7.85 (1 H, d, J = 8.4 Hz), 7.90 (1 H, dd, J = 13.2 Hz, 2.5 Hz), 
               
               
                   
                   
                 7.94 (1 H, dd, J = 8.4 Hz, 2.1 Hz), 8.21 (1 H, d, J = 2.1 Hz), 
               
               
                   
                   
                 8.34 (1 H, brt), 10.58 (1 H, s). 
               
               
                 380 
                 2-CH 3 Ph- 
                 2.21 (3 H, s), 2.44 (2 H, t, J = 7.5 Hz), 2.82 (2 H, t, J = 7.5 Hz), 
               
               
                   
                   
                 4.21 (2 H, d, J = 5.7 Hz), 6.87 (2 H, d, J = 8.6 Hz), 7.00-7.07 (1 H, 
               
               
                   
                   
                 m), 7.07-7.23 (6 H, m), 7.55 (1 H, d, J = 9.0 Hz), 7.85 (1 H, d, 
               
               
                   
                   
                 J = 8.4 Hz), 7.90 (1 H, dd, J = 13.2 Hz, 2.4 Hz), 7.94 (1 H, dd,  
               
               
                   
                   
                 J = 8.4 Hz, 2.1 Hz), 8.16 (1 H, brt), 8.22 (1 H, d, , J = 2.1 Hz), 
               
               
                   
                   
                 10.58 (1 H, s). 
               
               
                 381 
                 4-CH 3 OPh- 
                 2.41 (2 H, t, J = 7.6 Hz), 2.81 (2 H, t, J = 7.6 Hz), 3.71 (3 H, s), 
               
               
                   
                   
                 4.17 (2 H, d, J = 5.8 Hz), 6.80-6.91 (4 H, m), 7.07 (2 H, d, J = 8.5 Hz), 
               
               
                   
                   
                 7.13-7.25 (3 H, m), 7.55 (1 H, d, J = 8.5 Hz), 7.85 (1 H, d, 
               
               
                   
                   
                 J = 8.4 Hz), 7.90 (1 H, dd, J = 13.2 Hz, 2.4 Hz), 7.94 (1 H, dd, 
               
               
                   
                   
                 J = 8.4 Hz, 2.1 Hz), 8.21 (1 H, d, J = 2.1 Hz), 8.24 (1 H, brt), 
               
               
                   
                   
                 10.58 (1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 174 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 580   
                   1 H NMR (DMSO-d 6 ) δ ppm 
               
               
                   
               
               
                 382 
                 Ph- 
                 2.33 (2 H, t, J = 7.7 Hz), 2.66 (2 H, t, J = 7.3 Hz), 2.77 (2 H, 
               
               
                   
                   
                 t, J = 7.7 Hz), 3.20-3.29 (2 H, m), 6.87 (2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                 7.12-7.22 (6 H, m), 7.23-7.30 (2 H, m), 7.54 (1 H, dd, 
               
               
                   
                   
                 J = 8.9 Hz, 1.1 Hz), 7.85 (1 H, d, J = 8.4 Hz), 7.85-7.91 (2 H, 
               
               
                   
                   
                 m), 7.94 (1 H, dd, J = 8.4 Hz, 2.1 Hz), 8.21 (1 H, d, J = 2.1 Hz), 
               
               
                   
                   
                 10.57 (1 H, s). 
               
               
                 383 
                 4-FPh- 
                 2.33 (2 H, t, J = 7.7 Hz), 2.65 (2 H, t, J = 7.2 Hz), 2.76 (2 H, 
               
               
                   
                   
                 t, J = 7.7 Hz), 3.30-3.37 (2 H, m), 6.87 (2 H, d, J = 8.5 Hz), 
               
               
                   
                   
                 7.04-7.11 (2 H, m), 7.13-7.22 (5 H, m), 7.54 (1 H, d, J = 9.1 Hz), 
               
               
                   
                   
                 7.85 (1 H, d, J = 8.4 Hz), 7.80-7.92 (2 H, m), 7.94 (1 H, 
               
               
                   
                   
                 dd, J = 8.4 Hz, 2.0 Hz), 8.21 (1 H, d, J = 2.0 Hz), 
               
               
                   
                   
                 10.58 (1 H, s). 
               
               
                 384 
                 4-ClPh- 
                 2.32 (2 H, t, J = 7.6 Hz), 2.66 (2 H, t, J = 7.1 Hz), 2.76 (2 H, 
               
               
                   
                   
                 t, J = 7.6 Hz), 3.18-3.27 (2 H, m), 6.87 (2 H, d, J = 8.5 Hz), 
               
               
                   
                   
                 7.10-7.22 (5 H, m), 7.31 (2 H, d, J = 8.3 Hz), 7.54 (1 H, d, 
               
               
                   
                   
                 J = 8.9 Hz), 7.84 (1 H, d, J = 8.4 Hz), 7.85-7.92 (2 H, m), 
               
               
                   
                   
                 7.94 (1 H, dd, J = 8.4 Hz, 2.0 Hz), 8.21 (1 H, d, J = 2.0 Hz), 
               
               
                   
                   
                 10.57 (1 H, s). 
               
               
                 385 
                 3-CH 3 OPh- 
                 2.33 (2 H, t, J = 7.7 Hz), 2.64 (2 H, t, J = 7.3 Hz), 2.78 (2 H, 
               
               
                   
                   
                 t, J = 7.7 Hz), 3.18-3.27 (2 H, m), 3.72 (3 H, s), 6.70- 
               
               
                   
                   
                 6.78 (3 H, m), 6.87 (2 H, d, J = 8.6 Hz), 7.12-7.23 (4 H, m), 
               
               
                   
                   
                 7.54 (1 H, dd, J = 8.9 Hz, 1.2 Hz), 7.85 (1 H, d, J = 8.4 Hz), 
               
               
                   
                   
                 7.85-7.92 (2 H, m), 7.94 (1 H, dd, J = 8.4 Hz, 2.1 Hz), 
               
               
                   
                   
                 8.21 (1 H, d, J = 2.0 Hz), 10.57 (1 H, s). 
               
               
                 386 
                 4-CH 3 OPh- 
                 2.33 (2 H, t, J = 7.6 Hz), 2.59 (2 H, t, J = 7.2 Hz), 2.77 (2 H, 
               
               
                   
                   
                 t, J = 7.6 Hz), 3.16-3.24 (2 H, m), 3.71 (3 H, s), 6.83 (2 H, d, 
               
               
                   
                   
                 J = 8.5 Hz), 6.87 (2 H, d, J = 8.5 Hz), 7.07 (2 H, d, J = 8.4 Hz), 
               
               
                   
                   
                 7.13-7.23 (3 H, m), 7.54 (1 H, d, J = 8.5 Hz), 7.80- 
               
               
                   
                   
                 7.98 (4 H, m), 8.21 (1 H, d, J = 1.8 Hz), 10.57 (1 H, s). 
               
               
                 387 
                 PhO— 
                 2.38 (2 H, t, J = 7.7 Hz), 2.79 (2 H, t, J = 7.7 Hz), 3.38- 
               
               
                   
                   
                 3.43 (2 H, m), 3.94 (2 H, t, J = 5.7 Hz), 6.79-6.85 (2 H, m), 
               
               
                   
                   
                 6.89-6.96 (3 H, m), 7.12-7.20 (3 H, m), 7.23-7.31 (2 H, m), 
               
               
                   
                   
                 7.50-7.57 (1 H, m), 7.85 (1 H, d, J = 8.4 Hz), 7.89 (1 H, dd, 
               
               
                   
                   
                 J = 13.2 Hz, 2.4 Hz), 8.10 (1 h, brt), 8.22 (1 H, d, J = 2.1 Hz), 
               
               
                   
                   
                 10.58 (1 H, s). 
               
               
                 388 
                 PhCH 2 — 
                 1.60-1.70 (2 H, m), 2.36 (2 H, t, J = 7.4 Hz), 2.49-2.55 (2 H, 
               
               
                   
                   
                 m), 2.79 (2 H, t, J = 7.4 Hz), 3.00-3.08 (2 H, m), 6.83- 
               
               
                   
                   
                 6.90 (2 H, m), 7.10-7.21 (6 H, m), 7.21-7.29 (2 H, m), 
               
               
                   
                   
                 7.53 (1 H, d, J = 8.9 Hz), 7.89-7.92 (3 H, m), 8.21 (1 H, d, 
               
               
                   
                   
                 J = 2.1 Hz), 10.57 (1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 175 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 581   
                 MS 
               
               
                   
               
               
                 389 
                 —CHPh 2   
                 681 (M +  + 1) 
               
               
                 390 
                 —NHCOPh 
                 633 (M + ) 
               
               
                 391 
                 —O(CH 2 ) 2 Ph 
                 634 (M + ) 
               
               
                 392 
                 —(CH 2 ) 2 N(CH 3 )Ph 
                 647 (M + ) 
               
               
                   
               
               
                 393 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 675 (M + ) 
               
               
                   
               
               
                 394 
                 morpholino 
                 599 (M + ) 
               
               
                   
               
               
                 395 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 626 (M + ) 
               
               
                   
               
               
                 396 
                 cyclohexyl 
                 596 (M + ) 
               
               
                   
               
               
                 397 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 656 (M + ) 
               
               
                   
               
               
                 398 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 626 (M + ) 
               
               
                   
               
               
                 399 
                 4-CH 3 OPhCONH— 
                 664 (M +  + 1) 
               
               
                   
               
               
                 400 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 644 (M + ) 
               
               
                   
               
               
                 401 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 620 (M +  − 1) 
               
               
                   
               
               
                 402 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 623 (M +  + 2) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 176 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 582   
                 R 583   
                 Property 
               
               
                   
               
               
                 403 
                 —H 
                 4-CF 3 OPhNH— 
                 mp 91-95° C. 
               
               
                 404 
                 —F 
                 4-CF 3 OPhNH— 
                 mp 145-147° C. 
               
               
                 405 
                 —H 
                 4-CF 3 PhO— 
                 mp 118-121° C. 
               
               
                 406 
                 —H 
                 4-CF 3 OPhO— 
                 mp 126-127° C. 
               
               
                 407 
                 —F 
                 4-CF 3 PhO— 
                 mp 129-134° C. 
               
               
                 408 
                 —H 
                 4-CNPhO— 
                 mp 148-149° C. 
               
               
                 409 
                 —F 
                 4-CNPhO— 
                 mp 147-150° C. 
               
               
                 410 
                 —F 
                 4-CF 3 OPhO— 
                   1 H NMR (CDCl 3 ) δ 1.69-1.85 (4 H, m), 2.62 (2 H, 
               
               
                   
                   
                   
                 t, J = 7.5 Hz), 2.90 (2 H, t, J = 7.5 Hz), 3.36 (1 H, 
               
               
                   
                   
                   
                 m), 3.57-3.67 (3 H, m), 4.47 (1 H, m), 6.85- 
               
               
                   
                   
                   
                 6.90 (4 H, m), 7.00 (1 H, t, J = 8.5 Hz), 7.10 (2 H, 
               
               
                   
                   
                   
                 d, J = 8.5 Hz), 7.13 (2 H, d, J = 8.5 Hz), 
               
               
                   
                   
                   
                 7.30 (1 H, brd, J = 8.5 Hz), 7.52 (1 H, d, J = 8.5 Hz), 
               
               
                   
                   
                   
                 7.69-7.75 (2 H, m), 7.98 (1 H, d, J = 2.0 Hz), 
               
               
                   
                   
                   
                 8.80 (1 H, s). 
               
               
                 411 
                 —F 
                 PhO— 
                 MS 606 (M + ) 
               
               
                 412 
                 —F 
                 4-ClPhCH 2 — 
                 MS 638 (M + ) 
               
               
                 413 
                 —F 
                 4-CH 3 PhCH 2 — 
                 MS 618 (M + ) 
               
               
                 414 
                 —F 
                 4-ClPh- 
                 MS 626 (M + ) 
               
               
                 415 
                 —F 
                 Ph- 
                 MS 590 (M + ) 
               
               
                 416 
                 —F 
                 2-NH 2 PhCO— 
                 MS 633 (M + ) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 177 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                 mp (° C.) 
               
               
                 No. 
                 R 584   
                 R 585   
                 Form 
                 or MS 
               
               
                   
               
               
                 417 
                 —F 
                 —H 
                 free 
                 MS 543 (M + ) 
               
               
                 418 
                 —F 
                 —(CH 2 ) 2 OPh 
                 free 
                 MS 664 (M +  + H) 
               
               
                 419 
                 —F 
                 —(CH 2 ) 2 Ph 
                 free 
                 MS 648 (M +  + H) 
               
               
                 420 
                 —F 
                 —(CH 2 ) 2 N(C 2 H 5 ) 2   
                 free 
                 MS 643 (M +  + H) 
               
               
                 421 
                 —H 
                 —(CH 2 ) 2 Ph 
                 fumarate 
                 mp 148-151 
               
               
                 422 
                 —F 
                 —(CH 2 ) 3 Ph 
                 free 
                 MS 661 (M + ) 
               
               
                 423 
                 —F 
                 —(CH 2 ) 2 CHPh 2   
                 free 
                 MS 737 (M + ) 
               
               
                   
               
               
                 424 
                 —F 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 MS 638 (M + ) 
               
               
                   
               
               
                 425 
                 —F 
                 4-CH 3 SPh(CH 2 ) 2 — 
                 free 
                 MS 692 (M +  − 1) 
               
               
                 426 
                 —F 
                 4-CH 3 PhO(CH 2 ) 2 — 
                 free 
                 MS 678 (M +  + H) 
               
               
                   
               
               
                 427 
                 —F 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 MS 723 (M +  + H) 
               
               
                   
               
               
                 428 
                 —F 
                 4-CH 3 OPh(CH 2 ) 4 — 
                 free 
                 MS 705 (M + ) 
               
               
                   
               
               
                 429 
                 —F 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 MS 658 (M +  + H) 
               
               
                   
               
               
                 430 
                 —F 
                 4-CH 3 Ph(CH 2 ) 2 — 
                 free 
                 MS 661 (M + ) 
               
               
                 431 
                 —F 
                 —(CH 2 ) 2 N(CH 3 )Ph 
                 free 
                 MS 676 (M + ) 
               
               
                   
               
               
                 432 
                 —F 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 MS 653 (M + ) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 178 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                 mp (° C.) 
               
               
                 No. 
                 R 586   
                 R 587   
                 R 588   
                 R 589   
                 R 590   
                 or MS 
               
               
                   
               
               
                 433 
                 —H 
                 —H 
                 —H 
                 —CF 3   
                 —H 
                 mp 124-126 
               
               
                 434 
                 —F 
                 —H 
                 —H 
                 —CF 3   
                 —H 
                 mp 132-134 
               
               
                 435 
                 —F 
                 —H 
                 —H 
                 —Cl 
                 —H 
                 MS 654 (M + ) 
               
               
                 436 
                 —F 
                 —F 
                 —H 
                 —H 
                 —H 
                 MS 638 (M + ) 
               
               
                 437 
                 —F 
                 —H 
                 —H 
                 —H 
                 —H 
                 MS 620 (M + ) 
               
               
                 438 
                 —F 
                 —H 
                 —H 
                 —OCH 3   
                 —H 
                 MS 651 (M +  + H) 
               
               
                 439 
                 —F 
                 —H 
                 —Cl 
                 —H 
                 —H 
                 MS 656 (M + ) 
               
               
                 440 
                 —F 
                 —Cl 
                 —H 
                 —H 
                 —H 
                 MS 654 (M) 
               
               
                 441 
                 —F 
                 —H 
                 —Cl 
                 —Cl 
                 —H 
                 MS 690 (M + ) 
               
               
                 442 
                 —F 
                 —H 
                 —OCH 3   
                 —H 
                 —H 
                 MS 650 (M + ) 
               
               
                 443 
                 —F 
                 —H 
                 —OCH 3   
                 —H 
                 —OCH 3   
                 MS 680 (M + ) 
               
               
                 444 
                 —F 
                 —H 
                 —H 
                 —CH 3   
                 —H 
                 MS 635 (M +  + H) 
               
               
                 445 
                 —F 
                 —H 
                 —CH 3   
                 —H 
                 —H 
                 MS 636 (M +  + 2) 
               
               
                 446 
                 —F 
                 —CH 3   
                 —H 
                 —H 
                 —H 
                 MS 635 (M +  + H) 
               
               
                 447 
                 —F 
                 —H 
                 —CH 3   
                 —CH 3   
                 —H 
                 MS 648 (M + ) 
               
               
                 448 
                 —F 
                 —H 
                 —H 
                 —F 
                 —H 
                 MS 638 (M + ) 
               
               
                 449 
                 —F 
                 —H 
                 —F 
                 —H 
                 —H 
                 MS 638 (M + ) 
               
               
                 450 
                 —F 
                 —H 
                 —F 
                 —H 
                 —F 
                 MS 656 (M + ) 
               
               
                 451 
                 —F 
                 —CF 3   
                 —H 
                 —H 
                 —H 
                 MS 688 (M + ) 
               
               
                 452 
                 —F 
                 —H 
                 —H 
                 —OCF 3   
                 —H 
                 MS 705 (M +  + H) 
               
               
                 453 
                 —F 
                 —H 
                 —OCF 3   
                 —H 
                 —H 
                 MS 704 (M + ) 
               
               
                 454 
                 —F 
                 —OCF 3   
                 —H 
                 —H 
                 —H 
                 MS 704 (M + ) 
               
               
                 455 
                 —F 
                 —H 
                 —Cl 
                 —OCH 3   
                 —H 
                 MS 685 (M +  + H) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 179 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 591   
                 R 592   
                 Property 
               
               
                   
               
               
                 456 
                 —H 
                 —CH 2 CONHPh 
                   1 H NMR (CDCl 3 ) δ 2.45 (2 H, brt, J = 5.0 Hz), 
               
               
                   
                   
                   
                 2.55 (2 H, brt, J = 5.0 Hz), 2.63 (2 H, t, J = 7.5 Hz), 
               
               
                   
                   
                   
                 2.96 (2 H, t, J = 7.5 Hz), 3.11 (2 H, s), 
               
               
                   
                   
                   
                 3.47 (2 H, brs), 3.70 (2 H, brs), 6.93 (2 H, d, J = 8.5 Hz), 
               
               
                   
                   
                   
                 6.98 (2 H, d, J = 8.5 Hz), 7.13 (1 H, t, J = 8.5 Hz), 
               
               
                   
                   
                   
                 7.15 (2 H, d, J = 8.5 Hz), 7.34 (2 H, t, J = 8.5 Hz), 
               
               
                   
                   
                   
                 7.52-7.59 (5 H, m), 7.73 (1 H, dd, J = 8.5 Hz, 
               
               
                   
                   
                   
                 2.0 Hz), 7.99 (1 H, d, J = 2.0 Hz), 8.28 (1 H, s), 
               
               
                   
                   
                   
                 8.92 (1 H, s). 
               
               
                 457 
                 —F 
                 —CH 2 CONHPh 
                   1 H NMR (CDCl 3 ) δ 2.39 (2 H, brs), 2.51 (2 H, brs), 
               
               
                   
                   
                   
                 2.61 (2 H, t, J = 7.5 Hz), 2.93 (2 H, t, J = 7.5 Hz), 
               
               
                   
                   
                   
                 3.08 (2 H, s), 3.43 (2 H, brs), 3.67 (2 H, brs), 
               
               
                   
                   
                   
                 6.88 (2 H, d, J = 8.5 Hz), 7.03 (1 H, t, J = 8.5 Hz), 
               
               
                   
                   
                   
                 7.11-7.15 (3 H, m), 7.30-7.35 (3 H, m), 7.51- 
               
               
                   
                   
                   
                 7.54 (3 H, m), 7.70 (1 H, dd, J = 9.0 Hz, 2.0 Hz), 
               
               
                   
                   
                   
                 7.74 (1 H, dd, J = 8.5 Hz, 2.0 Hz), 8.00 (1 H, d, 
               
               
                   
                   
                   
                 J = 2.0 Hz), 8.74 (1 H, s), 8.93 (1 H, s). 
               
               
                 458 
                 —F 
                 —(CH 2 ) 3 Ph 
                 MS 633 (M + ) 
               
               
                 459 
                 —F 
                 —(CH 2 ) 4 Ph 
                 MS 647 (M + ) 
               
               
                 460 
                 —F 
                 —CH(C 2 H 5 ) 2   
                 MS 586 (M +  + 1) 
               
               
                 461 
                 —F 
                 —CH(CH 3 ) 2   
                 MS 556 (M +  − 1) 
               
               
                 462 
                 —F 
                 —(CH 2 ) 3 CH 3   
                 MS 571 (M + ) 
               
               
                 463 
                 —F 
                 —(CH 2 ) 2 N(CH 3 ) 2   
                 MS 585 (M +  − 1) 
               
               
                 464 
                 —F 
                 —COOC(CH 3 ) 3   
                 mp 155-157° C. 
               
               
                 465 
                 —F 
                 —CH 2 COPh 
                 MS 633 (M + ) 
               
               
                 466 
                 —H 
                 3-pyridyl 
                 mp 153-155° C. 
               
               
                 467 
                 —F 
                 3-pyridyl 
                 mp 183-185° C. 
               
               
                 468 
                 —F 
                 2-pyridyl 
                 MS 591 (M +  − 1) 
               
               
                 469 
                 —F 
                 4-pyridyl 
                 MS 592 (M + ) 
               
               
                   
               
               
                 470 
                 —F 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 593 (M + ) 
               
               
                   
               
               
                 471 
                 —F 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 593 (M + ) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 180 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 593   
                 R 594   
                 MS 
               
               
                   
               
               
                 472 
                 —CH 3   
                 benzyl 
                 619 (M + ) 
               
               
                 473 
                 2-pyridylmethyl 
                 —H 
                 606 (M + ) 
               
               
                 474 
                 3-pyridylmethyl 
                 —H 
                 606 (M + ) 
               
               
                 475 
                 4-pyridylmethyl 
                 —H 
                 605 (M +  − 1) 
               
               
                 476 
                 cyclopentyl 
                 —H 
                 583 (M + ) 
               
               
                 477 
                 cycloheptyl 
                 —H 
                 611 (M + ) 
               
               
                   
               
               
                 478 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 612 (M + ) 
               
               
                   
               
               
                 479 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 627 (M +  + H) 
               
               
                   
               
               
                 480 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 628 (M + ) 
               
               
                   
               
               
                 481 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 612 (M + ) 
               
               
                   
               
               
                 482 
                 2-quinolylmethyl 
                 —H 
                 657 (M +  + H) 
               
               
                   
               
               
                 483 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 686 (M +  − 1) 
               
               
                   
               
               
                 484 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 625 (M + ) 
               
               
                   
               
               
                 485 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 688 (M + ) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 181 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                 mp (° C.) 
               
               
                 No. 
                 R 595   
                 R 596   
                 R 597   
                 Form 
                 or MS 
               
               
                   
               
               
                 486 
                 —H 
                 —H 
                 —COOC(CH 3 ) 3   
                 free 
                 mp 188-189 
               
               
                 487 
                 —H 
                 —H 
                 —CH 3   
                 free 
                 mp 189-191 
               
               
                 488 
                 —H 
                 —H 
                 benzyl 
                 fumarate 
                 mp 190-192 
               
               
                 489 
                 —F 
                 —H 
                 —(CH 2 ) 2 Ph 
                 hydrochloride 
                 mp 191-200 
               
               
                 490 
                 —F 
                 —H 
                 piperonyl 
                 hydrochloride 
                 mp 226-228 
               
               
                 491 
                 —F 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 MS 714 (M +  − 1) 
               
               
                 492 
                 —F 
                 —H 
                 1-naphthylmethyl 
                 free 
                 MS 655 (M + ) 
               
               
                 493 
                 —F 
                 —CH 3   
                 3,4-(CH 3 O) 2 PhCH 2 — 
                 free 
                 MS 679 (M + ) 
               
               
                 494 
                 —F 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 MS 678 (M +  + 1) 
               
               
                 495 
                 —F 
                 —H 
                 —CH(CH 3 )Ph 
                 free 
                 MS 619 (M + ) 
               
               
                 496 
                 —F 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 MS 682 (M + ) 
               
               
                 497 
                 —F 
                 —H 
                 (4-FPh) 2 CH— 
                 free 
                 MS 717 (M + ) 
               
               
                 498 
                 —F 
                 —H 
                 4-CH 3 OPhCH(Ph)— 
                 free 
                 MS 711 (M + ) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 182 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
                 mp (° C.) 
               
               
                 No. 
                 R 598   
                 R 599   
                 R 600   
                 R 601   
                 R 602   
                 Form 
                 or MS 
               
               
                   
               
               
                 499 
                 —F 
                 —H 
                 —H 
                 —OCF 3   
                 —H 
                 hydrochloride 
                 mp 118-121 
               
               
                 500 
                 —F 
                 —H 
                 —H 
                 —CN 
                 —H 
                 free 
                 mp 190-192 
               
               
                 501 
                 —F 
                 —H 
                 —H 
                 —OCF 3   
                 —H 
                 hydrochloride 
                 mp 148-149 
               
               
                 502 
                 —H 
                 —H 
                 —H 
                 —CN 
                 —H 
                 free 
                 mp 186-188 
               
               
                 503 
                 —F 
                 —CF 3   
                 —H 
                 —H 
                 —H 
                 free 
                 MS 659 (M + ) 
               
               
                 504 
                 —F 
                 —H 
                 —CF 3   
                 —H 
                 —H 
                 free 
                 MS 659 (M + ) 
               
               
                 505 
                 —F 
                 —H 
                 —H 
                 —COOC(CH 3 ) 3   
                 —H 
                 free 
                 MS 691 (M + ) 
               
               
                 506 
                 —F 
                 —H 
                 —H 
                 —F 
                 —H 
                 free 
                 MS 609 (M + ) 
               
               
                 507 
                 —F 
                 —OCH 3   
                 —H 
                 —H 
                 —H 
                 free 
                 MS 621 (M + ) 
               
               
                 508 
                 —F 
                 —Cl 
                 —H 
                 —H 
                 —H 
                 free 
                 MS 625 (M + ) 
               
               
                 509 
                 —F 
                 —H 
                 —H 
                 —Cl 
                 —H 
                 free 
                 MS 627 (M + ) 
               
               
                 510 
                 —F 
                 —H 
                 —Cl 
                 —H 
                 —H 
                 free 
                 MS 625 (M + ) 
               
               
                 511 
                 —F 
                 —Cl 
                 —Cl 
                 —H 
                 —H 
                 free 
                 MS 661 (M + ) 
               
               
                 512 
                 —F 
                 —H 
                 —H 
                 —OCH 3   
                 —H 
                 free 
                 MS 621 (M + ) 
               
               
                 513 
                 —F 
                 —H 
                 —OCH 3   
                 —H 
                 —H 
                 free 
                 MS 621 (M + ) 
               
               
                 514 
                 —F 
                 —H 
                 —H 
                 —CH 3   
                 —H 
                 free 
                 MS 605 (M + ) 
               
               
                 515 
                 —F 
                 —H 
                 —CH 3   
                 —H 
                 —H 
                 free 
                 MS 605 (M + ) 
               
               
                 516 
                 —F 
                 —CH 3   
                 —H 
                 —H 
                 —H 
                 free 
                 MS 605 (M + ) 
               
               
                 517 
                 —F 
                 —CH 3   
                 —CH 3   
                 —H 
                 —H 
                 free 
                 MS 619 (M + ) 
               
               
                 518 
                 —F 
                 —H 
                 —CH 3   
                 —CH 3   
                 —H 
                 free 
                 MS 619 (M + ) 
               
               
                 519 
                 —F 
                 —H 
                 —H 
                 —CF 3   
                 —H 
                 free 
                 MS 659 (M + ) 
               
               
                 520 
                 —F 
                 —H 
                 —H 
                 —Ph 
                 —H 
                 free 
                 MS 667 (M + ) 
               
               
                 521 
                 —F 
                 —F 
                 —H 
                 —H 
                 —H 
                 free 
                 MS 609 (M + ) 
               
               
                 522 
                 —F 
                 —F 
                 —H 
                 —F 
                 —H 
                 free 
                 MS 627 (M + ) 
               
               
                 523 
                 —F 
                 —OCH 3   
                 —H 
                 —H 
                 —Cl 
                 free 
                 MS 657 (M + ) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 183 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
                 mp (° C.) 
               
               
                 No. 
                 R 603   
                 R 604   
                 R 605   
                 R 606   
                 R 607   
                 Form 
                 or MS 
               
               
                   
               
               
                 524 
                 —H 
                 —H 
                 —H 
                 —H 
                 —H 
                 fumarate 
                 mp 168-170 
               
               
                 525 
                 —H 
                 —H 
                 —Cl 
                 —H 
                 —H 
                 free 
                 MS 638 (M +  − 1) 
               
               
                 526 
                 —H 
                 —Cl 
                 —H 
                 —H 
                 —H 
                 free 
                 MS 639 (M + ) 
               
               
                 527 
                 —Cl 
                 —H 
                 —H 
                 —H 
                 —H 
                 free 
                 MS 641 (M +  + 2) 
               
               
                 528 
                 —Cl 
                 —Cl 
                 —H 
                 —H 
                 —H 
                 free 
                 MS 675 (M +  + 2) 
               
               
                 529 
                 —Cl 
                 —H 
                 —Cl 
                 —H 
                 —H 
                 free 
                 MS 673 (M + ) 
               
               
                 530 
                 —Cl 
                 —H 
                 —H 
                 —Cl 
                 —H 
                 free 
                 MS 673 (M + ) 
               
               
                 531 
                 —H 
                 —Cl 
                 —Cl 
                 —H 
                 —H 
                 free 
                 MS 676 (M +  + 3) 
               
               
                 532 
                 —H 
                 —OCH 3   
                 —H 
                 —H 
                 —H 
                 free 
                 MS 635 (M + ) 
               
               
                 533 
                 —OCH 3   
                 —H 
                 —H 
                 —H 
                 —H 
                 free 
                 MS 635 (M + ) 
               
               
                 534 
                 —H 
                 —OCH 3   
                 —H 
                 —OCH 3   
                 —H 
                 free 
                 MS 665 (M + ) 
               
               
                 535 
                 —H 
                 —CH 3   
                 —H 
                 —H 
                 —H 
                 free 
                 MS 619 (M + ) 
               
               
                 536 
                 —CH 3   
                 —H 
                 —H 
                 —H 
                 —H 
                 free 
                 MS 619 (M + ) 
               
               
                 537 
                 —H 
                 —CH 3   
                 —CH 3   
                 —H 
                 —H 
                 free 
                 MS 633 (M + ) 
               
               
                 538 
                 —H 
                 —H 
                 —F 
                 —H 
                 —H 
                 free 
                 MS 623 (M + ) 
               
               
                 539 
                 —H 
                 —F 
                 —H 
                 —H 
                 —H 
                 free 
                 MS 623 (M + ) 
               
               
                 540 
                 —F 
                 —H 
                 —H 
                 —H 
                 —H 
                 free 
                 MS 623 (M + ) 
               
               
                 541 
                 —F 
                 —H 
                 —F 
                 —H 
                 —H 
                 free 
                 MS 641 (M + ) 
               
               
                 542 
                 —F 
                 —H 
                 —H 
                 —H 
                 —F 
                 free 
                 MS 641 (M + ) 
               
               
                 543 
                 —H 
                 —H 
                 —NO 2   
                 —H 
                 —H 
                 free 
                 MS 650 (M + ) 
               
               
                 544 
                 —H 
                 —NO 2   
                 —H 
                 —H 
                 —H 
                 free 
                 MS 650 (M + ) 
               
               
                 545 
                 —NO 2   
                 —H 
                 —H 
                 —H 
                 —H 
                 free 
                 MS 650 (M + ) 
               
               
                 546 
                 —H 
                 —CF 3   
                 —H 
                 —H 
                 —H 
                 free 
                 MS 673 (M + ) 
               
               
                 547 
                 —H 
                 —H 
                 —CN 
                 —H 
                 —H 
                 free 
                 MS 630 (M + ) 
               
               
                 548 
                 —H 
                 —OCF 3   
                 —H 
                 —H 
                 —H 
                 free 
                 MS 689 (M + ) 
               
               
                 549 
                 —H 
                 —H 
                 —COOCH 3   
                 —H 
                 —H 
                 free 
                 MS 664 (M +  + 1) 
               
               
                 550 
                 —H 
                 —H 
                 —C(CH 3 ) 3   
                 —H 
                 —H 
                 free 
                 MS 661 (M + ) 
               
               
                 551 
                 —H 
                 —H 
                 —OCH 2 Ph 
                 —H 
                 —H 
                 free 
                 MS 710 (M +  − 1) 
               
               
                 552 
                 —H 
                 —H 
                 —Ph 
                 —H 
                 —H 
                 free 
                 MS 681 (M + ) 
               
               
                 553 
                 —Cl 
                 —H 
                 —H 
                 —H 
                 —Cl 
                 free 
                 MS 675 (M +  + 2) 
               
               
                 554 
                 —F 
                 —H 
                 —H 
                 —H 
                 —H 
                 free 
                 MS 641 (M + ) 
               
               
                 555 
                 —H 
                 —F 
                 —H 
                 —H 
                 —H 
                 free 
                 MS 641 (M + ) 
               
               
                 556 
                 —H 
                 —H 
                 —CF 3   
                 —H 
                 —H 
                 free 
                 MS 674 (M +  + 1) 
               
               
                 557 
                 —H 
                 —H 
                 —OCF 3   
                 —H 
                 —H 
                 free 
                 MS 689 (M + ) 
               
               
                 558 
                 —OCF 3   
                 —H 
                 —H 
                 —H 
                 —H 
                 free 
                 MS 689 (M + ) 
               
               
                 559 
                 —H 
                 —COOCH 3   
                 —H 
                 —H 
                 —H 
                 free 
                 MS 663 (M + ) 
               
               
                 560 
                 —H 
                 —H 
                 —C 2 H 5   
                 —H 
                 —H 
                 free 
                 MS 633 (M + ) 
               
               
                 561 
                 —H 
                 —H 
                 —CH(CH 3 ) 2   
                 —H 
                 —H 
                 free 
                 MS 647 (M + ) 
               
               
                 562 
                 —H 
                 —Cl 
                 —OCH 3   
                 —H 
                 —H 
                 free 
                 MS 669 (M + ) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 184 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                 mp (° C.) or 
               
               
                 No. 
                 R 608   
                 R 609   
                 R 610   
                 Form 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 563 
                 —H 
                 —CH 3   
                 piperonyl 
                 free 
                 mp 147-149 
               
               
                 564 
                 —H 
                 —H 
                 piperonyl 
                 free 
                 mp 138-140 
               
               
                 565 
                 —H 
                 —CH 3   
                 benzyl 
                 free 
                 mp 150-152 
               
               
                 566 
                 —H 
                 —H 
                 benzyl 
                 free 
                   1 H NMR (CDCl 3 ) 2.34-2.42 (4 H, 
               
               
                   
                   
                   
                   
                   
                 m), 2.58-2.64 (2 H, m), 2.91- 
               
               
                   
                   
                   
                   
                   
                 2.96 (2 H, m), 3.40-3.43 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                 3.51 (2 H, s), 3.60-3.64 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                 6.93 (1 H, d, J = 8.9 Hz), 7.01- 
               
               
                   
                   
                   
                   
                   
                 7.04 (2 H, m), 7.20 (2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.27-7.33 (5 H, m), 7.56 (1 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.3 Hz), 7.71-7.75 (1 H, m), 
               
               
                   
                   
                   
                   
                   
                 8.00 (1 H, d, J = 2.0 Hz), 8.16- 
               
               
                   
                   
                   
                   
                   
                 8.27 (3 H, m). 
               
               
                 567 
                 —OCH 3   
                 —H 
                 piperonyl 
                 free 
                 mp 142.0-144.5 
               
               
                 568 
                 —F 
                 —H 
                 piperonyl 
                 free 
                 mp 156.5-157.5 
               
               
                 569 
                 —H 
                 —H 
                 —COOC(CH 3 ) 3   
                 free 
                   1 H NMR (CDCl 3 ) 1.46 (9 H, s), 
               
               
                   
                   
                   
                   
                   
                 2.62-2.67 (2 H, m), 2.96-3.01 (2 H, 
               
               
                   
                   
                   
                   
                   
                 m), 3.33-3.39 (6 H, m), 3.57- 
               
               
                   
                   
                   
                   
                   
                 3.60 (2 H, m), 6.94-6.97 (1 H, m), 
               
               
                   
                   
                   
                   
                   
                 7.05 (2 H, d, J = 8.4 Hz), 7.23 (2 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.4 Hz), 7.57 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.1 Hz), 7.71-7.75 (1 H, m), 8.00 
               
               
                   
                   
                   
                   
                   
                 (1 H, d, J = 2.2 Hz), 8.13 (1 H, 
               
               
                   
                   
                   
                   
                   
                 brs), 8.21-8.24 (2 H, m). 
               
               
                 570 
                 —OC 2 H 5   
                 —H 
                 piperonyl 
                 oxalate 
                   1 H NMR (DMSO-d 6 ) 1.06 (3 H, t, 
               
               
                   
                   
                   
                   
                   
                 J = 6.9 Hz), 2.39-2.86 (8 H, m), 
               
               
                   
                   
                   
                   
                   
                 3.40-3.60 (4 H, m), 3.65 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                 3.70-5.20 (4 H, m), 6.00 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                 6.76-6.84 (2 H, m), 6.85-7.02 (5 H, 
               
               
                   
                   
                   
                   
                   
                 m), 7.82 (1 H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.92 (1 H, m), 8.03 (1 H, m), 
               
               
                   
                   
                   
                   
                   
                 8.20 (1 H, d, J = 2.0 Hz), 8.35 (1 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 2.5 Hz), 10.47 (1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 185 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                 mp (° C.) or 
               
               
                 No. 
                 R 611   
                 R 612   
                 R 613   
                 Form 
                   1 H NMR (CDCl 3 ) δppm 
               
               
                   
               
               
                 571 
                 —H 
                 —CH 3   
                 piperonyl 
                 hydro- 
                 mp 218-220 
               
               
                   
                   
                   
                   
                 chloride 
               
               
                 572 
                 —H 
                 —CH 3   
                 benzyl 
                 free 
                 mp 142-144 
               
               
                 573 
                 —OCH 3   
                 —H 
                 benzyl 
                 free 
                   1 H NMR 2.34-2.40 (4H, m), 2.58- 
               
               
                   
                   
                   
                   
                   
                 2.63 (2H, m), 2.89-2.94 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 3.39-3.42 (2H, m), 3.50 (2H, s), 
               
               
                   
                   
                   
                   
                   
                 3.58-3.61 (2H, m), 3.70 (3H, s), 
               
               
                   
                   
                   
                   
                   
                 6.75-6.80 (2H, m), 6.91 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.7 Hz), 7.00 (1H, d, J = 7.9 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.24-7.35 (5H, m), 7.69 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.1 Hz), 7.98 (2H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.14-8.18 (1H, m), 8.23 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 2.3 Hz), 8.59 (1H, s). 
               
               
                 574 
                 —OCH 3   
                 —H 
                 piperonyl 
                 free 
                   1 H NMR 2.31-2.37 (4H, m), 2.57- 
               
               
                   
                   
                   
                   
                   
                 2.63 (2H, m), 2.88-2.94 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 3.37-3.41 (4H, m), 3.57-3.60 (2H, 
               
               
                   
                   
                   
                   
                   
                 m), 3.70 (3H, s), 5.93 (2H, s), 6.69- 
               
               
                   
                   
                   
                   
                   
                 6.80 (4H, m), 6.84 (1H, brs), 
               
               
                   
                   
                   
                   
                   
                 6.90 (1H, d, J = 8.9 Hz), 7.00 (1H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 7.9 Hz), 7.69 (2H, d, J = 8.1 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.98 (2H, d, J = 8.1 Hz), 8.14- 
               
               
                   
                   
                   
                   
                   
                 8.19 (1H, m), 8.24 (1H, d, J = 2.5 
               
               
                   
                   
                   
                   
                   
                 Hz), 8.67 (1H, s). 
               
               
                 575 
                 —F 
                 —H 
                 piperonyl 
                 free 
                 mp 170.5-171.0 
               
               
                 576 
                 —H 
                 —H 
                 —COOC(CH 3 ) 3   
                 free 
                   1 H NMR 1.46 (9H, s), 2.66 (2H, t, J = 
               
               
                   
                   
                   
                   
                   
                 6.5 Hz), 2.97 (2H, t, J = 6.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 3.25-3.48 (6H, m), 3.51-3.65 (2H, 
               
               
                   
                   
                   
                   
                   
                 m), 6.95 (1H, d, J = 9.7 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.04 (2H, d, J = 8.4 Hz), 7.22 (2H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.4 Hz), 7.75 (2H, d, J = 8.2 
               
               
                   
                   
                   
                   
                   
                 Hz), 8.01 (2H, d, J = 8.2 Hz), 8.18- 
               
               
                   
                   
                   
                   
                   
                 8.33 (3H, m). 
               
               
                 577 
                 —OC 2 H 5   
                 —H 
                 piperonyl 
                 hydro- 
                 mp 147.5-149.0 
               
               
                   
                   
                   
                   
                 chloride 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 186 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                 mp (° C.) or 
               
               
                 No. 
                 R 614   
                 R 615   
                 R 616   
                 Xb 7   
                 Form 
                   1 H NMR 
               
               
                   
               
               
                 578 
                 —Cl 
                 —Cl 
                 morpholino 
                 —O— 
                 free 
                   1 H NMR (CDCl 3 ) δ 
               
               
                   
                   
                   
                   
                   
                   
                 2.60-2.66 (2H, m), 2.96- 
               
               
                   
                   
                   
                   
                   
                   
                 3.02 (2H, m), 3.37- 
               
               
                   
                   
                   
                   
                   
                   
                 3.41 (2H, m), 3.55- 
               
               
                   
                   
                   
                   
                   
                   
                 3.64 (6H, m), 6.96 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 8.4 Hz), 7.06 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 8.6 Hz), 7.23- 
               
               
                   
                   
                   
                   
                   
                   
                 7.26 (2H, m), 7.58 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 8.4 Hz), 7.70- 
               
               
                   
                   
                   
                   
                   
                   
                 7.74 (1H, m), 7.86 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs), 7.99 (1H, d, J = 1.9 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 8.19-8.25 (2H, m). 
               
               
                   
               
               
                 579 
                 —Cl 
                 —Cl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —NH— 
                 free 
                 mp 141-142 
               
               
                   
               
               
                 580 
                 —Cl 
                 —Cl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —S— 
                 free 
                 mp 169-170 
               
               
                   
               
               
                 581 
                 —Cl 
                 —Cl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —SO 2 — 
                 free 
                 mp 154-156 
               
               
                   
               
               
                 582 
                 —CF 3   
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —N(CH 3 )— 
                 free 
                 mp 175-176 
               
               
                   
               
               
                 583 
                 —Cl 
                 —Cl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —N(CH 2 Ph)— 
                 free 
                 mp 171-173 
               
               
                   
               
               
                 584 
                 —Cl 
                 —Cl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —N(CH 2 Ph)— 
                 free 
                 mp 144-146 
               
               
                   
               
               
                 585 
                 —Cl 
                 —Cl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CO— 
                 free 
                 mp 129-132 
               
               
                   
               
               
                 586 
                 —Cl 
                 —Cl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —O— 
                 free 
                 mp 208-210 
               
               
                   
               
               
                 587 
                 —Cl 
                 —Cl 
                 —NH(CH 2 ) 2 OPh 
                 —O— 
                 free 
                 mp 129-132 
               
               
                   
               
               
                 588 
                 —Cl 
                 —Cl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —SO— 
                 oxalate 
                 mp 128-130 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 187 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 617   
                 R 618   
                 Xb 8   
                 R 619   
                   1 H NMR (CDCl 3 ) δppm 
               
               
                   
               
               
                 589 
                 —Cl 
                 —Cl 
                 —CH═CH— 
                 piperonyl 
                 2.33-2.42 (4H, m), 2.62-2.68 (2H, m), 
               
               
                   
                   
                   
                 (trans) 
                   
                 2.96-3.01 (2H, m), 3.40-3.44 (4H, m), 
               
               
                   
                   
                   
                   
                   
                 3.62-3.66 (2H, m), 3.76 (3H, s), 5.95 (2H, 
               
               
                   
                   
                   
                   
                   
                 s), 6.71-6.77 (2H, m), 6.82-7.07 (7H, m), 
               
               
                   
                   
                   
                   
                   
                 7.28-7.32 (1H, m), 7.38-7.46 (1H, m), 
               
               
                   
                   
                   
                   
                   
                 7.57 (1H, d, J = 2.0 Hz), 7.83-7.87 (1H, 
               
               
                   
                   
                   
                   
                   
                 m), 8.19 (1H, d, J = 2.3 Hz). 
               
               
                 590 
                 —CF 3   
                 —H 
                 —CH═CH— 
                 piperonyl 
                 2.33-2.42 (4H, m), 2.62-2.68 (2H, m), 
               
               
                   
                   
                   
                 (trans) 
                   
                 2.96-3.02 (2H, m), 3.40-3.43 (4H, m), 
               
               
                   
                   
                   
                   
                   
                 3.63-3.66 (2H, m), 3.76 (3H, s), 5.94 (2H, 
               
               
                   
                   
                   
                   
                   
                 s) 6.71-6.79 (2H, m), 6.82-6.89 (3H, m), 
               
               
                   
                   
                   
                   
                   
                 6.95 (1H, d, J = 8.7 Hz), 7.00 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 16.5 Hz), 7.05-7.14 (2H, m), 7.55-7.62 
               
               
                   
                   
                   
                   
                   
                 (4H, m), 7.86-7.90 (1H, m), 8.22 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 2.3 Hz). 
               
               
                 591 
                 —CF 3   
                 —H 
                 —CO— 
                 benzyl 
                 2.38-2.43 (4H, m), 2.63-2.68 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 2.97-3.02 (2H, m), 3.43 (2H, brs), 
               
               
                   
                   
                   
                   
                   
                 3.51 (2H, s), 3.65 (2H, brs), 3.76 (3H, s), 
               
               
                   
                   
                   
                   
                   
                 6.84-6.89 (2H, m), 7.04-7.09 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 7.27-7.31 (5H, m), 7.73-7.88 (4H, m), 
               
               
                   
                   
                   
                   
                   
                 8.19-8.22 (1H, m), 8.55 (1H, brs). 
               
               
                 592 
                 —CF 3   
                 —H 
                 —CO— 
                 piperonyl 
                 2.35-2.39 (4H, m), 2.62-2.68 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 2.96-3.02 (2H, m), 3.41-3.44 (4H, m), 
               
               
                   
                   
                   
                   
                   
                 3.62-3.65 (2H, m), 3.76 (3H, s), 5.95 (2H, 
               
               
                   
                   
                   
                   
                   
                 s), 6.74-6.89 (5H, m), 7.04-7.09 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 7.73-7.88 (4H, m), 8.19-8.22 (1H, m), 
               
               
                   
                   
                   
                   
                   
                 8.55 (1H, brs). 
               
               
                 593 
                 —CF 3   
                 —H 
                 —CO— 
                 3-pyridyl 
                 2.69-2.75 (2H, m), 3.01-3.06 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 3.14-3.20 (4H, m), 3.59-3.62 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 3.77 (3H, s), 3.80-3.84 (2H, m), 6.86-6.92 
               
               
                   
                   
                   
                   
                   
                 (2H, m), 7.04-7.11 (2H, m), 7.18-7.20 (2H, 
               
               
                   
                   
                   
                   
                   
                 m), 7.75 (2H, d, J = 8.4 Hz), 7.87 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.1 Hz), 8.15 (1H, t, J = 3.0 Hz), 8.20 
               
               
                   
                   
                   
                   
                   
                 (1H, dd, J = 8.7 Hz, 2.3 Hz), 8.30 (1H, t, 
               
               
                   
                   
                   
                   
                   
                 J = 1.8 Hz), 8.53 (1H, d, J = 2.3 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 188 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 620   
                 R 621   
                 M 
                   1 H NMR (solvent) δppm 
               
               
                   
               
               
                 594 
                 3,4-Cl 2 PhNHCON(C 2 H 5 )— 
                 4-pyridyl- 
                 2 
                 (CDCl 3 ) 1.16 (3H, t, J = 7.1 Hz), 2.35- 
               
               
                   
                   
                 methyl 
                   
                 2.45 (4H, m), 2.62-2.67 (2H, m), 2.97- 
               
               
                   
                   
                   
                   
                 3.03 (2H, m), 3.42-3.46 (2H, m), 
               
               
                   
                   
                   
                   
                 3.51 (2H, s), 3.64-3.68 (2H, m), 
               
               
                   
                   
                   
                   
                 3.73 (2H, q, J = 7.1 Hz), 6.07 (1H, d, J = 
               
               
                   
                   
                   
                   
                 5.0 Hz), 7.04 (1H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                 7.09-7.14 (3H, m), 7.25-7.30 (5H, m), 
               
               
                   
                   
                   
                   
                 7.52 (1H, d, J = 2.6 Hz), 7.61 (1H, dd, J = 
               
               
                   
                   
                   
                   
                 8.7 Hz, 2.6 Hz), 8.11 (1H, d, J = 2.6 
               
               
                   
                   
                   
                   
                 Hz), 8.54 (2H, d, 4 = 5.9 Hz). 
               
               
                 595 
                 4-CF 3 PhNHCON(C 2 H 5 )— 
                 piperonyl 
                 2 
                 (CDCl 3 ) 1.18 (3H, t, J = 7.1 Hz), 2.32- 
               
               
                   
                   
                   
                   
                 2.41 (4H, m), 2.61-2.67 (2H, m), 2.97 
               
               
                   
                   
                   
                   
                 3.03 (2H, m), 3.39-3.43 (4H, m), 3.61- 
               
               
                   
                   
                   
                   
                 3.65 (2H, m), 3.75 (2H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 5.94 (2H, s), 6.15 (1H, brs), 6.72 
               
               
                   
                   
                   
                   
                 6.76 (2H, m), 6.83 (1H, d, J = 0.7 Hz), 
               
               
                   
                   
                   
                   
                 7.05 (1H, dd, J = 8.7 Hz, 0.5 Hz), 
               
               
                   
                   
                   
                   
                 7.11 (2H, d, J = 8.6 Hz), 7.29 (2H, d, J = 
               
               
                   
                   
                   
                   
                 8.6 Hz), 7.40 (2H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                 7.49 (2H, d, 4 = 8.7 Hz), 7.63 (1H, dd, J = 
               
               
                   
                   
                   
                   
                 8.7 Hz, 2.8 Hz), 8.14 (1H, dd, J = 
               
               
                   
                   
                   
                   
                 2.8 Hz, 0.5 Hz). 
               
               
                 596 
                 4-CF 3 PhNHCON(C 2 H 5 )— 
                 4-pyridyl- 
                 2 
                 (CDCl 3 ) 1.18 (3H, t, J = 7.1 Hz), 2.35- 
               
               
                   
                   
                 methyl 
                   
                 2.45 (4H, m), 2.62-2.68 (2H, m), 2.98- 
               
               
                   
                   
                   
                   
                 3.03 (2H, m), 3.42-3.46 (2H, m), 
               
               
                   
                   
                   
                   
                 3.51 (2H, s), 3.66 (2H, t, J = 5.0 Hz), 
               
               
                   
                   
                   
                   
                 3.75 (2H, q, J = 7.1 Hz), 6.18 (1H, brs), 
               
               
                   
                   
                   
                   
                 7.05 (1H, dd, J = 8.7 Hz, 0.5 Hz), 
               
               
                   
                   
                   
                   
                 7.11 (2H, d, J = 8.4 Hz), 7.25-7.31 (4H, 
               
               
                   
                   
                   
                   
                 m), 7.40 (2H, d, J = 8.7 Hz), 7.49 (2H, 
               
               
                   
                   
                   
                   
                 d, J = 8.7 Hz), 7.63 (1H, dd, J = 8.7 
               
               
                   
                   
                   
                   
                 Hz, 2.8 Hz), 8.13 (1H, dd, J = 2.6 Hz, 
               
               
                   
                   
                   
                   
                 0.5 Hz), 8.53-8.55 (2H, m). 
               
               
                 597 
                 4-CF 3 PhNHCON(C 2 H 5 )— 
                 2-pyridyl 
                 2 
                 (CDCl 3 ) 1.17 (3H, t, J = 7.1 Hz), 2.68- 
               
               
                   
                   
                   
                   
                 2.74 (2H, m), 3.02-3.07 (2H, m), 3.46- 
               
               
                   
                   
                   
                   
                 3.53 (6H, m), 3.70-3.78 (4H, m), 
               
               
                   
                   
                   
                   
                 6.12 (1H, brs), 6.62-6.67 (2H, m), 
               
               
                   
                   
                   
                   
                 7.04 (1H, d, J = 8.7 Hz), 7.12 (2H, d, J = 
               
               
                   
                   
                   
                   
                 8.6 Hz), 7.31 (2H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                 7.40 (2H, d, J = 8.7 Hz), 7.45-7.52 (3H, 
               
               
                   
                   
                   
                   
                 m), 7.60 (1H, dd, J = 8.7 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                   
                 8.07 (1H, d, J = 2.5 Hz), 8.16-8.19 (1H, 
               
               
                   
                   
                   
                   
                 m). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 189 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                 mp (° C.) or 
               
               
                 No. 
                 R 622   
                 R 623   
                 R 624   
                 R 625   
                   1 H NMR (CDCl 3 ) δppm 
               
               
                   
               
               
                 598 
                 —Cl 
                 —Cl 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 mp 169-171 
               
               
                   
               
               
                 599 
                 —Cl 
                 —Cl 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 mp 158-160 
               
               
                   
               
               
                 600 
                 —Cl 
                 —Cl 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 mp 183-186 
               
               
                   
               
               
                 601 
                 —CF 3   
                 —H 
                 —F 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 3.00 (3H, s), 3.20- 3.36 (2H, m), 3.57-3.80 (2H, m), 4.07 (2H, s), 4.14-4.34 (2H, m), 4.51 (2H, s), 5.94 (2H, s), 6.32- 6.50 (2H, m), 6.65-6.80 (3H, m), 6.92 (1H, d, J = 9.4 Hz), 7.02 (1H, t, J = 8.8 Hz), 7.71 (2H, d, J = 8.1 Hz), 7.98 (2H, d, J = 8.1 Hz), 8.10-8.20 (1H, m), 8.18 (1H, s), 8.30 (1H, s). 
               
               
                   
               
               
                 602 
                 —CF 3   
                 —H 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.45 (6H, s), 2.14 (2H, brs), 2.33 (2H, brs), 2.87 (3H, s), 3.32 (2H, s), 3.63 (2H, brs), 3.92 (2H, brs), 5.93 (2H, s), 6.68- 6.75 (2H, m), 6.82 (1H, d, J = 1.0 Hz), 6.92 (2H, d, J = 9.2 Hz), 6.93 (1H, d, J = 9.1 Hz), 7.00 (2H, d, J = 9.2 Hz), 7.77 (2H, d, J = 8.1 Hz), 7.81 (1H, s), 8.00 (2H, d, J = 8.1 Hz), 8.19 (1H, dd, J = 8.7 Hz, 2.8 Hz), 8.26 (1H, d, J = 2.1 Hz). 
               
               
                   
               
               
                 603 
                 —CF 3   
                 —H 
                 —OCH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.33-1.45 (2H, m), 1.82-1.96 (3H, m), 2.28 (2H, d, J = 6.8 Hz), 2.39-2.41 (4H, m), 2.72 (2H, t, J = 10.1 Hz), 3.43 (2H, s), 3.48 (2H, brs), 3.57- 3.62 (4H, m), 3.72 (3H, s), 5.95 (2H, s), 6.48 (1H, dd, J = 8.7 Hz, 2.5 Hz), 6.56 (1H, d, J = 2.5 Hz), 6.71-6.77 (2H, m), 6.86 (2H, d, J = 8.6 Hz), 6.97 (1H, d, J = 8.6 Hz), 7.70 (2H, d, J = 8.4 Hz), 8.00 (2H, d, J = 8.1 Hz), 8.13 (1H, dd, J = 8.7 Hz, 2.6 Hz), 8.22 (1H, d, J = 2.5 Hz), 8.40 (1H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 190 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                 mp (° C.) or 
               
               
                 No. 
                 R 626   
                 R 627   
                 R 628   
                 R 629   
                   1 H NMR (DMSO-d 6 ) δppm 
               
               
                   
               
             
          
           
               
                 604 
                 —CF 3   
                 —H 
                 —CH 3   
                 —OC 2 H 5   
                   1 H NMR 1.03 (3H, t, J = 6.9 Hz), 2.52-2.68 (6H, m), 
               
               
                   
                   
                   
                   
                   
                 3.89 (2H, q, J = 6.9 Hz), 4.00-5.90 (4H, m), 6.01 (2H, 
               
               
                   
                   
                   
                   
                   
                 s), 6.74 (1H, dd, J = 8.0 Hz, 1.8 Hz), 6.76 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.9 Hz), 6.82 (1H, dd, J = 8.0 Hz, 1.3 Hz), 6.84- 
               
               
                   
                   
                   
                   
                   
                 6.97 (4H, m), 7.26 (1H, dd, J = 9.0 Hz, 3.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.41 (2H, d, J = 8.0 Hz), 7.50 (1H, d, J = 3.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.65 (2H, d, J = 8.0 Hz). 
               
               
                 605 
                 —CF 3   
                 —H 
                 —C 2 H 5   
                 —OC 2 H 5   
                   1 H NMR 1.02 (3H, t, J = 6.9 Hz), 1.08 (3H, t, J = 
               
               
                   
                   
                   
                   
                   
                 6.9 Hz), 2.53-2.84 (8H, m), 3.43 (2H, q, J = 6.9 Hz), 
               
               
                   
                   
                   
                   
                   
                 3.46-3.62 (4H, m), 3.72 (2H, s), 3.88 (2H, q, J = 
               
               
                   
                   
                   
                   
                   
                 6.9 Hz), 4.30-5.90 (4H, m), 6.01 (2H, s), 6.69- 
               
               
                   
                   
                   
                   
                   
                 6.78 (2H, m), 6.82 (1H, dd, J = 8.0 Hz, 1.4 Hz), 6.83- 
               
               
                   
                   
                   
                   
                   
                 6.97 (4H, m), 7.19 (1H, dd, J = 9.0 Hz, 3.1 Hz), 7.37- 
               
               
                   
                   
                   
                   
                   
                 7.48 (3H, m), 7.65 (2H, d, J = 8.1 Hz). 
               
               
                 606 
                 —Cl 
                 —Cl 
                 —CH 3   
                 —H 
                   1 H NMR 2.48-2.67 (6H, m), 2.68-2.82 (2H, m) 
               
               
                   
                   
                   
                   
                   
                 2.98 (3H, s) 3.37-3.62 (4H, m), 3.70 (2H, s), 4.50- 
               
               
                   
                   
                   
                   
                   
                 5.90 (4H, m), 6.01 (2H, s), 6.78-6.95 (6H, m), 7.13- 
               
               
                   
                   
                   
                   
                   
                 7.23 (3H, m), 7.28 (1H, dd, J = 9.0 Hz, 3.3 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.48 (1H, d, J = 2.0 Hz), 7.57 (1H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.61 (1H, d, J = 3.1 Hz). 
               
               
                 607 
                 —Cl 
                 —Cl 
                 —C 2 H 5   
                 —H 
                   1 H NMR 1.09 (3H, t, J = 6.9 Hz), 2.48-2.66 (6H, m), 
               
               
                   
                   
                   
                   
                   
                 2.69-2.82 (2H, m), 3.35-3.59 (6H, m), 3.67 (2H, s), 
               
               
                   
                   
                   
                   
                   
                 4.00-5.90 (4H, m), 6.00 (2H, s), 6.76-6.94 (6H, m), 
               
               
                   
                   
                   
                   
                   
                 7.13-7.25 (4H, m), 7.47 (1H, d, J = 1.9 Hz), 7.52- 
               
               
                   
                   
                   
                   
                   
                 7.61 (2H, m). 
               
               
                 608 
                 —CF 3   
                 —H 
                 —CH 3   
                 —F 
                   1 H NMR 2.50-2.72 (6H, m), 2.72-2.88 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 2.98 (3H, s), 3.32-3.61 (4H, m) 3.70 (2H, brs), 
               
               
                   
                   
                   
                   
                   
                 4.67 (2H, s), 6.00 (2H, s), 6.80 (1H, dd, J = 7.9 Hz, 
               
               
                   
                   
                   
                   
                   
                 1.4 Hz), 6.85-6.95 (3H, m), 6.98-7.11 (2H, m) 7.11- 
               
               
                   
                   
                   
                   
                   
                 7.22 (1H, m), 7.29 (1H, dd, J = 9.0 Hz, 3.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.41 (2H, d, J = 8.0 Hz), 7.50 (1H, d, J = 3.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.66 (2H, d, J = 8.0 Hz). 
               
               
                 609 
                 —Cl 
                 —Cl 
                 —C 2 H 5   
                 —F 
                   1 H NMR 1.00-1.20 (3H, m), 2.46-2.72 (6H, m), 2.72- 
               
               
                   
                   
                   
                   
                   
                 2.89 (2H, m), 3.29-3.61 (6H, m), 3.71 (2H, brs), 
               
               
                   
                   
                   
                   
                   
                 4.46 (2H, s), 6.01 (2H, s), 6.81 (1H, dd, J = 8.0 Hz, 
               
               
                   
                   
                   
                   
                   
                 1.4 Hz), 6.85-6.95 (3H, m), 6.98-7.11 (2H, m), 7.13- 
               
               
                   
                   
                   
                   
                   
                 7.28 (3H, m), 7.45 (1H, d, J = 3.1 Hz), 7.46 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 1.9 Hz), 7.56 (1H, d, J = 8.3 Hz). 
               
               
                 610 
                 —Cl 
                 —Cl 
                 —CH 3   
                 —OC 2 H 5   
                   1 H NMR 1.02 (3H, t, J = 6.9 Hz), 2.42-2.81 (8H, m), 
               
               
                   
                   
                   
                   
                   
                 2.94 (3H, s), 3.00-4.30 (10H, m), 4.49 (2H, s), 
               
               
                   
                   
                   
                   
                   
                 6.00 (2H, s), 6.71-6.83 (3H, m), 6.84-6.95 (4H, m), 
               
               
                   
                   
                   
                   
                   
                 7.18 (1H, dd, J = 8.3 Hz, 2.0 Hz), 7.26 (1H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 9.0 Hz, 3.2 Hz), 7.44 (1H, d, J = 2.0 Hz), 7.50 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 3.0 Hz), 7.55 (1H, d, J = 8.3 Hz). 
               
               
                 611 
                 —Cl 
                 —Cl 
                 —C 2 H 5   
                 —OC 2 H 5   
                   1 H NMR 1.01 (3H, t, J = 7.0 Hz), 1.06 (3H, t, J = 
               
               
                   
                   
                   
                   
                   
                 7.0 Hz), 2.40-2.83 (8H, m), 2.90-4.50 (14H, m), 
               
               
                   
                   
                   
                   
                   
                 6.00 (2H, s), 6.70-6.82 (3H, m), 6.84-6.95 (4H, m), 
               
               
                   
                   
                   
                   
                   
                 7.15-7.24 (2H, m), 7.39-7.48 (2H, m), 7.55 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.3 Hz). 
               
               
                 612 
                 —Cl 
                 —Cl 
                 —C 2 H 5   
                 —OCH 3   
                 mp 91.0-96.5 dec 
               
               
                 613 
                 —CF 3   
                 —H 
                 —C 2 H 5   
                 —F 
                 mp 104-107 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 191 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 630   
                 R 631   
                 Form 
                   1 H NMR (solvent) δppm 
               
               
                   
               
               
                 614 
                 —H 
                 piperonyl 
                 free 
                 (CDCl 3 ) 2.30-2.34 (2H, m), 2.36-2.40 (2H, 
               
               
                   
                   
                   
                   
                 m), 2.56-2.62 (2H, m), 2.91-2.96 (2H, m), 
               
               
                   
                   
                   
                   
                 3.01 (3H, s), 3.37-3.40 (4H, m), 3.60- 
               
               
                   
                   
                   
                   
                 3.64 (2H, m), 4.50 (2H, s), 5.94 (2H, s), 6.72- 
               
               
                   
                   
                   
                   
                 6.73 (2H, m), 6.80 (1H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                 6.84 (1H, brs), 6.98 (2H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                 7.11 (1H, dd, J = 8.9 Hz, 3.3 Hz), 7.18 (2H, 
               
               
                   
                   
                   
                   
                 d, J = 8.4 Hz), 7.34 (2H, d, J = 7.9 Hz), 
               
               
                   
                   
                   
                   
                 7.58 (2H, d, J = 8.3 Hz), 7.70 (1H, d, J = 3.3 
               
               
                   
                   
                   
                   
                 Hz). 
               
               
                 615 
                 —H 
                 3-pyridyl 
                 free 
                 (CDCl 3 ) 2.63-2.69 (2H, m), 2.95-3.01 (5H, 
               
               
                   
                   
                   
                   
                 m), 3.08-3.18 (4H, m), 3.54-3.58 (2H, m), 
               
               
                   
                   
                   
                   
                 3.78-3.81 (2H, m), 4.50 (2H, s), 6.79 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 8.9 Hz), 6.99 (2H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                 7.10 (1H, dd, 4 = 8.9 Hz, 3.1 Hz), 7.17- 
               
               
                   
                   
                   
                   
                 7.22 (4H, m), 7.34 (2H, d, 4 = 8.1 Hz), 
               
               
                   
                   
                   
                   
                 7.58 (2H, d, J = 7.9 Hz), 7.67 (1H, d, J = 2.8 
               
               
                   
                   
                   
                   
                 Hz), 8.12-8.14 (1H, m), 8.29-8.30 (1H, m). 
               
               
                 616 
                 —H 
                 4-pyridylmethyl 
                 free 
                 (CDCl 3 ) 2.33 (2H, t, J = 5.0 Hz), 2.41 (2H, t, 
               
               
                   
                   
                   
                   
                 J = 5.1 Hz), 2.57-2.63 (2H, m), 2.92- 
               
               
                   
                   
                   
                   
                 2.97 (2H, m), 3.02 (3H, s), 3.41 (2H, t, J = 
               
               
                   
                   
                   
                   
                 5.0 Hz), 3.50 (2H, s), 3.65 (2H, t, J = 5.1 
               
               
                   
                   
                   
                   
                 Hz), 4.51 (2H, s), 6.80 (1H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                 6.98 (2H, d, J = 8.4 Hz), 7.11 (1H, dd, J = 
               
               
                   
                   
                   
                   
                 8.9 Hz, 3.1 Hz), 7.18 (2H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                 7.27 (2H, d, J = 5.6 Hz), 7.34 (2H, d, J = 8.3 
               
               
                   
                   
                   
                   
                 Hz), 7.58 (2H, d, J = 8.3 Hz), 7.69 (1H, d, J = 
               
               
                   
                   
                   
                   
                 3.1 Hz), 8.55 (2H, d, J = 5.8 Hz). 
               
               
                 617 
                 —H 
                 benzyl 
                 hydrochloride 
                 (DMSO-d 6 ) 2.64-2.69 (2H, m), 2.75- 
               
               
                   
                   
                   
                   
                 2.81 (2H, m), 2.92-3.02 (5H, m), 3.23- 
               
               
                   
                   
                   
                   
                 3.32 (2H, m), 3.41-3.51 (2H, m), 4.02- 
               
               
                   
                   
                   
                   
                 4.08 (1H, m), 4.31 (2H, brs), 4.43-4.48 (1H, 
               
               
                   
                   
                   
                   
                 m) 4.64 (2H, brs), 6.86 (1H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                   
                 6.90 (2H, d, J = 8.6 Hz), 7.20 (2H, d, J = 8.4 
               
               
                   
                   
                   
                   
                 Hz), 7.29 (1H, dd, J = 9.1 Hz, 3.1 Hz), 7.42- 
               
               
                   
                   
                   
                   
                 7.47 (5H, m), 7.56-7.57 (2H, m), 7.62 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 3.1 Hz), 7.69 (2H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                 11.08 (1H, brs). 
               
               
                 618 
                 —OCH 3   
                 piperonyl 
                 hydrochloride 
                 (DMSO-d 6 ) 2.59-3.09 (6H, m), 2.97 (3H, s), 
               
               
                   
                   
                   
                   
                 3.16-3.61 (4H, m), 3.65 (3H, s), 3.97- 
               
               
                   
                   
                   
                   
                 4.13 (1H, m), 4.14-4.28 (2H, m), 4.38- 
               
               
                   
                   
                   
                   
                 4.51 (1H, m), 4.58 (2H, s), 6.06 (2H, s), 6.72- 
               
               
                   
                   
                   
                   
                 6.80 (2H, m), 6.89 (1H, d, J = 8.0 Hz), 6.93- 
               
               
                   
                   
                   
                   
                 7.03 (3H, m), 7.18 (1H, s), 7.26 (1H, dd, J = 
               
               
                   
                   
                   
                   
                 9.0 Hz, 3.2 Hz), 7.42 (2H, d, J = 8.0 Hz), 
               
               
                   
                   
                   
                   
                 7.49 (1H, d, J = 3.1 Hz), 7.67 (2H, d, J = 8.0 
               
               
                   
                   
                   
                   
                 Hz), 10.81 (1H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 192 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 632   
                 R 633   
                 R 634   
                 R 635   
                 Form 
                   1 H NMR (DMSO-d 6 ) δppm 
               
               
                   
               
               
                 619 
                 —CF 3   
                 —H 
                 —C 2 H 5   
                 —H 
                 TsOH 
                 1.11 (3H, t, J = 6.9 Hz), 2.28 (3H, s), 
               
               
                   
                   
                   
                   
                   
                 salt 
                 2.54-3.02 (7H, m), 3.17-3.48 (3H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 3.47 (2H, q, J = 6.9 Hz), 3.97-4.12 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 4.15-4.31 (2H, m), 4.38-4.52 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 4.58 (2H, s), 6.07 (2H, s), 6.78- 
               
               
                   
                   
                   
                   
                   
                   
                 7.26 (11H, m), 7.39-7.49 (4H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.53 (1H, d, J = 3.1 Hz), 7.68 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.2 Hz), 9.45-9.69 (1H, m). 
               
               
                 620 
                 —CF 3   
                 —H 
                 —(CH 2 ) 2 OCH 3   
                 —H 
                 TsOH 
                 2.27 (3H, s), 2.52-3.03 (7H, m), 
               
               
                   
                   
                   
                   
                   
                 salt 
                 3.24 (3H, s), 3.17-3.70 (10H, m), 3.95- 
               
               
                   
                   
                   
                   
                   
                   
                 4.13 (1H, m), 4.15-4.32 (2H, m), 4.36- 
               
               
                   
                   
                   
                   
                   
                   
                 4.54 (1H, m), 4.66 (2H, s), 6.07 (2H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 6.80 (1H, d, J = 8.9 Hz), 6.83-7.07 (5H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 7.10 (2H, d, J = 7.8 Hz), 7.13 
               
               
                   
                   
                   
                   
                   
                   
                 7.26 (3H, m), 7.37-7.49 (4H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.52 (1H, d, J = 3.1 Hz), 7.67 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.1 Hz), 9.46-9.69 (1H, m). 
               
               
                 621 
                 —Cl 
                 —Cl 
                 —CH 3   
                 —OCH 3   
                 hydro- 
                 2.60-3.15 (7H, m), 2.94 (3H, s), 3.15- 
               
               
                   
                   
                   
                   
                   
                 chloride 
                 3.38 (2H, m), 3.38-3.60 (1H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 3.65 (3H, s), 4.07 (1H, d, J = 15.7 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 4.20 (2H, brs), 4.38-4.60 (1H, m), 4.48 
               
               
                   
                   
                   
                   
                   
                   
                 (2H, s), 6.06 (2H, s), 6.73-6.81 (2H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 6.90 (1H, d, J = 8.0 Hz), 6.93-7.05 (3H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 7.16-7.24 (2H, m), 7.29 (1H, dd, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.9 Hz, 3.2 Hz), 7.47 (1H, d, J = 1.9 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.50 (1H, d, J = 3.1 Hz), 7.56 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 8.2 Hz), 11.10 (1H, brs). 
               
               
                 622 
                 —Cl 
                 —Cl 
                 —CH 3   
                 —F 
                 hydro- 
                 2.58-3.17 (7H, m), 2.96 (3H, s), 3.18- 
               
               
                   
                   
                   
                   
                   
                 chloride 
                 3.38 (2H, m), 3.38-3.70 (1H, m), 4.00- 
               
               
                   
                   
                   
                   
                   
                   
                 4.18 (1H, m), 4.20 (2H, brs), 4.33 
               
               
                   
                   
                   
                   
                   
                   
                 4.60 (1H, m), 4.50 (2H, s), 6.06 (2H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 6.92 (1H, d, J = 9.0 Hz), 6.95-7.14 (4H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 7.16-7.25 (3H, m), 7.31 (1H, dd, J = 
               
               
                   
                   
                   
                   
                   
                   
                 9.0 Hz, 3.1 Hz), 7.47 (1H, d, J = 1.9 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.51 (1H, d, J = 3.1 Hz), 7.56 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 8.2 Hz), 11.10 (1H, brs). 
               
               
                 623 
                 —CF 3   
                 —H 
                 —C 2 H 5   
                 —OCH 3   
                 hydro- 
                 1.09 (3H, t, J = 6.9 Hz), 2.58-3.11 (8H, 
               
               
                   
                   
                   
                   
                   
                 chloride 
                 m), 3.15-3.58 (4H, m), 3.64 (3H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 3.94-4.12 (1H, m), 4.14-4.28 (2H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 4.36-4.50 (1H, m), 4.54 (2H, s), 6.69- 
               
               
                   
                   
                   
                   
                   
                   
                 6.79 (2H, m), 6.88 (1H, d, J = 8.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 6.92-7.02 (3H, m), 7.12-7.24 (2H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.37-7.49 (3H, m), 7.67 (2H, d, J = 8.1 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 10.77 (1H, brs). 
               
               
                   
               
               
                 (TsOH means a p-toluenesulfonic acid. Hereinafter TsOH indicates the same meaning) 
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
               
             
               
             
           
               
                 TABLE 193 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
                   
                 mp (° C.) or 
               
               
                 No. 
                 R 636   
                 R 637   
                 R 638   
                 R 639   
                 R 640   
                 R 641   
                 Form 
                   1 H NMR 
               
               
                   
               
               
                 624 
                 Ya 2   
                 —H 
                 —H 
                 Ya 1   
                 —H 
                 —H 
                 hydrochloride 
                   1 H NMR (DMSO-d 6 ) δ 2.56- 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 2.72 (2H, m), 2.73-2.94 (3H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 m), 2.96-3.10 (1H, m), 3.12- 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 3.52 (4H, m), 3.91-4.07 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 m), 4.10-4.26 (2H, m), 4.33 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 4.48 (1H, m), 6.05 (2H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 6.82 (1H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 6.89-7.02 (4H, m), 7.09 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 t, J = 7.6 Hz), 7.14-7.25 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 m), 7.35 (1H, d, J = 7.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 7.74 (2H, d, J = 9.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 7.81 (1H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 7.94 (1H, dd, J = 8.4 Hz, 2.1 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 Hz), 8.22 (1H, d, J = 2.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 10.45 (1H, s), 11.15 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 brs). 
               
               
                 625 
                 Ya 2   
                 —H 
                 —H 
                 —H 
                 Ya 1   
                 —H 
                 oxalate 
                 mp 134-143 
               
               
                 626 
                 —H 
                 —H 
                 Ya 2   
                 —H 
                 —H 
                 Ya 1   
                 fumarate 
                 mp 123-126 
               
               
                 627 
                 —H 
                 Ya 2   
                 —H 
                 —H 
                 —H 
                 Ya 1   
                 hydrochloride 
                 mp 141-153 
               
               
                   
               
             
          
           
               
                 In the above-mentioned Table, Ya 1  means a group of 
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                 and Ya 2  means a group of 
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 194 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                 MS 
               
               
                 No. 
                 R 642   
                 (M +  + H) 
               
               
                   
               
               
                 628 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 540 
               
               
                   
               
               
                 629 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 574 
               
               
                   
               
               
                 630 
                 morpholino 
                 528 
               
               
                   
               
               
                 631 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 574 
               
               
                   
               
               
                 632 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 673 
               
               
                   
               
               
                 633 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 513 
               
               
                   
               
               
                 634 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 543 
               
               
                   
               
               
                 635 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 632 
               
               
                   
               
               
                 636 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 555 
               
               
                   
               
               
                 637 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 689 
               
               
                   
               
               
                 638 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 655 
               
               
                   
               
               
                 639 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 626 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 195 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                   
                 Example 
                   
                   
                 MS 
               
               
                   
                 No. 
                 R 643   
                 R 644   
                 (M +  + H) 
               
               
                   
                   
               
               
                   
                 640 
                 —CH 3   
                 cyclohexyl 
                 554 
               
               
                   
                 641 
                 —H 
                 cyclohexyl 
                 540 
               
               
                   
                 642 
                 —C 2 H 5   
                 —Ph 
                 562 
               
               
                   
                 643 
                 —CH 3   
                 4-CH 3 Ph— 
                 562 
               
               
                   
                 644 
                 —H 
                 cycloheptyl 
                 554 
               
               
                   
                 645 
                 —H 
                 cyclooctyl 
                 569 
               
               
                   
                 646 
                 —H 
                 benzyl 
                 548 
               
               
                   
                 647 
                 —H 
                 2-ClPhCH 2 — 
                 584 
               
               
                   
                 648 
                 —H 
                 3-ClPhCH 2 — 
                 584 
               
               
                   
                 649 
                 —H 
                 4-ClPhCH 2 — 
                 584 
               
               
                   
                 650 
                 —CH 3   
                 Ph(CH 2 ) 2 — 
                 577 
               
               
                   
                 651 
                 —CH 3   
                 3,4-(CH 3 O) 2 PhCH 2 — 
                 623 
               
               
                   
                 652 
                 —CH 3   
                 benzyl 
                 562 
               
               
                   
                 653 
                 —C 2 H 5   
                 benzyl 
                 576 
               
               
                   
                 654 
                 —H 
                 PhOCH 2 CH(CH 3 )— 
                 593 
               
               
                   
                 655 
                 —C 2 H 5   
                 cyclohexyl 
                 569 
               
               
                   
                 656 
                 —H 
                 —C 2 H 5   
                 486 
               
               
                   
                 657 
                 —H 
                 -(CH 2 ) 2 CH 3   
                 500 
               
               
                   
                 658 
                 —H 
                 -(CH 2 ) 2 OCH 3   
                 516 
               
               
                   
                 659 
                 —C 2 H 5   
                 cyclohexylmethyl 
                 583 
               
               
                   
                 660 
                 —H 
                 4-CH 3 OPhCH 2 — 
                 578 
               
               
                   
                 661 
                 —H 
                 4-CH 3 OPh(CH 2 ) 2 — 
                 593 
               
               
                   
                 662 
                 —H 
                 4-CF 3 OPhCH 2 — 
                 632 
               
               
                   
                 663 
                 —H 
                 4-CF 3 OPh— 
                 618 
               
               
                   
                 664 
                 —H 
                 4-ClPh(CH 2 ) 2 — 
                 598 
               
               
                   
                 665 
                 —H 
                 piperonyl 
                 592 
               
               
                   
                 666 
                 —H 
                 —(CH 2 ) 2 OPh 
                 579 
               
               
                   
                 667 
                 —H 
                 cyclopentyl 
                 527 
               
               
                   
                 668 
                 —H 
                 cyclohexylmethyl 
                 554 
               
               
                   
                 669 
                 —H 
                 4-hydroxycyclohexan-1-yl 
                 556 
               
               
                   
                 670 
                 —H 
                 4-FPhCH 2 — 
                 566 
               
               
                   
                 671 
                 —H 
                 —CH(CH 3 )Ph 
                 562 
               
               
                   
                 672 
                 —H 
                 —(CH 2 ) 3 Ph 
                 576 
               
               
                   
                 673 
                 —H 
                 —Ph 
                 534 
               
               
                   
                 674 
                 —H 
                 4-CH 3 OPh— 
                 564 
               
               
                   
                 675 
                 —H 
                 —(CH 2 ) 2 Ph 
                 562 
               
               
                   
                 676 
                 —H 
                 3-PhOPh— 
                 627 
               
               
                   
                 677 
                 —H 
                 4-PhOPh— 
                 627 
               
               
                   
                 678 
                 —H 
                 2-CH 3 OPh(CH 2 ) 2 — 
                 593 
               
               
                   
                 679 
                 —H 
                 2-FPh(CH 2 ) 2 — 
                 580 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 196 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                   
                 Example 
                   
                   
                 MS 
               
               
                   
                 No. 
                 R 645   
                 R 646   
                 (M +  + H) 
               
               
                   
                   
               
               
                   
                 680 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 632 
               
               
                   
                   
               
               
                   
                 681 
                 —H 
                 —CH(CH 3 ) 2   
                 501 
               
               
                   
                   
               
               
                   
                 682 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 578 
               
               
                   
                   
               
               
                   
                 683 
                 —(CH 2 ) 2 OH 
                 —(CH 2 ) 2 OH 
                 547 
               
               
                   
                 684 
                 —CH 3   
                 —(CH 2 ) 2 N(CH 3 ) 2   
                 544 
               
               
                   
                 685 
                 —H 
                 —(CH 2 ) 3 CH 3   
                 515 
               
               
                   
                 686 
                 —H 
                 cyclopropyl 
                 499 
               
               
                   
                 687 
                 —H 
                 2-pyridylmethyl 
                 550 
               
               
                   
                 688 
                 —H 
                 3-pyridylmethyl 
                 550 
               
               
                   
                 689 
                 —H 
                 —CH 2 CH(CH 3 ) 2   
                 515 
               
               
                   
                 690 
                 —H 
                 cyclopropylmethyl 
                 513 
               
               
                   
                   
               
               
                   
                 691 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 567 
               
               
                   
                   
               
               
                   
                 692 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 570 
               
               
                   
                   
               
               
                   
                 693 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 572 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 197 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                   
                 Example 
                   
                   
                   
               
               
                   
                 No. 
                 R 647   
                 R 648   
                   1 H NMR or MS 
               
               
                   
                   
               
               
                   
                 694 
                 —H 
                 4-CF 3 OPhO— 
                 MS 702 (M +  + H) 
               
               
                   
                 695 
                 —H 
                 benzyl 
                 MS 617 (M +  + H) 
               
               
                   
                 696 
                 —OH 
                 4-ClPh— 
                 MS 654 (M +  + H) 
               
               
                   
                 697 
                 —H 
                 —H 
                 MS 526 (M +  + H) 
               
               
                   
                 698 
                 —H 
                 —Ph 
                 MS 602 (M +  + H) 
               
               
                   
                 699 
                 —H 
                 piperonyl 
                   1 H NMR (CDCl 3 ) δ 1.11-1.16 (5H, 
               
               
                   
                   
                   
                   
                 m), 1.65-1.71 (3H, m), 2.48 (2H, d, J = 
               
               
                   
                   
                   
                   
                 6.4 Hz), 2.54-2.58 (1H, m), 2.95- 
               
               
                   
                   
                   
                   
                 3.04 (1H, m), 3.35 (2H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 3.84-3.89 (1H, m), 4.01 (2H, s), 4.52- 
               
               
                   
                   
                   
                   
                 4.57 (1H, m), 5.93 (2H, s), 6.56 
               
               
                   
                   
                   
                   
                 6.63 (4H, m), 6.73 (1H, d, J = 7.8 Hz), 
               
               
                   
                   
                   
                   
                 6.79 (1H, d, J = 8.7 Hz), 6.92 (2H, d, 
               
               
                   
                   
                   
                   
                 J = 9.1 Hz), 7.52 (1H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                 7.72 (1H, dd, J = 8.4 Hz, 2.0 Hz), 
               
               
                   
                   
                   
                   
                 7.99 (1H, d, J = 2.0 Hz), 8.04 (1H, dd, 
               
               
                   
                   
                   
                   
                 J = 8.9 Hz, 2.8 Hz), 8.26 (1H, d, J = 
               
               
                   
                   
                   
                   
                 2.5 Hz), 8.56 (1H, brs). 
               
               
                   
                   
               
               
                   
                 700 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 610 (M +  + H) 
               
               
                   
                   
               
               
                   
                 701 
                 —H 
                 4-CH 3 OPhCONH— 
                 MS 676 (M +  + H) 
               
               
                   
                 702 
                 —H 
                 —N(CH 3 )CH 2 Ph 
                 MS 646 (M +  + H) 
               
               
                   
                 703 
                 —H 
                 4-CH 3 PhO 
                 MS 690 (M +  + H) 
               
               
                   
                   
                   
                 (CH 2 ) 2 N(CH 3 )— 
               
               
                   
                 704 
                 —OH 
                 —Ph 
                 MS 619 (M +  + H) 
               
               
                   
                 705 
                 —H 
                 4-CNPhO— 
                 MS 644 (M +  + H) 
               
               
                   
                 706 
                 —H 
                 2-ClPhCH 2 — 
                 MS 653 (M +  + H) 
               
               
                   
                 707 
                 —CH 2 (CH 2 ) 3 CH 2 — 
                 MS 595 (M +  + H) 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 198 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 649   
                 R 650   
                 R 651   
                 R 652   
                 R 653   
                 M 
                   1 H NMR (solvent) δppm 
               
               
                   
               
               
                 708 
                 —Cl 
                 —Cl 
                 —CH 3   
                 —CONH 2   
                 —H 
                 1 
                 (DMSO-d 6 ) 1.79-2.02 (4H, m), 2.96 (3H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 s), 3.37-3.67 (3H, m), 4.19 (2H, s), 6.61- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.70 (2H, m), 6.89-6.95 (3H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.83 (1H, d, J = 8.4 Hz), 7.94 (1H, dd, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.4 Hz, 2.0 Hz), 8.13 (1H, dd, J = 8.9 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz, 2.6 Hz), 8.22 (1H, d, J = 2.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.43 (1H, d, J = 2.6 Hz), 10.51 (1H, s). 
               
               
                 709 
                 —Cl 
                 —Cl 
                 —CH 3   
                 —H 
                 benzyl 
                 2 
                 (CDCl 3 ) 1.18-1.26 (2H, m), 1.57 (3H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 brs), 1.58-1.74 (2H, m), 2.49-2.58 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 m), 3.83 (1H, d, J = 13.5 Hz), 4.08 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 s), 4.56 (1H, d, J = 13.5 Hz), 6.40 (1H, d, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 J = 8.9 Hz), 6.67 (2H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.98 (2H, d, J = 9.1 Hz), 7.12-7.32 (5H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 m), 7.56 (1H, d, J = 8.4 Hz), 7.71 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dd, J = 8.4 Hz, 2.1 Hz), 7.98 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 2.1 Hz), 8.03-8.10 (2H, m), 8.24 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 2.6 Hz). 
               
               
                 710 
                 —CF 3   
                 —H 
                 —C 2 H 5   
                 —H 
                 piperonyl 
                 2 
                 (CDCl 3 ) 1.12-1.17 (5H, m), 1.64- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 1.71 (3H, m), 2.48 (2H, d, J = 6.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 2.53-2.58 (1H, m), 2.94-3.03 (1H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 3.37 (2H, q, J = 7.1 Hz), 3.84-3.89 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 m), 4.01 (2H, s), 4.53-4.58 (1H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 5.93 (2H, s), 6.56-6.63 (4H, m), 6.73 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 d, J = 7.8 Hz), 6.82 (1H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.95 (2H, d, J = 9.1 Hz), 7.72 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.3 Hz), 7.99 (2H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.10 (1H, dd, J = 8.9 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.27 (1H, d, J = 2.6 Hz), 8.37 (1H, brs). 
               
               
                 711 
                 —Cl 
                 —Cl 
                 —CH 3   
                 —H 
                 piperonyl 
                 2 
                 (CDCl 3 ) 1.03-1.17 (2H, m), 1.64-1.74 
               
               
                   
                   
                   
                   
                   
                   
                   
                 (3H, m), 2.46-2.57 (3H, m), 2.97-3.04 
               
               
                   
                   
                   
                   
                   
                   
                   
                 (4H, m), 3.80-3.85 (1H, m), 4.07 (2H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 4.51-4.55 (1H, m), 5.92 (2H, s), 6.56 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.63 (4H, m), 6.73 (1H, d, J = 7.8 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.79 (1H, d, J = 8.9 Hz), 6.94 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.9 Hz), 7.52 (1H, d, J = 8.4 Hz), 7.71 
               
               
                   
                   
                   
                   
                   
                   
                   
                 (1H, dd, J = 8.4 Hz, 2.1 Hz), 7.98 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 d, J = 2.1 Hz), 8.04 (1H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.25 (1H, d, J = 2.3 Hz), 8.49 (1H, brs). 
               
               
                 712 
                 —CF 3   
                 —H 
                 —CH 3   
                 —H 
                 piperonyl 
                 2 
                 (CDCl 3 ) 1.09-1.17 (2H, m), 1.67- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 1.70 (3H, m), 2.47-2.52 (3H, m), 2.94- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 3.03 (4H, m), 3.80-3.85 (1H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 4.06 (2H, s), 4.50-4.55 (1H, m), 5.92 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 s), 6.55-6.65 (4H, m), 6.73 (1H, d, J = 7.9 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz), 6.81 (1H, d, J = 8.9 Hz), 6.95 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 d, J = 8.9 Hz), 7.70 (2H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.99 (2H, d, J = 8.1 Hz), 8.09 (1H, dd, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.9 Hz, 2.1 Hz), 8.26 (1H, d, J = 2.6 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz), 8.48 (1H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 199 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 654   
                 R 655   
                 R 656   
                   1 H NMR (solvent) δppm 
               
               
                   
               
               
                 713 
                 —OCH 3   
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 2.38-2.43 (4H, m), 2.95 (3H, s), 3.40 (2H, s), 3.47.-3.58 (4H, m), 3.63 (3H, s), 4.05 (2H, s), 4.24 (4H, s), 6.12 (1H, dd, J = 8.7 Hz, 2.6 Hz), 6.21 (1H, d, J = 2.6 Hz), 6.74-6.87 (5H, m), 7.44 (1H, d, J = 8.4 Hz), 7.69 (1H, dd, J = 8.4 Hz, 2.0 Hz), 7.96 (1H, d, J = 2.0 Hz), 8.02 (1H, dd, J = 8.9 Hz, 2.6 Hz), 8.19 (1H, d, J = 2.6 Hz), 9.00 (1H, s). 
               
               
                   
               
               
                 714 
                 —F 
                 —CH 3   
                 3-furylmethyl 
                 (DMSO-d 6 ) 2.32 (2H, brs), 2.41 (2H, brs), 
               
               
                   
                   
                   
                   
                 2.93 (3H, s), 3.37 (2H, s), 3.44 (4H, brs), 
               
               
                   
                   
                   
                   
                 4.29 (2H, s), 6.40-6.44 (2H, m), 6.56 (1H, 
               
               
                   
                   
                   
                   
                 dd, J = 14.5 Hz, 2.8 Hz), 7.01-7.08 (2H, 
               
               
                   
                   
                   
                   
                 m), 7.58 (1H, s), 7.62 (1H, s), 7.84 (1H, d, J = 
               
               
                   
                   
                   
                   
                 8.4 Hz), 7.94 (1H, dd, J = 8.4 Hz, 2.0 
               
               
                   
                   
                   
                   
                 Hz), 8.16 (1H, dd, J = 8.9 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                   
                 8.22 (1H, d, J = 2.0 Hz), 8.39 (1H, d, J = 
               
               
                   
                   
                   
                   
                 2.6 Hz), 10.53 (1H, s). 
               
               
                   
               
               
                 715 
                 —F 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (DMSO-d 6 ) 2.30 (2H, brs), 2.39 (2H, brs), 2.93 (3H, s), 3.38 (2H, s), 3.44 (4H, brs), 4.22 (4H, s), 4.28 (2H, s), 6.41 (1H, dd, J = 8.6 Hz, 2.2. Hz), 6.56 (1H, dd, J = 14.4 Hz, 2.8 Hz), 6.76-6.81 (3H, m), 7.01-7.08 (2H, m), 7.84 (1H, d, J = 8.4 Hz), 7.94 (1H, dd, J = 8.4 Hz, 2.0 Hz), 8.16 (1H, dd, J = 8.9 Hz, 2.8 Hz), 8.22 (1H, d, J = 2.0 Hz), 8.39 (1H, d, J = 2.5 Hz), 10.53 (1H, s). 
               
               
                   
               
               
                 716 
                 —H 
                 —CH 3   
                 3-furylmethyl 
                 (CDCl 3 ) 2.42 (4H, brs), 2.97 (3H, s), 
               
               
                   
                   
                   
                   
                 3.40 (2H, s), 3.50 (2H, brs), 3.61 (2H, brs), 
               
               
                   
                   
                   
                   
                 4.07 (2H, s), 6.38 (1H, d, J = 1.5 Hz), 
               
               
                   
                   
                   
                   
                 6.63 (2H, d, J = 9.1 Hz), 6.80 (1H, d, J = 
               
               
                   
                   
                   
                   
                 8.9 Hz), 6.95 (2H, d, J = 9.1 Hz), 7.34 (1H, 
               
               
                   
                   
                   
                   
                 s), 7.40 (1H, t, J = 1.5 Hz), 7.52 (1H, d, J = 
               
               
                   
                   
                   
                   
                 8.4 Hz), 7.70 (1H, dd, J = 8.4 Hz, 2.0 Hz), 
               
               
                   
                   
                   
                   
                 7.97 (1H, d, J = 2.0 Hz), 8.04 (1H, dd, J = 
               
               
                   
                   
                   
                   
                 8.9 Hz, 2.6 Hz), 8.24 (1H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                 8.42 (1H, s). 
               
               
                 717 
                 —OCH 3   
                 —CH 3   
                 3-furylmethyl 
                 (CDCl 3 ) 2.40-2.44 (4H, m), 2.96 (3H, s), 
               
               
                   
                   
                   
                   
                 3.39 (2H, s), 3.49-3.63 (4H, m), 3.63 (3H, s), 
               
               
                   
                   
                   
                   
                 4.06 (2H, s), 6.12 (1H, dd, J = 8.7 Hz, 2.6 
               
               
                   
                   
                   
                   
                 Hz) 6.22 (1H, d, J = 2.5 Hz), 6.38 (1H, s), 
               
               
                   
                   
                   
                   
                 6.76 (1H, d, J = 8.7 Hz), 6.86 (1H, d, J = 
               
               
                   
                   
                   
                   
                 8.7 Hz), 7.33-7.47 (3H, m), 7.69 (1H, dd, J = 
               
               
                   
                   
                   
                   
                 8.4 Hz, 2.0 Hz), 7.96-8.04 (2H, m), 
               
               
                   
                   
                   
                   
                 8.20 (1H, d, J = 2.3 Hz), 8.92 (1H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 200 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 657   
                 R 658   
                 R 659   
                 Property 
               
               
                   
               
               
                 718 
                 —CH 3   
                 —CH 3   
                 3-furylmethyl 
                 mp 116.5-118.0° C. 
               
               
                   
               
               
                 719 
                 —H 
                 —C 2 H 5   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 606(M +  + H) 
               
               
                   
               
               
                 720 
                 —H 
                 —C 2 H 5   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 645(M +  + H) 
               
               
                   
               
               
                 721 
                 —H 
                 —C 2 H 5   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (CDCl 3 ) δ 1.16 (3 H, t, J = 7.1 Hz), 3.04 (4 H, brs), 3.40 (2 H, q, J = 7.1 Hz), 3.66-3.76 (4 H, m), 4.07 (2 H, s), 5.91 (2 H, s), 6.36 (1 H, dd, J = 8.4 Hz, 2.5 Hz), 6.55 (1 H, d, J = 2.3 Hz), 6.66 (2 H, d, J = 9.1 Hz), 6.73 (1 H, d, J = 8.4 Hz), 6.83 (1 H, d, J = 8.9 Hz), 6.96 (2 H, d, J = 8.9 Hz), 7.54 (1 H, d, J = 8.4 Hz), 7.71 (1 H, dd, J = 8.4 Hz, 2.1 Hz), 7.98 (1 H, d, J = 2.1 Hz), 8.07 (1 H, dd, J = 8.9 Hz, 2.6 Hz), 8.22 (1 H, brs), 8.24 (1 H, d, J = 2.5 Hz). 
               
               
                   
               
               
                 722 
                 —H 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (CDCl 3 ) δ 3.00-3.03 (7 H, m), 3.64 (2 H, brs), 3.75 (2 H, brs), 4.12 (2 H, s), 5.91 (2 H, s), 6.36 (1 H, dd, J = 8.4 Hz, 2.5 Hz), 6.55 (1 H, d, J = 2.3 Hz), 6.68 (2 H, d, J = 9.1 Hz), 6.73 (1 H, d, J = 8.4 Hz), 6.83 (1 H, d, J = 8.9 Hz), 6.98 (2 H, d, J = 9.1 Hz), 7.54 (1 H, d, J = 8.4 Hz), 7.71 (1 H, dd, J = 8.4 Hz, 2.1 Hz), 7.98 (1 H, d, J = 2.1 Hz), 8.07 (1 H, dd, J = 8.9 Hz, 2.8 Hz), 8.22 (1 H, brs), 8.23 (1 H, d, J = 3.0 Hz). 
               
               
                   
               
               
                 723 
                 —H 
                 —C 2 H 5   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (DMSO-d 6 ) δ 1.11 (3 H, t, J = 7.1 Hz), 2.31 (2 H, brs), 2.38 (2 H, brs), 3.22-3.58 (8 H, m), 4.16 (2 H, s), 4.21 (4 H, s), 6.56 (2 H, d, J = 9.0 Hz), 6.71-6.85 (3 H, m), 6.90 (2 H, d, J = 9.0 Hz), 6.93 (1 H, d, J = 8.9 Hz), 7.83 (1 H, d, J = 8.4 Hz), 7.95 (1 H, dd, J = 8.4 Hz, 2.0 Hz), 8.12 (1 H, dd, J = 8.9 Hz, 2.6 Hz), 8.22 (1 H, d, J = 2.0 Hz), 8.43 (1 H, d, J = 2.6 Hz), 10.51 (1 H, s). 
               
               
                   
               
               
                 724 
                 —H 
                 —C 2 H 5   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (CDCl 3 ) δ 1.13 (3 H, t, J = 7.0 Hz, 2.10-2.25 (2 H, m), 2.42 (4 H, brs), 3.34 (2 H, q, J = 7.0 Hz), 3.42 (2 H, s), 3.50 (2 H, brs), 3.61 (2 H, brs), 4.01 (2 H, s), 4.11-4.31 (4 H, m), 6.59 (2 H, d, J = 9.2 Hz), 6.79 (1 H, d, J = 8.9 Hz), 6.82-6.98 (5 H, m), 7.51 (1 H, d, J = 8.4 Hz), 7.70 (1 H, dd, J = 8.4 Hz, 2.0 Hz), 7.98 (1 H, d, J = 2.8 Hz), 8.03 (1 H, dd, J = 8.9 Hz, 2.8 Hz), 8.24 (1 H, d, J = 2.8 Hz), 8.54 (1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 201 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 660   
                 R 661   
                 R 662   
                 mp (° C.) or  1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 725 
                 —CH 3   
                 —Ac 
                 piperonyl 
                 mp 216-217 
               
               
                 726 
                 —CH 3   
                 —Ac 
                 benzyl 
                   1 H NMR (DMSO-d 6 ) 1.82 (3 H, s), 2.09 (3 H, 
               
               
                   
                   
                   
                   
                 s), 2.28-2.36 (4 H, m), 3.35-3.50 (6 H, m), 
               
               
                   
                   
                   
                   
                 4.44 (2 H, s), 7.05-7.10 (2 H, m), 7.20-7.32 (7 H, 
               
               
                   
                   
                   
                   
                 m, 7.82 (1 H, d, J = 8.5 Hz), 7.92 (1 H, dd, J = 
               
               
                   
                   
                   
                   
                 1.9 Hz, 8.5 Hz), 8.15-8.20 (2 H, m), 8.42 (1 H, 
               
               
                   
                   
                   
                   
                 d, J = 2.5 Hz), 10.53 (1 H, s). 
               
               
                 727 
                 —H 
                 —C 2 H 5   
                 3-pyridyl 
                   1 H NMR (DMSO-d 6 ) 1.13 (3 H, t, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 3.21 (2 H, brs), 3.29 (2 H, brs), 3.37 (2 H, q, J = 
               
               
                   
                   
                   
                   
                 7.1 Hz), 3.51-3.78 (4 H, m), 4.26 (2 H, s), 
               
               
                   
                   
                   
                   
                 6.60 (2 H, d, J = 9.0 Hz), 6.92 (2 H, d, J = 9.0 
               
               
                   
                   
                   
                   
                 Hz), 6.94 (1 H, d, J = 8.9 Hz), 7.23 (1 H, dd, J = 
               
               
                   
                   
                   
                   
                 8.5 Hz, 4.6 Hz), 7.36 (1 H, dd, J = 8.5 Hz, 
               
               
                   
                   
                   
                   
                 1.6 Hz), 7.83 (1 H, d, J = 8.5 Hz), 7.94 (1 H, 
               
               
                   
                   
                   
                   
                 dd, J = 8.5 Hz, 2.0 Hz), 8.03 (1 H, d, J = 4.6 
               
               
                   
                   
                   
                   
                 Hz), 8.12 (1 H, dd, J = 8.9 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                   
                 8.22 (1 H, d, J = 2.0 Hz), 8.34 (1 H, d, J = 2.8 
               
               
                   
                   
                   
                   
                 Hz), 8.43 (1 H, d, J = 2.8 Hz), 10.51 (1 H, s). 
               
               
                 728 
                 —F 
                 —C 2 H 5   
                 piperonyl 
                 mp 149-151 
               
               
                 729 
                 —F 
                 —CH 3   
                 piperonyl 
                 mp 199-201 
               
               
                 730 
                 —F 
                 —Ac 
                 piperonyl 
                 mp 233-235 
               
               
                 731 
                 —OCH 3   
                 —CH 3   
                 piperonyl 
                   1 H NMR (CDCl 3 ) 2.41-2.43 (4 H, m), 
               
               
                   
                   
                   
                   
                 3.02 (3 H, s), 3.42 (2 H, s), 3.49-3.62 (4 H, m), 
               
               
                   
                   
                   
                   
                 3.72 (3 H, s), 4.08 (2 H, s), 5.95 (2 H, s), 
               
               
                   
                   
                   
                   
                 6.21 (1 H, dd, J = 8.7 Hz, 2.6 Hz), 6.32 (1 H, d, 
               
               
                   
                   
                   
                   
                 J = 2.8 Hz), 6.73-6.77 (2 H, m), 6.84 (2 H, t, J = 
               
               
                   
                   
                   
                   
                 4.5 Hz), 6.95 (1 H, d, J = 8.7 Hz), 7.54 (1 H, 
               
               
                   
                   
                   
                   
                 d, J = 8.4 Hz), 7.70 (1 H, dd, J = 8.2 Hz, 2.0 
               
               
                   
                   
                   
                   
                 Hz), 7.97 (2 H, d, J = 2.0 Hz), 8.05-8.09 (1 H, 
               
               
                   
                   
                   
                   
                 m), 8.19 (1 H, d, J = 2.5 Hz). 
               
               
                 732 
                 —H 
                 —CH 3   
                 3-pyridylmetyl 
                   1 H NMR (CDCl 3 ) 2.40-2.42 (4 H, m), 
               
               
                   
                   
                   
                   
                 2.93 (3 H, s), 3.44 (2 H, s), 3.48-3.58 (4 H, m), 
               
               
                   
                   
                   
                   
                 4.06 (2 H, s), 6.58 (2 H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                   
                 6.74 (1 H, d, J = 8.9 Hz), 6.90 (2 H, d, J = 9.1 
               
               
                   
                   
                   
                   
                 Hz), 7.25-7.30 (1 H, m), 7.43 (1 H, d, J = 8.4 
               
               
                   
                   
                   
                   
                 Hz), 7.66-7.73 (2 H, m), 7.97 (1 H, d, J = 2.0 
               
               
                   
                   
                   
                   
                 Hz), 8.03 (1 H, dd, J = 8.9 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                   
                 8.25 (1 H, d, J = 2.5 Hz), 8.47-8.51 (2 H, m), 
               
               
                   
                   
                   
                   
                 9.59 (1 H, s). 
               
               
                   
               
               
                 733 
                 —H 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (DMSO-d 6 ) 2.96 (3 H, s), 3.07-3.15 (4 H, m), 3.59 (4 H, brs), 3.83 (2 H, s), 4.31 (2 H, s), 6.66 (2 H, d, J = 9.1 Hz), 6.88-6.95 (5 H, m, 7.05-7.13 (4 H, m), 7.20-7.24 (2 H, m), 7.83 (1 H, d, J = 8.4 Hz), 7.95 (1 H, dd, J = 8.4 Hz, 2.0 Hz), 8.12 (1 H, dd, J = 8.9 Hz, 2.8 Hz), 8.22 (1 H, d, J = 2.0 Hz), 8.43 (1 H, d, J = 2.5 Hz), 10.50 (1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 202 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 663   
                 R 664   
                 MS or  1 H NMR 
               
               
                   
               
               
                 734 
                 —H 
                 —CHPh 2   
                 MS 694(M +  + H) 
               
               
                 735 
                 —H 
                 3-CH 3 OPh- 
                 MS 634(M +  + H) 
               
               
                 736 
                 —H 
                 4-CH 3 OPh- 
                 MS 634(M +  + H) 
               
               
                 737 
                 —H 
                 3,4- (CH 3 ) 2 Ph- 
                 MS 632(M +  + H) 
               
               
                 738 
                 —H 
                 2,3-Cl 2 Ph- 
                 MS 673(M +  + H) 
               
               
                 739 
                 —H 
                 2,4-F 2 Ph- 
                 MS 640(M +  + H) 
               
               
                 740 
                 —H 
                 2-CH 3 OPh- 
                 MS 634(M +  + H) 
               
               
                 741 
                 —H 
                 3-CF 3 Ph- 
                 MS 671(M +  + H) 
               
               
                 742 
                 —H 
                 2-ClPh- 
                 MS 639(M +  + H) 
               
               
                 743 
                 —H 
                 4-CF 3 Ph- 
                 MS 671(M +  + H) 
               
               
                 744 
                 —H 
                 -Ph 
                 MS 604(M +  + H) 
               
               
                 745 
                 —H 
                 2-pyridylmethyl 
                 MS 619(M +  + H) 
               
               
                 746 
                 —H 
                 2-pyridyl 
                 MS 605(M +  + H) 
               
               
                 747 
                 —H 
                 —(CH 2 ) 3 Ph 
                 MS 646(M +  + H) 
               
               
                 748 
                 —H 
                 —(CH 2 ) 4 Ph 
                 MS 660(M +  + H) 
               
               
                 749 
                 —H 
                 —(CH 2 ) 2 N (CH 3 ) 2   
                 MS 599(M +  + H) 
               
               
                 750 
                 —H 
                 cyclopentyl 
                 MS 596(M +  + H) 
               
               
                   
               
               
                 751 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 625(M +  + H) 
               
               
                   
               
               
                 752 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 641(M +  + H) 
               
               
                   
               
               
                 753 
                 —H 
                 —CH (CH 3 )Ph 
                 MS 634(M +  + H) 
               
               
                 754 
                 —H 
                 —(CH 2 ) 2 Ph 
                 MS 632(M +  + H) 
               
               
                 755 
                 —H 
                 —CH 2 CONHPh 
                 MS 661(M +  + H) 
               
               
                 756 
                 —H 
                 —(CH 2 ) 3 N (CH 3 ) 2   
                 MS 613(M +  + H) 
               
               
                   
               
               
                 757 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 639(M +  + H) 
               
               
                   
               
               
                 758 
                 —H 
                 —CH 3   
                 MS 542(M +  + H) 
               
               
                 759 
                 —OCH 3   
                 —H 
                   1 H NMR (CDCl 3 ) δ 1.26 (3 H, t, J = 6.9 Hz), 
               
               
                   
                   
                   
                 2.70 (1 H, brs), 2.82-2.87 (4 H, m), 3.33 (2 H, 
               
               
                   
                   
                   
                 q, J = 6.9 Hz), 3.49-3.57 (4 H, m), 3.62 (3 H, 
               
               
                   
                   
                   
                 s), 4.00 (2 H, s), 6.09 (1 H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                 6.20 (1 H, s), 6.73 (1 H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                 6.83 (1 H, d, J = 8.6 Hz), 7.42 (1 H, d, J = 8.3 
               
               
                   
                   
                   
                 Hz), 7.70 (1 H, d, J = 7.4 Hz), 7.97-8.03 (2 H, 
               
               
                   
                   
                   
                 m), 8.23 (1 H, s), 9.26 (1 H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 203 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 665    
                 R 666   
                 Form 
                   1 H NMR (DMSO-d 6 ) δ ppm 
               
               
                   
               
               
                 760 
                 —Ac 
                 piperonyl 
                 hydro- 
                 1.84 (3 H, s), 2.83-3.14 (2 H, m), 3.23-3.32 (2 H, 
               
               
                   
                   
                   
                 chloride 
                 m), 4.02 (1 H, d, J = 13.6 Hz), 4.18-4.27 (2 H, 
               
               
                   
                   
                   
                   
                 m), 4.40 (1 H, d, J = 13.6 Hz), 4.50-4.60 (2 H, 
               
               
                   
                   
                   
                   
                 m), 6.07 (2 H, s), 6.96-7.03 (2 H, m), 
               
               
                   
                   
                   
                   
                 7.10-7.25 (4 H, m), 7.43 (2 H, d, J = 8.8 Hz), 
               
               
                   
                   
                   
                   
                 7.85 (1 H, d, J = 8.4 Hz), 7.98 (1 H, dd, J = 2.0 
               
               
                   
                   
                   
                   
                 Hz, 8.4 Hz), 8.24 (1 H, dd, J = 2.6 Hz, 8.9 Hz), 
               
               
                   
                   
                   
                   
                 8.26 (1 H, d, J = 2.0 Hz), 8.54 (1 H, d, J = 2.6 
               
               
                   
                   
                   
                   
                 Hz), 10.69 (1 H, s), 11.07 (1 H, brs). 
               
               
                 761 
                 —Ac 
                 benzyl 
                 hydro- 
                 1.84 (3 H, s), 2.90-3.17 (2 H, m), 3.23-3.35 (2 H, 
               
               
                   
                   
                   
                 chloride 
                 m), 4.03 (1 H, d, J = 14.4 Hz), 4.28-4.43 (3 H, 
               
               
                   
                   
                   
                   
                 m), 4.50-4.62 (2 H, m), 7.13 (1 H, d, J = 8.8 Hz), 
               
               
                   
                   
                   
                   
                 7.17 (2 H, d, J = 8.8 Hz), 7.40-7.50 (5 H, m), 
               
               
                   
                   
                   
                   
                 7.58-7.62 (2 H, m), 7.85 (1 H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                 8.00 (1 H, dd, J = 2.0 Hz, 8.4 Hz), 
               
               
                   
                   
                   
                   
                 8.20-8.29 (2 H, m), 8.54 (1 H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                 10.70 (1 H, s), 11.21 (1 H, brs). 
               
               
                 762 
                 —C 2 H 5   
                 3-furylmethyl 
                 trihydro- 
                 1.11 (3 H, t, J = 7.1 Hz), 2.75-3.30 (3 H, m), 
               
               
                   
                   
                   
                 chloride 
                 3.30-3.50 (2 H, m), 3.40 (2 H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 3.51-3.72 (1 H, m), 3.95-4.15 (1 H, m), 4.22 (2 H, 
               
               
                   
                   
                   
                   
                 s), 4.30-4.62 (3 H, m), 6.80-6.85 (1 H, m), 
               
               
                   
                   
                   
                   
                 6.89 (2 H, d, J = 8.9 Hz), 7.00 (1 H, d, J = 8.9 
               
               
                   
                   
                   
                   
                 Hz), 7.0 1 (2 H, d, J = 8.9 Hz), 7.70-7.80 (1 H, 
               
               
                   
                   
                   
                   
                 m), 7.84 (1 H, d, J = 8.5 Hz), 7.88 (1 H, s), 
               
               
                   
                   
                   
                   
                 7.99 (1 H, dd, J = 8.5 Hz, 2.0 Hz), 8.19 (1 H, dd, 
               
               
                   
                   
                   
                   
                 J = 8.9 Hz, 2.7 Hz), 8.27 (1 H, d, J = 2.0 Hz), 
               
               
                   
                   
                   
                   
                 8.50 (1 H, d, J = 2.7 Hz), 10.69 (1 H, s). 
               
               
                 763 
                 —C 2 H 5   
                 4-pyridylmethyl 
                 tetrahydro- 
                 1.11 (3 H, t, J = 7.0 Hz), 3.00-3.60 (6 H, m), 
               
               
                   
                   
                   
                 chloride 
                 3.41 (2 H, q, J = 7.0 Hz), 3.90 (2 H, brs), 
               
               
                   
                   
                   
                   
                 4.42 (2 H, brs), 4.63 (2 H, brs), 6.82 (2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.8 Hz), 6.98 (3 H, d, J = 8.8 Hz), 7.84 (1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.4 Hz), 7.98 (1 H, dd, J = 8.4 Hz, 2.0 Hz), 
               
               
                   
                   
                   
                   
                 8.17 (1 H, dd, J = 8.9 Hz, 2.6 Hz), 8.22-8.39 (3 
               
               
                   
                   
                   
                   
                 H, m), 8.49 (1 H, d, J = 2.5 Hz), 8.99 (2 H, 
               
               
                   
                   
                   
                   
                 d, J = 6.2 Hz), 10.67 (1 H, s). 
               
               
                   
               
               
                 764 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 dihydro- chloride 
                 2.94 (3 H, s), 2.80-3.22 (3 H, m), 3.22-3.70 (3 H, m), 3.95-4.60 (6 H, m), 6.68 (2 H, d, J = 9.1 Hz), 6.92 (2 H, d, J = 9.1 Hz), 6.95 (1 H, d, J = 8.9 Hz), 7.79 (1 H, dd, J = 8.4 Hz, 1.6 Hz), 7.84 (1 H, d, J = 8.4 Hz), 7.96 (1 H, dd, J = 8.4 Hz, 2.0 Hz), 8.14 (1 H, dd, J = 8.9 Hz, 2.3 Hz), 8.20 (1 H, d, J = 8.4 Hz), 8.24 (1 H, d, J = 2.0 Hz), 8.40 (1 H, d, J = 1.6 Hz), 8.44 (1 H, d, J = 2.3 Hz), 9.51 (1 H, s), 10.57 (1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 204 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 667   
                 R 668   
                 R 669   
                 R 670   
                 R 671   
                 mp (° C.) or  1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 765 
                 —Cl 
                 —Cl 
                 —H 
                 —CH 3   
                 piperonyl 
                 mp 198-200 
               
               
                 766 
                 —Cl 
                 —Cl 
                 —H 
                 —C 2 H 5   
                 benzyl 
                   1 H NMR (DMSO-d 6 ) 1.12 (3 H, t, J = 
               
               
                   
                   
                   
                   
                   
                   
                 7.1 Hz), 2.98 (4 H, brs), 3.34 (2 H, q, J = 
               
               
                   
                   
                   
                   
                   
                   
                 7.1 Hz), 3.20-3.50 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 3.67 (2 H, brs), 4.10 (2 H, brs), 
               
               
                   
                   
                   
                   
                   
                   
                 4.23 (2 H, s), 6.11 (2 H, s), 6.59 (2 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 9.2 Hz), 6.91 (2 H, d, J = 9.2 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 6.94 (1 H, d, J = 8.9 Hz), 7.45 (5 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 7.84 (1 H, d, J = 8.4 Hz), 7.94 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 dd, J = 8.4 Hz, 2.6 Hz), 8.12 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 dd, J = 8.9 Hz, 2.6 Hz), 8.22 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 2.0 Hz), 8.43 (1 H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 10.51 (1 H, s). 
               
               
                   
               
               
                 767 
                 —Cl 
                 —Cl 
                 —H 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (DMSO-d 6 ) 2.94 (3 H, s), 3.05 (4 H, brs), 3.40 (2 H, brs), 3.63 (2 H, brs), 4.04 (2 H, brs), 4.26 (4 H, s), 4.31 (2 H, brs), 6.09 (2 H, s), 6.65 (2 H, d, J = 9.1 Hz), 6.82-7.06 (6 H, m), 7.84 (1 H, d, J = 8.4 Hz), 7.94 (1 H, dd, J = 8.4 Hz, 2.0 Hz), 8.12 (1 H, dd, J = 8.8 Hz, 2.5 Hz), 8.22 (1 H, d, J = 2.0 Hz), 8.43 (1 H, d, J = 2.5 Hz), 10.51 (1 H, s). 
               
               
                   
               
               
                 768 
                 —Cl 
                 —Cl 
                 —OCH 3   
                 —C 2 H 5   
                 piperonyl 
                 mp 172-177 
               
               
                 769 
                 —CF 3   
                 —H 
                 —H 
                 —C 2 H 5   
                 benzyl 
                   1 H NMR (CDCl 3  + CD 3 OD) 1.13 (3 H, 
               
               
                   
                   
                   
                   
                   
                   
                 t, J = 6.9 Hz), 3.08 (4 H, brs), 
               
               
                   
                   
                   
                   
                   
                   
                 3.36 (2 H, q, J = 6.9 Hz), 3.85 (4 H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs), 4.09 (2 H, s), 4.18 (2 H, s), 6.31 
               
               
                   
                   
                   
                   
                   
                   
                 (2 H, s), 6.73 (2 H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 6.87 (1 H, d, J = 9.2 Hz), 6.98 (2 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.9 Hz), 7.40-7.44 (5 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.73 (2 H, d, J = 8.4 Hz), 8.07 (2 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.3 Hz), 8.27 (2 H, d, J = 7.4 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 9.63 (1 H, s). 
               
               
                   
               
               
                 770 
                 —CF 3   
                 —H 
                 —H 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (DMSO-d 6 ) 2.94 (3 H, s), 2.95 (4 H, brs), 3.33 (4 H, brs), 4.03 (2 H, brs), 4.26 (4 H, s), 4.31 (2 H, brs), 6.09 (2 H, s), 6.65 (2 H, d, J = 9.2 Hz), 6.85-7.03 (6 H, m, 7.93 (2 H, d, J = 8.2 Hz), 8.14 (1 H, dd, J = 8.9 Hz, 2.5 Hz), 8.16 (2 H, d, J = 8.2 Hz), 8.45 (1 H, d, J = 2.5 Hz), 10.59 (1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 205 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 672   
                 R 673   
                 R 674   
                 mp (° C.) or  1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 771 
                 —H 
                 —Ac 
                 benzyl 
                 mp 161-162 
               
               
                 772 
                 —CH 3   
                 —Ac 
                 piperonyl 
                   1 H NMR (DMSO-d 6 ) 1.82 (3 H, s), 2.10 (3 H, s), 
               
               
                   
                   
                   
                   
                 2.23-2.36 (4 H, m), 3.33-3.45 (6 H, m), 4.44 (2 H, 
               
               
                   
                   
                   
                   
                 s), 5.96 (2 H, s), 6.72 (1 H, d, J = 8.0 Hz), 
               
               
                   
                   
                   
                   
                 6.82 (1 H, d, J = 8.0 Hz), 6.84 (1 H, s), 7.02-7.10 (2 
               
               
                   
                   
                   
                   
                 H, m), 7.23 (1 H, d, J = 8.6 Hz), 7.33 (1 H, 
               
               
                   
                   
                   
                   
                 s), 7.91 (2 H, d, J = 8.4 Hz), 8.14 (2 H, d, J = 8.4 
               
               
                   
                   
                   
                   
                 Hz), 8.20 (1 H, d, J = 8.6 Hz), 8.45 (1 H, s), 
               
               
                   
                   
                   
                   
                 10.60 (1 H, s). 
               
               
                 773 
                 —CH 3   
                 —Ac 
                 benzyl 
                   1 H NMR (DMSO-d 6 ) 1.82 (3 H, s), 2.10 (3 H, s), 
               
               
                   
                   
                   
                   
                 2.30-2.37 (4 H, m), 3.35-3.45 (4 H, m), 3.47 (2 H, 
               
               
                   
                   
                   
                   
                 s), 4.44 (2 H, s), 7.03-7.10 (2 H, m), 7.20-7.35 (7 
               
               
                   
                   
                   
                   
                 H, m), 7.91 (2 H, d, J = 8.4 Hz), 8.14 (2 H, 
               
               
                   
                   
                   
                   
                 d, J = 8.4 Hz), 8.21 (1 H, dd, J = 2.5 Hz, 8.9 
               
               
                   
                   
                   
                   
                 Hz), 8.45 (1 H, d, J = 2.5 Hz), 10.60 (1 H, s). 
               
               
                 774 
                 —H 
                 —C 2 H 5   
                 piperonyl 
                 mp 178-180 
               
               
                 775 
                 —F 
                 —C 2 H 5   
                 piperonyl 
                 mp 170-172 
               
               
                 776 
                 —F 
                 —CH 3   
                 piperonyl 
                 mp 220-221 
               
               
                 777 
                 —OCH 3   
                 —CH 3   
                 piperonyl 
                   1 H NMR (CDCl 3 ) 2.38-2.42 (4 H, m), 2.96 (3 H, 
               
               
                   
                   
                   
                   
                 s), 3.41 (2 H, s), 3.47-3.58 (4 H, m), 3.64 (3 H, s), 
               
               
                   
                   
                   
                   
                 4.05 (2 H, s), 5.94 (2 H, s), 6.13 (1 H, dd, J = 8.9 
               
               
                   
                   
                   
                   
                 Hz, 2.8 Hz), 6.24 (1 H, d, J = 2.8 Hz), 6.70-6.89 (5 
               
               
                   
                   
                   
                   
                 H, m), 7.64 (2 H, d, J = 8.3 Hz), 7.96 (2 H, 
               
               
                   
                   
                   
                   
                 d, J = 8.1 Hz), 8.06 (1 H, dd, J = 8.9 Hz, 2.6 
               
               
                   
                   
                   
                   
                 Hz), 8.20 (1 H, d, J = 2.6 Hz), 8.93 (1 H, s). 
               
               
                   
               
               
                 778 
                 —OCH 3   
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (CDCl 3 ) 2.38-2.42 (4 H, m), 2.96 (3 H, s), 3.40 (2 H, s), 3.47-3.57 (4 H, m), 3.98 (3 H, s), 4.05 (2 H, s), 4.24 (4 H, s), 6.13 (1 H, dd, J = 8.9 Hz, 2.8 Hz), 6.23 (1 H, d, J = 2.6 Hz), 6.73-6.88 (5 H, m), 7.63 (2 H, d, J = 8.3 Hz), 7.97 (2 H, d, J = 8.1 Hz), 8.07 (1 H, dd, J = 8.9 Hz, 2.6 Hz), 8.20 (1 H, d, J = 2.5 Hz), 9.11 (1 H, s). 
               
               
                   
               
               
                 779 
                 —F 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (DMSO-d 6 ) 2.30 (2 H, brs), 2.39 (2 H, brs), 2.93 (3 H, s), 3.38 (2 H, s), 3.44 (4 H, brs), 4.22 (4 H, s), 4.28 (2 H, s), 6.40-6.43 (1 H, m), 6.56 (1 H, dd, J = 14.2 Hz, 2.6 Hz), 6.73-6.81 (3 H, m), 7.02-7.08 (2 H, m), 7.93 (2 H, d, J = 8.6 Hz), 8.14-8.21 (3 H, m), 8.49 (1 H, d, J = 2.6 Hz), 10.61 (1 H, s). 
               
               
                   
               
               
                 780 
                 —F 
                 —CH 3   
                 3-furylmethyl 
                   1 H NMR (DMSO-d 6 ) 2.32 (2 H, s), 2.41 (2 H, s), 
               
               
                   
                   
                   
                   
                 2.93 (3 H, s), 3.37 (2 H, s), 3.44 (4 H, brs), 
               
               
                   
                   
                   
                   
                 4.29 (2 H, s), 6.40-6.44 (2 H, m), 6.55 (1 H, dd, J = 
               
               
                   
                   
                   
                   
                 14.5 Hz, 2.8 Hz), 7.02-7.08 (2 H, m), 7.58-7.62 (2 
               
               
                   
                   
                   
                   
                 H, m), 7.93 (2 H, d, J = 8.4 Hz), 8.14-8.21 (3 
               
               
                   
                   
                   
                   
                 H, m), 8.41 (1 H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                 10.61 (1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 206 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 675   
                 R 676   
                 R 677   
                 mp (° C.) or  1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 781 
                 —OCH 3   
                 —C 2 H 5   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (CDCl 3 ) 1.16 (3 H, t, J = 6.9 Hz), 2.38-2.43 (4 H, m), 3.33-3.62 (8 H, m), 3.66 (3 H, s), 4.02 (2 H, s), 4.26 (4 H, s), 6.14 (1 H, dd, J = 8.7 Hz, 2.6 Hz), 6.25 (1 H, d, J = 2.6 Hz), 6.75-6.90 (5 H, m), 7.66 (2 H, d, J = 8.3 Hz), 8.01 (2 H, d, J = 8.3 Hz), 8.09 (1 H, dd, J = 9.1 Hz, 2.8 Hz), 8.26 (1 H, d, J = 2.6 Hz), 9.19 (1 H, s). 
               
               
                   
               
               
                 782 
                 —F 
                 —Ac 
                 piperonyl 
                   1 H NMR (DMSO-d 6 ) 1.88 (3 H, s), 2.33 (4 H, brs), 
               
               
                   
                   
                   
                   
                 3.40 (2 H, s), 3.40 (4 H, brs), 4.50 (2 H, s), 
               
               
                   
                   
                   
                   
                 5.99 (2 H, s), 6.73-6.76 (1 H, m), 6.83-6.86 (2 H, 
               
               
                   
                   
                   
                   
                 m), 7.21 (1 H, d, J = 8.9 Hz), 7.32-7.49 (3 H, m), 
               
               
                   
                   
                   
                   
                 7.94 (2 H, d, J = 8.3 Hz), 8.16 (2 H, d, J = 8.1 
               
               
                   
                   
                   
                   
                 Hz), 8.25 (1 H, dd, J = 8.9 Hz, 2.6 Hz), 8.46 (1 H, 
               
               
                   
                   
                   
                   
                 d, J = 2.6 Hz), 10.66 (1 H, s). 
               
               
                 783 
                 —H 
                 —CH 3   
                 3-furylmethyl 
                   1 H NMR (CDCl 3 ) 2.44 (4 H, brs), 2.99 (3 H, s), 
               
               
                   
                   
                   
                   
                 3.40 (2 H, s), 3.50 (2 H, t, J = 4.9 Hz), 3.62 (2 H, 
               
               
                   
                   
                   
                   
                 t, J = 4.9 Hz), 4.07 (2 H, s), 6.38 (1 H, d, J = 1.0 
               
               
                   
                   
                   
                   
                 Hz), 6.67 (2 H, d, J = 9.1 Hz), 6.84 (1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.8 Hz), 6.98 (2 H, d, J = 9.1 Hz), 7.34 (1 H, s), 
               
               
                   
                   
                   
                   
                 7.40 (1 H, t, J = 1.6 Hz), 7.73 (2 H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                 7.99 (2 H, d, J = 8.2 Hz), 8.11 (1 H, dd, J = 8.8 
               
               
                   
                   
                   
                   
                 Hz, 2.6 Hz), 8.24 (1 H, s), 8.25 (1 H, d, J = 2.6 
               
               
                   
                   
                   
                   
                 Hz). 
               
               
                 784 
                 —OCH 3   
                 —C 2 H 5   
                 3-furylmethyl 
                 mp 174-176 
               
               
                 785 
                 —OCH 3   
                 —CH 3   
                 3-furylmethyl 
                 mp 160-164 
               
               
                 786 
                 —CH 3   
                 —CH 3   
                 —COOC (CH 3 ) 3   
                   1 H NMR (CDCl 3 ) 1.47 (9 H, s), 2.12 (3 H, s), 
               
               
                   
                   
                   
                   
                 3.01 (3 H, s), 3.30-3.71 (8 H, m), 4.09 (2 H, s), 
               
               
                   
                   
                   
                   
                 6.44-6.66 (2 H, m), 6.83 (1 H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                 6.93 (1 H, d, J = 8.4 Hz), 7.75 (2 H, d, J = 8.1 
               
               
                   
                   
                   
                   
                 Hz), 7.94 (1 H, s), 7.99 (2 H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                 8.15 (1 H, d, J = 9.2 Hz), 8.22 (1 H, s). 
               
               
                   
               
               
                 787 
                 —H 
                 —C 2 H 5   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (CDCl 3 ) 1.18 (3 H, t, J = 7.1 Hz), 3.03 (4 H, brs), 3.43 (2 H, q, J = 7.1 Hz), 3.67-3.77 (4 H, m), 4.08 (2 H, s), 5.91 (2 H, s), 6.36 (1 H, dd, J = 8.4 Hz, 2.3 Hz), 6.55 (1 H, d, J = 2.5 Hz), 6.68-6.75 (3 H, m), 6.87 (1 H, d, J = 8.7 Hz), 7.00 (2 H, d, J = 8.9 Hz), 7.75 (2 H, d, J = 8.4 Hz), 7.98 (1 H, brs), 7.99 (2 H, d, J = 8.3 Hz), 8.13 (1 H, dd, J = 8.7 Hz, 2.6 Hz), 8.25 (1 H, d, J = 2.6 Hz) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 207 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 678   
                 R 679   
                 R 680   
                 Form 
                 mp (° C.) or  1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 788 
                 —F 
                 —(CH 2 ) 2 CH 3   
                 piperonyl 
                 free 
                   1 H NMR (CDCl 3 ) 0.94 (3 H, t, J = 7.3 
               
               
                   
                   
                   
                   
                   
                 Hz), 1.58-1.69 (2 H, m), 2.45 (4 H, 
               
               
                   
                   
                   
                   
                   
                 brs), 3.29 (2 H, t, J = 7.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 3.45 (2 H, s), 3.49 (2 H, brs), 3.64 (2 H, 
               
               
                   
                   
                   
                   
                   
                 brs), 4.05 (2 H, s), 5.95 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                 6.34-6.44 (2 H, m), 6.75 (2 H, s), 6.86 (1 H, 
               
               
                   
                   
                   
                   
                   
                 s), 6.96 (1 H, d, J = 8.9 Hz), 7.03 (1 H, 
               
               
                   
                   
                   
                   
                   
                 t, J = 9.1 Hz), 7.76 (2 H, d, J = 8.2 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.86 (1 H, brs), 8.00 (2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.1 Hz), 8.16-8.22 (2 H, m). 
               
               
                   
               
               
                 789 
                 —H 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                   1 H NMR (CDCl 3 ) 3.02 (7 H, brs), 3.64 (2 H, brs), 3.75 (2 H, brs), 4.12 (2 H, s), 5.91 (2 H, s), 6.36 (1 H, dd, J = 8.4 Hz, 2.5 Hz), 6.55 (1 H, d, J = 2.5 Hz), 6.70 (2 H, d, J = 9.1 Hz), 6.73 (1 H, d, J = 8.3 Hz), 6.85 (1 H, d, J = 8.9 Hz), 6.99 (2 H, d, J = 9.2 Hz), 7.73 (2 H, d, J = 8.3 Hz), 7.98 (2 H, d, J = 8.3 Hz), 8.12 (1 H, dd, J = 9.1 Hz, 2.8 Hz), 8.15 (1 H, brs), 8.24 (1 H, d, J = 2.5 Hz). 
               
               
                   
               
               
                 790 
                 —OCH 3   
                 —CH 3   
                 4- (4-FPhCO)Ph- 
                 free 
                   1 H NMR (CDCl 3 ) 3.03 (3 H, s), 
               
               
                   
                   
                   
                   
                   
                 3.39 (4 H, brs), 3.70 (3 H, s), 3.71-3.79 (4 
               
               
                   
                   
                   
                   
                   
                 H, m), 4.14 (2 H, s), 6.23 (1 H, 
               
               
                   
                   
                   
                   
                   
                 dd, J = 8.9 Hz, 2.8 Hz), 6.36 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 2.6 Hz), 6.81-6.96 (4 H, m), 
               
               
                   
                   
                   
                   
                   
                 7.09-7.17 (2 H, m), 7.68 (2 H, d, J = 8.4 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.72-7.78 (4 H, m), 7.99 (2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.3 Hz), 8.09 (1 H, dd, J = 8.9 Hz, 
               
               
                   
                   
                   
                   
                   
                 2.8 Hz), 8.21 (1 H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.53 (1 H, s). 
               
               
                 791 
                 —OCH 3   
                 —C 2 H 5   
                 4- (4-FPhCO)Ph- 
                 free 
                   1 H NMR (CDCl 3 ) 1.17 (3 H, t, J = 6.9 
               
               
                   
                   
                   
                   
                   
                 Hz), 3.37-3.42 (6 H, m), 3.67 (3 H, s), 
               
               
                   
                   
                   
                   
                   
                 3.71-3.76 (4 H, m), 4.08 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                 6.19 (1 H, dd, J = 8.9 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.33 (1 H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.77-6.92 (4 H, m), 7.09-7.15 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                 7.64 (2 H, d, J = 8.3 Hz), 7.71-7.77 (4 
               
               
                   
                   
                   
                   
                   
                 H, m), 7.98 (2 H, d, J = 8.1 
               
               
                   
                   
                   
                   
                   
                 Hz), 8.07 (1 H, dd, J = 8.9 Hz, 2.6 
               
               
                   
                   
                   
                   
                   
                 Hz), 8.23 (1 H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.83 (1 H, s). 
               
               
                 792 
                 —CH 3   
                 —CH 3   
                 3-furylmethyl 
                 hydro- 
                 mp 158.5-161.0 
               
               
                   
                   
                   
                   
                 chloride 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 208 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 681   
                 R 682   
                 R 683   
                   1 H NMR (DMSO-d 6 ) δ ppm 
               
               
                   
               
               
                 793 
                 —Cl 
                 —Cl 
                 piperonyl 
                 1.74 (3 H, s), 2.19-2.34 (4 H, m), 2.54 (2 H, t, J = 7.7 
               
               
                   
                   
                   
                   
                 Hz), 3.32-3.46 (6 H, m), 3.76 (2 H, t, J = 7.7 Hz), 
               
               
                   
                   
                   
                   
                 5.96 (2 H, s), 6.72 (1 H, d, J = 7.9 Hz), 6.77-6.85 (2 H, 
               
               
                   
                   
                   
                   
                 m), 7.11 (1 H, d, J = 8.8 Hz), 7.17 (2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                 7.31 (2 H, d, J = 8.6 Hz), 7.83 (1 H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                 7.93 (1 H, dd, J = 8.4 Hz, 2.1 Hz), 8.17-8.25 (2 H, m, 
               
               
                   
                   
                   
                   
                 8.51 (1 H, d, J = 2.4 Hz), 10.57 (1 H, s). 
               
               
                 794 
                 —Cl 
                 —Cl 
                 benzyl 
                 1.74 (3 H, s), 2.25-2.37 (4 H, m), 2.54 (2 H, t, J = 7.7 
               
               
                   
                   
                   
                   
                 Hz), 3.36-3.42 (4 H, m), 3.46 (2 H, s), 3.76 (2 H, t, J = 
               
               
                   
                   
                   
                   
                 7.7 Hz), 7.11 (1 H, d, J = 8.8 Hz), 7.16 (2 H, d, J = 8.6 
               
               
                   
                   
                   
                   
                 Hz), 7.20-7.31 (5 H, m), 7.34 (2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                 7.83 (1 H, d, J = 8.4 Hz), 7.93 (1 H, dd, J = 8.4 Hz, 2.1 
               
               
                   
                   
                   
                   
                 Hz), 8.19-8.25 (2 H, m), 8.51 (1 H, d, J = 2.5 Hz), 
               
               
                   
                   
                   
                   
                 10.57 (1 H, s). 
               
               
                 795 
                 —CF 3   
                 —H 
                 piperonyl 
                 1.74 (3 H, s), 2.20-2.35 (4 H, m), 2.54 (2 H, t, J = 7.7 
               
               
                   
                   
                   
                   
                 Hz), 3.34-3.42 (6 H, m), 3.76 (2 H, t, J = 7.7 Hz), 
               
               
                   
                   
                   
                   
                 5.96 (2 H, s), 6.72 (1 H, d, J = 7.8 Hz), 6.78-6.86 (2 H, 
               
               
                   
                   
                   
                   
                 m), 7.12 (1 H, d, J = 8.8 Hz), 7.17 (2 H, d, J = 8.5 Hz), 
               
               
                   
                   
                   
                   
                 7.35 (2 H, d, J = 8.5 Hz), 7.92 (2 H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                 8.15 (2 H, d, J = 8.2 Hz), 8.24 (1 H, dd, J = 8.8 Hz, 2.5 
               
               
                   
                   
                   
                   
                 Hz), 8.54 (1 H, d, J = 2.5 Hz), 10.65 (1 H, s). 
               
               
                 796 
                 —CF 3   
                 —H 
                 benzyl 
                 1.74 (3 H, s), 2.18-2.36 (4 H, m), 2.54 (2 H, t, J = 7.7 
               
               
                   
                   
                   
                   
                 Hz), 3.35-3.45 (4 H, m), 3.46 (2 H, s), 3.76 (2 H, t, J = 
               
               
                   
                   
                   
                   
                 7.7 Hz), 7.12 (1 H, d, J = 8.8 Hz), 7.17 (2 H, d, J = 8.6 
               
               
                   
                   
                   
                   
                 Hz), 7.20-7.33 (5 H, m), 7.34 (2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                 7.92 (2 H, d, J = 8.3 Hz), 8.15 (2 H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                   
                 8.24 (1 H, dd, J = 8.8 Hz, 2.5 Hz), 8.54 (1 H, d, J = 2.5 
               
               
                   
                   
                   
                   
                 Hz), 10.65 (1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 209 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 684   
                 R 685   
                 R 686   
                   1 H NMR (DMSO-d 6 ) δ ppm 
               
               
                   
               
               
                 797 
                 —Cl 
                 —Cl 
                 benzyl 
                 1.80 (3 H, s), 3.02 (3 H, s), 2.70-3.40 (5 H, m), 
               
               
                   
                   
                   
                   
                 3.41-3.68 (1 H, m), 3.88-4.10 (1 H, m), 4.32 (2 H, brs), 4.25- 
               
               
                   
                   
                   
                   
                 4.50 (1 H, m), 4.50 (2 H, d, J = 3.8 Hz), 4.57 (2 H, s), 6.94 
               
               
                   
                   
                   
                   
                 (1 H, d, J = 8.9 Hz), 7.02 (2 H, d, J = 8.7 Hz), 7.22 (1 H, 
               
               
                   
                   
                   
                   
                 dd, J = 8.2 Hz, 2.0 Hz), 7.34 (1 H, dd, J = 8.9 Hz, 3.2 Hz), 
               
               
                   
                   
                   
                   
                 7.36 (2 H, d, J = 8.7 Hz), 7.42-7.49 (3 H, m), 7.50 (1 H, d, 
               
               
                   
                   
                   
                   
                 J = 2.0 Hz), 7.55-7.64 (1 H, m), 7.62 (2 H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                 7.66 (1 H, d, J = 6.1 Hz). 
               
               
                 798 
                 —Cl 
                 —Cl 
                 piperonyl 
                 1.81 (3 H, s), 2.75-3.40 (5 H, m), 3.02 (3 H, s), 
               
               
                   
                   
                   
                   
                 3.43-3.67 (1 H, m), 3.90-4.10 (1 H, m), 4.22 (2 H, brs), 4.30- 
               
               
                   
                   
                   
                   
                 4.50 (1 H, m), 4.50 (2 H, d, J = 4.6 Hz), 4.57 (2 H, s), 6.07 
               
               
                   
                   
                   
                   
                 (2 H, s), 6.94 (2 H, d, J = 8.8 Hz), 6.97-7.07 (1 H, m), 7.02 
               
               
                   
                   
                   
                   
                 (2 H, d, J = 8.9 Hz), 7.22 (1 H, dd, J = 8.3 Hz, 1.8 Hz), 
               
               
                   
                   
                   
                   
                 7.24 (1 H, s), 7.34 (1 H, dd, J = 8.8 Hz, 3.0 Hz), 7.36 (2 H, d, 
               
               
                   
                   
                   
                   
                 J = 8.9 Hz), 7.50 (1 H, d, J = 1.8 Hz), 7.60 (1 H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                   
                 7.67 (1 H, d, J = 3.0 Hz). 
               
               
                 799 
                 —CF 3   
                 —H 
                 benzyl 
                 1.80 (3 H, s), 3.05 (3 H, s), 2.70-3.40 (5 H, m), 
               
               
                   
                   
                   
                   
                 3.41-3.68 (1 H, m), 3.90-4.08 (1 H, m), 4.22-4.45 (1 H, m), 4.32 
               
               
                   
                   
                   
                   
                 (2 H, brs), 4.50 (2 H, d, J = 3.5 Hz), 4.67 (2 H, s), 6.94 (1 H, 
               
               
                   
                   
                   
                   
                 d, J = 8.9 Hz), 7.02 (2 H, d, J = 8.8 Hz), 7.34 (1 H, dd, 
               
               
                   
                   
                   
                   
                 J = 8.9 Hz, 3.3 Hz), 7.36 (2 H, d, J = 8.8 Hz), 7.39-7.50 
               
               
                   
                   
                   
                   
                 (5 H, m), 7.54-7.64 (2 H, m), 7.67 (1 H, d, J = 3.3 Hz), 7.70 
               
               
                   
                   
                   
                   
                 (2 H, d, J = 8.1 Hz). 
               
               
                 800 
                 —CF 3   
                 —H 
                 piperonyl 
                 1.80 (3 H, s), 2.70-3.40 (5 H, m), 3.05 (3 H, s), 
               
               
                   
                   
                   
                   
                 3.43-3.65 (1 H, m), 3.90-4.09 (1 H, m), 4.22 (2 H, s), 4.29- 
               
               
                   
                   
                   
                   
                 4.48 (1 H, m), 4.50 (2 H, d, J = 4.8 Hz), 4.67 (2 H, s), 6.07 
               
               
                   
                   
                   
                   
                 (2 H, s), 6.94 (1 H, d, J = 8.9 Hz), 7.00 (2 H, d, J = 7.0 Hz), 
               
               
                   
                   
                   
                   
                 7.02 (2 H, d, J = 8.8 Hz), 7.24 (1 H, d, J = 1.1 Hz), 7.35 
               
               
                   
                   
                   
                   
                 (1 H, dd, J = 8.9 Hz, 2.3 Hz), 7.36 (2 H, d, J = 8.8 Hz), 
               
               
                   
                   
                   
                   
                 7.45 (2 H, d, J = 8.1 Hz), 7.67 (1 H, d, J = 3.3 Hz), 7.70 
               
               
                   
                   
                   
                   
                 (2 H, d, J = 8.1 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 210 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 687   
                 R 688   
                 R 689   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 801 
                 4-CF 3 PhCO— 
                 —CH 3   
                 —C 2 H 5   
                 1.19 (3 H, t, J = 7.1 Hz), 2.11 (3 H, s), 
               
               
                   
                   
                   
                   
                 2.42-2.45 (4 H, m), 3.39-3.53 (6 H, m), 
               
               
                   
                   
                   
                   
                 3.63-3.66 (2 H, m), 4.04 (2 H, s), 5.95 (2 H, s), 
               
               
                   
                   
                   
                   
                 6.50-6.54 (2 H, m), 6.71-6.77 (2 H, m), 
               
               
                   
                   
                   
                   
                 6.85 (1 H, s), 6.90-6.95 (2 H, m), 7.75 (2 H, d, 
               
               
                   
                   
                   
                   
                 J = 8.2 Hz), 7.87 (2 H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                 8.17 (1 H, dd, J = 8.7 Hz, 2.5 Hz), 
               
               
                   
                   
                   
                   
                 8.59 (1 H, d, J = 2.0 Hz). 
               
               
                 802 
                 3,4-Cl 2 PhNHCO— 
                 —OCH 3   
                 —C 2 H 5   
                 1.19 (5 H, t, J = 7.1 Hz), 2.42 (4 H, brs), 
               
               
                   
                   
                   
                   
                 3.42 (2 H, q, J = 7.1 Hz), 3.43 (2 H, s), 
               
               
                   
                   
                   
                   
                 3.51 (2 H, s), 3.62 (2 H, brs), 3.68 (3 H, s), 
               
               
                   
                   
                   
                   
                 4.04 (2 H, s), 5.95 (2 H, s), 6.17 (1 H, dd, J = 
               
               
                   
                   
                   
                   
                 8.7 Hz, 2.6 Hz), 6.28 (1 H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                 6.73-6.74 (2 H, m), 6.85 (1 H, brs), 6.88 (1 H, 
               
               
                   
                   
                   
                   
                 d, J = 8.6 Hz), 6.90 (1 H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                 7.37 (1 H, d, J = 8.7 Hz), 7.47 (1 H, dd, J = 
               
               
                   
                   
                   
                   
                 8.7 Hz, 2.5 Hz), 7.86 (1 H, d, J = 2.5 Hz), 
               
               
                   
                   
                   
                   
                 8.11 (1 H, dd, J = 8.6 Hz, 2.5 Hz), 
               
               
                   
                   
                   
                   
                 8.31 (1 H, brs), 8.58 (1 H, d, J = 2.3 Hz). 
               
               
                 803 
                 4-CF 3 PhNHCO— 
                 —OCH 3   
                 —C 2 H 5   
                 1.19 (3 H, t, J = 7.1 Hz), 2.42 (4 H, brs), 
               
               
                   
                   
                   
                   
                 3.38-3.47 (4 H, m), 3.51 (2 H, brs), 3.62 (2 H, 
               
               
                   
                   
                   
                   
                 brs), 3.68 (3 H, s), 4.05 (2 H, s), 5.94 (2 H, 
               
               
                   
                   
                   
                   
                 s), 6.17 (1 H, dd, J = 8.7 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                   
                 6.29 (1 H, d, J = 2.8 Hz), 6.73-6.74 (2 H, m), 
               
               
                   
                   
                   
                   
                 6.84 (1 H, brs), 6.89 (1 H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                 6.91 (1 H, d, J = 8.7 Hz), 7.58 (2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.7 Hz), 7.76 (2 H, d, J = 8.7 Hz), 8.13 (1 H, 
               
               
                   
                   
                   
                   
                 dd, J = 8.7 Hz, 2.5 Hz), 8.44 (1 H, brs), 
               
               
                   
                   
                   
                   
                 8.64 (1 H, d, J = 2.5 Hz). 
               
               
                 804 
                 3,4-Cl 2 PhNHCONH— 
                 —CONHCH 3   
                 —C 2 H 5   
                 1.07 (3 H, t, J = 7.0 Hz), 2.30-2.45 (4 H, m), 
               
               
                   
                   
                   
                   
                 2.85 (3 H, d, J = 4.9 Hz), 3.33 (2 H, q, J = 
               
               
                   
                   
                   
                   
                 7.0 Hz), 3.38 (2 H, s), 3.38-3.50 (2 H, m), 
               
               
                   
                   
                   
                   
                 3.50-3.65 (2 H, m), 4.01 (2 H, s), 5.95 (2 H, 
               
               
                   
                   
                   
                   
                 s), 6.55-6.65 (1 H, m), 6.69-6.84 (5 H, m), 
               
               
                   
                   
                   
                   
                 7.14 (1 H, d, J = 3.1 Hz), 7.25-7.35 (2 H, m), 
               
               
                   
                   
                   
                   
                 7.35-7.45 (1 H, m), 7.65 (1 H, d, J = 1.5 Hz), 
               
               
                   
                   
                   
                   
                 7.72 (1 H, d, J = 2.6 Hz), 7.84 (1 H, dd, J = 
               
               
                   
                   
                   
                   
                 8.9 Hz, 2.7 Hz), 8.02 (1 H, s), 8.61 (1 H, s). 
               
               
                 805 
                 4-CF 3 PhCH 2 — 
                 —H 
                 —CH 3   
                 2.42 (4 H, t, J = 5.1 Hz), 3.02 (3 H, s), 
               
               
                   
                   
                   
                   
                 3.43 (2 H, s), 3.48 (2 H, brs), 3.63 (2 H, brs), 
               
               
                   
                   
                   
                   
                 3.95 (2 H, s), 4.06 (2 H, s), 5.94 (2 H, s), 
               
               
                   
                   
                   
                   
                 6.70 (2 H, d, J = 9.0 Hz), 6.73 (2 H, s), 
               
               
                   
                   
                   
                   
                 6.74 (1 H, d, J = 10.0 Hz), 6.84 (1 H, s), 
               
               
                   
                   
                   
                   
                 7.00 (2 H, d, J = 9.0 Hz), 7.27 (2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.1 Hz), 7.38 (1 H, dd, J = 8.4 Hz, 2.5 Hz), 
               
               
                   
                   
                   
                   
                 7.54 (2 H, d, J = 8.1 Hz), 8.03 (1 H, d, J = 
               
               
                   
                   
                   
                   
                 2.5 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 211 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 690   
                 R 691   
                 R 692   
                 R 693   
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 806 
                 4-CF 3 PhNHCO— 
                 —CH 3   
                 —H 
                 piperonyl 
                 (CDCl 3 ) 2.17 (3 H, s), 2.49-2.54 (4 H, 
               
               
                   
                   
                   
                   
                   
                 m), 3.45 (2 H, s), 3.71-3.75 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                 4.26 (2 H, brs), 5.96 (2 H, s), 6.75 (2 H, 
               
               
                   
                   
                   
                   
                   
                 brs), 6.86 (1 H, brs), 7.02 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.7 Hz), 7.06 (1 H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.47 (1 H, dd, J = 8.7 Hz, 2.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.58 (1 H, d, J = 2.3 Hz), 7.63 (2 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.4 Hz), 7.75 (2 H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.84 (1 H, brs), 8.22 (1 H, dd, J = 8.7 
               
               
                   
                   
                   
                   
                   
                 Hz, 2.6 Hz), 8.64 (1 H, d, J = 2.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 9.20 (1 H, brs). 
               
               
                 807 
                 4-CF 3 PhOCH 2 — 
                 —H 
                 —H 
                 piperonyl 
                 (CDCl 3 ) 2.51-2.54 (4 H, m), 3.45 (2 H, 
               
               
                   
                   
                   
                   
                   
                 s), 3.71-3.75 (2 H, m), 4.27-4.29 (2 H, 
               
               
                   
                   
                   
                   
                   
                 m), 5.05 (2 H, s), 5.95 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                 6.85 (2 H, brs), 6.86 (1 H, brs), 
               
               
                   
                   
                   
                   
                   
                 6.96 (1 H, d, J = 8.4 Hz), 7.02 (2 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.6 Hz), 7.14 (2 H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.56 (2 H, d, J = 8.6 Hz), 7.64 (2 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.9 Hz), 7.78 (1 H, dd, J = 8.4 Hz, 
               
               
                   
                   
                   
                   
                   
                 2.3 Hz), 8.22 (1 H, d, J = 2.3 Hz), 
               
               
                   
                   
                   
                   
                   
                 9.21 (1 H, brs). 
               
               
                 808 
                 4-CF 3 PhOCH 2 — 
                 —H 
                 —H 
                 4-pyridylmethyl 
                 (CDCl 3 ) 2.52-2.58 (4 H, m), 3.55 (2 H, 
               
               
                   
                   
                   
                   
                   
                 s), 3.74-3.77 (2 H, m), 4.29-4.32 (2 H, 
               
               
                   
                   
                   
                   
                   
                 m), 5.04 (2 H, s), 6.96 (1 H, d, J = 8.4 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.02 (2 H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.15 (2 H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.26-7.30 (2 H, m), 7.56 (2 H, d, J = 8.6 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.64 (2 H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.78 (1 H, dd, J = 8.6 Hz, 2.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.22 (1 H, d, J = 2.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.56-8.58 (2 H, m), 9.24 (1 H, brs). 
               
               
                 809 
                 4-CF 3 PhOCH 2 — 
                 —CH 3   
                 —CH 3   
                 piperonyl 
                 a mixture of the rotational isomers 
               
               
                   
                   
                   
                   
                   
                 (DMSO-d 6 ) 2.07-2.43 (7 H, m), 
               
               
                   
                   
                   
                   
                   
                 3.24-3.57 (11 H, m), 5.17 (2 H, brs), 
               
               
                   
                   
                   
                   
                   
                 5.95-5.99 (2 H, m), 6.66-6.89 (3 H, m), 
               
               
                   
                   
                   
                   
                   
                 7.07-7.12 (2 H, m), 7.16-7.37 (4 H, m), 
               
               
                   
                   
                   
                   
                   
                 7.66 (2 H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.85-8.00 (1 H, m), 8.22 (1 H, d, J = 2.0 
               
               
                   
                   
                   
                   
                   
                 Hz). 
               
               
                 810 
                 4-CF 3 PhOCH 2 — 
                 —CH 3   
                 —CH 3   
                 3,4- 
                 a mixture of the rotational isomers 
               
               
                   
                   
                   
                   
                 (CH 3 O) 2 PhCH 2 — 
                 (DMSO-d 6 ) 2.07-2.43 (7 H, m), 
               
               
                   
                   
                   
                   
                   
                 3.26-3.75 (15 H, m), 5.17 (2 H, brs), 
               
               
                   
                   
                   
                   
                   
                 6.70-6.91 (3 H, m), 7.07-7.12 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                 7.16-7.37 (4 H, m), 7.66 (2 H, d, J = 8.9 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.95-8.00 (1 H, m), 8.22 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 2.0 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 212 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 694   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 811 
                 piperonyl 
                 2.18 (3 H, s), 2.49-2.54 (4 H, m), 3.45 (2 H, s), 3.70-3.74 (2 H, 
               
               
                   
                   
                 m), 4.23-4.27 (2 H, m), 5.03 (2 H, s), 5.95 (2 H, s), 6.71 
               
               
                   
                   
                 6.78 (2 H, m), 6.86 (1 H, brs), 6.92 (1 H, d, J = 8.6 Hz), 
               
               
                   
                   
                 7.00-7.06 (3 H, m), 7.44 (1 H, dd, J = 8.7 Hz, 2.6 Hz), 
               
               
                   
                   
                 7.54-7.58 (3 H, m), 7.77 (1 H, dd, J = 8.6 Hz, 2.5 Hz), 8.20 (1 H, d, 
               
               
                   
                   
                 J = 2.3 Hz), 9.20 (1 H, brs). 
               
               
                 812 
                 3,4- (CH 3 O) 2 PhCH 2 — 
                 2.18 (3 H, s), 2.50-2.55 (4 H, m), 3.48 (2 H, s), 3.71-3.75 (2 H, 
               
               
                   
                   
                 m), 3.88 (3 H, s), 3.90 (3 H, s), 4.24-4.28 (2 H, m), 5.03 (2 H, s), 
               
               
                   
                   
                 6.79-6.86 (2 H, m), 6.88 (1 H, brs), 6.93 (1 H, d, J = 8.4 Hz), 
               
               
                   
                   
                 7.00-7.06 (3 H, m), 7.44 (1 H, dd, J = 8.6 Hz, 2.6 Hz), 
               
               
                   
                   
                 7.54-7.58 (3 H, m), 7.77 (1 H, dd, J = 8.4 Hz, 2.5 Hz), 8.20 (1 H, d, 
               
               
                   
                   
                 J = 2.5 Hz), 9.19 (1 H, brs). 
               
               
                 813 
                 4-pyridylmethyl 
                 2.18 (3 H, s), 2.52-2.58 (4 H, m), 3.55 (2 H, s), 3.73-3.77 (2 H, 
               
               
                   
                   
                 m), 4.27-4.31 (2 H, m), 5.03 (2 H, s), 6.93 (1 H, d, J = 8.4 Hz), 
               
               
                   
                   
                 7.00-7.06 (3 H, m), 7.28 (2 H, d, J = 5.9 Hz), 7.44 (1 H, dd, J = 
               
               
                   
                   
                 8.7 Hz, 2.6 Hz), 7.54-7.57 (3 H, m), 7.77 (1 H, dd, J = 8.4 Hz, 
               
               
                   
                   
                 2.3 Hz), 8.19 (1 H, d, J = 2.1 Hz), 8.56 (2 H, d, J = 5.9 Hz), 
               
               
                   
                   
                 9.23 (1 H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 213 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 695   
                 R 696   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 814 
                 —H 
                 piperonyl 
                 2.42 (4 H, brs), 3.21 (3 H, s), 3.37 (2 H, brs), 3.42 (2 H, 
               
               
                   
                   
                   
                 s), 3.62 (2 H, brs), 4.54 (2 H, s), 5.06 (2 H, s), 5.94 (2 H, 
               
               
                   
                   
                   
                 s), 6.70-6.77 (2 H, m), 6.83 (1 H, brs), 6.98-7.04 (3 H, 
               
               
                   
                   
                   
                 m), 7.14 (2 H, d, J = 8.7 Hz), 7.56 (2 H, d, J = 8.7 
               
               
                   
                   
                   
                 Hz), 7.62 (2 H, d, J = 8.9 Hz), 7.81 (1 H, dd, J = 8.4 
               
               
                   
                   
                   
                 Hz, 2.3 Hz), 8.23 (1 H, d, J = 2.1 Hz). 
               
               
                 815 
                 —H 
                 4-pyridylmethyl 
                 2.48 (4 H, brs), 3.21 (3 H, s), 3.41 (2 H, brs), 3.53 (2 H, 
               
               
                   
                   
                   
                 s), 3.65 (2 H, brs), 4.55 (2 H, s), 5.06 (2 H, s), 7.01 (1 H, 
               
               
                   
                   
                   
                 d, J = 8.2 Hz), 7.03 (2 H, d, J = 8.4 Hz), 7.14 (2 H, d, 
               
               
                   
                   
                   
                 J = 8.9 Hz), 7.26-7.28 (2 H, m), 7.57 (2 H, d, J = 8.7 
               
               
                   
                   
                   
                 Hz), 7.62 (2 H, d, J = 8.7 Hz), 7.81 (1 H, dd, J = 8.4 
               
               
                   
                   
                   
                 Hz, 2.3 Hz), 8.23 (1 H, d, J = 2.1 Hz), 8.56 (2 H, d, J = 
               
               
                   
                   
                   
                 5.6 Hz). 
               
               
                 816 
                 —CH 3   
                 piperonyl 
                 2.18 (3 H, s), 2.41-2.44 (4 H, m), 3.22 (3 H, s), 
               
               
                   
                   
                   
                 3.36-3.39 (2 H, m), 3.43 (2 H, s), 3.60-3.64 (2 H, m), 
               
               
                   
                   
                   
                 4.54 (2 H, s), 5.05 (2 H, s), 5.94 (2 H, s), 6.73-6.74 (2 H, 
               
               
                   
                   
                   
                 m), 6.84 (1 H, brs), 6.97 (1 H, d, J = 8. 4 Hz), 
               
               
                   
                   
                   
                 7.02 (1 H, d, J = 8.6 Hz), 7.04 (2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                 7.45 (1 H, dd, J = 8.6 Hz, 2.6 Hz), 7.49 (1 H, d, J = 
               
               
                   
                   
                   
                 2.5 Hz), 7.56 (2 H, d, J = 8.4 Hz), 7.80 (1 H, dd, J = 
               
               
                   
                   
                   
                 8.6 Hz, 2.5 Hz), 8.20 (1 H, d, J = 2.0 Hz). 
               
               
                 817 
                 —CH 3   
                 3,4- (CH 3 O) 2 PhCH 2 — 
                 2.18 (3 H, s), 2.44 (4 H, brs), 3.22 (3 H, s), 
               
               
                   
                   
                   
                 3.38-3.40 (2 H, m), 3.46 (2 H, s), 3.63-3.65 (2 H, m), 
               
               
                   
                   
                   
                 3.87 (3 H, s), 3.89 (3 H, s), 4.55 (2 H, s), 5.04 (2 H, s), 
               
               
                   
                   
                   
                 6.81 (2 H, brs), 6.87 (1 H, brs), 6.98 (1 H, d, J = 8.6 
               
               
                   
                   
                   
                 Hz), 7.02 (1 H, d, J = 8.4 Hz), 7.04 (2 H, d, J = 8.4 
               
               
                   
                   
                   
                 Hz), 7.45 (1 H, dd, J = 8.6 Hz, 2.6 Hz), 7.49 (1 H, d, J = 
               
               
                   
                   
                   
                 2.6 Hz), 7.56 (2 H, d, J = 8.4 Hz), 7.80 (1 H, dd, J = 
               
               
                   
                   
                   
                 8.4 Hz, 2.5 Hz), 8.20 (1 H, d, J = 2.3 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 214 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 697   
                 R 698   
                 mp (° C.) 
               
               
                   
               
               
                 818 
                 4-CF 3 PhCO— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 207.0-209.0 
               
               
                   
               
               
                 819 
                 4-CF 3 PhCO— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 237.0-238.0 
               
               
                   
               
               
                 820 
                 3,4-Cl 2 PhSO 2 — 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 115.0-116.0 
               
               
                   
               
               
                 821 
                 3,4-Cl 2 PhNHCO— 
                 —CH 2 CONHPh 
                 147.0-148.0 
               
               
                   
               
               
                 822 
                 3,4-Cl 2 PhNHCO— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 207.0-208.0 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 215 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 699   
                   1 H NMR or MS 
               
               
                   
               
               
                 823 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (DMSO-d 6 ) δ 1.40-1.80 (2 H, m), 1.80-2.10 (2 H, m), 2.93 (3 H, s), 3.15-3.50 (2 H, m), 3.60-3.90 (2 H, 3 m), 4.31 (2 H, s), 4.60-4.70 (1 H, m), 6.35-6.45 (1 H, m), 6.54 (1 H, dd, J = 14.4 Hz, 2.6 Hz), 6.96-7.11 (4 H, m), 7.27-7.31 (2 H, m), 7.52 (1 H, dd, J = 8.7 Hz, 2.7 Hz), 7.63 (1 H, dd, J = 8.5 Hz, 2.1 Hz), 7.76 (1 H, d, J = 2.7 Hz), 7.84-7.88 (2 H, m), 10.39 (1 H, brs). 
               
               
                   
               
               
                 824 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 682 (M +  + H) 
               
               
                   
               
               
                 825 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 618 (M +  + H) 
               
               
                   
               
               
                 826 
                 —N[CH 2 CH(CH 3 ) 2 ] 2   
                 MS 611 (M +  + H) 
               
               
                   
               
               
                 827 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 571 (M +  + H) 
               
               
                   
               
               
                 828 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 635 (M +  + H) 
               
               
                   
               
               
                 829 
                 —N[(CH 2 ) 3 N(CH 3 ) 2 ] 2   
                 MS 669 (M +  + H) 
               
               
                   
               
               
                 830 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 645 (M +  + H) 
               
               
                   
               
               
                 831 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 712 (M +  + H) 
               
               
                   
               
               
                 832 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 665 (M +  + H) 
               
               
                   
               
               
                 833 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 595 (M +  + H) 
               
               
                   
               
               
                 834 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 764 (M +  + H) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 216 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 699   
                 MS (M +  + H) 
               
               
                   
               
               
                 835 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 635 
               
               
                   
               
               
                 836 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 714 
               
               
                   
               
               
                 837 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 581 
               
               
                   
               
               
                 838 
                 4-CF 3 OPhCH 2 NH— 
                 673 
               
               
                   
               
               
                 839 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 553 
               
               
                   
               
               
                 840 
                 —NH(CH 2 ) 5 OH 
                 585 
               
               
                 841 
                 —NHCH(CH 3 )COOCH 3   
                 585 
               
               
                 842 
                 3,5-F 2 PhCH 2 N(C 2 H 5 )— 
                 653 
               
               
                 843 
                 4-CH 3 PhNHCOCH 2 N(CH 3 )— 
                 660 
               
               
                 844 
                 3,4-(CH 3 O) 2 PhCH 2 N(C 2 H 5 )— 
                 677 
               
               
                 845 
                 4-CH 3 PhCH 2 N(C 2 H 5 )— 
                 631 
               
               
                   
               
               
                 846 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 614 
               
               
                   
               
               
                 847 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 686 
               
               
                   
               
               
                 848 
                 3,4-Cl 2 Ph- 
                 714 
               
               
                   
               
               
                 849 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 695 
               
               
                   
               
               
                 850 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 734 
               
               
                   
               
               
                 851 
                 —N(CH 2 Ph)CH 2 CH 2 CN 
                 642 
               
               
                 852 
                 —N(C 2 H 5 )CH(CH 3 ) 2   
                 569 
               
               
                 853 
                 —NHC(CH 3 ) 2 CH 2 Ph 
                 631 
               
               
                 854 
                 3-CNPhNH— 
                 600 
               
               
                 855 
                 3,5-F 2 PhNH— 
                 611 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 217 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Ex- 
                   
                   
               
               
                 am- 
               
               
                 ple 
                   
               
               
                 No. 
                 R 701   
                 MS (M +  + H) 
               
               
                   
               
               
                 856 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 700 
               
               
                   
               
               
                 857 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 652 
               
               
                   
               
               
                 858 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 583 
               
               
                   
               
               
                 859 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 662 
               
               
                   
               
               
                 860 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 665 
               
               
                   
               
               
                 861 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 659 
               
               
                   
               
               
                 862 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 673 
               
               
                   
               
               
                 863 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 702 
               
               
                   
               
               
                 864 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 674 
               
               
                   
               
               
                 865 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 674 
               
               
                   
               
               
                 866 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 666 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 218 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 702   
                 MS (M +  + H) 
               
               
                   
               
               
                 867 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 698 
               
               
                   
               
               
                 868 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 639 
               
               
                   
               
               
                 869 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 639 
               
               
                   
               
               
                 870 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 673 
               
               
                   
               
               
                 871 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 610 
               
               
                   
               
               
                 872 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 596 
               
               
                   
               
               
                 873 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 555 
               
               
                   
               
               
                 874 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 569 
               
               
                   
               
               
                 875 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 663 
               
               
                   
               
               
                 876 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 692 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 219 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                 MS 
               
               
                 No. 
                 R 703   
                 R 704   
                 R 705   
                 R 706   
                 (M +  + H) 
               
               
                   
               
               
                 877 
                 —H 
                 —H 
                 —OCF 3   
                 —H 
                 659 
               
               
                 878 
                 —H 
                 —H 
                 —CH 3   
                 —H 
                 589 
               
               
                 879 
                 —OCH 3   
                 —OCH 3   
                 —H 
                 —H 
                 635 
               
               
                 880 
                 —H 
                 —H 
                 —SCH 3   
                 —H 
                 621 
               
               
                 881 
                 —CH(CH 3 ) 2   
                 —H 
                 —H 
                 —H 
                 617 
               
               
                 882 
                 —H 
                 —H 
                 cyclohexyl 
                 —H 
                 657 
               
               
                 883 
                 —NHPh 
                 —H 
                 —Cl 
                 —H 
                 702 
               
               
                 884 
                 4-ClPhNH— 
                 —H 
                 —H 
                 —COOC 2 H 5   
                 774 
               
               
                 885 
                 —H 
                 —H 
                 —O(CH 2 ) 2 N(C 2 H 5 ) 2   
                 —H 
                 690 
               
               
                   
               
               
                 886 
                 —H 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 673 
               
               
                   
               
               
                 887 
                 —H 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 658 
               
               
                   
               
               
                 888 
                 —H 
                 —H 
                 —NHSO 2 CH 3   
                 —H 
                 668 
               
               
                 889 
                 —H 
                 —H 
                 —(CH 2 )OH 
                 —H 
                 619 
               
               
                 890 
                 —H 
                 —H 
                 —(CH 2 ) 4 CH 3   
                 —H 
                 645 
               
               
                 891 
                 —H 
                 —H 
                 benzyl 
                 —H 
                 665 
               
               
                 892 
                 —H 
                 —H 
                 —SPh 
                 —H 
                 683 
               
               
                   
               
               
                 893 
                 —H 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 709 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 220 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 707   
                 R 708   
                 R 709    
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 894 
                 4-CF 3 Ph- 
                 —CH 3   
                 piperonyl 
                 1.34-1.42 (2 H, m), 1.80-1.98 (3 H, m), 2.03 (3 H, 
               
               
                   
                   
                   
                   
                 s), 2.29 (2 H, d, J = 6.6 Hz), 2.41 (4 H, brs), 
               
               
                   
                   
                   
                   
                 2.65 (2 H, t, J = 12.0 Hz), 3.43 (2 H, s), 3.49- 
               
               
                   
                   
                   
                   
                 3.65 (6 H, m), 5.94 (2 H, s), 6.69-6.87 (8 H, m), 
               
               
                   
                   
                   
                   
                 7.56 (1 H, dd, J = 8.9 Hz, 2.8 Hz), 7.68 (2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.6 Hz), 7.76-7.85 (3 H, m). 
               
               
                 895 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 piperonyl 
                 1.34-1.39 (2 H, m), 1.79-1.98 (3 H, m), 2.04 (3 H, 
               
               
                   
                   
                   
                   
                 s), 2.29 (2 H, d, J = 6.6 Hz), 2.41 (4 H, brs), 
               
               
                   
                   
                   
                   
                 2.64 (2 H, t, J = 11.9 Hz), 3.43 (2 H, s), 3.49- 
               
               
                   
                   
                   
                   
                 3.65 (6 H, m), 5.94 (2 H, s), 6.70-6.88 (7 H, m), 
               
               
                   
                   
                   
                   
                 7.45-7.50 (3 H, m), 7.55 (1 H, dd, 
               
               
                   
                   
                   
                   
                 J = 8.9 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                   
                 7.78-7.82 (2 H, m). 
               
               
                 896 
                 4-CF 3 Ph- 
                 —CH 3   
                 benzyl 
                 1.34-1.43 (2 H, m), 1.80-2.01 (3 H, m), 2.03 (3 H, 
               
               
                   
                   
                   
                   
                 s), 2.29 (2 H, d, J = 6.6 Hz), 2.43 (4 H, brs), 
               
               
                   
                   
                   
                   
                 2.65 (2 H, t, J = 12.0 Hz), 3.49-3.65 (8 H, m), 
               
               
                   
                   
                   
                   
                 6.70-6.76 (3 H, m), 6.86 (1 H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                 7.26-7.32 (6 H, m), 7.55 (1 H, dd, 
               
               
                   
                   
                   
                   
                 J = 8.7 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                   
                 7.68 (2 H, d, J = 8.6 Hz), 7.76 (1 H, d, J = 
               
               
                   
                   
                   
                   
                 2.8 Hz), 7.84 (2 H, d, J = 8.4 Hz). 
               
               
                 897 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 benzyl 
                 1.27-1.39 (2 H, m), 1.79-2.01 (3 H, m), 2.04 (3 H, 
               
               
                   
                   
                   
                   
                 s), 2.29 (2 H, d, J = 6.8 Hz), 2.43 (4 H, brs), 
               
               
                   
                   
                   
                   
                 2.64 (2 H, t, J = 11.9 Hz), 3.53-3.66 (8 H, m), 
               
               
                   
                   
                   
                   
                 6.69-6.76 (3 H, m), 6.86 (1 H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                 7.29-7.32 (6 H, m), 7.44-7.50 (2 H, m), 7.55 (1 H, 
               
               
                   
                   
                   
                   
                 dd, J = 8.7 Hz, 2.6 Hz), 7.79-7.82 (2 H, m). 
               
               
                 898 
                 4-CF 3 Ph- 
                 —H 
                 3,4-Cl 2 Ph- 
                 1.34-1.46 (2 H, m), 1.83-2.02 (3 H, m), 2.34 (2 H, 
               
               
                   
                   
                   
                   
                 d, J = 6.8 Hz), 2.67 (2 H, t, J = 12.0 Hz), 3.15- 
               
               
                   
                   
                   
                   
                 3.17 (4 H, m), 3.55-3.65 (4 H, m), 3.78-3.80 (2 H, 
               
               
                   
                   
                   
                   
                 m), 6.72-6.97 (7 H, m), 7.26-7.31 (2 H, m), 7.56 
               
               
                   
                   
                   
                   
                 (1 H, dd, J = 8.9 Hz, 2.8 Hz), 7.70 (2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.24 Hz), 7.78-7.86 (3 H, m). 
               
               
                 899 
                 4-CF 3 Ph- 
                 —H 
                 3,4-CF 3 Ph- 
                 1.35-1.47 (2 H, m), 1.83-2.02 (3 H, m), 2.36 (2 H, 
               
               
                   
                   
                   
                   
                 d, J = 6.8 Hz), 2.67 (2 H, t, J = 12.0 Hz), 3.28- 
               
               
                   
                   
                   
                   
                 3.30 (4 H, m), 3.57 (2 H, d, 
               
               
                   
                   
                   
                   
                 J = 12.2 Hz), 
               
               
                   
                   
                   
                   
                 3.68 (2 H, brs), 3.82 (2 H, brs), 6.76 (1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.7 Hz), 6.87-6.96 (7 H, m), 7.50 (2 H, d, 
               
               
                   
                   
                   
                   
                 J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                 7.56 (1 H, dd, J = 8.9 Hz, 2.8 Hz), 7.69 (2 H, 
               
               
                   
                   
                   
                   
                 d, J = 8.4 Hz), 7.80-7.86 (3 H, m). 
               
               
                 900 
                 3,4-Cl 2 Ph- 
                 —H 
                 4-CF 3 Ph- 
                 1.34-1.47 (2 H, m), 1.83-2.02 (3 H, m), 2.35 (2 H, 
               
               
                   
                   
                   
                   
                 d, J = 6.8 Hz), 2.68 (2 H, t, J = 12.0 Hz), 3.29- 
               
               
                   
                   
                   
                   
                 3.31 (4 H, m), 3.58 (2 H, d, J = 12.2 Hz), 
               
               
                   
                   
                   
                   
                 3.68 (2 H, brs), 3.83 (2 H, brs), 6.79 (1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.7 Hz), 6.88-6.98 (7 H, m), 7.50-7.59 (5 H, m), 
               
               
                   
                   
                   
                   
                 7.79 (1 H, d, J = 2.8 Hz), 7.83-7.84 (1 H, m). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 221 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 710   
                 R 711   
                 R 712   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 901 
                 3,4-Cl 2 Ph- 
                 —H 
                 3,4-Cl 2 Ph- 
                 1.34-1.46 (2 H, m), 1.82-2.02 (3 H, m), 2.35 (2 H, d, 
               
               
                   
                   
                   
                   
                 J = 6.6 Hz), 2.66 (2 H, t, J = 12.0 Hz), 3.16- 
               
               
                   
                   
                   
                   
                 3.17 (4 H, m), 3.57 (2 H, d, J = 12.2 Hz), 3.65 (2 H, 
               
               
                   
                   
                   
                   
                 brs), 3.80 (2 H, brs), 6.72-6.78 (2 H, m), 6.87- 
               
               
                   
                   
                   
                   
                 6.97 (6 H, m), 7.29 (1 H, d, J = 8.9 Hz), 7.49 (2 H, 
               
               
                   
                   
                   
                   
                 s), 7.57 (1 H, dd, J = 8.7 Hz, 2.6 Hz), 7.81- 
               
               
                   
                   
                   
                   
                 7.84 (2 H, m). 
               
               
                 902 
                 4-CF 3 Ph- 
                 —CH 3   
                 3,4-Cl 2 Ph- 
                 1.34-1.46 (2 H, m), 1.82-2.01 
               
               
                   
                   
                   
                   
                 (3 H, m), 2.03 (3 H, 
               
               
                   
                   
                   
                   
                 s), 2.35 (2 H, d, J = 6.8 Hz), 
               
               
                   
                   
                   
                   
                 2.67 (2 H, t, J = 12.0 Hz), 
               
               
                   
                   
                   
                   
                 3.15-3.17 (4 H, m), 3.58 (2 H, d, J = 12.2 Hz), 
               
               
                   
                   
                   
                   
                 3.65 (2 H, brs), 3.79 (2 H, brs), 6.70-6.76 (4 H, m), 
               
               
                   
                   
                   
                   
                 6.86 (1 H, d, J = 8.6 Hz), 6.96 (1 H, d, J = 2.8 Hz), 
               
               
                   
                   
                   
                   
                 7.29 (1 H, d, J = 8.7 Hz), 7.53-7.57 (1 H, m), 
               
               
                   
                   
                   
                   
                 7.68 (2 H, d, J = 8.2 Hz), 7.77 (1 H, d, J = 2.5 Hz), 
               
               
                   
                   
                   
                   
                 7.84 (2 H, d, J = 8.2 Hz), 8.05 (1 H, s). 
               
               
                 903 
                 4-CF 3 Ph- 
                 —H 
                 piperonyl 
                 1.27-1.41 (2 H, m), 1.83-2.05 (3 H, m), 2.29 (2 H, d, 
               
               
                   
                   
                   
                   
                 J = 6.8 Hz), 2.40-2.44 (4 H, m), 2.66-2.75 (2 H, 
               
               
                   
                   
                   
                   
                 m), 3.44-3.56 (4 H, m), 3.65-3.74 (4 H, m), 
               
               
                   
                   
                   
                   
                 5.95 (2 H, s), 6.75-6.99 (8 H, m), 7.57 (1 H, dd, J = 
               
               
                   
                   
                   
                   
                 8.9 Hz, 2.8 Hz), 7.71-7.74 (4 H, m), 7.85 (2 H, d, J = 
               
               
                   
                   
                   
                   
                 = 8.2 Hz). 
               
               
                 904 
                 3,4-Cl 2 Ph- 
                 —H 
                 benzyl 
                 1.31-1.40 (2 H, m), 1.80-2.05 (3 H, m), 2.29 (2 H, d, 
               
               
                   
                   
                   
                   
                 J = 6.8 Hz), 2.62-2.71 (2 H, m), 3.53-3.58 (6 H, 
               
               
                   
                   
                   
                   
                 m), 3.66 (2 H, brs), 6.79 (1 H, d, J = 8.7 Hz), 6.88- 
               
               
                   
                   
                   
                   
                 6.98 (4 H, m), 7.31 (5 H, brs), 7.50 (2 H, s), 7.56 
               
               
                   
                   
                   
                   
                 (1 H, dd, J = 8.9 Hz, 2.8 Hz), 7.77-7.84 (3 H, m). 
               
               
                 905 
                 4-CF 3 Ph- 
                 —H 
                 benzyl 
                 1.30-1.43 (2 H, m), 1.80-2.04 (3 H, m), 2.28 (2 H, d, 
               
               
                   
                   
                   
                   
                 J = 6.8 Hz), 2.42-2.46 (4 H, m), 2.62-2.70 (2 H, 
               
               
                   
                   
                   
                   
                 m), 3.47-3.58 (6 H, m), 3.66 (2 H, brs), 6.78 (1 H, d, 
               
               
                   
                   
                   
                   
                 J = 8.7 Hz), 6.87-6.97 (4 H, m), 7.26-7.32 (6 H, 
               
               
                   
                   
                   
                   
                 m), 7.56 (1 H, dd, J = 8.9 Hz, 2.8 Hz), 7.68- 
               
               
                   
                   
                   
                   
                 7.77 (3 H, m), 7.83-7.86 (2 H, m). 
               
               
                 906 
                 3,4-Cl 2 Ph- 
                 —H 
                 piperonyl 
                 1.33-1.39 (2 H, m), 1.79-2.00 (3 H, m) 2.30 (2 H, d, 
               
               
                   
                   
                   
                   
                 J = 6.8 Hz), 2.42-2.44 (4 H, m), 2.65 (2 H, t, J = 
               
               
                   
                   
                   
                   
                 10.4 Hz), 3.43 (2 H, s), 3.49-3.57 (4 H, m), 
               
               
                   
                   
                   
                   
                 3.65 (2 H, brs), 5.94 (2 H, s), 6.74-6.77 (3 H, m), 
               
               
                   
                   
                   
                   
                 6.84-6.97 (5 H, m), 7.49-7.59 (3 H, m), 7.81- 
               
               
                   
                   
                   
                   
                 7.85 (3 H, m). 
               
               
                 907 
                 4-CF 3 Ph- 
                 —OCH 3   
                 piperonyl 
                 1.33-1.44 (2 H, m), 1.82-1.95 (3 H, m), 2.29 (2 H, d), 
               
               
                   
                   
                   
                   
                 J = 6.8 Hz), 2.41 (4 H, brs), 2.70 (2 H, t, J = 12.2 Hz), 
               
               
                   
                   
                   
                   
                 3.43-3.64 (8 H, m), 3.67 (3 H, s), 5.94 (2 H, s), 
               
               
                   
                   
                   
                   
                 6.46 (1 H, dd, J = 8.7 Hz, 2.6 Hz), 6.54 (1 H, d, J = 
               
               
                   
                   
                   
                   
                 2.5 Hz, 6.70-6.78 (4 H, m), 6.85 (1 H, s), 
               
               
                   
                   
                   
                   
                 6.92 (1 H, d, J = 8.6 Hz), 7.55 (1 H, dd, J = 8.7 Hz, 
               
               
                   
                   
                   
                   
                 2.6 Hz), 7.67 (2 H, d, J = 8.4 Hz), 7.74 (1 H, d, 
               
               
                   
                   
                   
                   
                 J = 2.6 Hz), 7.84 (2 H, d, J = 8.2 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 222 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 713   
                 R 714   
                 R 715   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 908 
                 3,4-Cl 2 Ph- 
                 —H 
                 benzyl 
                 1.76-1.99 (4 H, m), 2.45-2.73 (7 H, m), 3.53 (4 H, 
               
               
                   
                   
                   
                   
                 brs), 3.66 (4 H, brs), 6.75 (1 H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                 6.87-6.97 (4 H, m), 7.29-7.59 (9H, m), 7.83 (2 H, 
               
               
                   
                   
                   
                   
                 d, J = 2.0 Hz). 
               
               
                 909 
                 4-CF 3 Ph- 
                 —H 
                 benzyl 
                 1.77-1.99 (4 H, m), 2.45 (4 H, brs), 2.53-2.76 (3 H, 
               
               
                   
                   
                   
                   
                 m), 3.54 (4 H, brs), 3.65-3.69 (4 H, m), 6.81 (1 H, 
               
               
                   
                   
                   
                   
                 d, J = 8.7 Hz), 6.90-6.99 (4 H, m), 7.28-7.34 (6 H, 
               
               
                   
                   
                   
                   
                 m), 7.57 (1 H, dd, J = 8.9 Hz, 2.8 Hz), 7.71- 
               
               
                   
                   
                   
                   
                 7.75 (3 H, m), 7.85 (2 H, d, J = 8.2 Hz). 
               
               
                 910 
                 4-CF 3 Ph- 
                 —CH 3   
                 piperonyl 
                 1.75-1.96 (4 H, m), 2.04 (3 H, s), 2.44 (4 H, brs), 
               
               
                   
                   
                   
                   
                 2.53-2.73 (3 H, m), 3.43 (2 H, s), 3.53 (2 H, brs), 
               
               
                   
                   
                   
                   
                 3.63 (4 H, brs), 5.94 (2 H, s), 6.70-6.89 (8 H, m), 
               
               
                   
                   
                   
                   
                 7.56 (1 H, dd, J = 8.9 Hz, 2.8 Hz), 7.67 (2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.6 Hz), 7.78 (1 H, d, J = 2.6 Hz), 7.84 (2 H, d, 
               
               
                   
                   
                   
                   
                 J = 8.2 Hz). 
               
               
                 911 
                 4-CF 3 Ph- 
                 —CH 3   
                 benzyl 
                 1.75-2.02 (4 H, m), 2.03 (3 H, s), 2.45 (4 H, brs), 
               
               
                   
                   
                   
                   
                 2.55-2.72 (3 H, m), 3.53 (4 H, brs), 3.66 (4 H, brs), 
               
               
                   
                   
                   
                   
                 6.72-6.77 (3 H, m), 6.87 (1 H, 
               
               
                   
                   
                   
                   
                 d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                 7.25-7.31 (6 H, m), 7.56 (1 H, dd, J = 8.7 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                   
                 7.66 (2 H, d, J = 8.2 Hz), 7.78-7.86 (3 H, m). 
               
               
                 912 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 piperonyl 
                 1.76-1.98 (4 H, m), 2.04 (3 H, s), 2.44 (4 H, brs), 
               
               
                   
                   
                   
                   
                 2.54-2.72 (3 H, m), 3.43 (2 H, s), 3.54 (2 H, brs), 
               
               
                   
                   
                   
                   
                 3.63-3.67 (4 H, m), 5.94 (2 H, s), 6.70-6.89 (8 H, 
               
               
                   
                   
                   
                   
                 m), 7.44-7.59 (3 H, m), 7.80 (2 H, J = 2.0 Hz). 
               
               
                 913 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 benzyl 
                 1.77-1.97 (4 H, m), 2.07 (3 H, s), 2.45 (4 H, brs), 
               
               
                   
                   
                   
                   
                 2.53-2.75 (3 H, m), 3.54 (4 H, brs), 3.66 (4 H, brs), 
               
               
                   
                   
                   
                   
                 6.75-6.81 (3 H, m), 6.90 (1 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                 7.26-7.33 (6 H, m), 7.51-7.58 (3 H, m), 7.72 (1 H, 
               
               
                   
                   
                   
                   
                 d, J = 2.6 Hz), 7.79 (1 H, s). 
               
               
                 914 
                 3,4-Cl 2 Ph- 
                 —H 
                 piperonyl 
                 1.76-1.99 (4 H, m), 2.44 (4 H, brs), 2.54-2.74 (3 H, 
               
               
                   
                   
                   
                   
                 m), 3.43 (2 H, s), 3.54 (2 H, brs), 3.63-3.67 (4 H, 
               
               
                   
                   
                   
                   
                 m), 5.94 (2 H, s), 6.74-6.98 (8 H, m), 7.45- 
               
               
                   
                   
                   
                   
                 7.59 (3 H, m), 7.81-7.84 (3 H, m). 
               
               
                 915 
                 4-CF 3 Ph- 
                 —H 
                 piperonyl 
                 1.76-1.80 (2 H, m), 1.91-1.95 (2 H, m), 2.43 (4 H, 
               
               
                   
                   
                   
                   
                 brs), 2.59-2.73 (3 H, m), 3.43 (2 H, s), 3.54 (2 H, 
               
               
                   
                   
                   
                   
                 brs), 3.62 (4 H, brs), 5.94 (2 H, s), 6.72-6.75 (3 H, 
               
               
                   
                   
                   
                   
                 m), 6.84-6.96 (5 H, m), 7.57 (1 H, dd, J = 8.7 Hz, 
               
               
                   
                   
                   
                   
                 2.8 Hz), 7.66 (2 H, d, J = 8.4 Hz), 7.82-7.87 (4 H, 
               
               
                   
                   
                   
                   
                 m). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 223 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 716   
                 R 717   
                 M 
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 916 
                 —H 
                 piperonyl 
                 1 
                 1.31-1.45 (2 H, m), 1.82-2.02 (3 H, m), 2.33 (2 H, d, J = 
               
               
                   
                   
                   
                   
                 6.8 Hz), 2.43 (4 H, brs), 2.69 (2 H, t, J = 12.0 Hz), 
               
               
                   
                   
                   
                   
                 3.43 (2 H, s), 3.51-3.67 (6 H, m), 5.93 (2 H, s), 6.73- 
               
               
                   
                   
                   
                   
                 6.99 (8 H, m), 7.28 (2 H, d, J = 8.6 Hz), 7.50 (2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.6 Hz), 8.28 (1 H, d, J = 2.1 Hz), 8.43 (1 H, d, J = 2.1 Hz). 
               
               
                 917 
                 —H 
                 benzyl 
                 1 
                 1.34-1.44 (2 H, m), 1.82-2.00 (3 H, m), 2.32 (2 H, d, J = 
               
               
                   
                   
                   
                   
                 6.8 Hz), 2.43-2.47 (4 H, m), 2.69 (2 H, t, J = 12.0 Hz), 
               
               
                   
                   
                   
                   
                 3.51-3.67 (8 H, m), 6.88 (2 H, d, 
               
               
                   
                   
                   
                   
                 J = 9.2 Hz), 6.98 (2 H, 
               
               
                   
                   
                   
                   
                 d, J = 9.2 Hz), 7.25-7.32 (8 H, m), 7.50 (2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                 8.28 (1 H, d, J = 2.3 Hz), 
               
               
                   
                   
                   
                   
                 8.43 (1 H, d, J = 2.1 Hz). 
               
               
                 918 
                 —CH 3   
                 piperonyl 
                 1 
                 1.31-1.45 (2 H, m), 1.82-2.00 (3 H, m), 2.02 (3 H, s), 
               
               
                   
                   
                   
                   
                 2.33 (2 H, d, J = 6.8 Hz), 2.43 (4 H, brs), 2.68 (2 H, t, J = 
               
               
                   
                   
                   
                   
                 11.9 Hz), 3.41-3.67 (8 H, m), 5.92 (2 H, s), 6.73- 
               
               
                   
                   
                   
                   
                 6.92 (7 H, m), 7.25-7.30 (2 H, m), 7.50 (2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                 8.30 (1 H, d, J = 2.3 Hz), 8.41 (1 H, d, J = 2.3 Hz). 
               
               
                 919 
                 —CH 3   
                 benzyl 
                 1 
                 1.37-1.40 (2 H, m), 1.83-2.01 (3 H, m), 2.03 (3 H, s), 
               
               
                   
                   
                   
                   
                 2.31 (2 H, d, J = 6.9 Hz), 2.43-2.47 (4 H, m), 2.70 (2 H, t, 
               
               
                   
                   
                   
                   
                 J = 12.0 Hz), 3.51-3.67 (8 H, m), 6.74-6.80 (2 H, m), 
               
               
                   
                   
                   
                   
                 6.91 (1 H, d, J = 8.6 Hz), 7.24-7.33 (8 H, m), 7.52 (2 H, 
               
               
                   
                   
                   
                   
                 d, J = 8.4 Hz), 8.29 (1 H, d, 
               
               
                   
                   
                   
                   
                 J = 2.1 Hz), 8.42 (1 H, d, J = 2.3 Hz). 
               
               
                 920 
                 —H 
                 piperonyl 
                 0 
                 1.79-2.03 (4 H, m), 2.45 (4 H, brs), 2.57-2.76 (3 H, m), 
               
               
                   
                   
                   
                   
                 3.44 (2 H, s), 3.55 (2 H, brs), 3.66 (4 H, brs), 5.94 (2 H, s), 
               
               
                   
                   
                   
                   
                 6.72-6.78 (2 H, m), 6.85-7.00 (6 H, m), 7.28 (2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.6 Hz), 7.50 (2 H, d, J = 8.6 Hz), 8.28 (1 H, d, J = 2.1 Hz), 
               
               
                   
                   
                   
                   
                 8.42 (1 H, d, J = 2.1 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 224 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 718   
                 R 719   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 921 
                 3,4-Cl 2 Ph- 
                 piperonyl 
                 1.37-1.44 (2 H, m), 1.81-2.02 (3 H, m), 2.30 (2 H, d, J = 6.8 Hz), 
               
               
                   
                   
                   
                 2.42 (4 H, brs), 2.69 (2 H, t, J = 11.9 Hz), 3.43 (2 H, s), 
               
               
                   
                   
                   
                 3.43-3.65 (6 H, m), 3.68 (3 H, s), 5.94 (2 H, s), 6.46 (1 H, dd, 
               
               
                   
                   
                   
                 J = 8.7 Hz, 2.5 Hz), 6.54 (1 H, d, J = 2.3 Hz), 6.73- 
               
               
                   
                   
                   
                 6.76 (3 H, m), 6.85 (1 H, s), 6.93 (1 H, d, J = 8.6 Hz), 7.44- 
               
               
                   
                   
                   
                 7.57 (3 H, m), 7.79-7.83 (3 H, m). 
               
               
                 922 
                 4-CF 3 Ph- 
                 benzyl 
                 1.37-1.44 (2 H, m), 1.81-2.02 (3 H, m), 2.29 (2 H, d, J = 6.8 Hz), 
               
               
                   
                   
                   
                 2.42-2.46 (4 H, m), 2.69 (2 H, t, J = 12.0 Hz), 3.48- 
               
               
                   
                   
                   
                 3.63 (8 H, m), 3.67 (3 H, s), 6.46 (1 H, dd, J = 8.7 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                 6.54 (1 H, d, J = 2.6 Hz), 6.75 (1 H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                 6.92 (1 H, d, J = 8.7 Hz), 7.26-7.36 (6 H, m), 7.54 (1 H, dd, 
               
               
                   
                   
                   
                 J = 8.7 Hz, 2.8 Hz), 7.67 (2 H, d, J = 8.6 Hz), 7.75 (1 H, d, 
               
               
                   
                   
                   
                 J = 2.8 Hz), 7.83 (2 H, d, J = 8.1 Hz). 
               
               
                 923 
                 3,4-Cl 2 Ph- 
                 benzyl 
                 1.37-1.44 (2 H, m), 1.81-2.02 (3 H, m), 2.30 (2 H, d, J = 6.8 Hz), 
               
               
                   
                   
                   
                 2.42-2.46 (4 H, m), 2.69 (2 H, t, J = 11.9 Hz), 3.50- 
               
               
                   
                   
                   
                 3.66 (8 H, m), 3.67 (3 H, s), 6.45 (1 H, dd, J = 8.7 Hz, 2.5 Hz), 
               
               
                   
                   
                   
                 6.54 (1 H, d, J = 2.5 Hz), 6.74 (1 H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                 6.93 (1 H, d, J = 8.6 Hz), 7.26-7.32 (5 H, m), 7.43-7.56 (3 H, 
               
               
                   
                   
                   
                 m), 7.79-7.83 (3 H, m). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 225 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 720   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 924 
                 benzyl 
                 1.63-1.77 (2 H, m), 1.81-1.98 (2 H, m), 2.44 (4 H, brs), 2.53-2.72 (3 H, m), 
               
               
                   
                   
                 3.53 (4 H, brs), 3.65-3.69 (4 H, m), 6.90-7.04 (5 H, m), 7.26-7.33 (5 H, m), 
               
               
                   
                   
                 7.74 (2 H, d, J = 8.2 Hz), 7.99 (2 H, d, J = 8.2 Hz), 8.14-8.19 (2 H, m), 
               
               
                   
                   
                 8.27 (1 H, d, J = 2.6 Hz). 
               
               
                 925 
                 piperonyl 
                 1.64-1.77 (2 H, m), 1.89-1.97 (2 H, m), 2.39-2.41 (4 H, m), 2.56-2.75 (3 H, 
               
               
                   
                   
                 m), 3.43 (2 H, s), 3.52-3.69 (6 H, m), 5.94 (2 H, s), 6.70-6.77 (2 H, m), 6.85- 
               
               
                   
                   
                 7.04 (6 H, m), 7.74 (2 H, d, J = 8.2 Hz), 7.99 (2 H, d, J = 8.2 Hz), 8.14- 
               
               
                   
                   
                 8.18 (2 H, m), 8.27 (1 H, d, J = 2.5 Hz). 
               
               
                   
               
             
          
         
       
     
         [1081]    The following compounds were made in the same manner as in Reference Example 918. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 226 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 721   
                 Xb 9   
                 R 722   
                 M 
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 926 
                 4-CF 3 Ph- 
                 —CH 2 — 
                 benzyl 
                 1 
                 2.38-2.44 (4 H, m), 2.63-2.68 (2 H, m), 2.89- 
               
               
                   
                   
                   
                   
                   
                 2.95 (2 H, m), 3.45-3.49 (2 H, m), 3.52 (2 H, 
               
               
                   
                   
                   
                   
                   
                 s), 3.64-3.68 (2 H, m), 6.85 (1 H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.93-6.98 (2 H, m), 7.08-7.13 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                 7.28-7.36 (5 H, m), 7.44-7.51 (4 H, m), 7.96 
               
               
                   
                   
                   
                   
                   
                 (1 H, d, J = 2.5 Hz), 8.00-8.04 (1 H, m), 
               
               
                   
                   
                   
                   
                   
                 8.14 (1 H, s), 8.18 (1 H, s). 
               
               
                 927 
                 3,4-Cl 2 Ph- 
                 —CH(CH 3 )— 
                 piperonyl 
                 0 
                 1.47 (3 H, d, J = 6.8 Hz), 2.00-2.15 (1 H, m), 
               
               
                   
                   
                   
                   
                   
                 2.25-2.50 (3 H, m), 3.36 (2 H, s), 3.36- 
               
               
                   
                   
                   
                   
                   
                 3.80 (4 H, m), 3.98 (1 H, q, J = 6.8 Hz), 
               
               
                   
                   
                   
                   
                   
                 5.93 (2 H, s), 6.65-6.75 (2 H, m), 6.79 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 1.2 Hz), 6.89 (1 H, d, J = 8.8 Hz), 7.02- 
               
               
                   
                   
                   
                   
                   
                 7.06 (2 H, m), 7.16-7.33 (4 H, m), 7.57 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 2.4 Hz), 7.91 (1 H, d, J = 2.7 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.00 (1 H, brs), 8.05-8.10 (2 H, m). 
               
               
                 928 
                 3,4-Cl 2 Ph- 
                 —C(CH 3 ) 2 — 
                 piperonyl 
                 0 
                 1.55 (6 H, s), 1.80-2.15 (2 H, m), 2.20- 
               
               
                   
                   
                   
                   
                   
                 2.55 (2 H, m), 2.95-3.20 (2 H, m), 3.31 (2 H, 
               
               
                   
                   
                   
                   
                   
                 s), 3.50-3.90 (2 H, m), 5.91 (2 H, s), 6.60- 
               
               
                   
                   
                   
                   
                   
                 6.72 (2 H, m), 6.76 (1 H, d, J = 1.3 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.90 (1 H, d, J = 8.9 Hz), 7.07-7.33 (6 H, m), 
               
               
                   
                   
                   
                   
                   
                 7.58 (1 H, d, J = 2.4 Hz), 7.88 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 2.7 Hz), 8.09-8.11 (2 H, m), 8.17 (1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 8.9 Hz, 2.8 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 227 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 723   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 929 
                 benzyl 
                 2.33-2.55 (4 H, m), 3.36-3.79 (6 H, m), 6.89 (1 H, d, J = 8.7 Hz), 7.07- 
               
               
                   
                   
                 7.15 (3 H, m), 7.24-7.38 (6 H, m), 7.67-7.70 (2 H, m), 8.00 (2 H, d, J = 7.9 Hz), 
               
               
                   
                   
                 8.09-8.13 (1 H, m), 8.32 (1 H, d, J = 2.3 Hz), 9.05 (1 H, brs). 
               
               
                 930 
                 piperonyl 
                 2.36-2.44 (4 H, m), 3.37-3.76 (6 H, m), 5.93 (2 H, s), 6.69-6.75 (2 H, m), 
               
               
                   
                   
                 6.83 (1 H, brs), 6.86 (1 H, d, J = 8.7 Hz), 7.04-7.06 (2 H, m), 7.10- 
               
               
                   
                   
                 7.14 (1 H, m), 7.27-7.36 (1 H, m), 7.65 (2 H, d, J = 8.4 Hz), 7.99 (2 H, d, J = 
               
               
                   
                   
                 8.1 Hz), 8.07-8.12 (1 H, m), 8.34 (1 H, d, J = 2.6 Hz), 9.41 (1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 228 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 724   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 931 
                 4-CF 3 PhCH 2 N(SO 2 CH 3 )— 
                 2.31-2.41 (4 H, m), 2.58-2.64 (2 H, m), 2.94-2.97 (2 H, m), 
               
               
                   
                   
                 2.99 (3 H, s), 3.38-3.41 (4 H, m), 3.60-3.65 (2 H, m), 
               
               
                   
                   
                 4.85 (2 H, s), 5.94 (2 H, s), 6.65-6.75 (2 H, m), 6.83- 
               
               
                   
                   
                 6.87 (2 H, m), 6.95-7.05 (2 H, m), 7.20-7.30 (2 H, m), 7.38- 
               
               
                   
                   
                 7.41 (2 H, m), 7.52 (1 H, dd, J = 8.8 Hz, 2.8 Hz), 7.54- 
               
               
                   
                   
                 7.57 (2 H, m), 8.04 (1 H, d, J = 2.3 Hz). 
               
               
                 932 
                 3,4-Cl 2 PhCH 2 N(SO 2 CH 3 )— 
                 2.25-2.45 (4 H, m), 2.59-2.65 (2 H, m), 2.94-3.05 (5 H, m), 
               
               
                   
                   
                 3.30-3.45 (4 H, m), 3.55-3.70 (2 H, m), 4.74 (2 H, s), 
               
               
                   
                   
                 5.95 (2 H, s), 6.65-6.80 (2 H, m), 6.84-6.89 (2 H, m), 7.02- 
               
               
                   
                   
                 7.15 (3 H, m), 7.23-7.30 (3 H, m), 7.30-7.40 (2 H, m), 
               
               
                   
                   
                 8.03 (1 H, d, J = 2.7 Hz). 
               
               
                 933 
                 3,4-Cl 2 PhCH 2 NHCO— 
                 2.25-2.45 (4 H, m), 2.59-2.65 (2 H, m), 2.94-3.00 (2 H, m), 
               
               
                   
                   
                 3.37-3.41 (4 H, m), 3.59-3.65 (2 H, m), 4.58 (2 H, d, J =5.9 Hz), 
               
               
                   
                   
                 5.94 (2 H, s), 6.50-6.65 (1 H, m), 6.65-6.80 (2 H, m), 
               
               
                   
                   
                 6.84 (1 H, s), 6.94 (1 H, d, J = 8.6 Hz), 7.03-7.06 (2 H, m), 
               
               
                   
                   
                 7.17 (1 H, dd, J = 8.2 Hz, 2.0 Hz), 7.22-7.26 (2 H, m), 
               
               
                   
                   
                 7.38-7.42 (2 H, m), 8.14 (1 H, dd, J = 8.6 Hz, 2.5 Hz), 
               
               
                   
                   
                 8.57 (1 H, d, J. 2.3 Hz). 
               
               
                 934 
                 3,4-Cl 2 PhNHCON(C 2 H 5 )— 
                 1.17 (3 H, t, J = 7.1 Hz), 2.32-2.42 (4 H, m), 2.61- 
               
               
                   
                   
                 2.67 (2 H, m), 2.97-3.03 (2 H, m), 3.39-3.43 (4 H, m), 3.61- 
               
               
                   
                   
                 3.65 (2 H, m), 3.74 (2 H, q, J = 7.1 Hz), 5.94 (2 H, s), 
               
               
                   
                   
                 6.00 (1 H, brs), 6.70-6.85 (3 H, m), 7.05 (1 H, d, J = 8.7 Hz), 
               
               
                   
                   
                 7.09-7.13 (3 H, m), 7.26-7.31 (3 H, m), 7.52 (1 H, d, J = 
               
               
                   
                   
                 2.5 Hz), 7.61 (1 H, dd, J = 8.7 Hz, 2.8 Hz), 8.12 (1 H, d, 
               
               
                   
                   
                 J = 2.4 Hz). 
               
               
                 935 
                 3,4-Cl 2 PhN(CH 3 )— 
                 2.25-2.45 (4 H, m), 2.59-2.65 (2 H, m), 2.95-3.00 (2 H, m), 
               
               
                   
                   
                 3.25 (3 H, s), 3.38-3.42 (4 H, m), 3.61-3.65 (2 H, m), 
               
               
                   
                   
                 5.94 (2 H, s), 6.55-6.65 (1 H, m), 6.65-6.80 (2 H, m), 6.80- 
               
               
                   
                   
                 6.85 (2 H, m), 6.89-6.93 (1 H, m), 7.06-7.10 (2 H, m), 7.20- 
               
               
                   
                   
                 7.27 (3 H, m), 7.45-7.50 (1 H, m), 8.01 (1 H, d, J = 2.4 Hz). 
               
               
                 936 
                 3,4-Cl 2 PhNH— 
                 2.31-2.41 (4 H, m), 2.59-2.65 (2 H, m), 2.94-3.00 (2 H, m), 
               
               
                   
                   
                 3.37-3.41 (4 H, m), 3.61-3.65 (2 H, m), 5.61 (1 H, brs), 
               
               
                   
                   
                 5.94 (2 H, s), 6.69-6.80 (3 H, m), 6.84 (1 H, s), 6.90 (1 H, d, 
               
               
                   
                   
                 J = 8.7 Hz), 6.96 (1 H, d, J = 2.7 Hz), 7.04-7.07 (2 H, m), 
               
               
                   
                   
                 7.21-7.25 (3 H, m), 7.49 (1 H, dd, J = 8.7 Hz, 2.9 Hz), 
               
               
                   
                   
                 8.00 (1 H, d, J = 2.8 Hz). 
               
               
                 937 
                 4-CF 3 PhCH 2 NHCO— 
                 2.31-2.40 (4 H, m), 2.59-2.65 (2 H, m), 2.95-3.01 (2 H, m), 
               
               
                   
                   
                 3.38-3.41 (4 H, m), 3.60-3.64 (2 H, m), 4.70 (2 H, d, J =5.8 Hz), 
               
               
                   
                   
                 5.94 (2 H, s), 6.35-6.50 (1 H, m), 6.70-6.77 (2 H, m), 
               
               
                   
                   
                 6.84 (1 H, s), 6.95 (1 H, d, J = 8.6 Hz), 7.03-7.07 (2 H, m), 
               
               
                   
                   
                 7.23-7.26 (2 H, m), 7.44-7.47 (2 H, m), 7.59-7.62 (2 H, m), 
               
               
                   
                   
                 8.14 (1 H, dd, J = 8.6 Hz, 2.5 Hz), 8.57 (1 H, d, J = 2.4 Hz). 
               
               
                 938 
                 3,4-Cl 2 PhN(C 2 H 5 )CONH— 
                 1.17 (3 H, t, J = 7.1 Hz), 2.30-2.40 (4 H, m), 2.57- 
               
               
                   
                   
                 2.63 (2 H, m), 2.92-2.98 (2 H, m), 3.37-3.40 (4 H, m), 3.60- 
               
               
                   
                   
                 3.64 (2 H, m), 3.77 (2 H, q, J = 7.1 Hz), 5.94 (2 H, s), 6.65- 
               
               
                   
                   
                 6.80 (2 H, m), 6.81-6.85 (2 H, m), 6.98-7.00 (2 H, m), 7.17- 
               
               
                   
                   
                 7.21 (3 H, m), 7.45 (1 H, d, J = 2.4 Hz), 7.57 (1 H, d, J = 
               
               
                   
                   
                 8.5 Hz), 7.85-7.91 (2 H, m). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 229 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 725   
                 R 726   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 939 
                 3,4-Cl 2 PhNHCO— 
                 —CH 3   
                 2.30-2.50 (4 H, m), 2.78 (3 H, s), 3.42 (2 H, s), 3.50- 
               
               
                   
                   
                   
                 3.65 (4 H, m), 3.82 (2 H, s), 5.95 (2 H, s), 6.65- 
               
               
                   
                   
                   
                 6.75 (2 H, m), 6.85 (1 H, s), 7.05 (1 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                 7.26-7.30 (1 H, m), 7.39-7.43 (2 H, m), 7.49- 
               
               
                   
                   
                   
                 7.53 (2 H, m), 7.88 (1 H, d, J = 2.4 Hz), 8.24 (1 H, 
               
               
                   
                   
                   
                 dd, J = 8.6 Hz, 2.5 Hz), 8.31 (1 H, brs), 8.66 (1 H, 
               
               
                   
                   
                   
                 d, J = 2.4 Hz). 
               
               
                 940 
                 4-CF 3 PhNHCO— 
                 —CH 3   
                 2.30-2.45 (4 H, m), 2.78 (3 H, s), 3.41 (2 H, s), 3.55- 
               
               
                   
                   
                   
                 3.59 (4 H, m), 3.82 (2 H, s), 5.94 (2 H, s), 6.65- 
               
               
                   
                   
                   
                 6.80 (2 H, m), 6.85 (1 H, s), 7.05 (1 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                 7.26-7.30 (1 H, m), 7.41 (1 H, d, J = 2.8 Hz), 
               
               
                   
                   
                   
                 7.51 (1 H; d, J = 8.8 Hz), 7.59-7.63 (2 H, m), 7.77- 
               
               
                   
                   
                   
                 7.80 (2 H, m), 8.26 (1 H, dd, J = 8.6 Hz, 2.5 Hz), 
               
               
                   
                   
                   
                 8.54 (1 H, brs), 8.66 (1 H, d, J = 2.2 Hz). 
               
               
                 941 
                 3,4-Cl 2 PhCH 2 NHCO— 
                 —CH 3   
                 2.30-2.45 (4 H, m), 2.80 (3 H, s), 3.42 (2 H, s), 3.50- 
               
               
                   
                   
                   
                 3.65 (4 H, m), 3.81 (2 H, s), 4.59 (2 H, d, J = 5.9 Hz), 
               
               
                   
                   
                   
                 5.95 (2 H, s), 6.50-6.60 (1 H, m), 6.65- 
               
               
                   
                   
                   
                 6.80 (2 H, m), 6.85 (1 H, s), 7.01 (1 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                 7.18 (1 H, dd, J = 8.2 Hz, 2.0 Hz), 7.30 (1 H, 
               
               
                   
                   
                   
                 dd, J = 8.8 Hz, 2.7 Hz), 7.39-7.43 (3 H, m), 
               
               
                   
                   
                   
                 7.54 (1 H, d, J = 8.8 Hz), 8.18 (1 H, dd, J = 8.6 Hz, 
               
               
                   
                   
                   
                 2.5 Hz), 8.56 (1 H, d, J = 2.4 Hz). 
               
               
                 942 
                 4-CF 3 PhCH 2 NHCO— 
                 —CH 3   
                 2.30-2.45 (4 H, m), 2.80 (3 H, s), 3.42 (2 H, s), 3.50- 
               
               
                   
                   
                   
                 3.65 (4 H, m), 3.81 (2 H, s), 4.70 (2 H, d, J = 5.9 Hz), 
               
               
                   
                   
                   
                 5.94 (2 H, s), 6.50-6.65 (1 H, m), 6.70- 
               
               
                   
                   
                   
                 6.80 (2 H, m), 6.85 (1 H, s), 7.00 (1 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                 7.29 (1 H, dd, J = 8.8 Hz, 2.7 Hz), 7.39- 
               
               
                   
                   
                   
                 7.62 (6 H, m), 8.18 (1 H, dd, J = 8.6 Hz, 2.5 Hz), 
               
               
                   
                   
                   
                 8.57 (1 H, d, J = 2.4 Hz). 
               
               
                 943 
                 3,4-Cl 2 PhN(CH 3 )— 
                 —C 2 H 5   
                 1.02 (3 H, t, J = 7.1 Hz), 2.35-2.40 (4 H, m), 
               
               
                   
                   
                   
                 3.22 (2 H, q, J = 7.1 Hz), 3.27 (3 H, s), 3.40 (2 H, s), 
               
               
                   
                   
                   
                 3.45-3.60 (4 H, m), 3.85 (2 H, s), 5.94 (2 H, s), 
               
               
                   
                   
                   
                 6.64 (1 H, dd, J = 8.9 Hz, 2.9 Hz), 6.65-6.75 (2 H, 
               
               
                   
                   
                   
                 m), 6.84 (1 H, s), 6.90 (1 H, d, J = 2.8 Hz), 
               
               
                   
                   
                   
                 6.96 (1 H, d, J = 8.7 Hz), 7.22-7.26 (1 H, m), 7.26- 
               
               
                   
                   
                   
                 7.35 (1 H, m), 7.42 (1 H, d, J = 2.8 Hz), 7.50 (1 H, 
               
               
                   
                   
                   
                 dd, J = 8.7 Hz, 2.9 Hz), 7.66 (1 H, d, J = 8.8 Hz), 
               
               
                   
                   
                   
                 8.00 (1 H, d, J = 2.6 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 230 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 727   
                 R 728   
                 R 729   
                 R 730   
                 R 731   
                 Xb 10   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 944 
                 —Cl 
                 —Cl 
                 —CH 3   
                 —CH 3   
                 —H 
                 —N(CH 3 )— 
                 2.30 (6 H, s), 2.32-2.45 (4 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 2.83 (3 H, s), 3.30-3.45 (4 H, m), 3.55- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 3.70 (2 H, m), 3.83 (2 H, s), 5.94 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.69-6.76 (4 H, m), 6.83 (1 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.96 (1 H, d, J = 8.6 Hz), 7.40 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.7 Hz), 7.50 (1 H, dd, J 8.8 Hz, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 2.5 Hz), 7.87 (1 H, d, J = 2.4 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.19 (1 H, dd, J = 8.6 Hz, 2.5 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.3 1 (1 H, brs), 8.68 (1 H, d, J = 2.2 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz). 
               
               
                 945 
                 —CF 3   
                 —H 
                 —CH 3   
                 —CH 3   
                 —H 
                 —N(CH 3 )— 
                 2.30-2.45 (10 H, m), 2.86 (3 H, s), 3.30- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 3.45 (4 H, m), 3.55-3.70 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 3.84 (2 H, s), 5.94 (2 H, s), 6.65- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.78 (4 H, m), 6.84 (1 H, s), 6.99 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 J = 8.6 Hz), 7.60-7.65 (2 H, m), 7.70- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.78 (2 H, m), 8.07 (1 H, brs), 8.21 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dd, J = 8.6 Hz, 2.6 Hz), 8.70 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 2.5 Hz). 
               
               
                 946 
                 —CF 3   
                 —H 
                 —H 
                 —H 
                 —H 
                 —CH(CH 3 )— 
                 1.30-1.36 (3 H, m), 2.10-2.40 (4 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 2.47-2.67 (2 H, m), 3.25-3.45 (5 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 3.50-3.65 (2 H, m), 5.93 (2 H, s), 6.65- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.75 (2 H, m), 6.83 (1 H, d, J = 0.9 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.01 (1 H, dd, J = 8.6 Hz, 0.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.06-7.15 (2 H, m), 7.25-7.30 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.60-7.64 (2 H, m), 7.74-7.78 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.14 (1 H, brs), 8.22 (1 H, dd, J = 8.6 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz, 2.6 Hz), 8.67-8.68 (1 H, m). 
               
               
                 947 
                 —CF 3   
                 —H 
                 —H 
                 —H 
                 —CH 3   
                 —CH 2 — 
                 1.14-1.17 (3 H, m), 1.95-2.10 (1 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 2.15-2.45 (3 H, m), 2.55-2.70 (1 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 3.45-3.70 (2 H, m), 5.92-5.94 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.65-6.85 (3 H, m), 6.95-7.06 (3 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.10-7.30 (2 H, m), 7.59-7.63 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.75-7.79 (2 H, m), 8.24 (1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.6 Hz, 2.6 Hz), 8.40 (1 H, brs), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.71 (1 H, d, J = 2.4 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 231 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example No. 
                 R 732   
                   1 H NMR (DMSO-d 6 ) δ ppm 
               
               
                   
               
               
                 948 
                 —Br 
                 2.20-2.35 (4 H, m), 2.59-2.65 (2 H, m), 2.79-2.85 (2 H, m), 3.20-3.60 (6 H, 
               
               
                   
                   
                 m), 5.99 (2 H, s), 6.73-6.77 (1 H, m), 6.83-6.86 (2 H, m), 7.07-7.10 (2 H, m), 
               
               
                   
                   
                 7.27-7.34 (4 H, m), 7.62-7.65 (2 H, m), 8.44-8.48 (2 H, m), 10.90 (1 H, brs). 
               
               
                 949 
                 —H 
                 2.20-2.35 (4 H, m), 2.59-2.65 (2 H, m), 2.78-2.84 (2 H, m), 3.38-3.44 (6 H, 
               
               
                   
                   
                 m), 5.98 (2 H, s), 6.72-6.76 (1 H, m), 6.82-6.86 (2 H, m), 7.04-7.08 (2 H, m), 
               
               
                   
                   
                 7.17 (1 H, d, J = 8.8 Hz), 7.26-7.33 (4 H, m), 7.61-7.65 (2 H, m), 8.17 (1 H, 
               
               
                   
                   
                 dd, J = 8.7 Hz, 2.6 Hz), 8.55 (1 H, d, J = 2.6 Hz), 10.98 (1 H, brs). 
               
               
                   
               
             
          
         
       
     
       Example 950 
     Production of 3,4-dichloro-N-{6-[4-(4-phenethylpiperazine-1-carbonyl)phenoxy]pyridin-3-yl}benzamide 
       [1082]    To a solution of ethyl 4-(5-aminopyridin-2-yloxy)benzoate (690 mg, 2.7 mmol) in THF (10 mL) were added triethylamine (0.73 mL, 5.3 mmol) and 3,4-dichlorobenzoyl chloride (570 mg, 2.7 mmol) under ice cooling, and the resulting solution was stirred for 1 hour under ice cooling. This reaction solution was concentrated under reduced pressure, and to the residue was added ethyl acetate. The resulting solution was washed with water, 1 N hydrochloric acid and brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was washed, when hot, with n-hexane:dichloromethane=1:2. The product was dissolved in THF (20 mL). To the residue was added 1 N aqueous sodium hydroxide (2.9 mL, 2.9 mmol), and this solution was stirred for 5 hours at 100° C. THF was evaporated, and the aqueous layer was made to have a pH of 3 with 1 N hydrochloric acid. Precipitated matter was collected by filtration, and dried. The resulting product was dissolved in bMF (10 mL), and 1-phenethylpiperazine (200 mg, 1.1 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (240 mg, 1.3 mmol) and 1-hydroxybenzotriazole monohydrate (170 mg, 1.3 mmol) were added to the solution. The resulting solution was stirred for 1 day at room temperature. This reaction solution was concentrated under reduced pressure, and to the residue was added chloroform. The resulting solution was washed with water, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel column chromatography (methanol:chloroform=1:99), to thereby yield 310 mg of the title compound. 
         [1083]    Appearance: White Powder 
         [1084]      1 H NMR (CDCl 3 ) δ 2.54 (4H, brs), 2.62-2.68 (2H, m), 2.79-2.85 (2H, m), 3.60-3.73 (4H, m), 6.95 (1H, d, J=8.9 Hz), 7.09-7.23 (5H, m), 7.27-7.33 (2H, m), 7.37-7.41 (2H, m), 7.55 (1H, d, J=8.3 Hz), 7.74-7.78 (1H, m), 8.04 (1H, d, J=2.0 Hz), 8.11-8.15 (1H, m), 8.31 (1H, d, J=2.6 Hz), 8.57 (1H, brs). 
         [1085]    The following compounds were produced in the same manner as in Example 950. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 232 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 733   
                 R 734   
                 R 735   
                 R 736   
                 R 737   
                 MS (M +  + H) 
               
               
                   
               
               
                 951 
                 —CH 3   
                 —F 
                 —H 
                 —H 
                 4-CNPhCH 2 — 
                 550 
               
               
                 952 
                 —H 
                 —F 
                 —F 
                 —H 
                 4-CNPhCH 2 — 
                 554 
               
               
                 953 
                 —H 
                 —Cl 
                 —H 
                 —Cl 
                 4-CNPhCH 2 — 
                 586 
               
               
                 954 
                 —H 
                 —OCF 3   
                 —H 
                 —H 
                 4-CNPhCH 2 — 
                 602 
               
               
                 955 
                 —CH 3   
                 —F 
                 —H 
                 —H 
                 2-pyridylmethyl 
                 526 
               
               
                 956 
                 —H 
                 —CH 3   
                 —CH 3   
                 —H 
                 2-pyridylmethyl 
                 522 
               
               
                 957 
                 —H 
                 —F 
                 —F 
                 —H 
                 2-pyridylmethyl 
                 530 
               
               
                 958 
                 —H 
                 —Cl 
                 —H 
                 —Cl 
                 2-pyridylmethyl 
                 530 
               
               
                 959 
                 —H 
                 —CF 3   
                 —H 
                 —H 
                 2-pyridylmethyl 
                 562 
               
               
                 960 
                 —H 
                 —H 
                 —Cl 
                 —H 
                 2-pyridylmethyl 
                 528 
               
               
                 961 
                 —H 
                 —CF 3   
                 —H 
                 —F 
                 2-pyridylmethyl 
                 580 
               
               
                 962 
                 —H 
                 —OCF 3   
                 —H 
                 —H 
                 2-pyridylmethyl 
                 578 
               
               
                 963 
                 —CH 3   
                 —F 
                 —H 
                 —H 
                 3-pyridylmethyl 
                 526 
               
               
                 964 
                 —H 
                 —CH 3   
                 —CH 3   
                 —H 
                 3-pyridylmethyl 
                 522 
               
               
                 965 
                 —H 
                 —F 
                 —F 
                 —H 
                 3-pyridylmethyl 
                 530 
               
               
                 966 
                 —H 
                 —Cl 
                 —H 
                 —Cl 
                 3-pyridylmethyl 
                 562 
               
               
                 967 
                 —H 
                 —CF 3   
                 —H 
                 —H 
                 3-pyridylmethyl 
                 562 
               
               
                 968 
                 —H 
                 —H 
                 —Cl 
                 —H 
                 3-pyridylmethyl 
                 528 
               
               
                 969 
                 —H 
                 —CF 3   
                 —H 
                 —F 
                 3-pyridylmethyl 
                 580 
               
               
                 970 
                 —CH 3   
                 —F 
                 —H 
                 —H 
                 4-pyridylmethyl 
                 526 
               
               
                 971 
                 —H 
                 —CH 3   
                 —CH 3   
                 —H 
                 4-pyridylmethyl 
                 522 
               
               
                 972 
                 —H 
                 —F 
                 —F 
                 —H 
                 4-pyridylmethyl 
                 530 
               
               
                 973 
                 —H 
                 —Cl 
                 —H 
                 —Cl 
                 4-pyridylmethyl 
                 562 
               
               
                 974 
                 —H 
                 —CF 3   
                 —H 
                 —H 
                 4-pyridylmethyl 
                 562 
               
               
                 975 
                 —H 
                 —H 
                 —Cl 
                 —H 
                 4-pyridylmethyl 
                 528 
               
               
                 976 
                 —H 
                 —CF 3   
                 —H 
                 —F 
                 4-pyridylmethyl 
                 580 
               
               
                 977 
                 —H 
                 —OCF 3   
                 —H 
                 —H 
                 4-pyridylmethyl 
                 578 
               
               
                 978 
                 —CH 3   
                 —F 
                 —H 
                 —H 
                 piperonyl 
                 569 
               
               
                 979 
                 —H 
                 —CH 3   
                 —CH 3   
                 —H 
                 piperonyl 
                 565 
               
               
                 980 
                 —H 
                 —F 
                 —F 
                 —H 
                 piperonyl 
                 573 
               
               
                 981 
                 —H 
                 —Cl 
                 —H 
                 —Cl 
                 piperonyl 
                 605 
               
               
                 982 
                 —H 
                 —CF 3   
                 —H 
                 —H 
                 piperonyl 
                 605 
               
               
                 983 
                 —H 
                 —CF 3   
                 —H 
                 —F 
                 piperonyl 
                 623 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 233 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 738   
                 R 739   
                 R 740   
                 R 741   
                 R 742   
                 MS (M +  + H) 
               
               
                   
               
             
          
           
               
                 984 
                 —H 
                 —OCF 3   
                 —H 
                 —H 
                 piperonyl 
                 621 
               
               
                 985 
                 —H 
                 —CH 3   
                 —CH 3   
                 —H 
                 benzyl 
                 521 
               
               
                 986 
                 —H 
                 —F 
                 —F 
                 —H 
                 benzyl 
                 529 
               
               
                 987 
                 —CH 3   
                 —F 
                 —H 
                 —H 
                 4-AcNHPhCH 2 — 
                 582 
               
               
                 988 
                 —H 
                 —CH 3   
                 —CH 3   
                 —H 
                 4-ACNHPhCH 2 — 
                 578 
               
               
                 989 
                 —H 
                 —F 
                 —F 
                 —H 
                 4-AcNHPhCH 2 — 
                 586 
               
               
                 990 
                 —H 
                 —Cl 
                 —H 
                 —Cl 
                 4-AcNHPhCH 2 — 
                 618 
               
               
                 991 
                 —H 
                 —CF 3   
                 —H 
                 —H 
                 4-AcNHPhCH 2 — 
                 618 
               
               
                 992 
                 —H 
                 —H 
                 —Cl 
                 —H 
                 4-AcNHPhCH 2 — 
                 584 
               
               
                 993 
                 —H 
                 —CF 3   
                 —H 
                 —F 
                 4-AcNHPhCH 2 — 
                 636 
               
               
                 994 
                 —H 
                 —OCF 3   
                 —H 
                 —H 
                 4-AcNHPhCH 2 — 
                 634 
               
               
                 995 
                 —CH 3   
                 —F 
                 —H 
                 —H 
                 2,3-(CH 3 ) 2 PhCH 2 — 
                 553 
               
               
                 996 
                 —H 
                 —CH 3   
                 —CH 3   
                 —H 
                 2,3-(CH 3 ) 2 PhCH 2 — 
                 549 
               
               
                 997 
                 —H 
                 —F 
                 —F 
                 —H 
                 2,3-(CH 3 ) 2 PhCH 2 — 
                 557 
               
               
                 998 
                 —H 
                 —Cl 
                 —H 
                 —Cl 
                 2,3-(CH 3 ) 2 PhCH 2 — 
                 589 
               
               
                 999 
                 —H 
                 —CF 3   
                 —H 
                 —H 
                 2,3-(CH 3 ) 2 PhCH 2 — 
                 589 
               
               
                 1000 
                 —H 
                 —H 
                 —Cl 
                 —H 
                 2,3-(CH 3 ) 2 PhCH 2 — 
                 555 
               
               
                 1001 
                 —H 
                 —CF 3   
                 —H 
                 —F 
                 2,3-(CH 3 ) 2 PhCH 2 — 
                 607 
               
               
                 1002 
                 —H 
                 —OCF 3   
                 —H 
                 —H 
                 2,3-(CH 3 ) 2 PhCH 2 — 
                 605 
               
               
                 1003 
                 —CH 3   
                 —F 
                 —H 
                 —H 
                 3-furylmethyl 
                 515 
               
               
                 1004 
                 —H 
                 —CH 3   
                 —CH 3   
                 —H 
                 3-furylmethyl 
                 511 
               
               
                 1005 
                 —H 
                 —F 
                 —F 
                 —H 
                 3-furylmethyl 
                 519 
               
               
                 1006 
                 —H 
                 —Cl 
                 —H 
                 —Cl 
                 3-furylmethyl 
                 551 
               
               
                 1007 
                 —H 
                 —CF 3   
                 —H 
                 —H 
                 3-furylmethyl 
                 551 
               
               
                 1008 
                 —H 
                 —H 
                 —Cl 
                 —H 
                 3-furylmethyl 
                 517 
               
               
                 1009 
                 —H 
                 —Cl 
                 —Cl 
                 —H 
                 3-furylmethyl 
                 551 
               
               
                 1010 
                 —H 
                 —CF 3   
                 —H 
                 —F 
                 3-furylmethyl 
                 569 
               
               
                 1011 
                 —H 
                 —OCF 3   
                 —H 
                 —H 
                 3-furylmethyl 
                 567 
               
               
                 1012 
                 —CH 3   
                 —F 
                 —H 
                 —H 
                 3-pyridyl 
                 512 
               
               
                 1013 
                 —H 
                 —CH 3   
                 —CH 3   
                 —H 
                 3-pyridyl 
                 508 
               
               
                 1014 
                 —H 
                 —F 
                 —F 
                 —H 
                 3-pyridyl 
                 516 
               
               
                 1015 
                 —H 
                 —Cl 
                 —H 
                 —Cl 
                 3-pyridyl 
                 548 
               
               
                 1016 
                 —H 
                 —CF 3   
                 —H 
                 —H 
                 3-pyridyl 
                 548 
               
               
                 1017 
                 —H 
                 —CF 3   
                 —H 
                 —F 
                 3-pyridyl 
                 566 
               
               
                 1018 
                 —H 
                 —OCF 3   
                 —H 
                 —H 
                 3-pyridyl 
                 564 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 234 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example No. 
                 R 743   
                 R 744   
                 R 745   
                 R 746   
                 MS (M +  + H) 
               
               
                   
               
               
                 1019 
                 —CH 3   
                 —F 
                 —H 
                 —H 
                 519 
               
               
                 1020 
                 —H 
                 —CH 3   
                 —CH 3   
                 —H 
                 515 
               
               
                 1021 
                 —H 
                 —F 
                 —F 
                 —H 
                 523 
               
               
                 1022 
                 —H 
                 —Cl 
                 —H 
                 —Cl 
                 555 
               
               
                 1023 
                 —H 
                 —CF 3   
                 —H 
                 —H 
                 555 
               
               
                 1024 
                 —H 
                 —H 
                 —Cl 
                 —H 
                 521 
               
               
                 1025 
                 —H 
                 —Cl 
                 —Cl 
                 —H 
                 555 
               
               
                 1026 
                 —H 
                 —CF 3   
                 —H 
                 —F 
                 573 
               
               
                 1027 
                 —H 
                 —OCF 3   
                 —H 
                 —H 
                 571 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 235 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example No. 
                 R 747   
                 MS (M +  + H) 
               
               
                   
               
               
                 1028 
                 4-CNPhCH 2 — 
                 544 
               
               
                 1029 
                 2-pyridylmethyl 
                 520 
               
               
                 1030 
                 3-pyridylmethyl 
                 520 
               
               
                 1031 
                 4-pyridylmethyl 
                 520 
               
               
                 1032 
                 4-AcNHPhCH 2 — 
                 576 
               
               
                 1033 
                 2,3-(CH 3 ) 2 PhCH 2 — 
                 547 
               
               
                 1034 
                 3-furylmethyl 
                 509 
               
               
                   
               
               
                 1035 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 513 
               
               
                   
               
             
          
         
       
     
       Example 1036 
     Production of 2-{3-methyl-4-[5-(4-trifluoromethylbenzoyl)pyridin-2-yloxy]phenylamino}-1-(4-piperonylpiperazin-1-yl)ethanone 
       [1086]    To a solution of 2-chloro-5-(4-trifluoromethylbenzoyl)pyridine (1.00 g, 3.5 mmol) in DMF (30 mL) were added N-(4-hydroxy-3-methylphenyl)glycine ethyl ester (0.81 g, 3.9 mmol), cesium carbonate (1.71 g, 5.2 mmol) and copper (I) iodide (200 mg, 1.05 mmol), and the resulting solution was stirred for 3.5 hours at 60° C. under an argon atmosphere. The resulting reaction solution was filtered and concentrated. To the residue was added water and extracted with ethyl acetate. The ethyl acetate layer was washed with water and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=3:1), to thereby yield 1.20 g of a yellow oil. The yellow oil was dissolved in THF (23 mL), and to the solution was added 1 M aqueous sodium hydroxide (3.9 mL, 3.9 mmol). The resulting solution was stirred for 3 hours at room temperature. This reaction solution was cooled with ice, and made to have a pH of 1 with 6 M hydrochloric acid. The resulting solution was extracted with ethyl acetate, and the ethyl acetate layer was washed with water and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, to thereby yield 1.04 g of a yellow oil. This yellow oil was dissolved in DMF (20 mL), and to the resulting solution were added 1-piperonylpiperazine (530 mg, 2.4 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (560 mg, 2.9 mmol) and 1-hydroxybenzotriazole monohydrate (390 mg, 2.6 mmol), and the resulting solution was stirred for 15 hours at room temperature. The reaction solution was concentrated under reduced pressure, and to the residue was added water, and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=1:2→ethyl acetate), to thereby yield 280 mg of a yellow oil. To this oil was added diethyl ether and left to stand. Precipitated matter, was collected by filtration, to thereby yield 220 mg of the title compound. 
         [1087]    Appearance: Yellow powder 
         [1088]      1 H NMR (CDCl 3 ) δ 2.11 (3H, s), 2.43-2.48 (4H, m), 3.45-3.48 (4H, m), 3.67-3.71 (2H, m), 3.86 (2H, d, J=4.1 Hz), 4.90 (1H, t, J=4.1 Hz), 5.96 (2H, s), 6.49-6.53 (2H, m), 6.71-6.78 (2H, m), 6.86-6.97 (3H, m), 7.75 (2H, d, J=8.1 Hz), 7.87 (2H, d, J=8.1 Hz), 8.18 (1H, dd, J=8.7 Hz, 2.5 Hz), 8.58 (1H, d, J=2.1 Hz). 
         [1089]    The following compound was produced in the same manner as in Example 1036. 
       Example 1037 
     6-(4-{[2-(4-Piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2,5-difluorophenoxy)-N-(4-trifluoromethylphenyl)nicotinamide hydrobromide 
       [1090]    Melting point: 224.5-226.0° C. 
       Example 1038 
     Production of N-(6-{2-methyl-4-[methyl-(2-oxo-2-piperazin-1-ylethyl)amino]phenoxy}pyridin-3-yl)-3,4-dichlorobenzamide 
       [1091]    To a solution of methyl{4-[5-(3,4-dichlorobenzoylamino)-pyridin-2-yloxy]-3-methylphenyl}aminoacetic acid (1.59 g, 3.5 mmol) in DMF (60 mL) were added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.79 g, 4.1 mmol), 1-hydroxybenzotriazole monohydrate (0.63 g, 4.1 mmol), and 1-t-butyloxycarbonylpiperazine (0.68 g, 3.6 mmol). The resulting solution was stirred for 15 hours at room temperature under a nitrogen atmosphere. Water was added to the solution, and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and then the ethyl acetate layer was dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=2:1→3:2), to thereby yield an amide product. This amide product was dissolved in THF (20 mL). To the solution was then added 10% hydrochloric acid (10 mL), and the resulting solution was stirred for 14 hours at room temperature. To this reaction solution was added a saturated sodium bicarbonate solution to make the solution neutral, and extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by silica gel column chromatography (dichloromethane:methanol=50:1→20:1), to thereby yield 0.38 g of the title compound. 
         [1092]    Appearance: Colorless amorphous powder 
         [1093]      1 H NMR (CDCl 3 ) δ 2.10 (3H, s), 2.75-2.94 (4H, m), 2.99 (3H, s), 3.40-3.70 (4H, m), 4.08 (2H, s), 6.46-6.59 (2H, m), 6.79 (1H, d, J=8.9 Hz), 6.89 (1H, d, J=8.6 Hz), 7.55 (1H, d, J=8.4 Hz), 7.71 (1H, dd, J=8.4 Hz, 2.1 Hz), 7.98 (1H, d, J=2.1 Hz), 8.03-8.14 (2H, m), 8.23 (1H, d, J=2.6 Hz). 
       Example 1039 
     Production of N-(6-{4-[3-(4-piperonylpiperazin-1-yl)-3-oxopropyl]phenoxy}pyridin-3-yl)-4-trifluoromethylbenzamide 
       [1094]    To a solution of 3-[4-(5-aminopyridin-2-yloxy)phenyl]-1-(4-piperonylpiperazin-1-yl)propan-1-one trihydrochloride (200 mg, 0.35 mmol) in THF (4 mL) were added triethylamine (0.243 mL, 1.8 mmol) and 4-trifluoromethylbenzoyl chloride (0.055 mL, 0.37 mmol), and the resulting solution was stirred for 1 hour at room temperature. Water was added to the residue, and extracted with ethyl acetate. The ethyl acetate layer was washed with water and brine, dried over anhydrous magnesium sulfate, evaporated, and the residue was recrystallized from diethyl ether, to thereby yield 170 mg of the title compound. 
         [1095]    Appearance: White powder 
         [1096]    Melting point: 140-141° C. 
         [1097]      1 H NMR (CDCl 3 ) δ 2.32-2.40 (4H, m), 2.59-2.65 (2H, m), 2.93-2.99 (2H, m), 3.41 (4H, brs), 3.60-3.64 (2H, m), 5.94 (2H, s), 6.71-6.77 (2H, m), 6.85 (1H, s), 6.96 (1H, d, J=8.9 Hz), 7.05 (2H, d, J=8.4 Hz), 7.22 (2H, d, J=8.4 Hz), 7.76 (2H, d, J=8.4 Hz), 8.01 (2H, d, J=8.4 Hz), 8.11-8.14 (1H, m), 8.23 (1H, dd, J=8.9 Hz, 2.7 Hz), 8.28 (1H, d, J=2.7 Hz). 
         [1098]    A crude titled product (77.4 g) obtained using the same procedures was recrystallized from ethyl acetate (400 mL), to thereby yield 49.66 g of the title compound. 
         [1099]    Appearance: White powder; Melting point: 142-144° C. 
         [1100]    The following compounds were produced in the same manner as in Example 1039. 
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 236 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 Xb 11   
                 Xb 12   
                 R 748   
                 mp (° C.) or  1 H NMR 
               
               
                   
               
               
                 1040 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —COOC(CH 3 ) 3   
                 mp 197-199 
               
               
                   
               
               
                 1041 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —OCH 2 OCH 3   
                 mp 152-154 
               
               
                   
               
               
                 1042 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —COOC 2 H 5   
                 mp 189-190 
               
               
                   
               
               
                 1043 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —N(CH 3 )COOC(CH 3 ) 3   
                 mp 146-147 
               
               
                   
               
               
                 1044 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —COOC(CH 3 ) 3   
                 mp 192-193 
               
               
                   
               
               
                 1045 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —OCH 2 COOC 2 H 5   
                   1 H NMR (CDCl 3 ) δ 1.30 (3 H, t, J = 7.0 Hz), 1.75-1.81 (2 H, m), 2.03 (2 H, brs), 2.85-2.90 (2 H, m), 3.45-3.49 (2 H, m), 3.56 (1 H, m), 4.15 (2 H, s), 4.23 (2 H, q, J = 7.0 Hz), 6.90-6.95 (6 H, m), 7.50-7.53 (3 H, m), 7.69 (1 H, dd, J = 8.5 Hz, 2.0 Hz), 7.95 (1 H, d, J = 2.0 Hz), 8.04 (1 H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 237 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 749   
                 R 750   
                 R 751   
                 Xb 13   
                 M 
                 Form 
                 mp (° C.) or  1 H NMR 
               
               
                   
               
               
                 1046 
                 —Cl 
                 —Cl 
                 —F 
                 —N(Ac)— 
                 1 
                 free 
                   1 H NMR (DMSO-d 6 ) δ 1.78 (3 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 s), 2.22-2.38 (4 H, m), 3.30- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 3.50 (6 H, m), 4.41 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 5.98 (2 H, s), 6.74 (1 H, d, J = 8.1 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz), 6.80-6.86 (2 H, m), 6.98 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 d, J = 8.8 Hz), 7.29 (1 H, t, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 9.2 Hz), 7.38 (2 H, d, J = 8.8 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.58 (1 H, d, J = 9.2 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.84 (1 H, d, J 8.4 Hz), 7.90- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.96 (2 H, m), 8.21 (1 H, d, J = 1.8 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz), 10.61 (1 H, s). 
               
               
                 1047 
                 —Cl 
                 —Cl 
                 —F 
                 —NH— 
                 0 
                 free 
                 mp 224-228 
               
               
                 1048 
                 —Cl 
                 —Cl 
                 —F 
                 —NH— 
                 1 
                 dihydrochloride 
                 mp 174-178 
               
               
                 1049 
                 —CF 3   
                 —H 
                 —H 
                 —N(CH 3 )— 
                 1 
                 free 
                   1 H NMR (ODCl 3 ) δ 2.45 (4 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 brs), 3.03 (3 H, s), 3.46 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 3.52 (2 H, brs), 3.64 (2 H, brs), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 4.08 (2 H, s), 5.95 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.67 (2 H, d, J = 9.1 Hz), 6.74- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.78 (2 H, m), 6.87 (1 H, s), 6.92- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.97 (4 H, m), 7.52 (2 H, d, J = 8.9 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz), 7.74-7.81 (3 H, m), 7.98 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 d, J = 8.2 Hz). 
               
               
                 1050 
                 —Cl 
                 —Cl 
                 —H 
                 —N(CH 3 )— 
                 1 
                 free 
                   1 H NMR (CDCl 3 ) δ 2.49 (4 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 brs), 3.02 (3 H, s), 3.50 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 3.55 (2 H, brs), 3.66 (2 H, brs), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 4.08 (2 H, s), 5.96 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.67 (2 H, d, J = 9.1 Hz), 6.74- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.78 (2 H, m), 6.88-6.96 (5 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.50 (2 H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.56 (1 H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.70 (1 H, dd, J = 8.4 Hz, 2.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.83 (1 H, s), 7.97 (1 H, d, J = 2.1 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz). 
               
               
                 1051 
                 —Cl 
                 —Cl 
                 —F 
                 —O— 
                 1 
                 hydrochloride 
                   1 H NMR (DMSO-d 6 ) δ 2.83- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 2.95 (1 H, m), 2.97-3.12 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 3.23-3.56 (3 H, m), 3.95-4.06 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 m), 4.18-4.29 (2 H, m), 4.33- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 4.44 (1 H, m), 4.75-4.92 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.07 (2 H, s), 6.90-6.96 (4 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.97-7.04 (2 H, m), 7.11 (1 H, t, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 9.1 Hz), 7.15-7.22 (1 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.52 (1 H, d, J = 9.1 Hz), 7.84 
               
               
                   
                   
                   
                   
                   
                   
                   
                 (1 H, d, J = 8.4 Hz), 7.88 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 J = 13.3 Hz), 7.94 (1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.4 Hz, 1.9 Hz), 8.23 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 1.9 Hz), 10.60 (1 H, s), 11.10 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 238 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 752   
                 R 753   
                 mp (° C.) or  1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 1052 
                 4-ClPh- 
                 benzyl 
                 mp 187-190 
               
               
                 1053 
                 3-ClPh- 
                 benzyl 
                   1 H NMR 2.38 (4 H, brs), 3.34-3.71 (6 H, m), 6.86 (1 H, 
               
               
                   
                   
                   
                 d, J = 8.8 Hz), 7.00-7.05 (2 H, m), 7.19-7.36 (8 H, m), 
               
               
                   
                   
                   
                 7.43-7.47 (1 H, m), 7.69-7.73 (1 H, m), 7.83 (1 H, t, J = 
               
               
                   
                   
                   
                 1.8 Hz), 8.08 (1 H, dd, J = 8.8 Hz, 2.8 Hz), 8.24 (1 H, 
               
               
                   
                   
                   
                 d, J = 2.6 Hz), 8.5 1 (1 H, brs). 
               
               
                 1054 
                 4-CH 3 Ph- 
                 4-CH 3 OPhCH 2 — 
                   1 H NMR 2.32-2.50 (7 H, m), 3.44-3.79 (9 H, m), 6.84- 
               
               
                   
                   
                   
                 6.92 (3 H, m), 7.06-7.11 (2 H, m), 7.20-7.23 (4 H, m), 
               
               
                   
                   
                   
                 7.34-7.39 (2 H, m), 7.79 (2 H, d, J = 8.3 Hz), 8.16- 
               
               
                   
                   
                   
                 8.21 (1 H, m), 8.35 (1 H, d, J = 2.8 Hz), 8.76 (1 H, brs). 
               
               
                 1055 
                 2-naphthyl 
                 4-CH 3 OPhCH 2 — 
                   1 H NMR 2.41 (4 H, bra), 3.46-3.80 (6 H, m), 3.81 (3 H, 
               
               
                   
                   
                   
                 s), 6.83-6.90 (2 H, m), 6.95 (1 H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                 7.10 (2 H, d, J = 8.7 Hz), 7.22 (2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                 7.38 (2 H, d, J = 8.7 Hz), 7.52-7.63 (2 H, m), 7.88- 
               
               
                   
                   
                   
                 7.97 (4 H, m), 8.27 (1 H, dd, J = 8.7 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                 8.41-8.43 (2 H, m), 8.80 (1 H, brs). 
               
               
                 1056 
                 4-ClPh- 
                 4-CH 3 OPhCH 2 — 
                   1 H NMR 2.43 (4 H, brs), 3.48-3.77 (6 H, m), 3.80 (3 H, 
               
               
                   
                   
                   
                 s), 6.83-6.89 (2 H, m), 6.96 (1 H, d, J = 8.9 Hz), 7.10- 
               
               
                   
                   
                   
                 7.15 (2 H, m), 7.22 (2 H, d, J = 8.6 Hz), 7.38-7.48 (4 H, 
               
               
                   
                   
                   
                 m), 7.82-7.87 (2 H, m), 8.17-8.21 (2 H, m), 8.30 (1 H, 
               
               
                   
                   
                   
                 d, J = 2.6 Hz). 
               
               
                 1057 
                 3-ClPh- 
                 4-CH 3 OPhCH 2 — 
                   1 H NMR 2.41 (4 H, brs), 3.46-3.76 (6 H, m), 3.79 (3 H, 
               
               
                   
                   
                   
                 s), 6.83-6.89 (3 H, m), 7.05 (2 H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                 7.21 (2 H, d, J = 8.6 Hz), 7.31-7.48 (4 H, m), 7.77 (1 H, 
               
               
                   
                   
                   
                 d, J = 7.8 Hz), 7.90 (1 H, s), 8.08-8.12 (1 H, m), 
               
               
                   
                   
                   
                 8.35 (1 H, d, J = 2.5 Hz), 9.26 (1 H, brs). 
               
               
                 1058 
                 4-CF 3 OPh- 
                 benzyl 
                 mp 152-153 
               
               
                 1059 
                 2,4-Cl 2 Ph- 
                 benzyl 
                 mp 196-197 
               
               
                 1060 
                 2,3-F 2 Ph- 
                 benzyl 
                 mp 172-175 
               
               
                 1061 
                 4-ClPh- 
                 piperonyl 
                   1 H NMR 2.45 (4 H, brs), 3.45 (2 H, s), 3.45-3.75 (4 H, 
               
               
                   
                   
                   
                 m), 5.95 (2 H, s), 6.74-6.77 (2 H, m), 6.86 (1 H, a), 
               
               
                   
                   
                   
                 6.99 (1 H, d, J = 8.9 Hz), 7.14 (2 H, d, 4 8.7 Hz), 
               
               
                   
                   
                   
                 7.42-7.51 (4 H, m), 7.84 (2 H, d, J = 8.7 Hz), 7.91 (1 H, 
               
               
                   
                   
                   
                 brs), 8.22 (1 H, dd, J = 8.7 Hz, 2.8 Hz), 8.29 (1 H, d, 
               
               
                   
                   
                   
                 2.1 Hz) 
               
               
                 1062 
                 4-ClPh- 
                 3-pyridyl 
                   1 H NMR 3.24 (4 H, brs), 3.49-3.82 (4 H, m), 7.02 (1 H, 
               
               
                   
                   
                   
                 d, J = 8.7 Hz), 7.16-7.24 (4 H, m), 7.48 (2 H, d, J = 
               
               
                   
                   
                   
                 8.9 Hz), 7.49 (2 H, d, J = 8.7 Hz), 7.85 (2 H, d, J = 8.7 
               
               
                   
                   
                   
                 Hz), 8.04 (1 H, brs), 8.15-8.17 (1 H, m), 8.24 (1 H, dd, 
               
               
                   
                   
                   
                 J = 8.7 Hz, 2.8 Hz), 8.31-8.32 (2 H, m). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 239 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 754   
                 R 755   
                 Xb 14   
                 Form 
                 Property 
               
               
                   
               
               
                 1063 
                 3-CF 3 OPh- 
                 benzyl 
                 —CO— 
                 maleate 
                 mp 155-157° C. 
               
               
                 1064 
                 3,5-Cl 2 Ph- 
                 benzyl 
                 —CO— 
                 dihydrochloride 
                   1 H NMR (DMSO-d 6 ) δ 3.15- 
               
               
                   
                   
                   
                   
                   
                 3.54 (8 H, m), 4.36 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                 7.15-7.22 (3 H, m), 7.47- 
               
               
                   
                   
                   
                   
                   
                 7.60 (7 H, m), 7.90-7.91 (1 H, 
               
               
                   
                   
                   
                   
                   
                 m), 8.00 (1 H, s), 8.01 (1 H, s), 
               
               
                   
                   
                   
                   
                   
                 8.22-8.27 (1 H, m), 8.54 (1 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 2.2 Hz), 10.69 (1 H, s). 
               
               
                 1065 
                 PhCH═CH— 
                 benzyl 
                 —CO— 
                 free 
                 MS 518(M + ) 
               
               
                   
                 (trans) 
               
               
                 1066 
                 PhCH═CH— 
                 piperonyl 
                 —CO— 
                 free 
                   1 H NMR (CDCl 3 ) δ 2.45 (4 H, 
               
               
                   
                 (trans) 
                   
                   
                   
                 brs), 3.44 (2 H, s), 3.52 (2 H, 
               
               
                   
                   
                   
                   
                   
                 brs), 3.76 (2 H, brs), 5.95 
               
               
                   
                   
                   
                   
                   
                 (2 H, s), 6.60 (1 H, d, J = 15.5 
               
               
                   
                   
                   
                   
                   
                 Hz), 6.74-6.77 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                 6.85 (1 H, s), 6.95 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.7 Hz), 7.12 (2 H, d, J = 8.6 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.38-7.45 (511, m), 7.53- 
               
               
                   
                   
                   
                   
                   
                 7.56 (211, m), 7.74 (1 H, brs), 
               
               
                   
                   
                   
                   
                   
                 7.77 (1 H, d, J = 15.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.21 (1 H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.25 (1 H, d, J = 2.5 Hz). 
               
               
                 1067 
                 PhCH═CH— 
                 3-pyridyl 
                 —CO— 
                 free 
                   1 H NMR (CDCl 3 ) δ 3.20 (4 H, 
               
               
                   
                 (trans) 
                   
                   
                   
                 brs), 3.79 (4 H, brs), 
               
               
                   
                   
                   
                   
                   
                 6.67 (1 H, d, J = 15.7 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.92 (1 H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.10-7.21 (4 H, m), 7.33- 
               
               
                   
                   
                   
                   
                   
                 7.46 (7 H, m), 7.73 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 15.7 Hz), 8.11-8.31 (4 H, m), 
               
               
                   
                   
                   
                   
                   
                 9.30 (1 H, s). 
               
               
                 1068 
                 3,4-Cl 2 Ph- 
                 benzyl 
                 —SO 2 — 
                 hydrochloride 
                 mp 253-256° C. 
               
               
                 1069 
                 4-CF 3 Ph- 
                 benzyl 
                 —SO 2 — 
                 hydrochloride 
                 mp 249-251° C. 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 240 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 756   
                 R 757   
                 Xb 15   
                 M 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 1070 
                 3,4- 
                 benzyl 
                 —CH(OH)— 
                 0 
                 (CDCl 3 ) 1.95-2.15 (1 H, m), 2.15-2.40 (3 H, 
               
               
                   
                   
                   
                   
                   
                 m), 3.42 (2 H, s), 3.49 (4 H, brs), 5.42 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 6.6 Hz), 5.61 (1 H, d, J = 6.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.08 (1 H, d, J = 8.9 Hz), 7.09 (2 H, d, J = 8.6 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.15-7.43 (5 H, m), 7.38 (2 H, d, J = 8.6 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.85 (1 H, d, J = 8.4 Hz), 7.95 (1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 8.4 Hz, 2.0 Hz), 8.20 (1 H, dd, J = 8.9 Hz, 
               
               
                   
                   
                   
                   
                   
                 2.7 Hz), 8.23 (1 H, d, J = 2.3 Hz), 8.50 (1 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 2.7 Hz), 10.57 (1 H, s). 
               
               
                 1071 
                 4-CF 3 Ph- 
                 benzyl 
                 —CH(OH)— 
                 0 
                 (CDCl 3 ) 1.90-2.05 (1 H, m), 2.22-2.57 (3 H, 
               
               
                   
                   
                   
                   
                   
                 m), 3.10-3.40 (2 H, m), 3.44 (2 H, s), 3.58-. 
               
               
                   
                   
                   
                   
                   
                 3.85 (2 H, m), 4.75 (1 H, d, J = 6.4 Hz), 
               
               
                   
                   
                   
                   
                   
                 5.21 (1 H, d, J 6.4 Hz), 6.96 (1 H, d, J = 8.9 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.12 (2 H, d, J = 8.6 Hz), 7.20-7.38 (5 H, 
               
               
                   
                   
                   
                   
                   
                 m), 7.32 (2 H, d, J = 8.6 Hz), 7.78 (2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.1 Hz), 7.92 (1 H, brs), 8.00 (2 H, d, J = 8.1 
               
               
                   
                   
                   
                   
                   
                 Hz), 8.22 (1 H, dd, J = 8.9 Hz, 2.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.29 (1 H, d, J = 2.5 Hz). 
               
               
                 1072 
                 4-CF 3 Ph- 
                 piperonyl 
                 —O— 
                 1 
                 (DMSO-d 6 ) 2.32 (2 H, brs), 2.40 (2 H, brs), 
               
               
                   
                   
                   
                   
                   
                 3.41 (2 H, s), 3.46 (4 H, brs), 4.81 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                 5.99 (2 H, s), 6.73-6.88 (3 H, m), 6.94 (2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 9.2 Hz), 7.02 (1 H, d, J = 8.7 Hz), 7.05 (2 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 9.2 Hz), 7.93 (2 H, d, J = 8.4 Hz), 8.16 
               
               
                   
                   
                   
                   
                   
                 (2 H, d, J = 8.4 Hz), 8.19 (1 H, dd, J = 8.7 
               
               
                   
                   
                   
                   
                   
                 Hz, 2.7 Hz), 8.47 (1 H, d, J = 2.7 Hz), 
               
               
                   
                   
                   
                   
                   
                 10.60 (1 H, s). 
               
               
                 1073 
                 4-CF 3 Ph- 
                 benzyl 
                 —O— 
                 1 
                 (CDCl 3 ) 2.35-2.53 (4 H, m), 3.51 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                 3.56 (2 H, t, J = 5.0 Hz), 3.62 (2 H, t, J = 5.0 
               
               
                   
                   
                   
                   
                   
                 Hz), 4.64 (2 H, s), 6.90 (1 H, d, J = 8.8 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.92 (2 H, d, J = 9.0 Hz), 7.04 (2 H, d, J = 9.0 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.21-7.41 (5 H, m), 7.73 (2 H, d, J = 8.1 
               
               
                   
                   
                   
                   
                   
                 Hz), 8.00 (2 H, d, J = 8.1 Hz), 8.18 (1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 8.8 Hz, 2.6 Hz), 8.27 (1 H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.32 (1 H, brs). 
               
               
                 1074 
                 3-ClPh- 
                 piperonyl 
                 none 
                 2 
                 (CDCl 3 ) 2.31-2.38 (4 H, m), 2.58-2.64 (2 H, 
               
               
                   
                   
                   
                   
                   
                 m), 2.90-2.96 (2 H, m), 3.37-3.40 (4 H, m), 
               
               
                   
                   
                   
                   
                   
                 3.59-3.62 (2 H, m), 5.94 (2 H, s), 6.70- 
               
               
                   
                   
                   
                   
                   
                 6.77 (2 H, m), 6.84 (1 H, a), 6.92 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.9 Hz), 7.03 (2 H, d, J = 8.4 Hz), 7.20 (2 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.4 Hz), 7.38-7.44 (1 H, m), 7.50- 
               
               
                   
                   
                   
                   
                   
                 7.54 (1 H, m), 7.77 (1 H, d, J = 7.8 Hz), 7.87- 
               
               
                   
                   
                   
                   
                   
                 7.88 (1 H, m), 8.21 (1 H, dd, J = 8.9 Hz, 2.7 
               
               
                   
                   
                   
                   
                   
                 Hz), 8.28 (1 H, d, J = 2.7 Hz), 8.36 (1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 241 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 758   
                 mp (° C.) or  1 H NMR 
               
               
                   
               
               
                 1075 
                 3-ClPh- 
                   1 H NMR (CDCl 3 ) δ 2.33-2.38 (4 H, m), 2.55-2.61 (2 H, m), 2.86- 
               
               
                   
                   
                 2.91 (2 H, m), 3.37-3.41 (2 H, m), 3.49 (2 H, s), 3.56-3.60 (2 H, m), 
               
               
                   
                   
                 6.87 (1 H, d, J = 8.9 Hz), 6.97-7.01 (2 H, m), 7.14 (2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                 7.25-7.37 (6 H, m), 7.45-7.48 (1 H, m), 7.75-7.79 (1 H, m), 7.87 (1 H, t, J = 
               
               
                   
                   
                 1.8 Hz), 8.18 (1 H, dd, J = 8.9 Hz, 2.8 Hz), 8.32 (1 H, d, J = 2.8 Hz), 
               
               
                   
                   
                 9.06 (1 H, brs). 
               
               
                 1076 
                 4-ClPh- 
                 mp 136-139 
               
               
                 1077 
                 2-ClPh- 
                   1 H NMR (CDCl 3 ) δ 2.32-2.41 (4 H, m), 2.56-2.61 (2 H, m), 2.90- 
               
               
                   
                   
                 2.96 (2 H, m), 3.37-3.41 (2 H, m), 3.50 (2 H, s), 3.58-3.61 (2 H, m), 
               
               
                   
                   
                 6.92 (1.H, d, J = 8.7 Hz), 7.03 (2 H, d, J = 8.4 Hz), 7.19-7.43 (10 H, m), 
               
               
                   
                   
                 7.69-7.72 (1 H, m), 8.21-8.27 (3 H, m). 
               
               
                 1078 
                 Ph- 
                   1 H NMR (CDCl 3 ) δ 2.36 (4 H, brs), 2.56-2.61 (2 H, m), 2.89-2.95 (2 H, 
               
               
                   
                   
                 m), 3.36-3.41 (2 H, m), 3.49 (2 H, s), 3.58-3.62 (2 H, m), 6.99 (1 H, d, J = 
               
               
                   
                   
                 8.7 Hz), 7.01 (2 H, d, J = 8.1 Hz), 7.18 (2 H, d, J = 8.1 Hz), 7.26- 
               
               
                   
                   
                 7.55 (8 H, m), 7.87 (2 H, d, J = 6.6 Hz), 8.20 (1 H, d, J = 8.7 Hz), 
               
               
                   
                   
                 8.28 (1 H, brs), 8.50 (1 H, brs). 
               
               
                 1079 
                 4-CNPh- 
                   1 H NMR (CDCl 3 ) δ 2.33-2.41 (4 H, m, 2.56-2.62 (2 H, m), 2.87 
               
               
                   
                   
                 2.92 (2 H, m), 3.38-3.42 (2 H, m), 3.50 (2 H, s), 3.56-3.60 (2 H, m), 
               
               
                   
                   
                 6.91 (1 H, d, J = 8.9 Hz), 6.98-7.01 (2 H, m), 7.14-7.19 (2 H, m), 7.25- 
               
               
                   
                   
                 7.35 (5 H, m), 7.71-7.75 (2 H, m), 7.99-8.02 (2 H, m), 8.17-8.29 (2 H, m), 
               
               
                   
                   
                 8.75-8.97 (1 H, m). 
               
               
                 1080 
                 3-CH 3 OPh- 
                   1 H NMR (CDCl 3 ) δ 2.33-2.41 (4 H, m), 2.56-2.62 (2 H, m), 2.90 
               
               
                   
                   
                 2.95 (2 H, m), 3.38-3.42 (2 H, m), 3.51 (2 H, s), 3.60-3.63 (2 H, m), 
               
               
                   
                   
                 3.83 (3 H, s), 6.90 (1 H, d, J = 8.7 Hz), 7.00-7.09 (3 H, m), 7.18 (2 H, d, J = 
               
               
                   
                   
                 8.6 Hz), 7.26-7.44 (8 H, m), 8.19-8.23 (1 H, m), 8.29 (1 H, d, J = 2.8 
               
               
                   
                   
                 Hz), 8.48 (1 H, brs). 
               
               
                 1081 
                 4-CH 3 Ph- 
                   1 H NMR (CDCl 3 ) δ 2.33-2.40 (7 H, m), 2.56-2.62 (2 H, m), 2.90- 
               
               
                   
                   
                 2.95 (2 H, m), 3.38-3.41 (2 H, m), 3.49 (2 H, s), 3.59-3.62 (2 H, m), 
               
               
                   
                   
                 6.89 (1 H, d, J 8.7 Hz), 7.01 (2 H,d, J = 8.6 Hz), 7.16-7.32 (9 H, m), 
               
               
                   
                   
                 7.78 (2 H, d, J = 8.2 Hz), 8.18-8.22 (1 H, m), 8.27 (1 H, d, J = 2.6 Hz), 
               
               
                   
                   
                 8.33-8.44 (1 H, m). 
               
               
                 1082 
                 2-CH 3 Ph- 
                   1 H NMR (CDCl 3 ) δ 2.32-2.40 (4 H, m), 2.48 (3 H, s), 2.55-2.60 (2 H, m), 
               
               
                   
                   
                 2.89-2.95 (2 H, m), 3.37-3.40 (2 H, m), 3.50 (2 H, s), 3.57-3.60 (2 H, m), 
               
               
                   
                   
                 6.89-6.92 (1 H, m), 7.00-7.05 (2 H, m), 7.18-7.47 (10 H, m), 7.45 (1 H, d, 
               
               
                   
                   
                 J = 2.2 Hz), 8.04 (1 H, brs), 8.23-8.25 (2 H, m). 
               
               
                 1083 
                 4-CH 3 OPh- 
                   1 H NMR (CDCl 3 ) δ 2.31-2.38 (4 H, m), 2.54-2.60 (2 H, m), 2.87- 
               
               
                   
                   
                 2.93 (2 H, m); 3.37-3.40 (2 H, m), 3.48 (2 H, s), 3.58-3.61 (2 H, m), 
               
               
                   
                   
                 3.82 (3 H, s), 6.84-6.90 (3 H, m), 6.99 (2 H, d, J = 8.4 Hz), 7.15 (2 H, d, J = 
               
               
                   
                   
                 8.6 Hz), 7.25-7.32 (5 H, m), 7.85 (2 H, d, J = 8.9 Hz), 8.17 (1 H, dd, J = 
               
               
                   
                   
                 8.9 Hz, 2.7 Hz), 8.28 (1 H, d, J = 2.7 Hz), 8.73 (1 H, brs). 
               
               
                 1084 
                 2-CH 3 OPh- 
                   1 H NMR (CDCl 3 ) δ 2.33-2.42 (4 H, m), 2.58-2.64 (2 H, m), 2.93- 
               
               
                   
                   
                 2.99 (2 H, m), 3.38-3.42 (2 H, m), 3.49 (2 H, s), 3.61-3.65 (2 H, m), 
               
               
                   
                   
                 8.23-8.29 (3 H, m), 9.76 (1 H, s). 
               
               
                 1085 
                 2-naphthyl 
                 mp 156-159 
               
               
                 1086 
                 4-CF 3 Ph- 
                   1 H NMR (DMSO-d 6 ) δ 2.30-2.32 (4 H, m), 2.59-2.65 (2 H, m), 2.79- 
               
               
                   
                   
                 2.84 (2 H, m), 3.44-3.47 (6 H, m), 7.02 (2 H, d, J = 8.6 Hz), 7.05 (1 H, d, 
               
               
                   
                   
                 J = 9.1 Hz), 7.25-7.35 (7 H, m), 7.93 (2 H, d, J = 8.3 Hz), 8.16 (2 H, d, J = 
               
               
                   
                   
                 8.3 Hz), 8.21 (1 H, dd, J = 8.9 Hz, 2.6 Hz), 8.49 (1 H, d, J = 2.6 Hz), 
               
               
                   
                   
                 10.62 (1 H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 242 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 759   
                 R 760   
                 Form 
                 mp (° C.) or  1 H NMR 
               
               
                   
               
               
                 1087 
                 4-CF 3 OPh- 
                 benzyl 
                 maleate 
                 mp 144-146 
               
               
                 1088 
                 3-CF 3 OPh- 
                 benzyl 
                 maleate 
                 mp 125-128 
               
               
                 1089 
                 4-CF 3 OPh- 
                 piperonyl 
                 free 
                 mp 187-190 
               
               
                 1090 
                 2-CF 3 OPh- 
                 piperonyl 
                 free 
                   1 H NMR (CDCl 3 ) δ 2.31-2.39 (4 H, m), 2.57- 
               
               
                   
                   
                   
                   
                 2.63 (2 H, m), 2.91-2.97 (2 H, m), 3.37- 
               
               
                   
                   
                   
                   
                 3.40 (4 H, m), 3.58-3.62 (2 H, m), 5.93 (2 H, s), 
               
               
                   
                   
                   
                   
                 6.70-6.76 (2 H, m), 6.84 (1 H, s), 6.93 (1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.9 Hz), 7.03-7.07 (2 H, m), 7.19-7.23 (2 H, 
               
               
                   
                   
                   
                   
                 m), 7.32-7.36 (1 H, m), 7.40-7.46 (1 H, m), 
               
               
                   
                   
                   
                   
                 7.53-7.59 (1 H, m), 7.99-8.03 (1 H, m), 
               
               
                   
                   
                   
                   
                 8.20 (1 H, dd, J = 8.9 Hz, 2.7 Hz), 8.27 (1 H, d, 
               
               
                   
                   
                   
                   
                 J = 2.7 Hz), 8.55 (1 H, brs). 
               
               
                 1091 
                 3-CF 3 OPh- 
                 piperonyl 
                 free 
                   1 H NMR (CDCl 3 ) δ 2.30-2.36 (4 H, m), 2.55- 
               
               
                   
                   
                   
                   
                 2.61 (2 H, m), 2.86-2.92 (2 H, m), 3.37 
               
               
                   
                   
                   
                   
                 3.40 (4 H, m), 3.56-3.60 (2 H, m), 5.93 (2 H, s), 
               
               
                   
                   
                   
                   
                 6.69-6.76 (2 H, m), 6.83 (1 H, s), 6.88-6.92 (1 H, 
               
               
                   
                   
                   
                   
                 m), 6.98-7.02 (2 H, m), 7.14-7.18 (2 H, m), 
               
               
                   
                   
                   
                   
                 7.36-7.40 (1 H, m), 7.44-7.52 (1 H, m), 7.78- 
               
               
                   
                   
                   
                   
                 7.85 (2 H, m), 8.19 (1 H, dd, J = 8.9 Hz, 2.7 
               
               
                   
                   
                   
                   
                 Hz), 8.29-8.31 (1 H, m), 8.78-8.92 (1 H, m). 
               
               
                 1092 
                 3,5-Cl 2 Ph- 
                 piperonyl 
                 dihydro- 
                   1 H NMR (DMSO-d 6 ) δ 2.69-3.33 (10 H, m), 
               
               
                   
                   
                   
                 chloride 
                 3.99-4.11 (1 H, m), 4.23 (2 H, s), 4.44-4.49 (1 H, 
               
               
                   
                   
                   
                   
                 m), 6.07 (2 H, s), 6.97-7.07 (5 H, m), 7.20- 
               
               
                   
                   
                   
                   
                 7.30 (3 H, m), 7.89-8.00 (1 H, m), 8.00 (2 H, d, J = 
               
               
                   
                   
                   
                   
                 1.8 Hz), 8.19 (1 H, dd, J = 8.9 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                   
                 8.48 (1 H, d, J = 2.3 Hz), 10.64 (1 H, s). 
               
               
                 1093 
                 PhCH═CH— 
                 piperonyl 
                 free 
                   1 H NMR (CDCl 3 ) δ 2.05-3.38 (9 H, m), 3.69- 
               
               
                   
                 (trans) 
                   
                   
                 4.71 (5 H, m), 5.96 (2 H, s), 6.72-6.79 (2 H, m), 
               
               
                   
                   
                   
                   
                 6.95-7.05 (4 H, m), 7.13-7.23 (3 H, m), 7.35- 
               
               
                   
                   
                   
                   
                 7.37 (3 H, m), 7.51-7.5.4 (2 H, m), 7.70- 
               
               
                   
                   
                   
                   
                 7.76 (1 H, m), 8.41 (1 H, d, J 2.3 Hz), 
               
               
                   
                   
                   
                   
                 8.50 (1 H, d, J = 8.7 Hz), 8.95 (1 H, brs). 
               
               
                 1094 
                 2-naphthyl 
                 piperonyl 
                 free 
                   1 H NMR (CDCl 3 ) δ 2.28-2.34 (4 H, m), 2.55- 
               
               
                   
                   
                   
                   
                 2.61 (2 H, m), 2.89-2.95 (2 H, m), 3.38 (4 H, 
               
               
                   
                   
                   
                   
                 brs), 3.58 (2 H, brs), 5.92 (2 H, s), 6.69- 
               
               
                   
                   
                   
                   
                 6.76 (2 H, m), 6.83 (1 H, s), 6.92 (1 H, d, J = 8.6 
               
               
                   
                   
                   
                   
                 Hz), 7.02 (2 H, d, J = 8.4 Hz), 7.18 (2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.4 Hz), 7.51-7.61 (2 H, m), 7.86-7.94 (4 H, m), 
               
               
                   
                   
                   
                   
                 8.27 (1 H, dd, J = 8.6 Hz, 2.7 Hz), 8.33- 
               
               
                   
                   
                   
                   
                 8.38 (2 H, m), 8.55 (1 H, brs). 
               
               
                 1095 
                 4-ClPh- 
                 piperonyl 
                 free 
                   1 H NMR (CDCl 3 ) δ 2.31-2.41 (4 H, m), 2.59- 
               
               
                   
                   
                   
                   
                 2.65 (2 H, m), 2.94-3.00 (2 H, m), 3.38- 
               
               
                   
                   
                   
                   
                 3.41 (4 H, m), 3.63 (2 H, brs), 5.94 (2 H, s), 6.71- 
               
               
                   
                   
                   
                   
                 6.77 (2 H, m), 6.85 (1 H, s), 6.95 (1 H, d, J = 8.9 
               
               
                   
                   
                   
                   
                 Hz), 7.05 (2 H, d, J = 8.4 Hz), 7.23 (2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.4 Hz), 7.48 (2 H, d, J = 8.6 Hz), 7.82- 
               
               
                   
                   
                   
                   
                 7.89 (3 H, m), 8.19-8.25 (2 H, m). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 243 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 761   
                 R 762   
                 R 763   
                 R 764   
                 R 765   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 1096 
                 4-CF 3 Ph- 
                 —H 
                 —H 
                 —OH 
                 —COOC(CH 3 ) 3   
                 1.44 (9 H, s), 2.82-3.00 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 3.00-3.80 (9 H, m), 4.60 (1 H, t, J = 
               
               
                   
                   
                   
                   
                   
                   
                 6.5 Hz), 6.97 (1 H, d, J = 8.8 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.06 (2 H, d, J = 8.6 Hz), 7.24 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 8.6 Hz), 7.75 (2 H, d, J = 8.1 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 8.00 (2 H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 8.07 (1 H, brs), 8.18 (1 H, d, J = 2.6 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 8.27 (1 H, dd, J = 8.8 Hz, 2.6 
               
               
                   
                   
                   
                   
                   
                   
                 Hz). 
               
               
                 1097 
                 4-CF 3 Ph- 
                 —H 
                 —CH 3   
                 —H 
                 piperonyl 
                 2.32 (3 H, s), 2.32-2.40 (4 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 2.59-2.64 (2 H, m), 2.93-2.98 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 3.30-3.45 (4 H, m), 3.55- 
               
               
                   
                   
                   
                   
                   
                   
                 3.70 (2 H, m), 5.94 (2 H, s), 6.65- 
               
               
                   
                   
                   
                   
                   
                   
                 6.75 (2 H, m), 6.82-6.84 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.03-7.07 (2 H, m), 7.20-7.24 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 7.72 (1 H, brs), 7.75-7.79 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 8.00-8.04 (2 H, m), 8.30 (1 H, s). 
               
               
                 1098 
                 4-CF 3 Ph- 
                 —CH 3   
                 —H 
                 —H 
                 piperonyl 
                 2.31-2.40 (4 H, m), 2.47 (3 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 2.59-2.65 (2 H, m), 2.94-3.00 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 3.38-3.41 (4 H, m), 3.60- 
               
               
                   
                   
                   
                   
                   
                   
                 3. 65 (2 H, m), 5.94 (2 H, s), 6.68- 
               
               
                   
                   
                   
                   
                   
                   
                 6.77 (3 H, m), 6.84 (1 H, s), 7.04- 
               
               
                   
                   
                   
                   
                   
                   
                 7.08 (2 H, m), 7.20-7.24 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.63 (1 H, brs), 7.77-7.80 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.99-8.11 (3 H, m). 
               
               
                 1099 
                 3,4- 
                 —CH 3   
                 —H 
                 —H 
                 piperonyl 
                 2.25-2.40 (4 H, m), 2.45 (3 H, s), 
               
               
                   
                 Cl 2 Ph- 
                   
                   
                   
                   
                 2.58-2.64 (2 H, m), 2.92-2.98 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 3.38-3.41 (4 H, m), 3.60- 
               
               
                   
                   
                   
                   
                   
                   
                 3.64 (2 H, m), 5.94 (2 H, s), 6.66- 
               
               
                   
                   
                   
                   
                   
                   
                 6.76 (3 H, m), 6.84 (1 H, s), 7.03- 
               
               
                   
                   
                   
                   
                   
                   
                 7.07 (2 H, m), 7.18-7.22 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.59 (1 H, d, J = 8.3 Hz), 7.67 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs), 7.72 (1 H, dd, J = 8.4 Hz, 2.0 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.98-8.02 (2 H, m). 
               
               
                 1100 
                 3,4- 
                 —H 
                 —CH 3   
                 —H 
                 piperonyl 
                 2.31 (3 H, s), 2.31-2.40 (4 H, m), 
               
               
                   
                 Cl 2 Ph- 
                   
                   
                   
                   
                 2.58-2.64 (2 H, m), 2.92-2.98 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 3.37-3.41 (4 H, m), 3.60- 
               
               
                   
                   
                   
                   
                   
                   
                 3.64 (2 H, m), 5.94 (2 H, s), 6.65- 
               
               
                   
                   
                   
                   
                   
                   
                 6.75 (2 H, m), 6.80-6.84 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.03-7.06 (2 H, m), 7.20-7.24 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 7.58 (1 H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.64 (1 H, brs), 7.73 (1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.3 Hz, 1.8 Hz), 8.01 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 1.9 Hz), 8.26 (1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 244 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 766   
                 R 767   
                 R 768   
                 R 769   
                 mp (° C.) or  1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 1101 
                 4-CF 3 Ph- 
                 —H 
                 —H 
                 —Ac 
                 mp 189-191 
               
               
                 1102 
                 3,4-Cl 2 Ph- 
                 —H 
                 —H 
                 —COC 2 H 5   
                 mp 204-206 
               
               
                 1103 
                 3,4-Cl 2 Ph- 
                 —H 
                 —H 
                 —H 
                 mp 188-189 
               
               
                   
               
               
                 1104 
                 3,4-Cl 2 Ph- 
                 —H 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (DMSO-d 6 ) 0.60-0.70 (2 H, m), 0.75- 0.80 (2 H, m), 1.42 (1 H, m), 2.25-2.35 (4 H, m), 3.35-3.45 (6 H, m), 4.49 (2 H, s), 5.98 (2 H, s), 6.74 (1 H, d, J = 7.9 Hz), 6.84 (1 H, d, J = 7.9 Hz), 6.86 (1 H, s), 7.12 (1 H, d, J = 8.8 Hz), 7.18 (2 H, d, J = 8.6 Hz), 7.47 (2 H, d, J = 8.6 Hz), 7.84 (1 H, d, J = 8.4 Hz), 7.95 (1 H, dd, J = 8.4 Hz, 2.0 Hz), 8.20-8.23 (2 H, m), 8.5 1 (1 H, d, J = 2.5 Hz), 10.58 (1 H, s). 
               
               
                   
               
               
                 1105 
                 4-CF 3 Ph- 
                 —H 
                 —H 
                 —CH 3   
                 H NMR (DMSO-d 6 ) 2.31-2.39 (4 H, m), 
               
               
                   
                   
                   
                   
                   
                 2.94 (3 H, s), 3.31 (2 H, s), 3.42 (4 H, brs), 
               
               
                   
                   
                   
                   
                   
                 4.24 (2 H, s), 5.99 (2 H, s), 6.64 (2 H, d, J = 9.1 
               
               
                   
                   
                   
                   
                   
                 Hz), 6.76 (1 H, dd, J = 7.9 Hz, 1.2 Hz), 6.84- 
               
               
                   
                   
                   
                   
                   
                 6.96 (5 H, m), 7.93 (2 H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.13 (1 H, s), 8.16 (2 H, d, J = 8.6 Hz), 8.45 (1 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 2.5 Hz), 10.58 (1 H, s). 
               
               
                   
               
               
                 1106 
                 3,4-Cl 2 Ph- 
                 —H 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (CDCl 3 ) 0.57-0.62 (2 H, m), 0.75- 0.82 (2 H, m), 2.37-2.49 (4 H, m), 2.70-2.74 (1 H, m), 3.45 (2 H, s), 3.49-3.59 (4 H, m), 4.17 (2 H, s), 5.95 (2 H, s), 6.74-6.94 (8 H, m), 7.49 (1 H, d, J = 8.2 Hz), 7.67-7.71 (1 H, m), 7.95 (1 H, d, J = 2.1 Hz), 8.00 (1 H, dd, J = 8.9 Hz, 2.6 Hz), 8.24 (1 H, d, J 2.6 Hz), 8.59 (1 H, brs). 
               
               
                   
               
               
                 1107 
                 4-CF 3 Ph- 
                 —H 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (CDCl 3 ) 0.57-0.62 (2 H, m), 0.74- 0.81 (2 H, m), 2.35-2.47 (4 H, m), 2.66-2.74 (1 H, m), 3.44 (2 H, s), 3.47-3.57 (4 H, m), 4.16 (2 H, s), 5.94 (2 H, s), 6.70-6.94 (8 H, m), 7.66 (2 H, d, J = 8.2 Hz), 7.95 (2 H, d, J = 8.0 Hz), 8.04 (1 H, dd, J = 8.9 Hz, 2.6 Hz), 8.25 (1 H, d, J = 2.6 Hz), 8.80 (1 H, s). 
               
               
                   
               
               
                 1108 
                 4-CF 3 Ph- 
                 —CH 3   
                 —CH 3   
                 —CH 3   
                   1 H NMR (CDCl 3 ) 2.09 (3 H, s), 2.26 (3 H, s), 
               
               
                   
                   
                   
                   
                   
                 2.39 (4 H, brs), 2.67 (3 H, s), 3.41 (2 H, s), 3.53 
               
               
                   
                   
                   
                   
                   
                 3.63 (4 H, m), 3.74 (2 H, s), 5.94 (2 H, s), 6.71- 
               
               
                   
                   
                   
                   
                   
                 6.77 (2 H, m), 6.85-6.90 (3 H, m), 6.98 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.7 Hz), 7.75 (2 H, d, J = 8.2 Hz), 7.98-8.01 
               
               
                   
                   
                   
                   
                   
                 (3 H, m), 8.18 (1 H, dd, J = 8.9 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.25 (1 H, d, J = 2.3 Hz). 
               
               
                 1109 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 —CH 3   
                 —CH 3   
                   1 H NMR (CDCl 3 ) 2.09 (3 H, s), 2.25 (3 H, s), 
               
               
                   
                   
                   
                   
                   
                 2.37-2.40 (4 H, m), 2.66 (3 H, s), 3.41 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                 3.53-3.63 (4 H, m), 3.73 (2 H, s), 5.94 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                 6.70-6.77 (2 H, m), 6.84-6.89 (3 H, m), 6.96 (1 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.7 Hz), 7.56 (1 H, d, J = 8.2 Hz), 7.70- 
               
               
                   
                   
                   
                   
                   
                 7.74 (1 H, m), 7.99 (1 H, d, J = 2.0 Hz), 8.10- 
               
               
                   
                   
                   
                   
                   
                 8.16 (2 H, m), 8.24 (1 H, d, J = 2.8 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 245 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 770   
                 R 771   
                 R 772   
                 Form 
                 mp (° C.) or  1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 1110 
                 4-CF 3 Ph- 
                 —OCH 3   
                 —C 2 H 5   
                 free 
                 mp 142.6-146.5 
               
               
                 1111 
                 4-CF 3 Ph- 
                 —CH 3   
                 —C 2 H 5   
                 hydrochloride 
                 mp 173-175 dec 
               
               
                 1112 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 —C 2 H 5   
                 hydrochloride 
                 mp 168.5-171.0 
               
               
                 1113 
                 2,3-Cl 2 Ph- 
                 —CH 3   
                 —CH 3   
                 free 
                   1 H NMR (CDCl 3 ) 2.12 (3H, s), 
               
               
                   
                   
                   
                   
                   
                 2.41-2.45 (4H, m), 3.01 (3H, s), 3.43 
               
               
                   
                   
                   
                   
                   
                 (2H, s), 3.50 (2H, s), 3.63 (2H, brs), 
               
               
                   
                   
                   
                   
                   
                 4.07 (2H, s), 5.95 (2H, s), 6.52-6.58 
               
               
                   
                   
                   
                   
                   
                 (2H, m), 6.71-6.77 (2H, m), 6.81-6.93 
               
               
                   
                   
                   
                   
                   
                 (3H, m), 7.32 (1H, t, J = 7.8 Hz), 7.56- 
               
               
                   
                   
                   
                   
                   
                 7.61 (2H, m), 7.68 (1H, brs), 8.16 (1H, 
               
               
                   
                   
                   
                   
                   
                 dd, J = 8.7 Hz, 2.8 Hz), 8.20 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 2.2 Hz). 
               
               
                 1114 
                 3,4-Cl 2 Ph- 
                 —OCH 3   
                 —H 
                 free 
                   1 H NMR (DMSO-d 6 ) 2.32-2.40 (4H, 
               
               
                   
                   
                   
                   
                   
                 m), 3.42 (2H, s), 3.51 (4H, brs), 3.63 
               
               
                   
                   
                   
                   
                   
                 (3H, s), 3.91 (2H, d, J = 4.8 Hz), 5.54 
               
               
                   
                   
                   
                   
                   
                 (1H, t, J = 4.8 Hz), 5.99 (2H, s), 6.21 
               
               
                   
                   
                   
                   
                   
                 (1H, dd, J = 8.6 Hz, 2.5 Hz), 6.50 (1H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 2.5 Hz), 6.76 (1H, dd, J = 7.9 
               
               
                   
                   
                   
                   
                   
                 Hz, 1.5 Hz), 6.82-6.88 (4H, m), 7.82 
               
               
                   
                   
                   
                   
                   
                 (1H, d, J = 8.4 Hz), 7.94 (1H, dd, 
               
               
                   
                   
                   
                   
                   
                 J = 8.4 Hz, 2.0 Hz), 8.07 (1H, dd, 
               
               
                   
                   
                   
                   
                   
                 J = 8.9 Hz, 2.6 Hz), 8.21 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 2.2 Hz), 8.37 (1H, d, J = 2.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 10.44 (1H, s). 
               
               
                 1115 
                 4-CF 3 Ph- 
                 —OCH 3   
                 —H 
                 free 
                   1 H NMR (CDCl 3 ) 2.32-2.40 (4H, m), 
               
               
                   
                   
                   
                   
                   
                 3.42 (2H, s), 3.50 (4H, brs), 3.63 (3H, 
               
               
                   
                   
                   
                   
                   
                 s), 3.91 (2H, d, J = 4.6 Hz), 5.55 (1H, 
               
               
                   
                   
                   
                   
                   
                 brt), 5.99 (2H, s), 6.20 (1H, dd, J = 8.6 
               
               
                   
                   
                   
                   
                   
                 Hz, 2.5 Hz), 6.49 (1H, d, J = 2.3 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.74-6.88 (5H, m), 7.92 (2H, d, J = 8.4 
               
               
                   
                   
                   
                   
                   
                 Hz), 8.07-8.17 (3H, m), 8.38 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 2.3 Hz), 10.53 (1H, s). 
               
               
                   
               
               
                 1116 
                 4-CF 3 Ph- 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                   1 H NMR (CDCl 3 ) 0.59-0.64 (2H, m), 0.76-0.82 (2H, m), 2.08 (3H, s), 2.37-2.47 (4H, m), 2.69-2.77 (1H, m), 3.44 (2H, s), 3.48-3.59 (4H, m), 4.16 (2H, s), 5.94 (2H, s), 6.67-6.77 (5H, m), 6.86 (2H, d, J = 8.6 Hz), 7.70 (2H, d, J = 8.2 Hz), 7.97 (2H, d, J = 8.1 Hz), 8.08 (1H, dd, J = 8.9 Hz, 2.8 Hz), 8.23 (1H, d, J = 2.8 Hz), 8.39 (1H, brs). 
               
               
                   
               
               
                 1117 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                   1 H NMR (CDCl 3 ) 0.59-0.65 (2H, m), 0.76-0.83 (2H, m), 2.08 (3H, s), 2.38-2.48 (4H, m), 2.71-2.78 (1H, m), 3.44 (2H, s), 3.49-3.59 (4H, m), 4.17 (2H, s), 5.95 (2H, s), 6.67-6.77 (5H, m), 6.85-6.88 (2H, m), 7.53 (1H, d, J = 8.2 Hz), 7.68-7.72 (1H, m), 7.96 (1H, d, J = 2.0 Hz), 8.02-8.07 (1H, m), 8.22-8.26 (2H, m). 
               
               
                   
               
               
                 1118 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 —CH 3   
                 free 
                   1 H NMR (CDCl 3 ) 0.83-0.85 (2H, m), 1.07-1.08 (2H, m), 1.46-1.63 (1H, m), 2.10 (3H, s), 2.41-2.44 (4H, m), 3.00 (3H, s), 3.43 (2H, s), 3.47-3.49 (2H, m), 3.63 (2H, brs), 4.06 (2H, s), 5.94 (2H, s), 6.51-6.55 (2H, m), 6.70-6.77 (3H, m), 6.85 (1H, brs), 6.89 (1H, d, J = 8.4 Hz), 7.44-7.64 (1H, m), 8.01-8.04 (1H, m), 8.08 (1H, d, J = 2.3 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 246 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 773   
                 R 774    
                 R 775   
                 Form 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 1119 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 —CH 3   
                 hydrochloride 
                 (DMSO-d 6 ) 2.01 (3H, s), 2.80-3.18 (3H, m), 2.93 (3H, s), 3.35 (2H, s), 3.38-3.62 (1H, m), 3.95-4.50 (4H, m), 4.27 (2H, s), 6.08 (2H, s), 6.49 (1H, dd, J = 8.7 Hz, 2.7 Hz), 6.58 (1H, d, J = 2.7 Hz), 6.83 (1H, d, J = 8.7 Hz), 6.92 (1H, d, J = 8.9 Hz), 7.02 (2H, s), 7.21 (1H, s), 7.74 (1H, d, J = 8.4 Hz), 7.90 (1H, d, J = 8.4 Hz), 7.88-7.95 (1H, m), 8.11 (1H, dd, J = 8.9 Hz, 2.7 Hz), 8.36 (1H, d, J = 2.7 Hz), 10.71 (1H, s). 
               
               
                   
               
               
                 1120 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 —CH 3   
                 free 
                  (CDCl 3 ) 2.11 (3H, s), 2.42 (4H, brs), 3.00 (3H, s), 3.43 (2H, s), 3.47-3.49 (2H, m), 3.63 (2H, brs), 4.07 (2H, s), 5.95 (2H, s), 6.01 (2H, s), 6.37 (1H, d, J = 15.2 Hz), 6.52-6.56 (2H, m), 6.74-6.85 (5H, m), 6.91 (1H, d, J = 8.6 Hz), 7.00-7.02 (2H, m), 7.49 (1H, brs), 7.65 (1H, d, J = 15.3 Hz), 8.16-8.17 (2H, m). 
               
               
                   
               
               
                 1121 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 —CH 3   
                 free 
                  (CDCl 3 ) 2.09 (3H, s), 2.42-2.43 (4H, m), 3.00 (3H, s), 3.43 (2H, s), 3.47-3.50 (2H, m), 3.63 (2H, brs), 4.08 (2H, s), 5.95 (2H, s), 6.49-6.61 (3H, m), 6.70-6.91 (6H, m), 7.01-7.03 (2H, m), 7.63 (1H, d, J = 15.3 Hz), 7.98 (1H, brs), 8.16-8.19 (2H, m). 
               
               
                   
               
               
                 1122 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 —CH 3   
                 free 
                  (CDCl 3 ) 2.17 (3H, s), 2.43 (4H, brs), 2.82 (3H, s), 3.01 (3H, s), 3.44 (2H, s), 3.50 (2H, brs), 3.63 (2H, brs), 4.08 (2H, s), 5.95 (2H, s), 6.53-6.57 (2H, m), 6.74 (2H, brs), 6.81 (1H, d, J = 8.9 Hz), 6.85 (1H, s), 6.92 (1H, d, J = 8.6 Hz), 7.52 (1H, brs), 7.73 (2H, d, J = 8.3 Hz), 8.04-8.09 (3H, m), 8.18 (1H, d, J = 2.8 Hz). 
               
               
                   
               
               
                 1123 
                 4-CF 3 Ph- 
                 —F 
                 allyl 
                 free 
                 (CDCl 3 ) 2.45 (4H, brs), 3.45 (2H, s), 
               
               
                   
                   
                   
                   
                   
                 3.45 (2H, brs), 3.64 (2H, brs), 3.99 
               
               
                   
                   
                   
                   
                   
                 (2H, d, J = 5.1 Hz), 4.05 (2H, s), 
               
               
                   
                   
                   
                   
                   
                 5.18-5.28 (2H, m), 5.83-5.93 (1H, 
               
               
                   
                   
                   
                   
                   
                 m), 5.95 (2H, s), 6.36-6.47 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 6.75 (2H, s), 6.86-6.87 (1H, m), 6.96 
               
               
                   
                   
                   
                   
                   
                 (1H, d, J = 9.1 Hz), 7.03 (1H, t, 
               
               
                   
                   
                   
                   
                   
                 J = 8.9 Hz), 7.75-7.78 (3H, m), 7.99 
               
               
                   
                   
                   
                   
                   
                 (2H, d, J = 8.1 Hz), 8.15-8.22 (2H, 
               
               
                   
                   
                   
                   
                   
                 m). 
               
               
                   
               
               
                 1124 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 —CH 3   
                 free 
                  (CDCl 3 ) 0.83-0.87 (1H, m), 1.19-1.22 (7H, m), 1.37-1.42 (1H, m), 2.10 (3H, s), 2.41-2.44 (4H, m), 3.00 (3H, s), 3.43 (2H, s), 3.48 (2H, brs), 3.63 (2H, brs), 4.06 (2H, s), 5.94 (2H, s), 6.51-6.56 (2H, m), 6.70-6.77 (3H, m), 6.85-6.91 (2H, m), 7.40 (1H, brs), 8.05-8.06 (2H, m). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 247 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 776   
                 R 777   
                 R 778   
                 R 779   
                 M 
                 mp (° C.) or  1 H NMR 
               
               
                   
               
               
                 1125 
                 4-CF 3 Ph- 
                 —F 
                 —F 
                 —CH 3   
                 1 
                 mp 160.0-161.5 
               
               
                 1126 
                 3,4-Cl 2 Ph- 
                 —F 
                 —F 
                 —CH 3   
                 1 
                 mp 207-209 
               
               
                 1127 
                 4-CF 3 Ph- 
                 —F 
                 —F 
                 —C 2 H 5   
                 1 
                   1 H NMR (DMSO-d 6 ) δ 1.07 (3H, t, J = 7.0 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 2.20-2.41 (4H, m), 3.20-3.30 (2H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 3.39 (2H, s), 3.39-3.52 (4H, m), 4.11 (2H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 5.97 (2H, s), 6.71-6.76 (1H, m), 6.78-6.88 (3H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 7.09-7.19 (2H, m), 7.92 (2H, d, J = 8.4 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 8.15 (2H, d, J = 8.4 Hz), 8.20 (1H, dd, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 2.7 Hz, 9.0 Hz), 8.42 (1H, d, J = 2.7 Hz). 
               
               
                 1128 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 —CH 3   
                 —C 2 H 5   
                 1 
                   1 H NMR (DMSO-d 6 ) δ 0.95 (3H, t, J = 7.0 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 2.01 (3H, s), 2.19 (3H, s), 2.20-2.40 (4H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 3.00 (2H, q, J = 7.0 Hz), 3.30-3.55 (6H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 3.79 (2H, s), 5.98 (2H, s), 6.74 (1H, dd, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 7.9 Hz, 1.4 Hz), 6.82-6.86 (3H, m), 6.97 
               
               
                   
                   
                   
                   
                   
                   
                 (1H, d, J = 8.9 Hz), 7.05 (1H, s), 7.84 (1H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.4 Hz), 7.94 (1H, dd, J = 8.4 Hz, 2.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 8.15 (1H, dd, J = 8.9 Hz, 2.7 Hz), 8.21 (1H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 2.0 Hz), 8.42 (1H, d, J = 2.6 Hz), 10.51 
               
               
                   
                   
                   
                   
                   
                   
                 (1H, brs). 
               
               
                 1129 
                 4-CF 3 Ph- 
                 —CH 3   
                 —CH 3   
                 —C 2 H 5   
                 1 
                   1 H NMR (DMSO-d 6 ) δ 0.95 (3H, t, J = 7.0 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 2.02 (3H, s), 2.19 (3H, s), 2.20-2.40 (4H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 3.00 (2H, q, J = 7.0 Hz), 3.30-3.60 (6H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 3.79 (2H, s), 5.98 (2H, s), 6.74 (1H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 7.9 Hz), 6.82-6.85 (3H, m), 6.98 (1H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.6 Hz), 7.05 (1H, s), 7.91-7.95 (2H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 8.14-8.20 (3H, m), 8.44 (1H, d, J = 1.8 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 10.59 (1H, brs). 
               
               
                 1130 
                 4-CF 3 Ph- 
                 —OCH 3   
                 —H 
                 —H 
                 2 
                   1 H NMR (CDCl 3 ) δ 2.44 (4H, brs), 3.43 (4H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs), 3.49 (2H, s), 3.66 (3H, s), 3.83 (2H, brs), 
               
               
                   
                   
                   
                   
                   
                   
                 4.25 (4H, s), 4.67 (1H, brs), 6.10 (1H, dd, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.6 Hz, 2.5 Hz), 6.23 (1H, d, J = 2.5 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 6.75-6.96 (5H, m), 7.67 (2H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.96 (2H, d, J = 8.1 Hz), 8.10 (1H, dd, J = 8.9 
               
               
                   
                   
                   
                   
                   
                   
                 Hz, 2.6 Hz), 8.20-8.24 (1H, m), 8.56 (1H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 248 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                 mp (° C.) or  1 H NMR (solvent) δ 
               
               
                 No. 
                 R 780   
                 R 781   
                 R 782   
                 R 783   
                 ppm 
               
               
                   
               
               
                 1131 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 —H 
                 —H 
                   1 H NMR (CDCl 3 ) 2.13 (3H, s), 2.43 (4H, t, J = 4.8 Hz), 3.02 (3H, s), 3.44 (2H, s), 3.50 (2H, brs), 3.64 (2H, brs), 4.08 (2H, s), 5.94 (2H, s), 6.53-6.58 (2H, m), 6.74 (2H, brs), 6.83 (1H, d, J = 8.9 Hz), 6.85 (1H, s), 6.93 (1H, d, J = 8.4 Hz), 7.42 (1H, dd, J = 8.9 Hz, 2.0 Hz), 7.50 (1H, d, J = 8.9 Hz), 7.53 (1H, s), 7.69 (1H, d, J = 1.8 Hz), 8.19 (1H, dd, J = 8.9 Hz, 2.8 Hz), 8.26 (1H, brs), 8.31 (1H, d, J = 2.6 Hz). 
               
               
                   
               
               
                 1132 
                 3,4-Cl 2 Ph- 
                 —F 
                 —F 
                 —H 
                 mp 203.5-204.5 
               
               
                 1133 
                 4-CF 3 Ph- 
                 —F 
                 —F 
                 —H 
                 mp 230.0-231.5 
               
               
                 1134 
                 4-ClPh- 
                 —CH 3   
                 —H 
                 —H 
                   1 H NMR (CDCl 3 ) 2.08 (3H, s), 2.42 
               
               
                   
                   
                   
                   
                   
                 (4H, brs), 2.97 (3H, s), 3.43 (2H, s), 
               
               
                   
                   
                   
                   
                   
                 3.49 (2H, brs), 3.60 (2H, brs), 4.05 
               
               
                   
                   
                   
                   
                   
                 (2H, s), 5.94 (2H, s), 6.48-6.52 (2H, 
               
               
                   
                   
                   
                   
                   
                 m), 6.74-6.89 (5H, m), 7.41 (2H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.6 Hz), 7.80 (2H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.08 (1H, dd, J = 8.9 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.21 (1H, d, J = 2.6 Hz), 8.29 (1H, 
               
               
                   
                   
                   
                   
                   
                 s). 
               
               
                   
               
               
                 1135 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 —H 
                 —H 
                   1 H NMR (CDCl 3 ) 2.11 (3H, s), 2.43-2.44 (4H, m), 3.00 (3H, s), 3.43 (2H, s), 3.47-3.49 (2H, m), 3.63 (2H, brs), 4.07 (2H, s), 5.95 (2H, s), 6.51-6.57 (2H, m), 6.69-6.93 (6H, m), 7.19 (1H, dd, J = 8.7 Hz, 7.5 Hz), 7.35-7.38 (2H, m), 7.55 (1H, brs), 7.86 (1H, d, J = 15.8 Hz), 8.17-8.20 (2H, m). 
               
               
                   
               
               
                 1136 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 —H 
                 —H 
                   1 H NMR (CDCl 3 ) 2.10 (3H, s), 2.43 (4H, brs), 3.00 (3H, s), 3.43 (2H, s), 3.50 (2H, brs), 3.64 (2H, brs), 4.07 (2H, s), 5.95 (2H, s), 6.50-6.56 (2H, m), 6.67-6.92 (6H, m), 7.07-7.19 (2H, m), 7.31-7.36 (1H, m), 7.47-7.52 (1H, m), 7.73 (1H, brs), 7.80 (1H, d, J = 15.7 Hz), 8.14-8.20 (2H, m). 
               
               
                   
               
               
                 1137 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 —H 
                 —H 
                   1 H NMR (CDCl 3 ) 2.11 (3H, s), 2.41-2.44 (4H, m), 3.00 (3H, s), 3.43 (2H, s), 3.47-3.49 (2H, m), 3.63 (2H, brs), 4.06 (2H, s), 5.94 (2H, s), 6.09 (1H, d, J = 14.7 Hz), 6.51-6.56 (2H, m), 6.70-6.96 (7H, m), 7.30-7.55 (7H, m), 8.14 (1H, d, J = 2.5 Hz), 8.14 (1H, brs). 
               
               
                   
               
               
                 1138 
                 4-CF 3 Ph- 
                 —F 
                 —H 
                 —F 
                 mp 169.0-170.0 
               
               
                 1139 
                 3,4-Cl 2 Ph- 
                 —F 
                 —H 
                 —F 
                 mp 138.0-139.0 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 249 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 784   
                 R 785   
                 R 786   
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 1140 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 —CH 3   
                 (DMSO-d 6 ) 2.00 (3H, s), 2.93 (3H, s), 3.23 (1H, brs), 
               
               
                   
                   
                   
                   
                 3.36 (1H, brs), 3.63 (1H, brs), 3.72 (1H, brs), 4.07 (1H, 
               
               
                   
                   
                   
                   
                 s), 4.27 (1H, s), 4.29 (2H, s), 4.47 (2H, s), 5.99 (2H, s), 
               
               
                   
                   
                   
                   
                 6.43-6.63 (2H, m), 6.77 (1H, dd, J = 8.0 Hz, 1.5 Hz), 
               
               
                   
                   
                   
                   
                 6.77-6.88 (2H, m), 6.82 (1H, d, J = 8.8 Hz), 6.90 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 8.6 Hz), 7.83 (1H, d, J = 8.4 Hz), 7.94 (1H, dd, 
               
               
                   
                   
                   
                   
                 J = 8.4 Hz, 2.0 Hz), 8.12 (1H, dd, J = 8.8 Hz, 2.6 
               
               
                   
                   
                   
                   
                 Hz), 8.21 (1H, d, J = 2.0 Hz), 8.40 (1H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                 10.48 (1H, s). 
               
               
                 1141 
                 4-CF 3 Ph- 
                 —CH 3   
                 —CH 3   
                 (CDCl 3 ) 2.10 (3H, s), 2.90-3.06 (3H, m), 3.20-3.34 (2H, 
               
               
                   
                   
                   
                   
                 m), 3.62-3.84 (2H, m), 4.08 (2H, s), 4.20-4.33 (2H, m), 
               
               
                   
                   
                   
                   
                 4.52 (2H, s), 5.95 (2H, s), 6.53 (1H, dd, J = 8.6 Hz, 3.0 
               
               
                   
                   
                   
                   
                 Hz), 6.58 (1H, d, J = 3.0 Hz), 6.67-6.79 (3H, m), 6.82 
               
               
                   
                   
                   
                   
                 (1H, d, J = 8.9 Hz), 6.91 (1H, d, J = 8.1 Hz), 7.74 
               
               
                   
                   
                   
                   
                 (2H, d, J = 8.2 Hz), 7.99 (2H, d, J = 8.2 Hz), 8.10 
               
               
                   
                   
                   
                   
                 (1H, s), 8.15 (1H, dd, J = 9.2 Hz, 2.3 Hz), 8.22 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 2.3 Hz). 
               
               
                 1142 
                 3,4-Cl 2 Ph- 
                 —OCH 3   
                 —C 2 H 5   
                 (CDCl 3 ) 1.17 (3H, t, J = 6.4 Hz), 3.17-3.30 (2H, m), 
               
               
                   
                   
                   
                   
                 3.32-3.52 (2H, m), 3.70 (3H, s), 3.62-3.86 (2H, m), 4.03 
               
               
                   
                   
                   
                   
                 (2H, s), 4.29 (2H, s), 4.50 (2H, s), 5.95 (2H, s), 6.22 
               
               
                   
                   
                   
                   
                 (1H, d, J = 8.9 Hz), 6.37 (1H, s), 6.70 (1H, d, J = 8.2 
               
               
                   
                   
                   
                   
                 Hz), 6.75 (1H, s), 6.76 (1H, d, J = 8.9 Hz), 6.86 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 8.9 Hz), 6.94 (1H, d, J = 8.7 Hz), 7.54 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 8.4 Hz), 7.70 (1H, dd, J = 8.4 Hz, 2.0 Hz), 7.98 (1H, 
               
               
                   
                   
                   
                   
                 d, J = 2.0 Hz), 8.08 (1H, s), 8.08 (1H, dd, J = 8.9 Hz, 
               
               
                   
                   
                   
                   
                 2.3 Hz), 8.20 (1H, d, J = 2.3 Hz). 
               
               
                 1143 
                 4-CF 3 Ph- 
                 —OCH 3   
                 —C 2 H 5   
                 (CDCl 3 ) 1.18 (3H, t, J = 6.7 Hz), 3.16-3.33 (2H, m), 
               
               
                   
                   
                   
                   
                 3.33-3.50 (2H, m), 3.72 (2H, s), 3.62-3.85 (3H, m), 4.04 
               
               
                   
                   
                   
                   
                 (2H, s), 4.29 (2H, s), 4.50 (2H, s), 5.95 (2H, s), 6.23 
               
               
                   
                   
                   
                   
                 (1H, dd, J = 8.7 Hz, 2.8 Hz), 6.38 (1H, s), 6.71 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 8.1 Hz), 6.76 (1H, s), 6.76 (1H, d, J = 8.7 Hz), 6.88 
               
               
                   
                   
                   
                   
                 (1H, d, J = 8.7 Hz), 6.95 (1H, d, J = 8.7 Hz), 7.74 (2H, 
               
               
                   
                   
                   
                   
                 d, J = 8.0 Hz), 7.99 (2H, d, J = 8.0 Hz), 8.03 (1H, s), 
               
               
                   
                   
                   
                   
                 8.13 (1H, dd, J = 8.7 Hz, 2.4 Hz), 8.21 (1H, d, J = 2.4 
               
               
                   
                   
                   
                   
                 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 250 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 787   
                 R 788   
                 Xb 16   
                 Xb 17   
                 Form 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 1144 
                 4-CF 3 Ph- 
                 —H 
                 —N(CH 3 )— 
                 —CH(CH 3 )— 
                 free 
                 (CDCl 3 ) 1.30 (3H, d, J = 6.3 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 2.16-2.48 (4H, m), 2.77 (3H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 3.26-3.56 (3H, m), 3.39 (2H, s), 3.78 
               
               
                   
                   
                   
                   
                   
                   
                 (1H, brs), 4.56 (1H, q, J = 6.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 5.92 (2H, s), 6.68-6.77 (4H, m), 6.82 
               
               
                   
                   
                   
                   
                   
                   
                 (1H, s), 6.91 (1H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.04 (2H, d, J = 9.1 Hz), 7.76 (2H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.2 Hz), 7.90 (1H, brs), 7.99 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 8.1 Hz), 8.17 (1H, dd, J = 8.9 
               
               
                   
                   
                   
                   
                   
                   
                 Hz, 2.6 Hz), 8.25 (1H, d, J = 2.6 
               
               
                   
                   
                   
                   
                   
                   
                 Hz). 
               
               
                 1145 
                 4-CF 3 Ph- 
                 —CH 3   
                 —N(CH 3 )— 
                 —CH(CH 3 )— 
                 free 
                 (CDCl 3 ) 1.29 (3H, d, J = 6.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 2.14 (3H, s), 2.14-2.22 (1H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 2.29-2.35 (2H, m), 2.48 (1H, brs), 
               
               
                   
                   
                   
                   
                   
                   
                 2.76 (3H, s), 3.26-3.56 (3H, m), 3.39 
               
               
                   
                   
                   
                   
                   
                   
                 (2H, s), 3.78 (1H, brs), 4.57 (1H, q, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 6.6 Hz), 5.93 (2H, s), 6.58-6.62 
               
               
                   
                   
                   
                   
                   
                   
                 (2H, m), 6.68-6.75 (2H, m), 6.83 
               
               
                   
                   
                   
                   
                   
                   
                 (1H, brs), 6.86 (1H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 6.95 (1H, d, J = 9.2 Hz), 7.76 (2H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.3 Hz), 7.90 (1H, brs), 7.99 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 8.3 Hz), 8.16 (1H, dd, J = 8.9 
               
               
                   
                   
                   
                   
                   
                   
                 Hz, 2.8 Hz), 8.23 (1H, d, J = 2.5 
               
               
                   
                   
                   
                   
                   
                   
                 Hz). 
               
               
                 1146 
                 3,4-Cl 2 Ph- 
                 —H 
                 —CH 2 — 
                 —NH— 
                 hydrochloride 
                 (DMSO-d 6 ) 2.78-3.10 (2H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 3.10-3.35 (4H, m), 4.00-4.19 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 4.18-4.32 (4H, m), 6.07 (2H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 6.95-7.10 (3H, m), 7.06 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.6 Hz), 7.23 (1H, s), 7.30 (2H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.6 Hz), 7.39 (1H, t, J = 5.5 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.84 (1H, d, J = 8.4 Hz), 7.97 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 dd, J = 8.4 Hz, 2.0 Hz), 8.19 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 dd, J = 8.7 Hz, 2.6 Hz), 8.25 (1H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 2.0 Hz), 8.48 (1H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 10.62 (1H, s). 
               
               
                 1147 
                 4-CF 3 Ph- 
                 —H 
                 —CH 2 — 
                 —NH— 
                 hydrochloride 
                 (DMSO-d 6 ) 2.80-3.05 (2H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 3.11-3.38 (4H, m), 4.00-4.35 (4H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 4.24 (2H, s), 6.07 (2H, s), 6.98 
               
               
                   
                   
                   
                   
                   
                   
                 (1H, d, J = 8.7 Hz), 6.92-7.10 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 7.06 (2H, d, J = 8.6 Hz), 7.24 
               
               
                   
                   
                   
                   
                   
                   
                 (1H, d, J = 1.3 Hz), 7.30 (2H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.6 Hz), 7.35-7.45 (1H, m), 7.93 
               
               
                   
                   
                   
                   
                   
                   
                 (2H, d, J = 8.3 Hz), 8.19 (2H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.3 Hz), 8.22 (1H, dd, J = 8.7 
               
               
                   
                   
                   
                   
                   
                   
                 Hz, 2.5 Hz), 8.51 (1H, d, J = 2.5 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 10.70 (1H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 251 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 789   
                 R 790   
                 R 791   
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 1148 
                 4-CF 3 Ph- 
                 —CH 3   
                 —H 
                 (CDCl 3 ) 2.17 (3H, s), 2.50-2.55 (4H, m), 3.46 (2H, s), 
               
               
                   
                   
                   
                   
                 3.71-3.74 (2H, m), 4.26 (2H, brs), 5.95 (2H, s), 
               
               
                   
                   
                   
                   
                 6.74-6.75 (2H, m), 6.86 (1H, brs), 6.91-6.95 (1H, m), 
               
               
                   
                   
                   
                   
                 7.04 (1H, d, J = 8.7 Hz), 7.43 (1H, dd, J = 8.7 Hz, 2.5 
               
               
                   
                   
                   
                   
                 Hz), 7.56 (1H, d, J = 2.3 Hz), 7.76 (2H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                 7.94 (1H, brs), 7.99 (2H, d, J = 8.1 Hz), 8.20-8.23 (2H, 
               
               
                   
                   
                   
                   
                 m), 9.17 (1H, brs). 
               
               
                 1149 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 —H 
                 (CDCl 3 ) 2.18 (3H, s), 2.50-2.56 (4H, m), 3.47 (2H, s), 
               
               
                   
                   
                   
                   
                 3.72-3.75 (2H, m), 4.25-4.29 (2H, m), 5.96 (2H, s), 6.75 
               
               
                   
                   
                   
                   
                 (2H, m), 6.86 (1H, brs), 6.93 (1H, d, J = 8.7 Hz), 7.04 
               
               
                   
                   
                   
                   
                 (1H, d, J = 8.7 Hz), 7.44 (1H, dd, J = 8.7 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                   
                 7.56-7.57 (1H, m), 7.58 (1H, d, J = 8.3 Hz), 7.70 (1H, 
               
               
                   
                   
                   
                   
                 brs), 7.71 (1H, dd, J = 8.3 Hz, 2.1 Hz), 7.98 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 2.1 Hz), 8.15-8.47 (1H, m), 10.54 (1H, brs). 
               
               
                 1150 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 —CH 3   
                 (DMSO-d 6 ) 2.10-2.49 (7H, m), 3.26-3.57 (9H, m), 
               
               
                   
                   
                   
                   
                 5.96-5.99 (2H, m), 6.69-6.89 (3H, m), 7.05-7.11 (2H, 
               
               
                   
                   
                   
                   
                 m), 7.16-7.28 (1H, m), 7.30-7.37 (1H, m), 7.84 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 8.4 Hz), 7.94 (1H, dd, J = 8.4 Hz, 2.0 Hz), 8.18-8.22 
               
               
                   
                   
                   
                   
                 (2H, m), 8.42-8.47 (1H, m), 10.54 (1H, brs). 
               
               
                 1151 
                 4-CF 3 Ph- 
                 —CH 3   
                 —CH 3   
                 (DMSO-d 6 ) 2.10-2.46 (7H, m), 3.26-3.57 (9H, m), 
               
               
                   
                   
                   
                   
                 5.96-6.00 (2H, m), 6.69-6.89 (3H, m), 7.06-7.12 (2H, 
               
               
                   
                   
                   
                   
                 m), 7.17-7.29 (1H, m), 7.31-7.37 (3H, m), 7.94 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 8.6 Hz), 8.16 (2H, d, J = 8.6 Hz), 8.21-8.25 (2H, m), 
               
               
                   
                   
                   
                   
                 8.45-8.49 (1H, m), 10.61 (1H, brs). 
               
               
                 1152 
                 4-CF 3 Ph- 
                 —H 
                 —SO 2 CH 3   
                 (CDCl 3 ) 2.45 (4H, brs), 3.19 (3H, s), 3.39 (2H, brs), 
               
               
                   
                   
                   
                   
                 3.46 (2H, s), 3.62 (2H, brs), 4.52 (2H, s), 5.94 (2H, s), 
               
               
                   
                   
                   
                   
                 6.74 (2H, brs), 6.84 (1H, brs), 7.00 (1H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                 7.10 (2H, d, J = 8.7 Hz), 7.57 (2H, d, J = 8.7 Hz), 7.75 
               
               
                   
                   
                   
                   
                 (2H, d, J = 8.1 Hz), 8.00 (2H, d, J = 8.1 Hz), 8.15-8.24 
               
               
                   
                   
                   
                   
                 (2H, m), 8.31 (1H, brs). 
               
               
                 1153 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 —SO 2 CH 3   
                 (CDCl 3 ) 2.16 (3H, s), 2.46 (4H, brs), 3.20 (3H, s), 3.40 
               
               
                   
                   
                   
                   
                 (2H, brs), 3.47 (2H, s), 3.63 (2H, brs), 4.52 (2H, s), 5.94 
               
               
                   
                   
                   
                   
                 (2H, s), 6.70-6.77 (2H, m), 6.83 (1H, brs), 6.95 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 9.1 Hz), 6.99 (1H, d, J = 8.7 Hz), 7.38-7.57 (3H, m), 
               
               
                   
                   
                   
                   
                 7.71 (1H, dd, J = 8.4 Hz, 2.0 Hz), 7.97 (1H, d, J = 2.0 
               
               
                   
                   
                   
                   
                 Hz), 8.11 (1H, brs), 8.17 (1H, dd, J = 8.9 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                   
                 8.25 (1H, d, J = 2.6 Hz). 
               
               
                 1154 
                 4-CF 3 Ph- 
                 —CH 3   
                 —SO 2 CH 3   
                 (CDCl 3 ) 2.18 (3H, s), 2.42-2.46 (4H, m), 3.21 (3H, s), 
               
               
                   
                   
                   
                   
                 3.39-3.40 (2H, m), 3.44 (2H, s), 3.62 (2H, brs), 4.53 
               
               
                   
                   
                   
                   
                 (2H, s), 5.94 (2H, s), 6.70-6.77 (2H, m), 6.84 (1H, brs), 
               
               
                   
                   
                   
                   
                 6.96-7.03 (2H, m), 7.41-7.46 (2H, m), 7.76 (2H, d, 
               
               
                   
                   
                   
                   
                 J = 8.2 Hz), 7.98-8.01 (3H, m), 8.21 (1H, dd, J = 8.7 Hz, 
               
               
                   
                   
                   
                   
                 2.8 Hz), 8.26 (1H, d, J = 2.3 Hz). 
               
               
                 1155 
                 3,4-Cl 2 Ph- 
                 —H 
                 —SO 2 CH 3   
                 (CDCl 3 ) 2.41-2.45 (4H, m), 3.19 (3H, s), 3.38 (2H, brs), 
               
               
                   
                   
                   
                   
                 3.44 (2H, s), 3.61 (2H, brs), 4.52 (2H, s), 5.94 (2H, s), 
               
               
                   
                   
                   
                   
                 6.72-6.74 (2H, m), 6.83 (1H, brs), 6.98 (1H, d, J = 8.7 
               
               
                   
                   
                   
                   
                 Hz), 7.09 (2H, d, J = 8.7 Hz), 7.55 (1H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                 7.56 (2H, d, J = 8.7 Hz), 7.72 (1H, dd, J = 8.4 Hz, 2.1 
               
               
                   
                   
                   
                   
                 Hz), 7.98 (1H, d, J = 2.1 Hz), 8.18 (1H, dd, J = 8.7 Hz, 
               
               
                   
                   
                   
                   
                 2.8 Hz), 8.27 (1H, brs), 8.30 (1H, d, J = 2.1 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 252 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 792   
                 R 793   
                 R 794   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 1156 
                 4-CF 3 Ph- 
                 —H 
                 —CH 3   
                 1.21 (3H, t, J = 6.8 Hz), 2.05-2.14 (1H, m), 2.44-2.51 (1H, 
               
               
                   
                   
                   
                   
                 m), 2.70-2.74 (1H, m), 2.83-3.32 (6H, m), 3.55-3.59 (1H, 
               
               
                   
                   
                   
                   
                 m), 3.84-4.08 (4H, m), 5.94 (2H, s), 6.66 (2H, d, J = 8.9 
               
               
                   
                   
                   
                   
                 Hz), 6.74 (2H, brs), 6.81-6.85 (2H, m), 6.97 (2H, d, J = 8.4 
               
               
                   
                   
                   
                   
                 Hz), 7.72 (2H, d, J = 8.3 Hz), 7.98 (2H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                   
                 8.11 (1H, d, J = 9.1 Hz), 8.25 (1H, d, J = 2.5 Hz), 8.31 
               
               
                   
                   
                   
                   
                 (1H, brs). 
               
               
                 1157 
                 4-CF 3 Ph- 
                 —CH 3   
                 —H 
                 1.26-1.39 (3H, m), 1.99-2.04 (1H, m), 2.13-2.17 (1H, m), 
               
               
                   
                   
                   
                   
                 2.64-2.67 (1H, m), 2.79-2.83 (1H, m), 2.98 (4H, brs), 
               
               
                   
                   
                   
                   
                 3.31-3.53 (3H, m), 3.97-4.66 (3H, m), 5.95 (2H, s), 6.64 
               
               
                   
                   
                   
                   
                 (2H, d, J = 9.1 Hz), 6.74 (2H, brs), 6.82 (1H, d, J = 8.9 
               
               
                   
                   
                   
                   
                 Hz), 6.87 (1H, brs), 6.96 (2H, d, J = 9.1 Hz), 7.71 (2H, d, 
               
               
                   
                   
                   
                   
                 J = 7.9 Hz), 7.98 (2H, d, J = 8.3 Hz), 8.10 (1H, dd, J = 8.9 
               
               
                   
                   
                   
                   
                 Hz, 2.5 Hz), 8.25 (1H, d, J = 2.5 Hz), 8.40 (1H, brs). 
               
               
                 1158 
                 3,4-Cl 2 Ph- 
                 —H 
                 —CH 3   
                 1.21 (3H, t, J = 6.8 Hz), 2.07-2.14 (1H, m), 2.43-2.52 (1H, 
               
               
                   
                   
                   
                   
                 m), 2.70 (1H, brs), 2.83-3.32 (6H, m), 3.55-3.60 (1H, m), 
               
               
                   
                   
                   
                   
                 3.83-4.08 (4H, m), 5.94 (2H, s), 6.64 (2H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                   
                 6.74 (2H, brs), 6.81 (1H, d, J = 8.9 Hz), 6.85 (1H, brs), 
               
               
                   
                   
                   
                   
                 6.96 (2H, d, J = 8.7 Hz), 7.53 (1H, d, J = 8.4 Hz), 7.71 
               
               
                   
                   
                   
                   
                 (1H, dd, J = 8.3 Hz, 2.1 Hz), 7.98 (1H, d, J = 2.0 Hz), 8.05 
               
               
                   
                   
                   
                   
                 (1H, dd, J = 8.9 Hz, 2.6 Hz), 8.24 (1H, d, J = 2.5 Hz), 8.31 
               
               
                   
                   
                   
                   
                 (1H, brs). 
               
               
                 1159 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 —H 
                 1.26-1.39 (3H, m), 1.99-2.17 (2H, m), 2.64-2.68 (1H, m), 
               
               
                   
                   
                   
                   
                 2.79-2.84 (1H, m), 2.99 (4H, brs), 3.31-3.54 (3H, m), 
               
               
                   
                   
                   
                   
                 4.01-4.68 (3H, m), 5.95 (2H, s), 6.64 (2H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                   
                 6.74 (2H, brs), 6.81 (1H, d, J = 8.9 Hz), 6.87 (1H, brs), 
               
               
                   
                   
                   
                   
                 6.96 (2H, d, J = 8.9 Hz), 7.53 (1H, d, J = 8.4 Hz), 7.71 
               
               
                   
                   
                   
                   
                 (1H, dd, J = 8.4 Hz, 2.0 Hz), 7.98 (1H, d, J = 2.0 Hz), 8.06 
               
               
                   
                   
                   
                   
                 (1H, dd, J = 8.9 Hz, 2.5 Hz), 8.24 (1H, d, J = 2.3 Hz), 8.26 
               
               
                   
                   
                   
                   
                 (1H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 253 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 795   
                 R 796   
                 R 797   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 1160 
                 3,4-Cl 2 Ph- 
                 —H 
                 —CH 3   
                 1.16-1.19 (6H, m), 2.04-2.14 (1H, m), 2.43-2.52 (1H, m), 
               
               
                   
                   
                   
                   
                 2.66-2.74 (1H, m), 2.83-3.36 (5H, m), 3.59-3.63 (1H, m), 
               
               
                   
                   
                   
                   
                 3.84-4.08 (4H, m), 5.94 (2H, s), 6.59 (2H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                 6.74 (2H, brs), 6.79 (1H, d, J = 8.9 Hz), 6.85 (1H, brs), 6.92 
               
               
                   
                   
                   
                   
                 (2H, d, J = 8.9 Hz), 7.50 (1H, d, J = 8.4 Hz), 7.71 (1H, dd, 
               
               
                   
                   
                   
                   
                 J = 8.4 Hz, 2.1 Hz), 7.98 (1H, d, J = 2.0 Hz), 8.03 (1H, dd, 
               
               
                   
                   
                   
                   
                 J = 8.9 Hz, 2.6 Hz), 8.25 (1H, d, J = 2.3 Hz), 8.64 (1H, brs). 
               
               
                 1161 
                 4-CF 3 Ph- 
                 —H 
                 —CH 3   
                 1.09-1.15 (6H, m), 2.04-2.13 (1H, m), 2.43-2.51 (1H, m), 
               
               
                   
                   
                   
                   
                 2.66-2.74 (1H, m), 2.83-3.38 (5H, m), 3.58-3.63 (1H, m), 
               
               
                   
                   
                   
                   
                 3.84-4.08 (4H, m), 5.94 (2H, s), 6.61 (2H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                 6.74 (2H, brs), 6.81 (1H, d, J = 8.9 Hz), 6.85 (1H, brs), 6.94 
               
               
                   
                   
                   
                   
                 (2H, d, J = 8.3 Hz), 7.71 (2H, d, J = 7.8 Hz), 7.99 (2H, d, 
               
               
                   
                   
                   
                   
                 J = 8.1 Hz), 8.10 (1H, d, J = 9.1 Hz), 8.26 (1H, d, J = 2.5 
               
               
                   
                   
                   
                   
                 Hz), 8.50 (1H, brs). 
               
               
                 1162 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 —H 
                 1.15 (3H, t, J = 7.1 Hz), 1.26-1.43 (3H, m), 2.00 (1H, brs), 
               
               
                   
                   
                   
                   
                 2.13 (1H, brs), 2.64-2.68 (1H, m), 2.79-2.83 (1H, m), 
               
               
                   
                   
                   
                   
                 3.02-4.68 (9H, m), 5.95 (2H, s), 6.61 (2H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                   
                 6.74 (2H, brs), 6.81 (1H, d, J = 8.7 Hz), 6.87 (1H, brs), 6.94 
               
               
                   
                   
                   
                   
                 (2H, d, J = 8.9 Hz), 7.53 (1H, d, J = 8.4 Hz), 7.71 (1H, dd, 
               
               
                   
                   
                   
                   
                 J = 8.4 Hz, 2.1 Hz), 7.99 (1H, d, J = 2.0 Hz), 8.06 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 8.9 Hz), 8.25 (1H, d, J = 2.6 Hz), 8.32 (1H, brs). 
               
               
                 1163 
                 4-CF 3 Ph- 
                 —CH 3   
                 —H 
                 1.15 (3H, t, J = 6.9 Hz), 1.26-1.39 (3H, m), 1.99 (1H, brs), 
               
               
                   
                   
                   
                   
                 2.13 (1H, brs), 2.63-2.67 (1H, m), 2.79-2.83 (1H, m), 
               
               
                   
                   
                   
                   
                 3.00-4.67 (9H, m), 5.95 (2H, s), 6.61 (2H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                 6.74 (2H, brs), 6.82 (1H, d, J = 8.7 Hz), 6.87 (1H, brs), 6.95 
               
               
                   
                   
                   
                   
                 (2H, d, J = 8.9 Hz), 7.71 (2H, d, J = 7.9 Hz), 7.99 (2H, d, 
               
               
                   
                   
                   
                   
                 J = 8.1 Hz), 8.10 (1H, d, J = 8.3 Hz), 8.27 (1H, d, J = 2.5 
               
               
                   
                   
                   
                   
                 Hz), 8.38 (1H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 254 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 798   
                 R 799   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 1164 
                 4-CF 3 Ph— 
                 —H 
                 2.52 (4H, brs), 2.64 (4H, brs), 3.12 (2H, s), 3.45 (2H, brs), 5.94 (2H, 
               
               
                   
                   
                   
                 s), 6.75 (2H, brs), 6.86 (1H, brs), 6.95 (1H, d, J = 8.7 Hz), 7.11 (2H, 
               
               
                   
                   
                   
                 d, J = 8.9 Hz), 7.60 (2H, d, J = 8.9 Hz), 7.76 (2H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                 7.98 (1H, brs), 8.00 (2H, d, J = 8.3 Hz), 8.21 (1H, dd, J = 8.9 Hz, 
               
               
                   
                   
                   
                 2.8 Hz), 8.26 (1H, d, J = 2.5 Hz), 9.16 (1H, brs). 
               
               
                 1165 
                 3,4-Cl 2 Ph- 
                 —H 
                 2.52 (4H, brs), 2.62-2.64 (4H, m), 3.12 (2H, s), 3.45 (2H, brs), 5.95 
               
               
                   
                   
                   
                 (2H, s), 6.75 (2H, brs), 6.86 (1H, brs), 6.94 (1H, d, J = 8.7 Hz), 7.10 
               
               
                   
                   
                   
                 (2H, d, J = 8.9 Hz), 7.57 (1H, d, J = 8.4 Hz), 7.59 (2H, d, J = 8.9 
               
               
                   
                   
                   
                 Hz), 7.72 (1H, dd, J = 8.4 Hz, 2.1 Hz), 7.99 (2H, brs), 8.17 (1H, dd, 
               
               
                   
                   
                   
                 J = 8.9 Hz, 2.8 Hz), 8.25 (1H, d, J = 2.8 Hz), 9.17 (1H, brs). 
               
               
                 1166 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 2.44 (8H, brs), 2.95 (2H, s), 3.26 (3H, s), 3.39 (2H, s), 5.92 (2H, s), 
               
               
                   
                   
                   
                 6.71 (2H, brs), 6.81 (1H, brs), 7.02 (1H, d, J = 8.7 Hz), 7.14-7.22 
               
               
                   
                   
                   
                 (4H, m), 7.58 (1H, d, J = 8.4 Hz), 7.77 (1H, dd, J = 8.4 Hz, 2.1 Hz), 
               
               
                   
                   
                   
                 8.05 (1H, d, J = 2.1 Hz), 8.27 (1H, dd, J = 8.7 Hz, 2.6 Hz), 8.32 
               
               
                   
                   
                   
                 (1H, d, J = 2.6 Hz), 8.33 (1H, brs). 
               
               
                 1167 
                 4-CF 3 Ph- 
                 —CH 3   
                 2.50 (8H, brs), 2.95 (2H, s), 3.24 (3H, s), 3.47 (2H, s), 5.92 (2H, s), 
               
               
                   
                   
                   
                 6.72 (2H, brs), 6.81 (1H, brs), 7.02 (1H, d, J = 8.7 Hz), 7.13-7.21 
               
               
                   
                   
                   
                 (4H, m), 7.74 (2H, d, J = 8.4 Hz), 8.05 (2H, d, J = 8.1 Hz), 8.30 
               
               
                   
                   
                   
                 (1H, dd, J = 8.9 Hz, 2.5 Hz), 8.35 (1H, d, J = 2.3 Hz), 8.61 (1H, 
               
               
                   
                   
                   
                 brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 255 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 800   
                 R 801   
                 M 
                 Form 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 1168 
                 3,4-Cl 2 Ph- 
                 piperonyl 
                 2 
                 hydrochloride 
                 (DMSO-d 6 ) 2.60-2.61 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 2.75-3.08 (6H, m), 3.22-3.60 (5H, 
               
               
                   
                   
                   
                   
                   
                 m), 4.03 (1H, d, J = 13.9 Hz), 4.20 
               
               
                   
                   
                   
                   
                   
                 (2H, d, J = 4.3 Hz), 4.46 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 13.9 Hz), 6.06 (2H, s), 6.73 (2H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.9 Hz), 6.93-6.99 (5H, m), 
               
               
                   
                   
                   
                   
                   
                 7.20 (1H, brs), 7.83 (1H, d, J = 8.4 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.96 (1H, dd, J = 8.4 Hz, 2.1 
               
               
                   
                   
                   
                   
                   
                 Hz), 8.14 (1H, dd, J = 8.9 Hz, 2.6 
               
               
                   
                   
                   
                   
                   
                 Hz), 8.23 (1H, d, J = 2.0 Hz), 8.45 
               
               
                   
                   
                   
                   
                   
                 (1H, d, J = 2.6 Hz), 10.57 (1H, brs), 
               
               
                   
                   
                   
                   
                   
                 11.00 (1H, brs). 
               
               
                 1169 
                 4-CF 3 Ph- 
                 piperonyl 
                 2 
                 hydrochloride 
                 (DMSO-d 6 ) 2.60-2.62 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 2.88-3.08 (6H, m), 3.23-3.60 (5H, 
               
               
                   
                   
                   
                   
                   
                 m), 4.01-4.06 (1H, m), 4.20-4.21 
               
               
                   
                   
                   
                   
                   
                 (2H, m), 4.43-4.49 (1H, m), 6.07 
               
               
                   
                   
                   
                   
                   
                 (2H, s), 6.73 (2H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.94-6.99 (5H, m), 7.20 (1H, brs), 
               
               
                   
                   
                   
                   
                   
                 7.93 (2H, d, J = 8.2 Hz), 8.14-8.19 
               
               
                   
                   
                   
                   
                   
                 (3H, m), 8.47 (1H, d, J = 2.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 10.64 (1H, brs), 11.00 (1H, brs). 
               
               
                 1170 
                 4-CF 3 Ph- 
                 benzyl 
                 0 
                 free 
                 (CDCl 3 ) 2.25 (4H, t, J = 4.9 Hz), 
               
               
                   
                   
                   
                   
                   
                 3.19 (3H, s), 3.23 (4H, t, J = 4.9 Hz), 
               
               
                   
                   
                   
                   
                   
                 3.43 (2H, s), 6.95 (1H, d, J = 8.7 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.08 (4H, s), 7.20-7.32 (5H, m), 
               
               
                   
                   
                   
                   
                   
                 7.75 (2H, d, J = 8.0 Hz), 8.02 (2H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.0 Hz), 8.24 (1H, dd, J = 8.7 
               
               
                   
                   
                   
                   
                   
                 Hz, 2.5 Hz), 8.31 (1H, d, J = 2.5 
               
               
                   
                   
                   
                   
                   
                 Hz), 8.34 (1H, s). 
               
               
                 1171 
                 3,4-Cl 2 Ph- 
                 benzyl 
                 0 
                 hydrochloride 
                 (DMSO-d 6 ) 2.70-3.00 (2H, m), 3.14 
               
               
                   
                   
                   
                   
                   
                 (3H, s), 2.95-3.30 (4H, m), 3.72 (2H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 13.7 Hz), 4.29 (2H, s), 7.08 
               
               
                   
                   
                   
                   
                   
                 (1H, d, J = 8.7 Hz), 7.11 (2H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.9 Hz), 7.23 (2H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.39-7.48 (3H, m), 7.51-7.60 (2H, 
               
               
                   
                   
                   
                   
                   
                 m), 7.84 (1H, d, J = 8.5 Hz), 7.97 
               
               
                   
                   
                   
                   
                   
                 (1H, dd, J = 8.5 Hz, 2.0 Hz), 8.22 
               
               
                   
                   
                   
                   
                   
                 (1H, dd, J = 8.7 Hz, 2.6 Hz), 8.25 
               
               
                   
                   
                   
                   
                   
                 (1H, d, J = 20 Hz), 8.53 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 2.6 Hz), 10.67 (1H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 256 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 802   
                 R 803   
                 R 804   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 1172 
                 3,4-Cl 2 Ph- 
                 —H 
                 —CH 3   
                 2.34 (3H, s), 2.34-2.50 (4H, m), 2.78 (3H, s), 3.42 (2H, s), 
               
               
                   
                   
                   
                   
                 3.50-3.70 (4H, m), 3.80 (2H, s), 5.95 (2H, s), 6.70-6.80 
               
               
                   
                   
                   
                   
                 (2H, m), 6.85-6.89 (2H, m), 7.26-7.35 (1H, m), 7.40 (1H, 
               
               
                   
                   
                   
                   
                 d, J = 2.8 Hz), 7.51 (1H, d, J = 8.9 Hz), 7.57-7.61 (2H, m), 
               
               
                   
                   
                   
                   
                 7.74 (1H, dd, J = 8.3 Hz, 2.0 Hz), 8.01 (1H, d, J = 2.0 Hz), 
               
               
                   
                   
                   
                   
                 8.29 (1H, s). 
               
               
                 1173 
                 4-CF 3 Ph- 
                 —H 
                 —CH 3   
                 2.36 (3H, s), 2.36-2.50 (4H, m), 2.79 (3H, s), 3.42 (2H, s), 
               
               
                   
                   
                   
                   
                 3.50-3.65 (4H, m), 3.80 (2H, s), 5.94 (2H, s), 6.70-6.75 
               
               
                   
                   
                   
                   
                 (2H, m), 6.85-6.90 (2H, m), 7.30 (1H, dd, J = 8.8 Hz, 2.7 
               
               
                   
                   
                   
                   
                 Hz), 7.40 (1H, d, J = 2.8 Hz), 7.51 (1H, d, J = 8.8 Hz), 
               
               
                   
                   
                   
                   
                 7.68 (1H, brs), 7.76-7.80 (2H, m), 8.01-8.04 (2H, m), 8.34 
               
               
                   
                   
                   
                   
                 (1H, s). 
               
               
                 1174 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 —H 
                 2.30-2.44 (4H, m), 2.44 (3H, s), 2.79 (3H, s), 3.42 (2H, s), 
               
               
                   
                   
                   
                   
                 3.50-3.65 (4H, m), 3.80 (2H, s), 5.95 (2H, s), 6.65-6.81 
               
               
                   
                   
                   
                   
                 (3H, m), 6.85 (1H, s), 7.29 (1H, dd, J = 8.8 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                   
                 7.41 (1H, d, J = 2.7 Hz), 7.49 (1H, d, J = 8.8 Hz), 7.59 
               
               
                   
                   
                   
                   
                 (1H, d, J = 8.3 Hz), 7.67 (1H, brs), 7.72 (1H, dd, J = 8.3 
               
               
                   
                   
                   
                   
                 Hz, 2.1 Hz), 8.00 (1H, d, J = 2.0 Hz), 8.09 (1H, d, J = 8.7 
               
               
                   
                   
                   
                   
                 Hz). 
               
               
                 1175 
                 4-CF 3 Ph- 
                 —CH 3   
                 —H 
                  2.35-2.45 (4H, m), 2.45 (3H, s), 2.79 (3H, s), 3.42 (2H, s), 
               
               
                   
                   
                   
                   
                 3.50-3.65 (4H, m), 3.80 (2H, s), 5.95 (2H, s), 6.65-6.82 
               
               
                   
                   
                   
                   
                 (2H, m), 6.85 (1H, s), 7.30 (1H, dd, J = 8.8 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                   
                 7.41 (1H, d, J = 2.8 Hz), 7.50 (1H, d, J = 8.8 Hz), 7.72 
               
               
                   
                   
                   
                   
                 (1H, brs), 7.77-7.80 (2H, m), 8.00-8.03 (2H, m), 8.15 (1H, 
               
               
                   
                   
                   
                   
                 d, J = 8.6 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 257 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 805   
                 R 806   
                 R 807   
                 R 808   
                 Form 
                   1 H NMR (DMSO-d 6 ) δ ppm 
               
               
                   
               
               
                 1176 
                 3,4-Cl 2 Ph- 
                 —H 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 3.14 (1H, dd, J = 14.0 Hz, 9.4 Hz), 3.40 (1H, dd, J = 14.0 Hz, 4.5 Hz), 4.93 (1H, dd, J = 9.4 Hz, 4.5 Hz), 7.07 (1H, d, J = 8.9 Hz), 7.07 (2H, d, J = 8.4 Hz), 7.29 (2H, d, J = 8.4 Hz), 7.84 (1H, d, J = 8.4 Hz), 7.95 (1H, dd, J = 8.4 Hz, 2.0 Hz), 8.20 (1H, dd, J = 8.9 Hz, 2.5 Hz), 8.22 (1H, d, J = 2.0 Hz), 8.48 (1H, d, J = 2.5 Hz), 10.56 (1H, s), 12.06 (1H, s). 
               
               
                   
               
               
                 1177 
                 4-CF 3 OPh- 
                 —CH 3   
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 hydrochloride 
                 2.09 (3H, s), 3.09 (1H, dd, J = 14.3 Hz, 9.6 Hz), 3.40 (1H, dd, J = 14.3 Hz, 4.3 Hz), 4.93 (1H, dd, J = 9.6 Hz, 4.3 Hz), 6.99 (1H, d, J = 8.1 Hz), 7.02 (1H, d, J = 8.9 Hz), 7.12 (1H, d, J = 8.1 Hz), 7.20 (1H, s), 7.55 (2H, d, J = 8.8 Hz), 8.10 (2H, d, J = 8.8 Hz), 8.20 (1H, dd, J = 8.9 Hz, 2.6 Hz), 8.44 (1H, d, J = 2.6 Hz), 10.54 (1H, s), 12.10 (1H, s). 
               
               
                   
               
               
                 1178 
                 3,4-Cl 2 Ph- 
                 —H 
                 —CH 3   
                 morpholino 
                 hydrochloride 
                 1.70 (3H, d, J = 6.9 Hz), 2.94-3.01 
               
               
                   
                   
                   
                   
                   
                   
                 (2H, m), 3.63-4.02 (6H, m), 4.50 
               
               
                   
                   
                   
                   
                   
                   
                 (1H, t, J = 6.6 Hz), 7.13 (1H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 9.1 Hz), 7.23 (2H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.64 (2H, d, J = 8.7 Hz), 7.85 (1H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.4 Hz), 7.96 (1H, dd, J = 8.4 
               
               
                   
                   
                   
                   
                   
                   
                 Hz, 2.2 Hz), 8.23 (1H, dd, J = 8.9 
               
               
                   
                   
                   
                   
                   
                   
                 Hz, 2.6 Hz), 8.24 (1H, d, J = 2.1 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 8.54 (1H, d, J = 2.1 Hz), 10.63 
               
               
                   
                   
                   
                   
                   
                   
                 (1H, brs), 10.89 (1H, brs). 
               
               
                 1179 
                 4-CF 3 Ph- 
                 —H 
                 —CH 3   
                 morpholino 
                 hydrochloride 
                 1.72 (3H, d, J = 6.6 Hz), 2.92 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs), 3.35 (2H, brs), 3.69-3.99 (4H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 4.49 (1H, brs), 7.14 (1H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.7 Hz), 7.22 (2H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.69 (2H, d, J = 8.3 Hz), 7.94 (2H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.3 Hz), 8.20 (2H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 8.28 (1H, d, J = 8.9 Hz), 8.58 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs), 10.77 (1H, brs), 11.47 (1H, brs). 
               
               
                 1180 
                 Ph- 
                 —H 
                 —CH 3   
                 morpholino 
                 hydrochloride 
                 1.70 (3H, d, J = 6.8 Hz), 2.94 (2H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs), 3.38-3.43 (2H, m), 3.62-4.02 
               
               
                   
                   
                   
                   
                   
                   
                 (4H, m), 4.50 (1H, t, J = 6.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.12 (1H, d, J = 8.7 Hz), 7.22 (2H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.6 Hz), 7.52-7.65 (5H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.96-8.00 (2H, m), 8.26 (1H, dd, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.7 Hz, 2.8 Hz), 8.56 (1H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 2.8 Hz), 10.47 (1H, brs), 10.91 
               
               
                   
                   
                   
                   
                   
                   
                 (1H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
           
               
                 TABLE 258 
               
               
                   
               
               
                 Example 
                   
                   
               
               
                 No. 
                 Chemical stracture 
                 mp (° C.) 
               
               
                   
               
             
             
               
                 1181 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 203.0-204.0 
               
               
                   
               
               
                 1182 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 186.0-187.0 
               
               
                   
               
               
                 1183 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 165.0-166.0 
               
               
                   
               
               
                 1184 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 122.0-124.0 
               
               
                   
               
               
                 1185 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 155.0-157.0 
               
               
                   
               
               
                 1186 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 182.0-183.5 
               
               
                   
               
               
                 1187 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 117.0-118.0 
               
               
                   
               
               
                 1188 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 160.0-161.0 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 259 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 809   
                 R 810   
                 R 811   
                 Xb 18   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 1189 
                 4-CF 3 Ph- 
                 —COOCH 3   
                 benzyl 
                 —O— 
                 2.62 (4H, brs), 3.23 (4H, brs), 3.58 
               
               
                   
                   
                   
                   
                   
                 (2H, s), 3.67 (3H, s), 6.95 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 9.7 Hz), 7.06-7.14 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 7.26-7.36 (5H, m), 7.49 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 2.3 Hz), 7.74 (2H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.87 (1H, s), 7.98 (2H, d, J = 8.1 
               
               
                   
                   
                   
                   
                   
                 Hz), 8.16-8.18 (2H, m). 
               
               
                 1190 
                 3,4-Cl 2 Ph- 
                 —H 
                 —COOC(CH 3 ) 3   
                 —O— 
                 1.49 (9H, s), 3.11 (4H, t, J = 4.8 Hz), 
               
               
                   
                   
                   
                   
                   
                 3.58 (4H, t, J = 4.8 Hz), 6.92 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 9.0 Hz), 6.96 (2H, d, J = 8.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.06 (2H, d, J = 8.5 Hz), 7.58 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.5 Hz), 7.70 (1H, dd, J = 8.5 
               
               
                   
                   
                   
                   
                   
                 Hz, 2.0 Hz), 7.74 (1H, brs), 7.98 
               
               
                   
                   
                   
                   
                   
                 (1H, d, J = 2.0 Hz), 8.15 (1H, brd, 
               
               
                   
                   
                   
                   
                   
                 J = 9.0 Hz), 8.24 (1H, d, J = 2.5 Hz). 
               
               
                 1191 
                 4-CF 3 Ph- 
                 —H 
                 —COOC(CH 3 ) 3   
                 —O— 
                 1.49 (2H, s), 3.11 (4H, t, J = 5.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 3.58 (4H, t, J = 5.0 Hz), 6.93 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 9.0 Hz), 6.96 (2H, d, J = 9.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.06 (2H, d, J = 9.0 Hz), 7.77 (2H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.0 Hz), 7.82 (2H, brs), 7.99 (2H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.0 Hz), 8.19 (1H, dd, J = 9.0 
               
               
                   
                   
                   
                   
                   
                 Hz, 2.5 Hz), 8.25 (1H, d, J = 2.5 
               
               
                   
                   
                   
                   
                   
                 Hz). 
               
               
                 1192 
                 4-CF 3 Ph- 
                 —H 
                 —CH 2 COOC 2 H 5   
                 —N(CH 3 )— 
                 1.30 (3H, t, J = 7.1 Hz), 2.77 (4H, t, 
               
               
                   
                   
                   
                   
                   
                 J = 5.0 Hz), 3.28 (4H, t, J = 5.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 3.29 (2H, s), 3.42 (3H, s), 4.22 (2H, 
               
               
                   
                   
                   
                   
                   
                 q, J = 7.1 Hz), 6.47 (1H, d, J = 9.2 
               
               
                   
                   
                   
                   
                   
                 Hz), 6.96 (2H, d, J = 9.0 Hz), 7.15 
               
               
                   
                   
                   
                   
                   
                 (2H, d, J = 9.0 Hz), 7.69 (1H, brs), 
               
               
                   
                   
                   
                   
                   
                 7.70 (1H, d, J = 2.5 Hz), 7.74 (2H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.1 Hz), 7.98 (2H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.26 (1H, d, J = 2.5 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 260 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 812   
                 R 813   
                 Xb 19   
                 Xb 20   
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 1193 
                 3,4-Cl 2 Ph- 
                 —COOC(CH 3 ) 3   
                 —CO— 
                 —CH 2 — 
                 (CDCl 3 ) 1.51 (9 H, s), 3.75 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                 3.79 (2 H, m), 4.26 (2 H, s), 6.98 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.8 Hz), 7.14 (2 H, dd, J = 6.9 Hz, 
               
               
                   
                   
                   
                   
                   
                 2.1 Hz), 7.28 (2 H, dd, J = 6.9 Hz, 2.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.58 (1 H, d, J = 8.3 Hz), 7.72 (1 H, 
               
               
                   
                   
                   
                   
                   
                 dd, J = 8.3 Hz, 2.1 Hz), 7.99 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 2.1 Hz), 8.13 (1 H, dd, J = 8.8 Hz, 
               
               
                   
                   
                   
                   
                   
                 2.7 Hz), 8.29 (1 H, d, J = 2.7 Hz). 
               
               
                 1194 
                 3,4-Cl 2 Ph- 
                 piperonyl 
                 —CH 2 — 
                 —CO— 
                 (DMSO-d 6 ) 3.22-3.50 (4 H, m), 
               
               
                   
                   
                   
                   
                   
                 3.84 (2 H, s), 4.50 (2 H, s), 6.00 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                 6.77 (1 H, dd, J = 8.0 Hz, 1.4 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.84 (1 H, d, J = 1.4 Hz), 6.87 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.0 Hz), 6.98 (2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.97-7.06 (3 H, m), 7.84 (1 H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.94 (1 H, dd, J = 8.4 Hz, 2.0 Hz),  
               
               
                   
                   
                   
                   
                   
                 8.15 (1 H, dd, J = 8.9 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.22 (1 H, d, J = 2.0 Hz), 8.44 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 2.3 Hz), 10.51 (1 H, s). 
               
               
                 1195 
                 4-CF 3 Ph- 
                 piperonyl 
                 —CH 2 — 
                 —CO— 
                 (DMSO-d 6 ) 3.27-3.40 (2 H, m), 3.40- 
               
               
                   
                   
                   
                   
                   
                 3.50 (2 H, m), 3.85 (2 H, s), 4.50 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                 6.00 (2 H, s), 6.77 (1 H, dd, J = 7.9 Hz, 
               
               
                   
                   
                   
                   
                   
                 1.5 Hz), 6.84 (1 H, d, J = 1.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.88 (1 H, d, J = 7.9 Hz), 6.95-7.07 (5 H, 
               
               
                   
                   
                   
                   
                   
                 m), 7.93 (2 H, d, J = 8.1 Hz), 8.16 (2 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.1 Hz), 8.17 (1 H, dd, J = 8.8 Hz, 
               
               
                   
                   
                   
                   
                   
                 2.5 Hz), 8.46 (1 H, d, J = 2.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 10.60 (1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 261 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 814   
                 R 815   
                 Xb 21   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 1196 
                 3,4-Cl 2 Ph- 
                 —COOC 2 H 5   
                 —O— 
                 1.28 (3 H, t, J = 7.0 Hz), 1.88-1.93 (2 H, m), 
               
               
                   
                   
                   
                   
                 2.03 (2 H, brd, J = 10.0 Hz), 2.42 (1 H, m), 
               
               
                   
                   
                   
                   
                 2.78 (1 H, t, J = 10.5 Hz), 3.59 (2 H, dt, 
               
               
                   
                   
                   
                   
                 J = 12.5 Hz, 3.5 Hz), 4.16 (2 H, q, J = 7.0 Hz), 
               
               
                   
                   
                   
                   
                 6.90 (1 H, d, J = 9.0 Hz), 6.95 (2 H, d, J = 9.0 Hz), 
               
               
                   
                   
                   
                   
                 7.03 (2 H, d, J = 9.0 Hz), 7.58 (1 H, d, 
               
               
                   
                   
                   
                   
                 J = 8.5 Hz), 7.70 (1 H, brs), 7.71 (1 H, dd, J = 8.5 Hz, 
               
               
                   
                   
                   
                   
                 2.0 Hz), 7.98 (1 H, d, J = 2.0 Hz), 
               
               
                   
                   
                   
                   
                 8.14 (1 H, dd, J = 9.0 Hz, 2.5 Hz), 8.24 (1 H, d, 
               
               
                   
                   
                   
                   
                 J = 2.5 Hz). 
               
               
                 1197 
                 3,4-Cl 2 Ph- 
                 —CH 2 COOC 2 H 5   
                 —O— 
                 1.27 (3 H, t, J = 7.0 Hz), 1.40-1.46 (2 H, m), 
               
               
                   
                   
                   
                   
                 1.82 (2 H, brd, J = 13.0 Hz), 1.90 (1 H, m), 
               
               
                   
                   
                   
                   
                 2.27 (2 H, d, J = 7.0 Hz), 2.69 (2 H, brt, 
               
               
                   
                   
                   
                   
                 J = 13.0 Hz), 3.57 (2 H, brd, J = 12.0 Hz), 4.15 
               
               
                   
                   
                   
                   
                 (2 H, q, J = 7.0 Hz), 6.83 (1 H, d, J = 9.0 Hz), 
               
               
                   
                   
                   
                   
                 6.90 (2 H, d, J = 9.0 Hz), 6.97 (2 H, d, J = 9.0 Hz), 
               
               
                   
                   
                   
                   
                 7.49 (1 H, d, J = 8.5 Hz), 7.68 (1 H, dd, 
               
               
                   
                   
                   
                   
                 J = 8.5 Hz, 2.0 Hz), 7.95 (1 H, d, J = 2.0 Hz), 
               
               
                   
                   
                   
                   
                 8.10 (1 H, dd, J = 9.0 Hz, 2.5 Hz), 8.21 (1 H, d, 
               
               
                   
                   
                   
                   
                 J = 2.5 Hz), 8.48 (1 H, brs). 
               
               
                 1198 
                 4-CF 3 Ph- 
                 —CH 2 COOC 2 H 5   
                 —N(CH 3 )— 
                 1.28 (3 H, t, J = 7.1 Hz), 1.46 (2 H, qd, J = 12.2 Hz, 
               
               
                   
                   
                   
                   
                 3.4 Hz), 1.86 (2 H, d, J = 13.5 Hz), 1.85- 
               
               
                   
                   
                   
                   
                 2.10 (1 H, m), 2.30 (2 H, d, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 2.76 (2 H, td, J = 12.2 Hz, 2.2 Hz), 3.42 (3 H, 
               
               
                   
                   
                   
                   
                 s), 3.68 (2 H, d, J = 12.2 Hz), 4.16 (2 H, q, 
               
               
                   
                   
                   
                   
                 J = 7.1 Hz), 6.46 (1 H, d, J = 9.0 Hz), 6.96 (2 H, d, 
               
               
                   
                   
                   
                   
                 J = 8.9 Hz), 7.13 (2 H, d, J = 8.9 Hz), 7.72 (1 H, 
               
               
                   
                   
                   
                   
                 dd, J = 9.0 Hz, 2.5 Hz), 7.73 (1 H, d, J = 2.5 Hz), 
               
               
                   
                   
                   
                   
                 7.74 (2 H, d, J = 8.2 Hz), 7.98 (2 H, d, 
               
               
                   
                   
                   
                   
                 J = 8.2 Hz), 8.26 (1 H, d, J = 2.5 Hz). 
               
               
                 1199 
                 4-CF 3 Ph- 
                 —CH 2 COOC 2 H 5   
                 —O— 
                 1.28 (3 H, t, J = 7.0 Hz), 1.44 (2 H, dq, J = 3.5 Hz, 
               
               
                   
                   
                   
                   
                 12.0 Hz), 1.84 (2 H, brd, J = 13.0 Hz), 
               
               
                   
                   
                   
                   
                 1.93 (1 H, m), 2.29 (2 H, d, J = 7.0 Hz), 
               
               
                   
                   
                   
                   
                 2.73 (2 H, dt, J = 2.5 Hz, 12.0 Hz), 3.61 (2 H, 
               
               
                   
                   
                   
                   
                 brd, J = 12.0 Hz), 4.15 (2 H, q, J = 7.0 Hz), 
               
               
                   
                   
                   
                   
                 6.91 (1 H, d, J = 9.0 Hz), 6.96 (2 H, d, J = 9.0 Hz), 
               
               
                   
                   
                   
                   
                 7.04 (2 H, d, J = 9.0 Hz), 7.74 (1 H, brs), 
               
               
                   
                   
                   
                   
                 7.77 (2 H, d, J = 8.5 Hz), 7.99 (2 H, d, J = 8.5 Hz), 
               
               
                   
                   
                   
                   
                 8.18 (1 H, dd, J = 9.0 Hz, 2.5 Hz), 
               
               
                   
                   
                   
                   
                 8.25 (1 H, d, J = 2.5 Hz). 
               
               
                 1200 
                 4-CF 3 Ph- 
                 —COOC 2 H 5   
                 —O— 
                 1.26 (3 H, t, J = 7.1 Hz), 1.77-1.98 (4 H, m), 
               
               
                   
                   
                   
                   
                 2.35-2.43 (1 H, m), 2.68-2.76 (2 H, m), 3.51- 
               
               
                   
                   
                   
                   
                 3.55 (2 H, m), 4.14 (2 H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 6.78 (1 H, d, J = 8.9 Hz), 6.85-6.95 (4 H, m), 
               
               
                   
                   
                   
                   
                 7.61 (2 H, d, J = 8.2 Hz), 7.93 (2 H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                 8.09 (1 H, dd, J = 8.9 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                   
                 8.25 (1 H, d, J = 2.6 Hz), 9.00 (1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 262 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 816   
                 R 817   
                 R 818   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 1201 
                 4-CF 3 Ph- 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.34-1.43 (2 H, m), 1.80-1.98 (3 H, m), 2.10 (3 H, s), 2.26 (2 H, d, J = 6.8 Hz), 2.38-2.44 (4 H, m), 2.66 (2 H, t, J = 12.2 Hz), 3.46-3.63 (8 H, m), 6.72-6.81 (3 H, m), 6.90 (1 H, d, J = 8.6 Hz), 7.26- 7.33 (5 H, m), 7.70 (2 H, d, J = 8.2 Hz), 8.00 (2 H, d, J = 8.1 Hz), 8.15 (1 H, dd, J = 8.9 Hz, 2.8 Hz), 8.25 (1 H, d, J = 2.5 Hz), 8.60 (1 H, s). 
               
               
                   
               
               
                 1202 
                 4-CF 3 Ph- 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.31-1.43 (2 H, m), 1.79-1.98 (3 H, m), 2.11 (3 H, s), 2.26 (2 H, d, J = 6.8 Hz), 2.36-2.39 (4 H, m), 2.66 (2 H, t, J = 12.0 Hz), 3.42 (2 H, s), 3.45-3.61 (6 H, m), 6.70-6.92 (7 H, m), 7.70 (2 H, d, J = 8.2 Hz), 7.99 (2 H, d, J = 8.1 Hz), 8.15 (1 H, dd, J = 8.9 Hz, 2.8 Hz), 8.25 (1 H, d, J = 2.5 Hz), 8.55 (1 H, s). 
               
               
                   
               
               
                 1203 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.29-1.41 (2 H, m), 1.77-1.98 (3 H, m), 2.09 (3 H, s), 2.26 (2 H, d, J = 6.8 Hz), 2.34-2.40 (4 H, m), 2.62 (2 H, t, J = 12.0 Hz), 3.41 (2 H, s), 3.46-3.60 (6 H, m), 6.70-6.90 (7 H, m), 7.49 (1 H, d, J = 8.4 Hz), 7.73 (1 H, dd, J = 8.2 Hz, 2.0 Hz), 7.99 (1 H, d, J = 2.0 Hz), 8.12 (1 H, dd, J = 8.9 Hz, 2.6 Hz), 8.25 (1 H, d, J = 2.6 Hz), 8.99 (1 H, s). 
               
               
                   
               
               
                 1204 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.29-1.41 (2 H, m), 1.77-1.98 (3 H, m), 2.09 (3 H, s), 2.26 (2 H, d, J = 6.8 Hz), 2.37-2.44 (4 H, m), 2.63 (2 H, t, J = 11.9 Hz), 3.48-3.63 (8 H, m), 6.70-6.78 (2 H, m), 6.88 (1 H, d, J = 8.6 Hz), 7.26- 7.33 (6 H, m), 7.48 (1 H, d, J = 8.4 Hz), 7.72 (1 H, dd, J = 8.4 Hz, 2.1 Hz), 7.99 (1 H, d, J = 2.1 Hz), 8.12 (1 H, dd, J = 8.9 Hz, 2.6 Hz), 8.26 (1 H, d, J = 2.6 Hz), 9.03 (1 H, s). 
               
               
                   
               
               
                 1205 
                 4-CF 3 Ph- 
                 —OCH 3   
                 —OC 2 H 5   
                 1.27 (3 H, t, J = 7.1 Hz), 1.39-1.42 (2 H, 
               
               
                   
                   
                   
                   
                 m), 1.80-1.85 (3 H, m), 2.28 (2 H, d, 
               
               
                   
                   
                   
                   
                 J = 6.9 Hz), 2.70 (3 H, t, J = 10.1 Hz), 
               
               
                   
                   
                   
                   
                 3.56 (2 H, d, J = 12.2 Hz), 3.66 (3 H, s), 
               
               
                   
                   
                   
                   
                 4.14 (2 H, q, J = 7.3 Hz), 6.43 (1 H, dd, 
               
               
                   
                   
                   
                   
                 J = 8.7 Hz, 2.5 Hz), 6.51 (1 H, d, J = 2.5 Hz), 
               
               
                   
                   
                   
                   
                 6.78 (1 H, d, J = 8.9 Hz), 6.90 (1 H, 
               
               
                   
                   
                   
                   
                 d, J = 8.7 Hz), 7.63 (2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                 7.96 (2 H, d, J = 8.2 Hz), 8.08 (1 H, dd, 
               
               
                   
                   
                   
                   
                 J = 8.9 Hz, 2.6 Hz), 8.18 (1 H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                 8.95 (1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 263 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                 R 819   
                 R 820   
                 mp (° C.) or  1 H NMR (solvent) δppm 
               
               
                   
               
               
                 1206 
                 3,4- 
                 morpholino 
                   1 H NMR (DMSO-d 6 ) 3.07-3.10(4 H, m), 3.73- 
               
               
                   
                 Cl 2 Ph- 
                   
                 3.77(4 H, m), 6.96-7.04(5 H, m), 7.83(1 H, d, J = 
               
               
                   
                   
                   
                 8.2 Hz), 7.94(1 H, dd, J = 8.2 Hz, 2.0 Hz), 
               
               
                   
                   
                   
                 8.15(1 H, dd, J = 8.9 Hz, 2.6 Hz), 8.22(1 H, d, J = 
               
               
                   
                   
                   
                 2.0 Hz), 8.45(1 H, d, J = 2.6 Hz), 8.;22(1 H, d, J = 
               
               
                   
                   
                   
                 2.0 Hz), 8.45(1 H, d, J = 2.6 Hz), 10.51(1 H, 
               
               
                   
                   
                   
                 brs). 
               
               
                   
               
               
                 1207 
                 3,4- Cl 2 Ph- 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (CDCl 3 ) 1.72-1.90(4 H, m), 2.40- 2.53(2 H, m), 3.20-3.32(2 H, m), 4.58(2 H, s), 6.95(1 H, d, J = 8.9 Hz), 7.08(2 H, d, J = 8.6 Hz), 7.27(2 H, d, J = 8.6 Hz), 7.58(1 H, d, J = 8.6 Hz), 7.73(1 H, dd, J = 8.6 Hz, 2.0 Hz), 8.01(1 H, d, J = 2.0 Hz), 8.11(1 H , s), 8.19(1 H, dd, J = 8.9 Hz, 2.3 Hz), 8.28(1 H, d, J = 2.3 Hz). 
               
               
                   
               
               
                 1208 
                 4-CF 3 Ph- 
                 —NHCONHPh 
                 mp 240.0-240.5 
               
               
                   
               
               
                 1209 
                 3,4- Cl 2 Ph- 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (CDCl 3 ) 1.28(3 H, t, J = 7.0 Hz), 1.60- 1.70(2 H, m), 1.83(1 H, m), 2.03(1 H, m), 2.69(1 H, m), 2.82(1 H, brt, J = 12.0 Hz), 3.03(1 H, dd, J = 12.0 Hz, 10.0 Hz),3.42(1 H, brd, J = 12.0 Hz), 3.65(1 H, brd, J = 12.0 Hz), 41.7(2 H, q, J = 7.0 Hz), 6.90(1 H, d, J = 9.0 Hz), 6.97(2 H, d, J = 9.0 Hz), 7.03(2 H, d, J = 9.0 Hz), 7.58(1 H, d, J = 8.5 Hz), 7.70(1 H, dd, J = 8.5 Hz, 2.0 Hz), 7.75(1 H, s), 7.97(1 H, d, J = 2.0 Hz), 8.14(1 H, brd, J = 9.0 Hz), 8.23(1 H, d, J = 2.5 Hz). 
               
               
                   
               
               
                 1210 
                 3,4- Cl 2 Ph- 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (DMSO-d 6 ) 2.33-2.38(4 H, m), 2.65- 2.83(2 H, m), 3.41(2 H, s), 3.45-3.57(4 H, m), 3.65-3.75(1 H, m), 3.91-4.08(2 H, m), 6.00(2 H, s), 6.76(1 H, dd, J = 1.5 Hz, 8.1 Hz), 6.84- 6.88(2 H, m), 7.07(1 H, d, J = 8.9 Hz), 7.14(2 H, d, J = 8.9 Hz), 7.67(2 H, d, J = 9.1 Hz), 7.85(1 H, d, J = 8.4 Hz), 7.95(1 H, dd, J = 2.0 Hz, 8.4 Hz), 8.19(1 H, dd, J = 2.6 Hz, 8.9 Hz), 8.23(1 H, d, J = 2.1 Hz), 8.47(1 H, d, J = 2.6 Hz), 10.56(1 H, s). 
               
               
                   
               
               
                 1211 
                 4-CF 3 Ph- 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (DMSO-d 6 ) 2.33-2.38(4 H, m), 2.65- 2.83(2 H, m), 3.41(2 H, s), 3.51(4 H, brs), 3.65- 3.75(1 H, m), 3.91-4.08(2 H, m), 5.99(2 H, s), 6.76(1 H, dd, J = 1.3 Hz, 7.9 Hz), 6.84-6.88(2 H, m), ), 7.08(1 H, d, J = 8.9 Hz), 7.15(2 H, d, J = 6.9 Hz), 7.68(2 H, d, J = 6.9 Hz), 7.94(2 H, d, J = 8.6 Hz), 8.17(2 H, d, J = 8.1 Hz), 8.23(1 H, dd, J = 2.6 Hz, 8.9 Hz), 8.50(1 H, d, J = 2.6 Hz), 10.64(1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 264 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 821   
                   1 H NMR (DMSO-d 6 ) δ ppm 
               
               
                   
               
               
                 1212 
                 3,4-Cl 2 Ph- 
                 2.25-2.33 (4 H, m), 2.92 (3 H, s), 3.36 (2 H, s), 3.42 (4 H, brs), 4.23 (2 H, s), 
               
               
                   
                   
                 5.98 (2 H, s), 6.29-6.32 (2 H, m), 6.42-6.45 (1 H, m), 6.70-6.74 (1 H, m), 
               
               
                   
                   
                 6.80-6.84 (2 H, m), 6.97 (1 H, d, J = 8.9 Hz), 7.11-7.17 (1 H, m), 
               
               
                   
                   
                 7.84 (1 H, d, J = 8.4 Hz), 7.95 (1 H, dd, J = 8.4 Hz, 2.0 Hz), 8.16- 
               
               
                   
                   
                 8.22 (2 H, m), 8.52 (1 H, d, J = 2.5 Hz), 10.55 (1 H, s). 
               
               
                 1213 
                 4-CF 3 Ph- 
                 2.26-2.33 (4 H, m), 2.92 (3 H, s), 3.37-3.41 (6 H, m), 4.23 (2 H, s), 
               
               
                   
                   
                 5.98 (2 H, s), 6.29-6.34 (2 H, m), 6.42-6.45 (1 H, m), 6.70-6.74 (1 H, m), 
               
               
                   
                   
                 6.80-6.84 (2 H, m), 6.98 (1 H, d, J = 8.9 Hz), 7.11-7.17 (1 H, m), 
               
               
                   
                   
                 7.93 (2 H, d, J = 8.3 Hz), 8.16 (2 H, d, J = 8.1 Hz), 8.21 (1 H, dd, 
               
               
                   
                   
                 J = 8.9 Hz, 2.6 Hz), 8.54 (1 H, d, J = 2.3 Hz), 10.63 (1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 265 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 822   
                 R 823   
                 Xb 22   
                 M 
                 Form 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 1214 
                 —CH 3   
                 piperonyl 
                 —N(CH 3 )— 
                 1 
                 free 
                 (CDCl 3 ) 1.90 (3 H, s), 2.41-2.45 (4 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 3.03 (3 H, s), 3.43 (2 H, s), 3.49( 2 H, brs), 
               
               
                   
                   
                   
                   
                   
                   
                 3.63 (2 H, brs), 4.09 (2 H, s), 4.77 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 5.95 (2 H, s), 6.70 (2 H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 6.74-6.75 (2 H, m), 6.81-6.85 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.00 (2 H, d, J = 9.1 Hz), 7.04 (1 H, dd, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.4 Hz, 2.1 Hz), 7.24 (1 H, dd, J = 8.7 Hz, 
               
               
                   
                   
                   
                   
                   
                   
                 2.87 Hz), 7.31 (1 H, d, J = 2.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.35 (1 H, d, J = 8.1 Hz), 7.83 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 2.6 Hz). 
               
               
                 1215 
                 —C 2 H 5   
                 piperonyl 
                 —N(CH 3 )— 
                 1 
                 free 
                 (CDCl 3 ) 1.08 (3 H, t, J = 7.4 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 2.07 (2 H, q, J = 7.4 Hz), 2.41-2.45 (4 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 3.03 (3 H, s), 3.43 (2 H, s), 3.48 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs), 3.63 (2 H, brs), 4.09 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 4.77 (2 H, s), 5.95 (2 H, s), 6.70 (2 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 9.2 Hz), 6.73-6.74 (2 H, m), 6.82 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 8.7 Hz), 6.85 (1 H, brs), 7.00 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 9.1 Hz), 7.04 (1 H, dd, J = 8.3 Hz, 
               
               
                   
                   
                   
                   
                   
                   
                 2.0 Hz), 7.22 (1 H, dd, J = 8.7 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.30 (1 H, d, J = 2.0 Hz), 7.34 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 8.3 Hz), 7.82 (1 H, d, J = 2.5 Hz). 
               
               
                 1216 
                 —CH 3   
                 benzyl 
                 none 
                 0 
                 hydro- 
                 (DMSO-d 6 ) 1.87 (3 H, s), 3.14 (2 H, brs), 
               
               
                   
                   
                   
                   
                   
                 chloride 
                 3.37 (6 H, brs), 4.35 (2 H, s), 4.85 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 7.13 (1 H, d, J = 8.9 Hz), 7.22 (2 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.4 Hz), 7.41-7.58 (10 H, m), 7.80 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 dd, J = 8.9 Hz, 2.6 Hz), 8.03 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 2.6 Hz), 10.88 (1 H, brs). 
               
               
                   
               
             
          
         
       
     
       Example 1217 
     Production of 1H-indole-2-carboxylic acid {6-[4-(2,4-dioxothiazolidine-5-ylmethyl)-2-methylphenoxy]pyridin-3-yl}amide 
       [1101]    To a solution of 5-[4-(5-aminopyridin-2-yloxy)-3-methylbenzyl]thiazolidine-2,4-dione (150 mg, 0.46 mmol) in DMF (5 mL) were added indole-2-carboxylic acid (74 mg, 0.46 mmol), 1-hydroxybenzotriazole monohydrate (70 mg, 0.46 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (110 mg, 0.57 mmol), and the resulting solution was stirred for 5 days at room temperature. This reaction solution was concentrated under reduced pressure. Water was added to the residue, and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, evaporated, and the residue was then purified by silica gel column chromatography (chloroform:methanol=30:1). To the obtained powdery substance was added ethanol, the resulting solution was filtered and the filtrate was washed with ethanol, to thereby yield 100 mg of the title compound. 
         [1102]    Appearance: White powder 
         [1103]      1 H NMR (DMSO-d 6 ) δ 2.10 (3H, s), 3.09 (1H, dd, J=14.2 Hz, 9.7 Hz), 3.40 (1H, dd, J=14.2 Hz, 4.2 Hz), 4.94 (1H, dd, J=9.7 Hz, 4.2 Hz), 6.99 (1H, d, J=8.2 Hz), 7.04 (1H, d, J=8.9 Hz), 7.05-7.16 (2H, m), 7.20 (1H, s), 7.24 (1H, dd, J=7.0 Hz, 1.0 Hz), 7.39 (1H, d, J=1.6 Hz), 7.46 (1H, d, J=8.2 Hz), 7.68 (1H, d, J=7.7 Hz), 8.21 (1H, dd, J=8.9 Hz, 2.8 Hz), 8.49 (1H, d, J=2.8 Hz), 10.37 (1H, s), 11.80 (1H, s), 12.09 (1H, s). 
         [1104]    The following compounds were produced in the same manner as in Example 1217. 
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 266 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 824   
                 R 825   
                 Form 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 1218 
                 3,4-(CH 3 ) 2 Ph- 
                 4-CH 3 OPhCH 2 — 
                 free 
                 (CDCl 3 ) 2.34 (6 H, s), 2.45 (4 H, brs), 
               
               
                   
                   
                   
                   
                 3.45 (2 H, s), 3.47-3.79 (4 H, m), 
               
               
                   
                   
                   
                   
                 3.81 (3 H, s), 6.83-6.89 (2 H, m), 
               
               
                   
                   
                   
                   
                 6.97 (1 H, d, J = 8.9 Hz), 7.11-7.16 (2 H, 
               
               
                   
                   
                   
                   
                 m), 7.21-7.26 (3 H, m), 7.41-7.46 (2 H, 
               
               
                   
                   
                   
                   
                 m), 7.59-7.62 (1 H, m), 7.67 (1 H, d, 
               
               
                   
                   
                   
                   
                 J = 1.9 Hz), 7.92 (1 H, brs), 8.23-8.30 (1 H, 
               
               
                   
                   
                   
                   
                 m), 8.31 (1 H, d, J = 2.4 Hz). 
               
               
                 1219 
                 2-(CH 3 ) 2 NPh- 
                 benzyl 
                 trihydro- 
                 (DMSO-d 6 ) 3.07 (6 H, s), 3.17-3.48 (8 H, 
               
               
                   
                   
                   
                 chloride 
                 m), 4.35 (2 H, s), 7.16-7.21 (3 H, m), 
               
               
                   
                   
                   
                   
                 7.41-7.54 (6 H, m), 7.59-7.70 (4 H, m), 
               
               
                   
                   
                   
                   
                 7.92 (1 H, d, J = 7.1 Hz), 8.27 (1 H, dd, 
               
               
                   
                   
                   
                   
                 J = 2.8 Hz, 8.7 Hz), 8.55 (1 H, d, J = 2.1 Hz), 
               
               
                   
                   
                   
                   
                 11.30 (1 H, s). 
               
               
                 1220 
                 3,5-(CH 3 ) 2 Ph- 
                 benzyl 
                 hydro- 
                 (DMSO-d 6 ) 2.36 (6 H, s), 3.00-3.20 (2 H, 
               
               
                   
                   
                   
                 chloride 
                 m), 3.20-3.40 (2 H, m), 3.47 (2 H, brs), 
               
               
                   
                   
                   
                   
                 4.40 (2 H, brs), 4.33 (2 H, s), 7.13 (1 H, d, 
               
               
                   
                   
                   
                   
                 J = 8.9 Hz), 7.19 (2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                 7.24 (1 H, s), 7.40-7.70 (7 H, m), 
               
               
                   
                   
                   
                   
                 7.51 (2 H, d, J = 8.6 Hz), 8.26 (1 H, dd, 
               
               
                   
                   
                   
                   
                 J = 8.9 Hz, 2.6 Hz), 8.56 (1 H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                 10.41 (1 H, s). 
               
               
                 1221 
                 2,3-(CH 3 O) 2 Ph- 
                 benzyl 
                 hydro- 
                 (DMSO-d 6 ) 3.00-3.65 (6 H, m), 3.80 (3 H, 
               
               
                   
                   
                   
                 chloride 
                 s), 3.86 (3 H, s), 4.20 (2 H, brs), 4.33 (2 H, 
               
               
                   
                   
                   
                   
                 brs), 7.09-7.25 (6 H, m), 7.40-7.80 (7 H, 
               
               
                   
                   
                   
                   
                 m), 8.23 (1 H, dd, J = 8.9 Hz, 2.3 Hz), 
               
               
                   
                   
                   
                   
                 8.52 (1 H, d, J = 2.3 Hz), 10.43 (1 H, s). 
               
               
                 1222 
                 4-(CH 3 ) 2 NPh- 
                 benzyl 
                 free 
                 (CDCl 3 ) 2.48 (4 H, brs), 3.06 (6 H, s), 
               
               
                   
                   
                   
                   
                 3.55 (2 H, s), 3.70 (4 H, brs), 6.71 (2 H, d, 
               
               
                   
                   
                   
                   
                 J = 9.0 Hz), 6.96 (1 H, d, J = 9.6 Hz), 
               
               
                   
                   
                   
                   
                 7.13 (2 H, d, J = 8.7 Hz), 7.20-7.38 (5 H, 
               
               
                   
                   
                   
                   
                 m), 7.43 (2 H, d, J = 8.7 Hz), 7.71 (1 H, 
               
               
                   
                   
                   
                   
                 brs), 7.78 (2 H, d, J = 9.0 Hz), 8.20- 
               
               
                   
                   
                   
                   
                 8.30 (2 H, m). 
               
               
                 1223 
                 1-naphthyl 
                 benzyl 
                 free 
                 (DMSO-d 6 ) 2.41 (4 H, brs), 3.51 (4 H, 
               
               
                   
                   
                   
                   
                 brs), 3.52 (2 H, s), 7.17 (3 H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                 7.21-7.38 (5 H, m), 7.44 (2 H, d, 
               
               
                   
                   
                   
                   
                 J = 8.7 Hz), 7.55-7.69 (3 H, m), 7.80 (1 H, d, 
               
               
                   
                   
                   
                   
                 J = 6.4 Hz), 7.98-8.06 (1 H, m), 8.10 
               
               
                   
                   
                   
                   
                 (1 H, d, J = 8.1 Hz), 8.18-8.27 (1 H, m), 
               
               
                   
                   
                   
                   
                 8.32 (1 H, dd, J = 8.7 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                   
                 8.58 (1 H, d, J = 2.6 Hz), 10.76 (1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 267 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                 mp 
               
               
                 No. 
                 R 826   
                 Form 
                 (° C.) 
               
               
                   
               
               
                 1224 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 maleate 
                 172-175 
               
               
                   
               
               
                 1225 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 maleate 
                 143-146 
               
               
                   
               
               
                 1226 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 187-189 
               
               
                   
               
               
                 1227 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 191-192 
               
               
                   
               
               
                 1228 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 maleate 
                 180-182 
               
               
                   
               
               
                 1229 
                 2,5-(CF 3 ) 2 Ph- 
                 dihydro- 
                 152-156 
               
               
                   
                   
                 chloride 
               
               
                 1230 
                 2,5-F 2 Ph- 
                 maleate 
                 182-184 
               
               
                 1231 
                 2,3-Cl 2 Ph- 
                 free 
                 195-196 
               
               
                 1232 
                 3-PhOPh- 
                 free 
                 171-172 
               
               
                 1233 
                 3-CF 3 Ph- 
                 dihydro- 
                 146-146 
               
               
                   
                   
                 chloride 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 268 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                 MS 
               
               
                 No. 
                 R 827   
                 R 828   
                 R 829   
                 R 830   
                 (M +  + H) 
               
               
                   
               
               
                 1234 
                 —H 
                 —H 
                 —H 
                 —H 
                 532 
               
               
                 1235 
                 —H 
                 —H 
                 —OCH 3   
                 —H 
                 562 
               
               
                 1236 
                 —H 
                 —H 
                 —Cl 
                 —H 
                 566 
               
               
                 1237 
                 —H 
                 —H 
                 —F 
                 —H 
                 550 
               
               
                 1238 
                 —CH 3   
                 —H 
                 —H 
                 —H 
                 546 
               
               
                 1239 
                 —H 
                 —H 
                 —Br 
                 —H 
                 612 
               
               
                 1240 
                 —H 
                 —H 
                 —CH 3   
                 —H 
                 546 
               
               
                 1241 
                 —H 
                 —H 
                 —OCF 3   
                 —H 
                 616 
               
               
                 1242 
                 —H 
                 —OCH 3   
                 —H 
                 —H 
                 562 
               
               
                 1243 
                 —H 
                 —Cl 
                 —H 
                 —H 
                 566 
               
               
                 1244 
                 —H 
                 —H 
                 —H 
                 —OCH 3   
                 562 
               
               
                 1245 
                 —H 
                 —Cl 
                 —H 
                 —Cl 
                 600 
               
               
                 1246 
                 —H 
                 —H 
                 —H 
                 —Cl 
                 566 
               
               
                 1247 
                 —H 
                 —H 
                 —OCH 3   
                 —OCH 3   
                 592 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 269 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
                 MS 
               
               
                 No. 
                 R 831   
                 R 832   
                 R 833   
                 R 834   
                 R 835   
                 M 
                 (M +  + H) 
               
               
                   
               
               
                 1248 
                 —H 
                 —H 
                 —H 
                 —H 
                 —H 
                 0 
                 532 
               
               
                 1249 
                 —H 
                 —H 
                 —H 
                 —H 
                 —H 
                 2 
                 560 
               
               
                 1250 
                 —H 
                 —H 
                 —H 
                 —H 
                 —H 
                 1 
                 546 
               
               
                 1251 
                 —H 
                 —H 
                 —Cl 
                 —H 
                 —H 
                 1 
                 580 
               
               
                 1252 
                 —H 
                 —CH 3   
                 —H 
                 —H 
                 —H 
                 1 
                 560 
               
               
                 1253 
                 —H 
                 —CH 3   
                 —CH 3   
                 —H 
                 —H 
                 1 
                 574 
               
               
                 1254 
                 —H 
                 —CH 3   
                 —OCH 3   
                 —H 
                 —H 
                 1 
                 590 
               
               
                 1255 
                 —H 
                 —CH 3   
                 —F 
                 —H 
                 —H 
                 1 
                 578 
               
               
                 1256 
                 —H 
                 —CH 3   
                 —C(CH 3 ) 3   
                 —H 
                 —H 
                 1 
                 616 
               
               
                 1257 
                 —H 
                 —CH 3   
                 —CH 3   
                 —H 
                 —CH 3   
                 1 
                 588 
               
               
                 1258 
                 —H 
                 —CH 3   
                 —Br 
                 —H 
                 —F 
                 1 
                 658 
               
               
                 1259 
                 —H 
                 —CH 3   
                 —H 
                 —H 
                 —F 
                 1 
                 578 
               
               
                 1260 
                 —H 
                 —CH 3   
                 —C 2 H 5   
                 —H 
                 —H 
                 1 
                 588 
               
               
                 1261 
                 —H 
                 —H 
                 —F 
                 —H 
                 —H 
                 1 
                 564 
               
               
                 1262 
                 —H 
                 —H 
                 —H 
                 —F 
                 —H 
                 1 
                 564 
               
               
                 1263 
                 —CH 3   
                 —H 
                 —H 
                 —H 
                 —H 
                 1 
                 560 
               
               
                 1264 
                 —H 
                 —H 
                 —OCH 3   
                 —H 
                 —H 
                 1 
                 576 
               
               
                 1265 
                 —H 
                 —H 
                 —H 
                 —H 
                 —CH 3   
                 1 
                 560 
               
               
                 1266 
                 —H 
                 —H 
                 —CH 3   
                 —H 
                 —H 
                 1 
                 560 
               
               
                 1267 
                 —H 
                 —H 
                 —Br 
                 —H 
                 —H 
                 1 
                 626 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 270 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 836   
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 1268 
                 3-CNPh- 
                 (CDCl 3 ) 2.37-2.44 (4 H, m), 2.57-2.63 (2 H, m), 2.88-2.95 (2 H, m), 
               
               
                   
                   
                 3.42-3.45 (2 H, m), 3.55 (2 H, s), 3.60-3.64 (2 H, m), 6.90 (1 H, d, 
               
               
                   
                   
                 J = 8.9 Hz), 7.00 (2 H, d, J = 8.6 Hz), 7.16 (2 H, d, J = 8.6 Hz), 7.25- 
               
               
                   
                   
                 7.31 (5 H, m), 7.54-7.76 (1 H, m) 7.76-7.80 (1 H, m), 8.19-8.26 (3 H, 
               
               
                   
                   
                 m), 8.37 (1 H, d, J = 2.6 Hz), 9.41 (1 H, brs). 
               
               
                 1269 
                 2-CNPh- 
                 (CDCl 3 ) 2.35-2.45 (4 H, m), 2.60-2.66 (2 H, m), 2.95-3.01 (2 H, m), 
               
               
                   
                   
                 3.40-3.44 (2 H, m), 3.52 (2 H, s), 3.63-3.67 (2 H, m), 7.05-7.13 (3 H, m), 
               
               
                   
                   
                 7.23-7.32 (8 H, m), 7.69-7.80 (3 H, m), 7.93-7.96 (2 H, m), 8.23 (1 H, d, 
               
               
                   
                   
                 J = 2.5 Hz). 
               
               
                 1270 
                 3-N(CH 3 ) 2 Ph- 
                 (CDCl 3 ) 2.35-2.44 (4 H, m), 2.57-2.62 (2 H, m), 2.91-2.98 (8 H, m), 
               
               
                   
                   
                 3.39-3.43 (2 H, m), 3.53 (2 H, s), 3.62-3.65 (2 H, m), 6.84-6.92 (2 H, m), 
               
               
                   
                   
                 7.02 (2 H, d, J = 8.6 Hz), 7.11 (1 H, d, J = 7.9 Hz), 7.19 (2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                 7.25-7.35 (7 H, m), 8.22-8.37 (3 H, m). 
               
               
                 1271 
                 3-CH 3 Ph- 
                 (CDCl 3 ) 2.36-2.46 (7 H, m), 2.57-2.63 (2 H, m), 2.91-2.97 (2 H, m), 
               
               
                   
                   
                 3.40-3.44 (2 H, m), 3.56 (2 H, s), 3.62-3.66 (2 H, m), 6.91 (1 H, d, 
               
               
                   
                   
                 J = 8.9 Hz), 7.00-7.05 (2 H, m), 7.19 (2 H, d, J = 8.6 Hz), 7.25-7.35 (7 H, 
               
               
                   
                   
                 m), 7.66-7.71 (2 H, m), 8.23-8.31 (2 H, m), 8.43 (1 H, brs). 
               
               
                 1272 
                 3,4-(CH 3 ) 2 Ph- 
                 (CDCl 3 ) 2.31 (3 H, s), 2.32 (3 H, s), 2.36-2.46 (4 H, m), 2.58-2.64 (2 H, 
               
               
                   
                   
                 m), 2.92-2.98 (2 H, m), 3.41-3.44 (2 H, m), 3.56 (2 H, s), 3.63-3.67 (2 H, 
               
               
                   
                   
                 m), 6.90-6.94 (1 H, m), 7.03 (2 H, d, J = 8.4 Hz), 7.19-7.37 (8 H, m), 
               
               
                   
                   
                 7.58-7.73 (2 H, m), 8.21-8.28 (3 H, m). 
               
               
                 1273 
                 2-FPh- 
                 (DMSO-d 6 ) 2.28-2.31 (4 H, m), 2.59-2.64 (2 H, m), 2.78-2.84 (2 H, m), 
               
               
                   
                   
                 3.44-3.47 (6 H, m), 7.01 (2 H, d, J = 8.4 Hz), 7.02-7.05 (1 H, m), 
               
               
                   
                   
                 7.26 (2 H, d, J = 8.4 Hz), 7.31-7.40 (7 H, m), 7.51-7.61 (1 H, m), 7.64- 
               
               
                   
                   
                 7.72 (1 H, m), 8.18 (1 H, dd, J = 8.9 Hz, 2.6 Hz), 8.45 (1 H, d, J = 2.5 Hz), 
               
               
                   
                   
                 10.54 (1 H, brs). 
               
               
                 1274 
                 3-FPh- 
                 (DMSO-d 6 ) 2.30 (4 H, brs), 2.62 (2 H, brs), 2.81 (2 H, brs), 3.47 (6 H, 
               
               
                   
                   
                 brs), 7.03 (3 H, brs), 7.25-7.30 (7 H, m), 7.47 (1 H, brs), 7.60 (1 H, d, 
               
               
                   
                   
                 J = 6.1 Hz), 7.77-7.81 (2 H, m), 8.20 (1 H, d, J = 7.6 Hz), 8.49 (1 H, brs), 
               
               
                   
                   
                 10.46 (1 H, brs). 
               
               
                 1275 
                 4-FPh- 
                 (DMSO-d 6 ) 2.28-2.30 (4 H, m), 2.58-2.64 (2 H, m), 2.77-2.83 (2 H, m), 
               
               
                   
                   
                 3.43-3.46 (6 H, m), 7.00 (2 H, d, J = 8.6 Hz), 7.02 (1 H, d, J = 8.7 Hz), 
               
               
                   
                   
                 7.25 (2 H, d, J = 8.6 Hz), 7.29-7.40 (7 H, m), 8.01-8.06 (2 H, m), 
               
               
                   
                   
                 8.18 (1 H, dd, J = 8.7 Hz, 2.6 Hz), 8.46 (1 H, d, J = 2.5 Hz), 
               
               
                   
                   
                 10.39 (1 H, brs). 
               
               
                 1276 
                 4-AcPh- 
                 (DMSO-d 6 ) 2.28-2.32 (4 H, m), 2.59-2.65 (5 H, m), 2.79-2.84 (2 H, m), 
               
               
                   
                   
                 3.44-3.47 (6 H, m), 6.99-7.06 (3 H, m), 7.27-7.36 (7 H, m), 8.09 (4 H, 
               
               
                   
                   
                 brs), 8.21 (1 H, dd, J = 8.9 Hz, 2.8 Hz), 8.50 (1 H, d, J = 2.6 Hz), 
               
               
                   
                   
                 10.56 (1 H, brs). 
               
               
                 1277 
                 3,4-F 2 Ph- 
                 (DMSO-d 6 ) 2.28-2.32 (4 H, m), 2.59-2.65 (2 H, m), 2.79-2.84 (2 H, m), 
               
               
                   
                   
                 3.44-3.47 (6 H, m), 7.01 (2 H, d, J = 8.4 Hz), 7.04 (1 H, d, J = 8.7 Hz), 
               
               
                   
                   
                 7.27 (2 H, d, J = 8.4 Hz), 7.31-7.36 (5 H, m), 7.59-7.69 (1 H, m), 7.85- 
               
               
                   
                   
                 7.89 (1 H, m), 8.00-8.07 (1 H, m), 8.18 (1 H, dd, J = 8.9 Hz, 2.6 Hz), 
               
               
                   
                   
                 8.46 (1 H, d, J = 2.5 Hz), 10.46 (1 H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 271 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 837   
                 R 838   
                 R 839   
                 R 840   
                 R 841   
                   1 H NMR (solvent) δ ppm or MS 
               
               
                   
               
               
                 1278 
                 —H 
                 —F 
                 —H 
                 —F 
                 —H 
                   1 H NMR (DMSO-d 6 ) 2.29- 
               
               
                   
                   
                   
                   
                   
                   
                 2.32 (4 H, m), 2.59-2.65 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 2.79-2.85 (2 H, m), 3.44-3.48 (6 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 7.00-7.06 (3 H, m), 7.25- 
               
               
                   
                   
                   
                   
                   
                   
                 7.36 (7 H, m), 7.51-7.59 (1 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.67-7.71 (2 H, m), 8.19 (1 H, dd, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.7 Hz, 2.6 Hz), 8.48 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 2.5 Hz), 10.51 (1 H, brs). 
               
               
                 1279 
                 —H 
                 —H 
                 —SO 2 NH 2   
                 —H 
                 —H 
                   1 H NMR (DMSO-d 6 ) 2.25- 
               
               
                   
                   
                   
                   
                   
                   
                 2.35 (4 H, m), 2.60-2.66 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 2.74-2.85 (2 H, m), 3.31 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 3.40-3.50 (4 H, m), 7.00-7.06 (3 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 7.25-7.34 (7 H, m), 7.53 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 7.97 (2 H, d, J = 8.6 Hz), 8.12 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 8.6 Hz), 8.21 (1 H, dd, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.9 Hz, 2.7 Hz), 8.49 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 2.7 Hz), 10.56 (1 H, s). 
               
               
                 1280 
                 —H 
                 —H 
                 —NHAc 
                 —H 
                 —H 
                 MS 576 (M +  − 1) 
               
               
                 1281 
                 —F 
                 —H 
                 —CF 3   
                 —H 
                 —H 
                 MS 607 (M +  + H) 
               
               
                 1282 
                 —COOC 2 H 5   
                 —H 
                 —H 
                 —H 
                 —H 
                 MS 593 (M +  + 1) 
               
               
                 1283 
                 —Cl 
                 —Cl 
                 —H 
                 —H 
                 —H 
                 MS 590 (M +  + 2) 
               
               
                 1284 
                 —H 
                 —H 
                 —COOCH 3   
                 —H 
                 —H 
                 MS 579 (M +  + H) 
               
               
                 1285 
                 —OCH 3   
                 —H 
                 —OCH 3   
                 —H 
                 —H 
                 MS 580 (M + ) 
               
               
                 1286 
                 —Cl 
                 —H 
                 —Cl 
                 —H 
                 —H 
                 MS 589 (M + ) 
               
               
                 1287 
                 —CH 3   
                 —H 
                 —CH 3   
                 —H 
                 —H 
                 MS 548 (M + ) 
               
               
                 1288 
                 —F 
                 —H 
                 —F 
                 —H 
                 —H 
                 MS 557 (M +  + H) 
               
               
                 1289 
                 —H 
                 —OCH 3   
                 —OCH 3   
                 —H 
                 —H 
                 MS 580 (M + ) 
               
               
                 1290 
                 —CF 3   
                 —H 
                 —H 
                 —H 
                 —H 
                 MS 589 (M +  + 1) 
               
               
                 1291 
                 —H 
                 —CF 3   
                 —H 
                 —H 
                 —H 
                 MS 588 (M + ) 
               
               
                 1292 
                 —H 
                 —COOCH 3   
                 —H 
                 —H 
                 —H 
                 MS 579 (M +  + 1) 
               
               
                 1293 
                 —F 
                 —H 
                 —H 
                 —H 
                 —F 
                 MS 557 (M +  + 1) 
               
               
                 1294 
                 —F 
                 —F 
                 —H 
                 —H 
                 —H 
                 MS 557 (M +  + H) 
               
               
                 1295 
                 —CF 3   
                 —H 
                 —H 
                 —CF 3   
                 —H 
                 MS 656 (M + ) 
               
               
                 1296 
                 —H 
                 —F 
                 —H 
                 —CF 3   
                 —H 
                 MS 606 (M + ) 
               
               
                 1297 
                 —F 
                 —CF 3   
                 —H 
                 —H 
                 —H 
                 MS 607 (M +  + H) 
               
               
                 1298 
                 —F 
                 —H 
                 —H 
                 —CF 3   
                 —H 
                 MS 607 (M +  + 1) 
               
               
                 1299 
                 —CH 3   
                 —H 
                 —H 
                 —CH 3   
                 —H 
                 MS 549 (M +  + 1) 
               
               
                 1300 
                 —F 
                 —H 
                 —H 
                 —F 
                 —H 
                 MS 557 (M +  + H) 
               
               
                 1301 
                 —Cl 
                 —H 
                 —F 
                 —H 
                 —H 
                 MS 572 (M + ) 
               
               
                 1302 
                 —H 
                 —OAc 
                 —H 
                 —H 
                 —H 
                 MS 579 (M +  + 1) 
               
               
                 1303 
                 —OCF 3   
                 —H 
                 —H 
                 —H 
                 —H 
                 MS 604 (M + ) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 272 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 842   
                 R 843   
                 R 844   
                 R 845   
                 R 846   
                   1 H NMR or MS 
               
               
                   
               
               
                 1304 
                 —H 
                 —CF 3   
                 —F 
                 —H 
                 —H 
                 MS 607 (M +  + 1) 
               
               
                 1305 
                 —OCH 3   
                 —H 
                 —H 
                 —OCH 3   
                 —H 
                 MS 580 (M + ) 
               
               
                 1306 
                 —Cl 
                 —H 
                 —H 
                 —Cl 
                 —H 
                 MS 590 (M +  + 1) 
               
               
                 1307 
                 —CH 3   
                 —H 
                 —H 
                 —F 
                 —H 
                 MS 552 (M + ) 
               
               
                 1308 
                 —N(CH 3 ) 2   
                 —H 
                 —H 
                 —H 
                 —H 
                 MS 564 (M +  + H) 
               
               
                 1309 
                 —OCH 3   
                 —H 
                 —H 
                 —H 
                 —OCH 3   
                 MS 581 (M +  + H) 
               
               
                 1310 
                 —H 
                 —OPh 
                 —H 
                 —H 
                 —H 
                 MS 613 (M +  + H) 
               
               
                 1311 
                 —H 
                 —OCH 3   
                 —H 
                 —OCH 3   
                 —H 
                 MS 581 (M +  + H) 
               
               
                 1312 
                 —H 
                 —Cl 
                 —H 
                 —Cl 
                 —H 
                 MS 589 (M +  + H) 
               
               
                 1313 
                 —H 
                 —CH 3   
                 —H 
                 —CH 3   
                 —H 
                 MS 549 (M +  + H) 
               
               
                 1314 
                 —OCH 3   
                 —OCH 3   
                 —H 
                 —H 
                 —H 
                 MS 581 (M +  + H) 
               
               
                 1315 
                 —CH 3   
                 —CH 3   
                 —H 
                 —H 
                 —H 
                 MS 549 (M +  + H) 
               
               
                 1316 
                 —CH 3   
                 —F 
                 —H 
                 —H 
                 —H 
                 MS 553 (M +  + H) 
               
               
                 1317 
                 —H 
                 —H 
                 —N(CH 3 ) 2   
                 —H 
                 —H 
                 MS 564 (M +  + H) 
               
               
                 1318 
                 —H 
                 —CF 3   
                 —H 
                 —CF 3   
                 —H 
                 MS 656 (M + ) 
               
               
                 1319 
                 —Cl 
                 —H 
                 —H 
                 —CF 3   
                 —H 
                 MS 622 (M + ) 
               
               
                 1320 
                 —H 
                 —CH 3   
                 —NHAc 
                 —H 
                 —H 
                 MS 591 (M + ) 
               
               
                 1321 
                 —H 
                 —Cl 
                 —NHAc 
                 —H 
                 —H 
                 MS 611 (M + ) 
               
               
                 1322 
                 —H 
                 —OCH 3   
                 —NHAc 
                 —H 
                 —H 
                 MS 607 (M + ) 
               
               
                 1323 
                 —H 
                 —NHAc 
                 —CH 3   
                 —H 
                 —H 
                 MS 591 (M + ) 
               
               
                 1324 
                 —H 
                 —NHAc 
                 —Cl 
                 —H 
                 —H 
                 MS 611 (M + ) 
               
               
                 1325 
                 —H 
                 —NHAc 
                 —OCH 3   
                 —H 
                 —H 
                 MS 607 (M + ) 
               
               
                 1326 
                 —H 
                 —NHAc 
                 —F 
                 —H 
                 —H 
                 MS 595 (M + ) 
               
               
                 1327 
                 —H 
                 —CH 3   
                 —NHCOPh 
                 —H 
                 —H 
                 MS 653 (M + ) 
               
               
                 1328 
                 —H 
                 —Cl 
                 —NHCOPh 
                 —H 
                 —H 
                 MS 673 (M + ) 
               
               
                 1329 
                 —H 
                 —OCH 3   
                 —NHCOPh 
                 —H 
                 —H 
                 MS 669 (M + ) 
               
               
                 1330 
                 —H 
                 —NHCOPh 
                 —CH 3   
                 —H 
                 —H 
                 MS 653 (M + ) 
               
               
                 1331 
                 —H 
                 —NHCOPh 
                 —Cl 
                 —H 
                 —H 
                 MS 673 (M + ) 
               
               
                 1332 
                 —H 
                 —NHCOPh 
                 —OCH 3   
                 —H 
                 —H 
                 MS 669 (M + ) 
               
               
                 1333 
                 —H 
                 —NHCOPh 
                 —F 
                 —H 
                 —H 
                 MS 657 (M + ) 
               
               
                 1334 
                 —COOH 
                 —H 
                 —Cl 
                 —Cl 
                 —H 
                   1 H NMR (DMSO-d 6 ) δ 
               
               
                   
                   
                   
                   
                   
                   
                 2.42 (4 H, brs), 2.62 (2 H, t, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 7.1 Hz), 2.81 (2 H, t, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 7.1 Hz), 3.33 (1 H, brs), 
               
               
                   
                   
                   
                   
                   
                   
                 3.47 (4 H, brs), 3.60 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 7.00 (2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.02 (1 H, d, J = 4.7 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.26 (2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.28-7.38 (5 H, m), 7.94 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 s), 8.05 (1 H, s), 8.10 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 dd, J = 8.7 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 8.36 (1 H, d, J = 2.8 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 10.68 (1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 273 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 847   
                 R 848   
                 R 849   
                 R 850   
                 R 851   
                 MS 
               
               
                   
               
               
                 1335 
                 —H 
                 —H 
                 —H 
                 —H 
                 —H 
                 546 (M + ) 
               
               
                 1336 
                 —H 
                 —OCH 3   
                 —H 
                 —H 
                 —H 
                 577 (M +  + H) 
               
               
                 1337 
                 —Cl 
                 —H 
                 —H 
                 —H 
                 —H 
                 581 (M +  + H) 
               
               
                 1338 
                 —H 
                 —Cl 
                 —H 
                 —H 
                 —H 
                 581 (M +  + H) 
               
               
                 1339 
                 —H 
                 —H 
                 —Cl 
                 —H 
                 —H 
                 581 (M +  + H) 
               
               
                 1340 
                 —F 
                 —H 
                 —H 
                 —H 
                 —H 
                 565 (M +  + H) 
               
               
                 1341 
                 —H 
                 —F 
                 —H 
                 —H 
                 —H 
                 565 (M +  + H) 
               
               
                 1342 
                 —H 
                 —H 
                 —F 
                 —H 
                 —H 
                 565 (M +  + H) 
               
               
                 1343 
                 —H 
                 —H 
                 —N(CH 3 ) 2   
                 —H 
                 —H 
                 590 (M +  + 1) 
               
               
                 1344 
                 —H 
                 —OCH 3   
                 —OCH 3   
                 —H 
                 —H 
                 606 (M + ) 
               
               
                 1345 
                 —Cl 
                 —H 
                 —H 
                 —H 
                 —Cl 
                 615 (M +  + 1) 
               
               
                 1346 
                 —H 
                 —Cl 
                 —Cl 
                 —H 
                 —H 
                 615 (M +  + H) 
               
               
                 1347 
                 —F 
                 —H 
                 —H 
                 —H 
                 —F 
                 583 (M +  + H) 
               
               
                 1348 
                 —H 
                 —F 
                 —H 
                 —F 
                 —H 
                 583 (M +  + H) 
               
             
          
           
               
                 1349 
                 —H 
                 —OCH 2 O— 
                 —H 
                 —H 
                 591 (M +  + H) 
               
             
          
           
               
                 1350 
                 —H 
                 —OCH 3   
                 —H 
                 —OCH 3   
                 —H 
                 607 (M +  + H) 
               
               
                 1351 
                 —H 
                 —H 
                 —CH 3   
                 —H 
                 —H 
                 561 (M +  + H) 
               
               
                 1352 
                 —H 
                 —CF 3   
                 —H 
                 —H 
                 —H 
                 615 (M +  + H) 
               
               
                 1353 
                 —H 
                 —H 
                 —OCH 3   
                 —H 
                 —H 
                 577 (M +  + 1) 
               
               
                 1354 
                 —OCH 3   
                 —OCH 3   
                 —H 
                 —H 
                 —H 
                 606 (M + ) 
               
               
                 1355 
                 —OCH 3   
                 —H 
                 —H 
                 —OCH 3   
                 —H 
                 607 (M +  + 1) 
               
               
                 1356 
                 —H 
                 —OCH 3   
                 —OCH 3   
                 —OCH 3   
                 —H 
                 637 (M +  + 1) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 274 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 852   
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 1357 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 1.68-1.86 (2 H, m), 1.91-2.03 (2 H, m), 2.12 (3 H, s), 2.34- 2.40 (2 H, m), 2.40-2.46 (2 H, m), 2.48-2.56 (1 H, m), 2.62 (2 H, t, J = 7.9 Hz), 2.66-2.75 (1 H, m), 2.96 (2 H, t, J = 7.9 Hz), 3.08- 3.18 (1 H, m), 3.38-3.45 (2 H, m), 3.51 (2 H, s), 3.59-3.69 (2 H, m), 3.88-3.97 (1 H, m), 4.59-4.69 (1 H, m), 6.89 (1 H, d, J = 9.7 Hz), 7.02 (2 H, d, J = 8.4 Hz), 7.22 (2 H, d, J = 8.4 Hz), 7.25-7.31 (1 H, m), 7.31-7.38 (4 H, m), 7.54 (1 H, brs), 8.08-8.16 (2 H, m). 
               
               
                   
               
               
                 1358 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 2.05-2.18 (1 H, m), 2.32-2.40 (2 H, m), 2.40-2.47 (2 H, m), 2.49-2.56 (1 H, m), 2.63 (2 H, t, J = 7.9 Hz), 2.80-2.90 (1 H, m), 2.90-3.02 (3 H, m), 3.36-3.46 (2 H, m), 3.51 (2 H, s), 3.60-3.70 (2 H, m), 4.64-4.70 (1 H, m), 6.88-7.02 (3 H, m), 7.04 (2 H, d, J = 8.4 Hz), 7.09-7.15 (1 H, m), 7.15-7.22 (1 H, m), 7.22-7.25 (1 H, m), 7.25-7.30 (2 H, m), 7.30-7.38 (4 H, m), 8.14 (1 H, dd, J = 8.8, 2.8 Hz), 8.25 (1 H, d, J = 2.8 Hz), 8.54 (1 H, brs). 
               
               
                   
               
               
                 1359 
                 —CH 2 OCH 3   
                 (CDCl 3 ) 2.30-2.38 (2 H, m), 2.38-2.45 (2 H, m), 2.62 (2 H, t, J = 7.9 Hz), 
               
               
                   
                   
                 2.96 (2 H, t, J = 7.9 Hz), 3.35-3.43 (2 H, m), 3.50 (2 H, s), 
               
               
                   
                   
                 3.52 (3 H, s), 3.58-3.68 (2 H, m), 4.04 (2 H, s), 6.90 (1 H, d, J = 8.8 Hz), 
               
               
                   
                   
                 7.03 (2 H, d, J = 8.4 Hz), 7.22 (2 H, d, J = 8.4 Hz), 7.25- 
               
               
                   
                   
                 7.29 (1 H, m), 7.29-7.37 (4 H, m), 8.14 (1 H, dd, J = 8.8, 2.8 Hz), 
               
               
                   
                   
                 8.18-8.25 (2 H, m). 
               
               
                 1360 
                 —CH 3   
                 (CDCl 3 ) 2.18 (3 H, s), 2.32-2.39 (2 H, m), 2.39-2.45 (2 H, m), 
               
               
                   
                   
                 2.61 (2 H, t, J = 7.9 Hz), 2.95 (2 H, t, J = 7.9 Hz), 3.36-3.44 (2 H, 
               
               
                   
                   
                 m), 3.50 (2 H, s), 3.60-3.68 (2 H, m), 6.85-6.92 (1 H, m), 7.02 (2 H, 
               
               
                   
                   
                 d, J = 8.4 Hz), 7.21 (2 H, d, J = 8.4 Hz), 7.25-7.30 (1 H, m), 7.30- 
               
               
                   
                   
                 7.35 (4 H, m), 7.38 (1 H, brs), 8.06-8.15 (2 H, m). 
               
               
                 1361 
                 —C(CH 3 ) 3   
                 (CDCl 3 ) 1.32 (9 H, s), 2.32-2.38 (2 H, m), 2.38-2.44 (2 H, m), 
               
               
                   
                   
                 2.62 (2 H, t, J = 7.9 Hz), 2.96 (2 H, t, J = 7.9 Hz), 3.37-3.43 (2 H, 
               
               
                   
                   
                 m), 3.50 (2 H, s), 3.60-3.69 (2 H, m), 6.87 (1 H, d, J = 9.8 Hz), 
               
               
                   
                   
                 7.02 (2 H, d, J = 8.4 Hz), 7.22 (2 H, d, J = 8.4 Hz), 7.25-7.30 (1 H, 
               
               
                   
                   
                 m), 7.30-7.37 (5 H, m), 8.07-8.15 (2 H, m). 
               
               
                 1362 
                 —(CH 2 ) 2 OPh 
                 (DMSO-d 6 ) 2.23-2.33 (4 H, m), 2.56-2.67 (2 H, m), 2.73-2.86 (4 H, 
               
               
                   
                   
                 m), 3.37-3.50 (6 H, m), 4.26 (2 H, t, J = 6.0 Hz), 6.90-6.96 (3 H, m), 
               
               
                   
                   
                 6.96-7.02 (3 H, m), 7.20-7.35 (9 H, m), 8.07 (1 H, dd, J = 8.8, 
               
               
                   
                   
                 2.7 Hz), 8.33 (1 H, d, J = 2.7 Hz), 10.23 (1 H, s). 
               
               
                 1363 
                 3-CH 3 OPhOCH 2 — 
                 (DMSO-d 6 ) 2.23-2.34 (4 H, m), 2.58-2.68 (2 H, m), 2.76-2.85 (2 H, 
               
               
                   
                   
                 m), 3.38-3.50 (6 H, m), 3.74 (3 H, s), 4.68 (2 H, s), 6.51-6.62 (3 H, 
               
               
                   
                   
                 m), 6.95-7.04 (3 H, m), 7.18-7.28 (4 H, m), 7.28-7.37 (4 H, m), 
               
               
                   
                   
                 8.09 (1 H, dd, J = 8.9, 2.7 Hz), 8.36 (1 H, d, J = 2.7 Hz), 
               
               
                   
                   
                 10.22 (1 H, s). 
               
               
                 1364 
                 3-CH 3 PhOCH 2 — 
                 (DMSO-d 6 ) 2.23-2.34 (7 H, m), 2.56-2.66 (2 H, m), 2.74-2.84 (2 H, 
               
               
                   
                   
                 m), 3.37-3.50 (6 H, m), 4.67 (2 H, s), 6.75-6.81 (2 H, m), 6.81- 
               
               
                   
                   
                 6.88 (1 H, m), 6.96-7.03 (3 H, m), 7.14-7.21 (1 H, m), 7.21-7.28 (3 H, 
               
               
                   
                   
                 m), 7.28-7.36 (4 H, m), 8.09 (1 H, dd, J = 8.9, 2.7 Hz), 8.36 (1 H, d, 
               
               
                   
                   
                 J = 2.7 Hz), 10.21 (1 H, s). 
               
               
                 1365 
                 4-CH 3 PhOCH 2 — 
                 (DMSO-d 6 ) 2.23 (3 H, s), 2.26-2.32 (4 H, m), 2.57-2.65 (2 H, m), 
               
               
                   
                   
                 2.73-2.83 (2 H, m), 3.36-3.50 (6 H, m), 4.65 (2 H, s), 6.90 (2 H, d, 
               
               
                   
                   
                 J = 8.5 Hz), 6.95-7.02 (3 H, m), 7.11 (2 H, d, J = 8.5 Hz), 7.20- 
               
               
                   
                   
                 7.29 (3 H, m), 7.29-7.35 (4 H, m), 8.08 (1 H, dd, J = 8.9, 2.7 Hz), 
               
               
                   
                   
                 8.36 (1 H, d, J = 2.7 Hz), 10.21 (1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 275 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 853   
                   1 H NMR (DMSO-d 6 ) δ ppm or MS 
               
               
                   
               
               
                 1366 
                 PhOCH 2 — 
                   1 H NMR 2.23-2.34 (4 H, m), 2.57-2.65 (2 H, m), 2.76- 
               
               
                   
                   
                 2.85 (2 H, m), 3.38-3.50 (6 H, m), 4.70 (2 H, s), 6.92- 
               
               
                   
                   
                 7.05 (6 H, m), 7.20-7.27 (3 H, m), 7.27-7.38 (6 H, m), 
               
               
                   
                   
                 8.09 (1 H, dd, J = 8.9, 2.7 Hz), 8.36 (1 H, d, J = 2.7 Hz), 
               
               
                   
                   
                 10.24 (1 H, s). 
               
               
                 1367 
                 4-CH 3 PhCH 2 — 
                   1 H NMR 2.21-2.32 (7 H, m), 2.56-2.65 (2 H, m), 2.73- 
               
               
                   
                   
                 2.82 (2 H, m), 3.37-3.49 (6 H, m), 3.58 (2 H, s), 6.92- 
               
               
                   
                   
                 7.00 (3 H, m), 7.09-7.16 (2 H, m), 7.19-7.21 (2 H, m), 7.21- 
               
               
                   
                   
                 7.27 (3 H, m), 7.27-7.35 (4 H, m), 8.04 (1 H, dd, J = 8.9, 
               
               
                   
                   
                 2.7 Hz), 8.30 (1 H, d, J = 2.7 Hz), 10.27 (1 H, s). 
               
               
                 1368 
                 4-ClPhCH 2 — 
                   1 H NMR 2.21-2.32 (4 H, m), 2.55-2.65 (2 H, m), 2.73- 
               
               
                   
                   
                 2.82 (2 H, m), 3.38-3.49 (6 H, m), 3.66 (2 H, s), 6.93- 
               
               
                   
                   
                 7.00 (3 H, m), 7.20-7.26 (3 H, m), 7.26-7.35 (6 H, m), 7.35- 
               
               
                   
                   
                 7.42 (2 H, m), 8.04 (1 H, dd, J = 8.9, 2.7 Hz), 8.30 (1 H, d, 
               
               
                   
                   
                 J = 2.7 Hz), 10.33 (1 H, s). 
               
               
                 1369 
                 4-CH 3 OPhCH 2 — 
                   1 H NMR 2.22-2.33 (4 H, m), 2.56-2.65 (2 H, m), 2.75- 
               
               
                   
                   
                 2.83 (2 H, m), 3.38-3.50 (6 H, m), 3.56 (2 H, s), 3.73 (3 H, s), 
               
               
                   
                   
                 6.84-6.90 (2 H, m), 6.92-7.00 (3 H, m), 7.19-7.28 (5 H, m), 
               
               
                   
                   
                 7.28-7.36 (4 H, m), 8.04 (1 H, dd, J = 8.9, 2.7 Hz), 
               
               
                   
                   
                 8.30 (1 H, d, J = 2.7 Hz), 10.25 (1 H, s). 
               
               
                 1370 
                 4-FPhCH 2 — 
                   1 H NMR 2.23-2.32 (4 H, m), 2.56-2.65 (2 H, m), 2.75- 
               
               
                   
                   
                 2.84 (2 H, m), 3.39-3.50 (6 H, m), 3.64 (2 H, s), 6.93- 
               
               
                   
                   
                 7.00 (3 H, m), 7.11-7.19 (2 H, m), 7.21-7.29 (3 H, m), 7.29- 
               
               
                   
                   
                 7.40 (6 H, m), 8.04 (1 H, dd, J = 8.9, 2.7 Hz), 8.30 (1 H, d, 
               
               
                   
                   
                 J = 2.7 Hz), 10.31 (1 H, s). 
               
               
                 1371 
                 benzyl 
                   1 H NMR 2.22-2.33 (4 H, m), 2.56-2.67 (2 H, m), 2.72- 
               
               
                   
                   
                 2.84 (2 H, m), 3.37-3.50 (6 H, m), 3.64 (2 H, s), 6.90- 
               
               
                   
                   
                 7.00 (3 H, m), 7.20-7.29 (4 H, m), 7.29-7.38 (8 H, m), 
               
               
                   
                   
                 8.05 (1 H, dd, J = 8.8, 2.7 Hz), 8.31 (1 H, d, J = 2.7 Hz), 
               
               
                   
                   
                 10.32 (1 H, s). 
               
               
                 1372 
                 —(CH 2 ) 3 Ph 
                 MS 563 (M +  + 1) 
               
               
                 1373 
                 —(CH 2 ) 2 CH 3   
                 MS 487 (M +  + 1) 
               
               
                 1374 
                 —CH(CH 3 ) 2   
                 MS 486 (M + ) 
               
               
                 1375 
                 cyclopentyl 
                 MS 512 (M + ) 
               
               
                   
               
               
                 1376 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 630 (M + ) 
               
               
                   
               
               
                 1377 
                 —(CH 2 ) 2 Ph 
                 MS 549 (M +  + H) 
               
               
                 1378 
                 2-furyl 
                 MS 511 (M +  + H) 
               
               
                 1379 
                 2-thienyl 
                 MS 527 (M +  + H) 
               
               
                 1380 
                 2-thenyl 
                 MS 541 (M +  + H) 
               
               
                 1381 
                 cyclohexyl 
                 MS 527 (M +  + H) 
               
               
                 1382 
                 cycloheptyl 
                 MS 541 (M +  + H) 
               
               
                 1383 
                 cyclopentylmethyl 
                 MS 527 (M +  + H) 
               
               
                 1384 
                 cyclohexylmethyl 
                 MS 541 (M +  + H) 
               
               
                 1385 
                 2-Ch 3 OPhOCH 2 — 
                 MS 581 (M +  + 1) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 276 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 854   
                 MS 
               
               
                   
               
               
                 1386 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 584 (M +  + 1) 
               
               
                   
               
               
                 1387 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 582 (M +  + 1) 
               
               
                   
               
               
                 1388 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 587 (M +  + H) 
               
               
                   
               
               
                 1389 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 547 (M + ) 
               
               
                   
               
               
                 1390 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 547 (M + ) 
               
               
                   
               
               
                 1391 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 561 (M +  + 1) 
               
               
                   
               
               
                 1392 
                 2-CH 3 PhOCH 2 — 
                 565 (M +  + H) 
               
               
                 1393 
                 2-ClPhOCH 2 — 
                 585 (M + ) 
               
               
                 1394 
                 3-ClPhOCH 2 — 
                 585 (M +  + H) 
               
               
                 1395 
                 4-CNPhOCH 2 — 
                 575 (M + ) 
               
               
                   
               
               
                 1396 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 595 (M +  + H) 
               
               
                   
               
               
                 1397 
                 3,4,5-(CH 3 O) 3 PhOCH 2 — 
                 641 (M +  + 1) 
               
               
                   
               
               
                 1398 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 556 (M +  + 1) 
               
               
                   
               
               
                 1399 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 556 (M +  + H) 
               
               
                   
               
               
                 1400 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 590 (M +  + H) 
               
               
                   
               
               
                 1401 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 567 (M + ) 
               
               
                   
               
               
                 1402 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 556 (M + ) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 277 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 855   
                 MS 
               
               
                   
               
               
                 1403 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 566 (M +  − 1) 
               
               
                   
               
               
                 1404 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 559 (M + ) 
               
               
                   
               
               
                 1405 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 562 (M +  + H) 
               
               
                   
               
               
                 1406 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 528 (M +  + 1) 
               
               
                   
               
               
                 1407 
                 2-quinolyl  
                 571 (M + ) 
               
               
                 1408 
                 3-quinolyl 
                 572 (M +  + H) 
               
               
                 1409 
                 4-quinolyl 
                 571 (M + ) 
               
               
                 1410 
                 6-quinolyl 
                 571 (M + ) 
               
               
                 1411 
                 1-isoquinolyl 
                 571 (M + ) 
               
               
                 1412 
                 3-isoquinolyl 
                 572 (M +  + H) 
               
               
                   
               
               
                 1413 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 560 (M + ) 
               
               
                   
               
               
                 1414 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 590 (M + ) 
               
               
                   
               
               
                 1415 
                 3,4-Cl 2 PhCH 2 — 
                 603 (M +  + H) 
               
               
                 1416 
                 2-CH 3 OPhCH 2 — 
                 564 (M + ) 
               
               
                 1417 
                 —CH(CH 2 Ph)NHAc 
                 605 (M + ) 
               
               
                   
               
               
                 1418 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 557 (M + ) 
               
               
                   
               
               
                 1419 
                 —CH 2 NHAc 
                 515 (M + ) 
               
               
                 1420 
                 —CH(CH 3 )NHAc 
                 529 (M + ) 
               
               
                 1421 
                 —CH(CH 2 Ph)NHCOPh 
                 667 (M + ) 
               
               
                   
               
               
                 1422 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 619 (M + ) 
               
               
                   
               
               
                 1423 
                 —CH 2 NHCOPh 
                 577 (M + ) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 278 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 856   
                 MS 
               
               
                   
               
               
                 1424 
                 —CH(CH 3 )NHCOPh 
                 591 (M + ) 
               
               
                 1425 
                 2-pyridyl 
                 522 (M +  + H) 
               
               
                 1426 
                 3-pyridyl 
                 522 (M +  + H) 
               
               
                 1427 
                 4-pyridyl 
                 522 (M +  + H) 
               
               
                 1428 
                 1-naphthyl 
                 571 (M +  + H) 
               
               
                   
               
               
                 1429 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 551 (M + ) 
               
               
                   
               
               
                 1430 
                 2-pyrrolyl 
                 509 (M + ) 
               
               
                 1431 
                 3-pyridylmethyl  
                 536 (M +  + H) 
               
               
                 1432 
                 3-furyl 
                 510 (M + ) 
               
               
                 1433 
                 3-thienyl 
                 526 (M + ) 
               
               
                 1434 
                 3-thenyl 
                 541 (M +  + H) 
               
               
                   
               
               
                 1435 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 592 (M + ) 
               
               
                   
               
               
                 1436 
                 3-CH 3 PhCH 2 — 
                 549 (M +  + H) 
               
               
                 1437 
                 3-ClPhCH 2 — 
                 569 (M +  + H) 
               
               
                 1438 
                 2-FPhCH 2 — 
                 553 (M +  + H) 
               
               
                 1439 
                 3-FPhCH 2 — 
                 553 (M +  + H) 
               
               
                 1440 
                 2,5-(CH 3 O) 2 PhCH 2 — 
                 594 (M + ) 
               
               
                 1441 
                 2,4-Cl 2 PhCH 2 — 
                 603 (M +  + H) 
               
               
                 1442 
                 2,6-Cl 2 PhCH 2 — 
                 602 (M + ) 
               
               
                 1443 
                 3,4,5-(CH 3 O) 3 PhCH 2 — 
                 624 (M + ) 
               
               
                 1444 
                 CH(OCH 3 )Ph 
                 564 (M + ) 
               
               
                   
               
               
                 1445 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 622 (M + ) 
               
               
                   
               
               
                 1446 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 588 (M +  + H) 
               
               
                   
               
               
                 1447 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 659 (M + ) 
               
               
                   
               
               
                 1448 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 589 (M + ) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 279 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 857   
                 MS 
               
               
                   
               
               
                 1449 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 589 (M + ) 
               
               
                   
               
               
                 1450 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 590 (M +  + H) 
               
               
                   
               
               
                 1451 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 573 (M + + H) 
               
               
                   
               
               
                 1452 
                 4-CH 3 OPhO(CH 2 ) 2 — 
                 595 (M +  + H) 
               
               
                 1453 
                 4-CH 3 OPh(CH 2 ) 2 — 
                 579 (M +  + H) 
               
               
                 1454 
                 3,4,5-(CH 3 O) 3 Ph(CH 2 ) 2 — 
                 638 (M + ) 
               
               
                 1455 
                 2,4-Cl 2 PhOCH 2 — 
                 618 (M + ) 
               
               
                 1456 
                 PhSCH 2 — 
                 567 (M +  + H) 
               
               
                 1457 
                 —(CH 2 ) 2 COPh 
                 577 (M +  + H) 
               
               
                   
               
               
                 1458 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 573 (M + ) 
               
               
                   
               
               
                 1459 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 588 (M +  + H) 
               
               
                   
               
               
                 1460 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 590 (M +  + H) 
               
               
                   
               
               
                 1461 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 594 (M +  + H) 
               
               
                   
               
               
                 1462 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 578 (M +  + H) 
               
               
                   
               
               
                 1463 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 573 (M + ) 
               
               
                   
               
               
                 1464 
                 4—CH 3 OPh(CH 2 ) 3 — 
                 593 (M +  + H) 
               
               
                   
               
               
                 1465 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 576 (M + ) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
             
               
               
               
             
           
               
                 TABLE 280 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 858   
                 mp (° C.) or  1 H NMR (DMSO-d 6 ) δ ppm 
               
               
                   
               
             
          
           
               
                 1466 
                 2,5-F 2 Ph- 
                 mp 173-176 
               
               
                   
               
               
                 1467 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 mp 181-182 
               
               
                   
               
               
                 1468 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 mp 199-201 
               
               
                   
               
               
                 1469 
                 2,3-Cl 2 Ph- 
                 mp 149-151 
               
               
                 1470 
                 2,4-Cl 2 Ph- 
                   1 H NMR 2.54 (4 H, brs), 2.64 (2 H, t, J = 7.5 Hz), 2.81 (2 H, t, J = 
               
               
                   
                   
                 7.5 Hz), 3.51 (4 H, brs), 3.65 (2 H, brs), 6.01 (2 H, s), 6.81 (1 H, 
               
               
                   
                   
                 d, J = 8.0 Hz), 6.89 (1 H, d, J = 8.0 Hz), 6.92 (1 H, s), 7.01 (2 H, 
               
               
                   
                   
                 d, J = 8.5 Hz), 7.04 (1 H, d, J = 9.0 Hz), 7.26 (2 H, d, J = 8.5 Hz), 
               
               
                   
                   
                 7.57 (1 H, dd, J = 8.5 Hz, 2.0 Hz), 7.65 (1 H, d, J = 8.5 Hz), 
               
               
                   
                   
                 7.78 (1 H, d, J = 2.0 Hz), 8.15 (1 H, dd, J = 9.0 Hz, 2.5 Hz), 
               
               
                   
                   
                 8.41 (1 H, d, J = 2.5 Hz), 10.69 (1 H, s). 
               
               
                 1471 
                 2,5-(CF 3 ) 2 Ph- 
                   1 H NMR 2.54 (4 H, brs), 2.64 (2 H, t, J = 7.5 Hz), 2.81 (2 H, t, J = 
               
               
                   
                   
                 7.5 Hz), 3.49 (4 H, brs), 3.59 (2 H, brs), 6.00 (2 H, s), 6.79 (1 H, 
               
               
                   
                   
                 d, J = 8.0 Hz), 6.88 (1 H, d, J = 8.0 Hz), 6.90 (1 H, s), 7.02 (2 H, 
               
               
                   
                   
                 d, J = 8.5 Hz), 7.05 (1 H, d, J = 9.0 Hz), 7.27 (2 H, d, J = 8.5 Hz), 
               
               
                   
                   
                 8.12-8.14 (3 H, m), 8.21 (1 H, s), 8.37 (1 H, d, J = 2.5 Hz), 
               
               
                   
                   
                 10.84 (1 H, s). 
               
               
                 1472 
                 3-CF 3 Ph- 
                   1 H NMR 2.54 (4 H, brs), 2.64 (2 H, t, J = 7.5 Hz), 2.82 (2 H, t, J = 
               
               
                   
                   
                 7.5 Hz), 3.51 (4 H, brs), 3.63 (2 H, brs), 6.01 (2 H, s), 6.81 (1 H, 
               
               
                   
                   
                 d, J = 8.0 Hz), 6.89 (1 H, d, J = 8.0 Hz), 6.92 (1 H, s), 7.02 (2 H, 
               
               
                   
                   
                 d, J = 8.5 Hz), 7.05 (1 H, d, J = 9.0 Hz), 7.27 (2 H, d, J = 8.5 Hz), 
               
               
                   
                   
                 7.80 (1 H, t, J = 8.0 Hz), 7.99 (1 H, d, J = 8.0 Hz), 
               
               
                   
                   
                 8.19 (1 H, dd, J = 9.0 Hz, 2.5 Hz), 8.27 (1 H, d, J = 8.0 Hz), 
               
               
                   
                   
                 8.30 (1 H, s), 8.48 (1 H, d, J = 2.5 Hz), 10.61 (1 H, s). 
               
               
                 1473 
                 2,3-F 2 Ph- 
                   1 H NMR 2.54 (4 H, brs), 2.64 (2 H, t, J = 7.5 Hz), 2.81 (2 H, t, J = 
               
               
                   
                   
                 7.5 Hz), 3.51 (4 H, brs), 3.62 (2 H, brs), 6.01 (2 H, s), 6.80 (1 H, 
               
               
                   
                   
                 d, J = 8.0 Hz), 6.89 (1 H, d, J = 8.0 Hz), 6.92 (1 H, s), 7.02 (2 H, 
               
               
                   
                   
                 d, J = 8.5 Hz), 7.04 (1 H, d, J = 9.0 Hz), 7.26 (2 H, d, J = 8.5 Hz), 
               
               
                   
                   
                 7.36 (1 H, m), 7.50 (1 H, m), 7.60 (1 H, m), 8.16 (1 H, dd, J = 
               
               
                   
                   
                 9.0 Hz, 2.5 Hz), 8.43 (1 H, d, J = 2.5 Hz), 10.67 (1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 281 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 859   
                 Xb 23   
                 Form 
                 mp (° C.) or  1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 1474 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —N(Ac)— 
                 free 
                 mp 142-144 
               
               
                   
               
               
                 1475 
                 3,4-F 2 Ph- 
                 —CH 2 — 
                 free 
                   1 H NMR (CDCl 3 ) 2.31-2.40 (4 H, m), 2.59- 
               
               
                   
                   
                   
                   
                 2.65 (2 H, m), 2.92-2.98 (2 H, m), 3.38-3.41 (4 H, 
               
               
                   
                   
                   
                   
                 m), 3.60-3.64 (2 H, m), 5.94 (2 H, s), 6.70- 
               
               
                   
                   
                   
                   
                 6.77 (2 H, m), 6.84 (1 H, s), 6.94 (1 H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                 7.01-7.07 (2 H, m), 7.19-7.24 (2 H, m), 
               
               
                   
                   
                   
                   
                 7.29-7.33 (1 H, m), 7.62-7.68 (1 H, m), 7.74- 
               
               
                   
                   
                   
                   
                 7.81 (1 H, m), 8.01 (1 H, brs), 8.16-8.20 (1 H, m), 
               
               
                   
                   
                   
                   
                 8.24 (1 H, d, J = 2.2 Hz). 
               
               
                   
               
               
                 1476 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 2 — 
                 hydro- chloride 
                   1 H NMR (DMSO-d 6 ) 2.60-2.98 (6 H, m), 3.01- 3.15 (1 H, m), 3.26 (2 H, t, J = 15.0 Hz), 3.46- 3.59 (1 H, m), 4.00-4.11 (1 H, m), 4.15-4.27 (2 H, m), 4.30-4.51 (1 H, m), 6.05 (2 H, s), 6.97 (1 H, d, J = 7.9 Hz), 6.98-7.09 (4 H, m), 7.20- 7.31 (3 H, m), 7.97 (1 H, d, J = 8.4 Hz), 8.11- 8.23 (3 H, m), 8.50 (1 H, d, J = 2.7 Hz), 10.78 (1 H, s), 11.38 (1 H, brs). 
               
               
                   
               
               
                 1477 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 2 — 
                 hydro- chloride 
                   1 H NMR (DMSO-d 6 ) 2.60-2.99 (6 H, m), 3.01- 3.17 (1 H, m), 3.25 (2 H, t, J = 15.0 Hz), 3.48- 3.60 (1 H, m), 4.00-4.12 (1 H, m), 4.15-4.28 (2 H, m), 4.39-4.51 (1 H, m), 6.05 (2 H, s), 6.96 (1 H, d, J = 8.8 Hz), 6.99-7.08 (4 H, m), 7.19- 7.31 (3 H, m), 7.55 (1 H, t, J = 7.8 Hz), 7.90- 8.04 (2 H, m), 8.16 (1 H, dd, J = 8.8 Hz, 2.7 Hz), 8.43 (1 H, d, J = 2.7 Hz), 10.82 (1 H, s), 11.44 (1 H, brs). 
               
               
                   
               
               
                 1478 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 2 — 
                 hydro- chloride 
                 mp 213-215 
               
               
                   
               
               
                 1479 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 2 — 
                 trihydro- chloride 
                   1 H NMR (DMSO-d 6 ) 2.69-3.40 (15 H, m), 3.99- 4.49 (5 H, m), 6.07 (2 H, s), 6.97-7.09 (5 H, m), 7.21-7.30 (3 H, m), 7.43-7.47 (1 H, m), 7.65- 7.70 (2 H, m), 7.91 (1 H, d, J = 9.4 Hz), 8.21 (1 H, dd, J = 8.9 Hz, 2.6 Hz), 8.48 (1 H, d, J = 2.1 Hz), 11.23 (1 H, s). 
               
               
                   
               
               
                 1480 
                 3-PhOPh- 
                 —CH 2 — 
                 hydro- chloride 
                   1 H NMR (DMSOd 6 ) 2.60-3.09 (7 H, m), 3.18- 
               
               
                   
                   
                   
                   
                 3.31 (2 H, m), 3.38-3.50 (1 H, m), 4.08 (1 H, d, J = 
               
               
                   
                   
                   
                   
                 14.0 Hz), 4.22 (2 H, brs), 4.45 (1 H, d, J = 
               
               
                   
                   
                   
                   
                 14.0 Hz), 6.07 (2 H, s), 6.90-7.08 (7 H, m), 7.15- 
               
               
                   
                   
                   
                   
                 7.26 (5 H, m), 7.44 (2 H, t, J = 7.9 Hz), 7.56 (1 H, 
               
               
                   
                   
                   
                   
                 t, J = 7.9 Hz), 7.61 (1 H, s), 7.79 (1 H, d, J = 7.6 Hz), 
               
               
                   
                   
                   
                   
                 8.19 (1 H, dd, J = 8.9 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                   
                 8.45 (1 H, d, J = 2.6 Hz), 10.45 (1 H, s), 10.90- 
               
               
                   
                   
                   
                   
                 11.20 (1 H, m). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 282 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 860   
                 R 861    
                 Xb 24   
                 Form 
                 mp (° C.) or  1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 1481 
                 1-naphthyl 
                 —H 
                 —CH 2 — 
                 hydro- 
                   1 H NMR (DMSO-d 6 ) 2.50- 
               
               
                   
                   
                   
                   
                 chloride 
                 3.60 (10 H, m), 4.00-4.20 (1 H, m), 
               
               
                   
                   
                   
                   
                   
                 4.22 (2 H, s), 4.35-4.51 (1 H, m), 
               
               
                   
                   
                   
                   
                   
                 6.07 (2 H, s), 6.91-7.08 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                 7.04 (2 H, d, J = 8.6 Hz), 7.08 (1 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.9 Hz), 7.21 (1 H, s), 7.39 
               
               
                   
                   
                   
                   
                   
                 (2 H, d, J = 8.6 Hz), 7.55-7.67 (3 H, 
               
               
                   
                   
                   
                   
                   
                 m), 7.79 (1 H, d, J = 7.1 Hz), 7.98- 
               
               
                   
                   
                   
                   
                   
                 8.05 (1 H, m), 8.10 (1 H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.16-8.22 (1 H, m), 8.26 (1 H, 
               
               
                   
                   
                   
                   
                   
                 dd, J = 8.9 Hz, 2.5 Hz), 8.54 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 2.5 Hz), 10.72 (1 H, s) 
               
               
                   
               
               
                 1482 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 —N(CH 3 )— 
                 free 
                   1 H NMR (CDCl 3 ) 2.13 (3 H, s), 2.43 (4 H, t, J = 4.8 Hz), 3.01 (3 H, s), 3.44 (2 H, s), 3.45-3.56 (2 H, m), 3.56-3.70 (2 H, m), 4.08 (2 H, s), 4.09 (3 H, s), 5.95 (2 H, s), 6.51-6.60 (2 H, m), 6.72-6.76 (2 H, m), 6.82 (1 H, d, J = 8.9 Hz), 6.85 (1 H, s), 6.92 (1 H, d, J = 8.4 Hz), 7.04 (1 H, s), 7.14- 7.23 (1 H, m), 7.28-7.40 (1 H, m), 7.42 (1 H, d, J = 7.9 Hz), 7.67 (1 H, d, J = 7.9 Hz), 7.94 (1 H, s), 8.14 (1 H, dd, J = 8.9 Hz, 2.8 Hz), 8.22 (1 H, d, J = 2.8 Hz). 
               
               
                   
               
               
                 1483 
                 3,5-(CH 3 ) 2 Ph- 
                 —H 
                 —CH 2 — 
                 hydro- 
                 H NMR (DMSO-d 6 ) 2.36 (6 H, s), 
               
               
                   
                   
                   
                   
                 chloride 
                 2.60-3.60 (10 H, m), 4.00-4.60 (2 H, 
               
               
                   
                   
                   
                   
                   
                 m), 4.29 (2 H, s), 6.07 (2 H, s), 6.85- 
               
               
                   
                   
                   
                   
                   
                 7.10 (5 H, m), 7.22 (2 H, s), 7.27 (2 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.5 Hz), 7.57 (2 H, s), 8.19 
               
               
                   
                   
                   
                   
                   
                 (1 H, dd, J = 8.9 Hz, 2.7 Hz), 8.48 
               
               
                   
                   
                   
                   
                   
                 (1 H, d, J = 2.7 Hz), 10.34 (1 H, s). 
               
               
                   
               
               
                 1484 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 —N(CH 3 )— 
                 free 
                 mp 143-144 
               
               
                   
               
               
                 1485 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 —N(CH 3 )— 
                 free 
                 mp 163-165 
               
               
                   
               
               
                 1486 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 —N(CH 3 )— 
                 free 
                 mp 224-227 dec 
               
               
                   
               
               
                 1487 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 —N(CH 3 )— 
                 free 
                 mp 131-134 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 283 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 862   
                 R 863   
                 Xb 25   
                 Form 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 1488 
                 2,3-(CH 3 O) 2 Ph- 
                 —H 
                 —CH 2 — 
                 hydro- 
                 (DMSO-d 6 ) 3.80 (3 H, s), 3.86 (3 H, s), 
               
               
                   
                   
                   
                   
                 chloride 
                 2.60-3.60 (10 H, m), 4.00-4.20 (1 H, m), 
               
               
                   
                   
                   
                   
                   
                 4.22 (2 H, s), 4.40-4.55 (1 H, m), 6.07 (2 H, 
               
               
                   
                   
                   
                   
                   
                 s), 6.90-7.30 (11 H, m), 8.18 (1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 8.8 Hz, 2.6 Hz), 8.45 (1 H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 10.37 (1 H, s). 
               
               
                   
               
               
                 1489 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 —N(CH 3 )— 
                 free 
                 (CDCl 3 ) 2.12 (3 H, s), 2.35-2.50 (4 H, m), 3.01 (3 H, s), 3.43 (2 H, s), 3.45-3.55 (2 H, m), 3.57-3.70 (2 H, m), 4.07 (2 H, s) 5.95 (2 H, s), 6.40 (2 H, t, J = 2.2 Hz), 6.50-6.59 (2 H, m), 6.74 (2 H, s), 6.81 (1 H, d, J = 8.9 Hz), 6.85 (1 H, s), 6.92 (1 H, d, J = 8.6 Hz), 7.17 (2 H, t, J = 2.2 Hz), 7.49 (2 H, d, J = 8.8 Hz), 7.90 (1 H, brs), 7.95 (2 H, d, J = 8.8 Hz), 8.15 (1 H, dd, J = 8.9 Hz, 2.3 Hz), 8.22 (1 H, d, J = 2.3 Hz). 
               
               
                   
               
               
                 1490 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 —N(CH 3 )— 
                 free 
                 (CDCl 3 ) 2.04 (3 H, s), 2.39-2.46 (4 H, m), 2.94 (3 H, s), 3.43-3.51 (4 H, m), 3.59- 3.63 (2 H, m), 4.05 (2 H, s), 5.94 (2 H, s), 6.41-6.48 (2 H, m), 6.67-6.84 (6 H, m), 7.44 (1 H, d, J = 4.1 Hz), 8.01 (1 H, dd, J = 8.9 Hz, 2.6 Hz), 8.17 (1 H, d, J = 2.6 Hz), 8.82 (1 H, brs). 
               
               
                   
               
               
                 1491 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 —N(CH 3 )— 
                 maleate 
                 (DMSO-d 6 ) 2.01 (3 H, s), 2.50 (4 H, brs), 2.93 (3 H, s), 3.33 (4 H, brs), 4.03 (2 H, s), 4.29 (2 H, s), 6.06 (2 H, s), 6.10 (2 H, s), 6.48 (1 H, dd, J = 8.9 Hz, 2.8 Hz), 6.56 (1 H, s), 6.81-7.01 (6 H, m), 7.43- 7.53 (2 H, m), 7.57 ( 1 H, dd, J = 5.9 Hz, 3.6 Hz), 7.77 (1 H, dd, J = 5.8 Hz, 3.6 Hz), 7.88 (1 H, d, J = 15.7 Hz), 8.11 (1 H, dd, J = 8.7 Hz, 2.5 Hz), 8.36 (1 H, d, J = 2.6 Hz), 10.42 (1 H, s). 
               
               
                   
               
               
                 1492 
                 4-(CH 3 ) 2 NPh- 
                 —H 
                 —CH 2 — 
                 free 
                 (CDCl 3 ) 2.33 (2 H, t, J = 5.0 Hz), 2.39 (2 H, 
               
               
                   
                   
                   
                   
                   
                 t, J = 5.0 Hz), 2.61 (2 H, t, J = 7.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 2.97 (2 H, t, J = 7.5 Hz), 3.05 (6 H, s), 
               
               
                   
                   
                   
                   
                   
                 3.32-3.45 (2 H, m), 3.41 (2 H, s), 3.63 (2 H, 
               
               
                   
                   
                   
                   
                   
                 t, J = 5.0 Hz), 5.94 (2 H, s), 6.70 (2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 9.0 Hz), 6.74 (2 H, s), 6.85 (1 H, s), 
               
               
                   
                   
                   
                   
                   
                 6.92 (1 H, d, J = 9.0 Hz), 7.04 (2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.6 Hz), 7.22 (2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.72 (1 H, s), 7.78 (2 H, d, J = 9.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.21 (1 H, d, J = 2.8 Hz), 8.23 (1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 8.6 Hz, 2.8 Hz). 
               
               
                 1493 
                 2,4-Cl 2 PhOCH 2 — 
                 —CH 3   
                 —N(CH 3 )— 
                 free 
                 (CDCl 3 ) 2.11 (3 H, s), 2.42 (4 H, brs), 
               
               
                   
                   
                   
                   
                   
                 3.00 (3 H, s), 3.43 (2 H, s), 3.49 (2 H, brs), 
               
               
                   
                   
                   
                   
                   
                 3.63 (2 H, brs), 4.07 (2 H, s), 4.62 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                 5.94 (2 H, s), 6.54 (1 H, dd, J = 11.1 Hz, 
               
               
                   
                   
                   
                   
                   
                 2.3 Hz), 6.74-6.92 (6 H, m), 7.24 (1 H, dd, 
               
               
                   
                   
                   
                   
                   
                 J = 8.7 Hz, 2.5 Hz), 7.43 (1 H, d, J = 2.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.06 (1 H, dd, J = 8.9 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.23 (1 H, d, J = 2.6 Hz), 8.55 (1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 284 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                 mp (° C.) or  1 H NMR (solvent) 
               
               
                 No. 
                 R 864   
                 R 865   
                 Xb 26   
                 Xb 27   
                 Form 
                 δ ppm 
               
               
                   
               
               
                 1494 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 —N(CH 3 )— 
                 —CH 2 — 
                 free 
                   1 H NMR (CDCl 3 ) 2.10 (3 H, s), 2.45 (4 H, brs), 3.01 (3 H, s), 3.45 (2 H, s), 3.51 (2 H, brs), 3.64 (2 H, brs), 4.08 (2 H, s), 5.95 (2 H, s), 6.51-6.59 (3 H, m), 6.75- 6.92 (5 H, m), 7.33 (1 H, d, J = 8.3 Hz), 7.45 (1 H, d, J = 8.4 Hz), 7.61-7.76 (3 H, m), 8.16 (1 H, d, J = 8.9 Hz), 8.18 (1 H, s). 
               
               
                   
               
               
                 1495 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 —N(CH 3 )— 
                 —CH 2 — 
                 free 
                   1 H NMR (CDCl 3 ) 2.09 (3 H, s), 2.34-2.48 (4 H, m), 2.98 (3 H, s), 3.42 (2 H, s), 3.40-3.55 (2 H, m), 3.55-3.70 (2 H, m), 3.84 (3 H, s), 4.06 (2 H, s), 5.94 (2 H, s), 6.46- 6.55 (2 H, m), 6.67-6.76 (2 H, m), 6.77 (1 H, d, J = 8.9 Hz), 6.85 (1 H, s), 6.89 (1 H, d, J = 8.5 Hz), 6.93- 6.98 (1 H, m), 6.97 (1 H, dd, J = 8.9 Hz, 2.3 Hz), 7.04 (1 H, d, J = 2.3 Hz), 7.30 (1 H, d, J = 8.9 Hz), 8.11 (1 H, dd, J = 8.9 Hz, 2.5 Hz), 8.22 (1 H, s), 8.25 (1 H, d, J = 2.5 Hz), 9.45 (1 H, s). 
               
               
                   
               
               
                 1496 
                 3,4-(CH 3 ) 2 Ph- 
                 —H 
                 —CH 2 — 
                 —CH 2 — 
                 free 
                   1 H NMR (CDCl 3 ) 2.31-2.38 (10 H, m), 2.57-2.63 (2 H, m), 2.91- 2.97 (2 H, m), 3.37-3.40 (4 H, m), 3.59-3.63 (2 H, m), 5.93 (2 H, s), 6.70-6.77 (2 H, m), 6.84 (1 H, s), 6.91 (1 H, d, J = 8.9 Hz), 7.00-7.05 (2 H, m), 7.17-7.22 (3 H, m), 7.60 (1 H, dd, J = 7.8 Hz, 1.9 Hz), 7.66 (1 H, d, J = 1.9 Hz), 8.16- 8.26 (3 H, m). 
               
               
                   
               
               
                 1497 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 —CH 2 — 
                 —CH 2 — 
                 free 
                   1 H NMR (DMSO-d 6 ) 2.41 (4 H, brs), 2.62 (2 H, t, J = 7.5 Hz), 2.81 (2 H, t, J = 7.5 Hz), 3.32 (1 H, brs), 3.47 (4 H, brs), 3.52 (2 H, s), 6.00 (2 H, s), 6.78 (1 H, d, J = 8.0 Hz), 6.87 (1 H, d, J = 8.0 Hz), 6.88 (1 H, d, J = 2.0 Hz), 7.00 (2 H, d, J = 8.5 Hz), 7.03 (1 H, d, J = 8.9 Hz), 7.26 (2 H, d, J = 8.5 Hz), 7.94 (1 H, s), 8.05 (1 H, s), 8.10 (1 H, dd, J = 8.9 Hz, 2.6 Hz), 8.36 (1 H, d, J = 2.6 Hz), 10.72 (1 H, s). 
               
               
                   
               
               
                 1498 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 —N(CH 3 )— 
                 —CH 2 — 
                 hydro- chloride 
                 mp 145.0-148.0 
               
               
                   
               
               
                 1499 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 —N(CH 3 )— 
                 —CO— 
                 free 
                 mp 269.0-272.0 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 285 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 866   
                 R 867   
                 R 868   
                 Form 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 1500 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 hydro- chloride 
                 (DMSO-d 6 ) 2.08 (3 H, s), 3.09 (1 H, dd, J = 14.2 Hz, 9.7 Hz), 3.40 (1 H, dd, J = 14.2 Hz, 4.2 Hz), 4.93 (1 H, dd, J = 9.7 Hz, 4.2 Hz), 7.00 (1 H, d, J = 8.3 Hz), 7.02 (1 H, d, J = 8.9 Hz), 7.11 (1 H, dd, J = 8.3 Hz, 2.0 Hz), 7.20 (1 H, d, J = 2.0 Hz), 7.83 (1 H, d, J = 8.4 Hz), 7.95 (1 H, dd, J = 8.4 Hz, 2.0 Hz), 8.18 (1 H, dd, J = 8.9 Hz, 2.5 Hz), 8.23 (1 H, d, J = 2.0 Hz), 8.44 (1 H, d, J = 2.5 Hz), 10.57 (1 H, s), 12.08 (1 H, s). 
               
               
                   
               
               
                 1501 
                 4-CF 3 Ph- 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 (DMSO-d 6 ) 2.09 (3 H, s), 3.09 (1 H, dd, J = 14.1 Hz, 9.6 Hz), 3.40 (1 H, dd, J = 14.1 Hz, 4.3 Hz), 4.93 (1 H, dd, J = 9.6 Hz, 4.3 Hz), 6.99 (1 H, d, J = 8.2 Hz), 7.03 (1 H, d, J = 8.9 Hz), 7.12 (1 H, dd, J = 8.2 Hz, 2.0 Hz), 7.20 (1 H, d, J = 2.0 Hz), 7.93 (2 H, d, J = 8.2 Hz), 8.16 (2 H, d, J = 8.2 Hz), 8.20 (1 H, dd, J = 8.9 Hz, 2.5 Hz), 8.45 (1 H, d, J = 2.5 Hz), 10.60 (1 H, s), 12.07 (1 H, s). 
               
               
                   
               
               
                 1502 
                 3-CF 3 Ph- 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 (CDCl 3 ) 1.28 (3 H, t, J = 7.0 Hz), 1.46 (2 H, dq, J = 4.0 Hz, 12.5 Hz), 1.85 (2 H, brd, J = 12.5 Hz), 1.93 (1 H, m), 2.73 (2 H, dt, J = 2.5 Hz, 12.0 Hz), Hz), 3.61 (2 H, brd, J = 12.0 Hz), 4.15 (2 H, q, J = 7.0 Hz), 6.90 (1 H, d, J = 9.0 Hz), 6.96 (2 H, d, J = 9.0 Hz), 7.03 (2 H, d, J = 9.0 Hz), 7.65 (1 H, t, J = 8.0 Hz), 7.83 (1 H, d, J = 8.0 Hz), 7.86 (1 H, brs), 8.07 (1 H, d, J = 8.0 Hz), 8.14 (1 H, brs), 8.18 (1 H, dd, J = 9.0 Hz, 2.5 Hz), 8.27 (1 H, d, J = 2.5 Hz). 
               
               
                   
               
             
          
         
       
     
       Example 1503 
     Production of N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-methylphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide 
       [1105]    To a suspension of 1-(4-piperonylpiperazin-1-yl)-2-{methyl-[3-methyl-4-(5-nitropyridin-2-yloxy)phenyl]amino}ethanone (2.65 g, 5.10 mmol) in ethyl acetate (50 mL) was added 5% platinum-carbon (0.20 g) under a nitrogen atmosphere, and the resulting mixture was stirred for 11 hours under a hydrogen atmosphere. The platinum-carbon was separated off by filtration using Celite. To a solution of the resulting filtrate in ethyl acetate was added triethylamine (0.78 mL, 5.61 mmol) under ice cooling, and then to the resulting solution was added 4-(trifluoromethyl)benzoyl chloride (0.80 mL, 5.36 mmol). This reaction solution was stirred for 16 hours, and then added a saturated sodium bicarbonate solution. The resulting solution was stirred at room temperature, and after 20 minutes, extracted with ethyl acetate. The ethyl acetate layer was washed with water, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was recrystallized from acetone-diethyl ether, to thereby yield 3.03 g of the title compound. 
         [1106]    Appearance: Pale yellow powder 
         [1107]    Melting point: 153.0-154.5° C.;  1 H NMR (CDCl 3 ) δ 2.12 (3H, s), 2.31-2.52 (4H, m), 3.01 (3H, s), 3.38-3.72 (6H, m), 4.07 (2H, s), 5.95 (2H, s), 6.49-6.61 (2H, m), 6.69-6.78 (2H, m), 6.79-6.88 (2H, m), 6.92 (1H, d, J=8.6 Hz), 7.76 (2H, d, J=8.3 Hz), 7.81-7.90 (1H, m), 7.99 (2H, d, J=8.3 Hz), 8.13 (1H, dd, J=8.8 Hz, 2.6 Hz), 8.23 (1H, d, J=2.6 Hz). 
         [1108]    A crude titled product (5.00 g, 7.6 mmol) obtained using the same procedures was recrystallized from ethanol (15 mL), to thereby yield 3.90 g of the title compound. 
         [1109]    Appearance: Pale yellow powder 
         [1110]    Melting point: 156-158° C. 
         [1111]    The following compounds were produced in the same manner as in Example 1503. 
       Example 1504 
     N-{6-[2-methyl-4-(2-oxo-3-piperonylimidazolidin-1-yl)phenoxy]pyridin-3-yl}-4-trifluoromethylbenzamide 
       [1112]    mp 188.0-189.0° C. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 286 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
                   
                 mp (° C.) or  1 H NMR 
               
               
                 No. 
                 R 869   
                 R 870   
                 R 871   
                 R 872   
                 R 873   
                 M 
                 Form 
                 (solvent) δ ppm 
               
               
                   
               
               
                 1505 
                 —Cl 
                 —Cl 
                 cyclopentyl 
                 —H 
                 piperonyl 
                 2 
                 oxalate 
                 mp 135-139 
               
               
                 1506 
                 —Cl 
                 —Cl 
                 —(CH 2 ) 2 CH 3   
                 —H 
                 piperonyl 
                 2 
                 free 
                   1 H NMR (DMSO-d 6 ) 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 0.86 (3 H, t, J = 7.5 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 1.56 (2 H, q, J = 7.5 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 2.27 (2 H, brs), 2.64 (2 H, t, 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 J = 7.4 Hz), 2.83 (2 H, t, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 7.4 Hz), 3.37-3.48 (6 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 3.84 (2 H, t, J = 7.5 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 5.98 (2 H, s), 6.36 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 9.1 Hz), 6.74 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 7.9 Hz), 6.83 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 7.9 Hz), 6.86 (1 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 7.16 (2 H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 7.30 (2 H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 7.70 (1 H, dd, 9.1 Hz, 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 2.6 Hz), 7.81 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 8.4 Hz), 7.93 (1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 8.4 Hz, 1.9 Hz), 8.19 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 d, J = 1.9 Hz), 8.43 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 J = 2.6 Hz), 10.27 (1 H, s). 
               
               
                 1507 
                 —Cl 
                 —Cl 
                 —CH 3   
                 —OCH 3   
                 piperonyl 
                 2 
                 free 
                   1 H NMR (CDCl 3 ) 2.34- 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 2.41 (4 H, m), 2.62-2.68 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 m), 2.95-3.01 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 3.34 (3 H, s), 3.38-3.45 (4 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 m), 3.62-3.65 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 3.75 (3 H, s), 5.94 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 6.25 (1 H, d, J = 9.2 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 6.70-6.84 (5 H, m), 7.12 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 d, J = 7.6 Hz), 7.53 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 J = 8.2 Hz), 7.67-7.72 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 m), 7.97 (2 H, d, J = 2.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 8.24 (1 H, d, J = 2.5 Hz). 
               
               
                 1508 
                 —CF 3   
                 —H 
                 —CH 3   
                 —OCH 3   
                 piperonyl 
                 2 
                 free 
                   1 H NMR (CDCl 3 ) 2.36- 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 2.37 (4 H, m), 2.62-2.67 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 m), 2.94-2.99 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 3.28-3.45 (7 H, m), 3.60- 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 3.64 (2 H, m), 3.74 (3 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 5.93 (2 H, s), 6.25 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 9.1 Hz), 6.70-6.84 (5 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 m), 7.11 (1 H, d, J = 7.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 7.67-7.75 (3 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 7.97 (2 H, d, J = 7.9 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 8.16-8.32 (2 H, m). 
               
               
                 1509 
                 —Cl 
                 —Cl 
                 —CH 3   
                 —H 
                 benzyl 
                 0 
                 oxalate 
                 mp 228-230 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 287 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
                 mp (° C.) or  1 H NMR 
               
               
                 No. 
                 R 874   
                 R 875   
                 R 876   
                 R 877   
                 R 878   
                 Form 
                 (solvent) δ ppm 
               
               
                   
               
             
          
           
               
                 1510 
                 —Cl 
                 —Cl 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 piperonyl 
                 dioxalate 
                   1 H NMR (DMSO-d 6 ) 2.36- 2.50 (4 H, m), 2.73 (6 H, s), 3.42-3.56 (6 H, m), 3.94 (2 H, s), 4.56 (2 H, s), 5.98 (2 H, s), 6.76 (1 H, d, J = 8.0 Hz), 6.85 (1 H, d, J = 8.0 Hz), 6.88 (1 H, s), 7.13 (1 H, d, J = 8.9 Hz), 7.23 (2 H, d; J = 8.8 Hz), 7.45 (2 H, d, J = 8.8 Hz), 7.83 (1 H, d, J = 8.4 Hz), 7.93 (1 H, dd, J = 8.4 Hz, 2.0 Hz), 8.20-8.25 (2 H, m), 8.52 (1 H, d, J = 2.7 Hz), 10.63 (1 H, s). 
               
               
                   
               
               
                 1511 
                 —CF 3   
                 —H 
                 —CH 3   
                 —H 
                 piperonyl 
                 free 
                   1 H NMR (CDCl 3 ) 2.11 (3 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 s), 2.42-2.48 (4 H, m), 3.45- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 3.48 (4 H, m), 3.66-3.70 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 m), 3.86 (2 H, s), 4.83 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 brs), 5.96 (2 H, s), 6.46- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.52 (2 H, m), 6.71-6.78 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 m), 6.83-6.91 (3 H, m), 7.75- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.82 (3 H, m), 7.99 (2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.1 Hz), 8.16 (1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.9 Hz, 2.8 Hz), 8.22 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 J = 2.8 Hz). 
               
               
                 1512 
                 —Cl 
                 —Cl 
                 —CH 3   
                 —CH 3   
                 piperonyl 
                 hydro- 
                 mp 183-185 dec 
               
               
                   
                   
                   
                   
                   
                   
                 chloride 
                   
               
               
                 1513 
                 —CF 3   
                 —H 
                 —CH 3   
                 —C 2 H 5   
                 benzyl 
                 maleate 
                 mp 165-167 
               
               
                 1514 
                 —Cl 
                 —Cl 
                 —CH 3   
                 —C 2 H 5   
                 benzyl 
                 free 
                 mp 102-105 
               
               
                 1515 
                 —CF 3   
                 —H 
                 —CH 3   
                 —CH 3   
                 benzyl 
                 free 
                 mp 110-111 
               
               
                 1516 
                 —Cl 
                 —Cl 
                 —CH 3   
                 —CH 3   
                 benzyl 
                 free 
                 mp 111-113 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 288 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 879   
                 Form 
                 mp (° C.) or MS 
               
               
                   
               
               
                 1517 
                 3,4-Cl 2 Ph- 
                 maleate 
                 mp 203-205 
               
               
                 1518 
                 3-PhOPh- 
                 free 
                 MS 686 (M +  + H) 
               
               
                 1519 
                 3,5-Cl 2 Ph- 
                 free 
                 MS 662 (M +  + H) 
               
               
                 1520 
                 3,5-(CH 3 ) 2 Ph- 
                 free 
                 MS 622 (M +  + H) 
               
               
                 1521 
                 2,3-(CH 3 ) 2 Ph- 
                 free 
                 MS 622 (M +  + H) 
               
               
                 1522 
                 2,3-Cl 2 Ph- 
                 free 
                 MS 662 (M +  + H) 
               
               
                 1523 
                 1-naphthyl 
                 free 
                 MS 644 (M +  + H) 
               
               
                 1524 
                 2,4-(CH 3 ) 2 Ph- 
                 free 
                 MS 622 (M +  + H) 
               
               
                 1525 
                 3,4-(CH 3 ) 2 Ph- 
                 free 
                 MS 622 (M +  + H) 
               
               
                 1526 
                 3,4-F 2 Ph- 
                 free 
                 MS 630 (M +  + H) 
               
               
                 1527 
                 3-CF 3 Ph- 
                 free 
                 MS 663 (M +  + H) 
               
               
                 1528 
                 3-CF 3 OPh- 
                 free 
                 MS 678 (M +  + H) 
               
               
                 1529 
                 4-CF 3 OPh- 
                 free 
                 MS 678 (M +  + H) 
               
               
                 1530 
                 3-ClPhOCH 2 — 
                 free 
                 MS 658 (M +  + H) 
               
               
                 1531 
                 2-quinolyl 
                 free 
                 MS 645 (M +  + H) 
               
               
                 1532 
                 4-quinolyl 
                 free 
                 MS 645 (M +  + H) 
               
               
                 1533 
                 1-isoquinolyl 
                 free 
                 MS 645 (M +  + H) 
               
               
                 1534 
                 3-isoquinolyl  
                 free 
                 MS 645 (M +  + H) 
               
               
                 1535 
                 3,4-Cl 2 PhCH 2 — 
                 free 
                 MS 676 (M +  + H) 
               
               
                 1536 
                 2,4-Cl 2 PhCH 2 — 
                 free 
                 MS 676 (M +  + H) 
               
               
                 1537 
                 3,5-(CF 3 ) 2 Ph- 
                 free 
                 MS 731 (M +  + H) 
               
               
                 1538 
                 2,4-Cl 2 PhOCH 2 — 
                 free 
                 MS 691 (M +  + H) 
               
               
                 1539 
                 4-CH 3 OPh- 
                 free 
                 MS 624 (M +  + H) 
               
               
                 1540 
                 4-CH 3 PhCH 2 — 
                 free 
                 MS 622 (M +  + H) 
               
               
                 1541 
                 PhOCH 2 — 
                 free 
                 MS 624 (M +  + H) 
               
               
                 1542 
                 3-pyridyl 
                 free 
                 MS 595 (M +  + H) 
               
               
                 1543 
                 —CH(CH 3 ) 2   
                 free 
                 MS 560 (M +  + H) 
               
               
                 1544 
                 cyclopentyl 
                 free 
                 MS 586 (M +  + H) 
               
               
                 1545 
                 cyclohexyl 
                 free 
                 MS 600 (M +  + H) 
               
               
                 1546 
                 cycloheptyl 
                 free 
                 MS 614 (M +  + H) 
               
               
                 1547 
                 cycloheptylmethyl 
                 free 
                 MS 628 (M +  + H) 
               
               
                 1548 
                 3-CH 3 Ph- 
                 free 
                 MS 608 (M +  + H) 
               
               
                 1549 
                 3-(CH 3 ) 2 NPh- 
                 free 
                 MS 637 (M +  + H) 
               
               
                 1550 
                 4-(CH 3 ) 2 NPh- 
                 free 
                 MS 637 (M +  + H) 
               
               
                 1551 
                 2,5-(CH 3 ) 2 Ph- 
                 free 
                 MS 622 (M +  + H) 
               
               
                 1552 
                 —CH(CH 3 )Ph 
                 free 
                 MS 622 (M +  + H) 
               
               
                 1553 
                 —C(CH 3 ) 3   
                 free 
                 MS 574 (M +  + H) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 289 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 880   
                 MS (M +  + H) 
               
               
                   
               
               
                 1554 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 626 
               
               
                   
               
               
                 1555 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 681 
               
               
                   
               
               
                 1556 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 681 
               
               
                   
               
               
                 1557 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 663 
               
               
                   
               
               
                 1558 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 646 
               
               
                   
               
               
                 1559 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 677 
               
               
                   
               
               
                 1560 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 661 
               
               
                   
               
               
                 1561 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 621 
               
               
                   
               
               
                 1562 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 601 
               
               
                   
               
               
                 1563 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 660 
               
               
                   
               
               
                 1564 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 661 
               
               
                   
               
               
                 1565 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 702 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 290 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 881   
                 MS (M +  + H) 
               
               
                   
               
               
                 1566 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 660 
               
               
                   
               
               
                 1567 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 679 
               
               
                   
               
               
                 1568 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 672 
               
               
                   
               
               
                 1569 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 759 
               
               
                   
               
               
                 1570 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 680 
               
               
                   
               
               
                 1571 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 651 
               
               
                   
               
               
                 1572 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 584 
               
               
                   
               
               
                 1573 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 616 
               
               
                   
               
               
                 1574 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 601 
               
               
                   
               
               
                 1575 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 601 
               
               
                   
               
               
                 1576 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 662 
               
               
                   
               
               
                 1577 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 704 
               
               
                   
               
               
                 1578 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 660 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 291 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                   
                 Example 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 No. 
                 Xb 28   
                 R 882   
                 R 883   
                 R 884   
                 R 885   
                 R 886   
                 MS (M +  + H) 
               
               
                   
                   
               
               
                   
                 1579 
                 —NH— 
                 —H 
                 —H 
                 —H 
                 —H 
                 —H 
                 634 
               
               
                   
                 1580 
                 —O— 
                 —H 
                 —H 
                 —H 
                 —H 
                 —H 
                 634 
               
               
                   
                 1581 
                 —O— 
                 —H 
                 —H 
                 —H 
                 —H 
                 —OCH 3   
                 664 
               
               
                   
                 1582 
                 —NH— 
                 —H 
                 —H 
                 —OCH 3   
                 —H 
                 —H 
                 663 
               
               
                   
                 1583 
                 —NH— 
                 —H 
                 —H 
                 —Cl 
                 —H 
                 —H 
                 667 
               
               
                   
                 1584 
                 —NH— 
                 —H 
                 —H 
                 —F 
                 —H 
                 —H 
                 651 
               
               
                   
                 1585 
                 —N(CH 3 )— 
                 —H 
                 —H 
                 —H 
                 —H 
                 —H 
                 647 
               
               
                   
                 1586 
                 —S— 
                 —H 
                 —H 
                 —H 
                 —H 
                 —H 
                 650 
               
               
                   
                 1587 
                 —NH— 
                 —H 
                 —H 
                 —Br 
                 —H 
                 —H 
                 711 
               
               
                   
                 1588 
                 —NH— 
                 —H 
                 —H 
                 —CH 3   
                 —H 
                 —H 
                 648 
               
               
                   
                 1589 
                 —NH— 
                 —H 
                 —H 
                 —OCF 3   
                 —H 
                 —H 
                 717 
               
               
                   
                 1590 
                 —NH— 
                 —H 
                 —OCH 3   
                 —H 
                 —H 
                 —H 
                 664 
               
               
                   
                 1591 
                 —NH— 
                 —H 
                 —Cl 
                 —H 
                 —H 
                 —H 
                 667 
               
               
                   
                 1592 
                 —NH— 
                 —H 
                 —H 
                 —H 
                 —OCH 3   
                 —H 
                 663 
               
               
                   
                 1593 
                 —NH— 
                 —H 
                 —Cl 
                 —H 
                 —Cl 
                 —H 
                 701 
               
               
                   
                 1594 
                 —NH— 
                 —H 
                 —H 
                 —H 
                 —Cl 
                 —H 
                 667 
               
               
                   
                 1595 
                 —NH— 
                 —H 
                 —H 
                 —OCH 3   
                 —OCH 3   
                 —H 
                 693 
               
               
                   
                 1596 
                 —O— 
                 —CH 3   
                 —H 
                 —H 
                 —H 
                 —H 
                 648 
               
               
                   
                 1597 
                 —O— 
                 —H 
                 —H 
                 —OCH 3   
                 —H 
                 —H 
                 664 
               
               
                   
                 1598 
                 —O— 
                 —H 
                 —H 
                 —Cl 
                 —H 
                 —H 
                 668 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 292 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 887   
                 R 888   
                 R 889   
                 R 890   
                 R 891   
                 MS (M +  + H) 
               
               
                   
               
               
                 1599 
                 —H 
                 —OCH 3   
                 —H 
                 —H 
                 —H 
                 650 
               
               
                 1600 
                 —H 
                 —H 
                 —OCH 3   
                 —H 
                 —H 
                 650 
               
               
                 1601 
                 —H 
                 —Cl 
                 —H 
                 —H 
                 —H 
                 654 
               
               
                 1602 
                 —F 
                 —H 
                 —H 
                 —H 
                 —H 
                 638 
               
               
                 1603 
                 —H 
                 —F 
                 —H 
                 —H 
                 —H 
                 638 
               
               
                 1604 
                 —OCH 3   
                 —OCH 3   
                 —H 
                 —H 
                 —H 
                 680 
               
               
                 1605 
                 —OCH 3   
                 —H 
                 —H 
                 —OCH 3   
                 —H 
                 680 
               
               
                 1606 
                 —H 
                 —OCH 3   
                 —OCH 3   
                 —H 
                 —H 
                 680 
               
               
                 1607 
                 —Cl 
                 —H 
                 —H 
                 —H 
                 —Cl 
                 688 
               
               
                 1608 
                 —H 
                 —Cl 
                 —Cl 
                 —H 
                 —H 
                 688 
               
               
                 1609 
                 —F 
                 —H 
                 —H 
                 —H 
                 —F 
                 656 
               
               
                 1610 
                 —H 
                 —F 
                 —H 
                 —F 
                 —H 
                 656 
               
             
          
           
               
                 1611 
                 —H 
                 —OCH 2 O— 
                 —H 
                 —H 
                 664 
               
             
          
           
               
                 1612 
                 —H 
                 —OCH 3   
                 —OCH 3   
                 —OCH 3   
                 —H 
                 711 
               
               
                 1613 
                 —H 
                 —OCH 3   
                 —H 
                 —OCH 3   
                 —H 
                 681 
               
               
                 1614 
                 —H 
                 —CF 3   
                 —H 
                 —H 
                 —H 
                 689 
               
               
                   
               
             
          
         
       
     
       Example 1615 
     Production of 3,4-dichloro-N-[6-(2-fluoro-4-{methyl[2-oxo-2-(4-piperonylpiperazin-1-yl)ethyl]amino}phenoxy)pyridin-3-yl]benzenesulfonamide 
       [1113]    To a solution of 2-{[4-(5-aminopyridin-2-yloxy)-3-fluorophenyl]methylamino}-1-(4-piperonylpiperazin-1-yl)ethanone (15.85 g, 1.9 mmol) in dichloromethane (150 mL) were added 3,4-dichlorobenzenesulfonyl chloride (12.92 g, 1.9 mmol) and pyridine (11 mL, 12.4 mmol), and the resulting solution was stirred for 1 hour at room temperature. 
         [1114]    Water was added to the reaction solution, and extracted with ethyl acetate. The organic layer was washed with water and brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate), and recrystallized from ethanol, to thereby yield 5.6 g of the title compound. 
         [1115]    Appearance: White powder; Melting point: 185.6-187.0° C.; 
         [1116]      1 H NMR (CDCl 3 ) δ 2.45 (4H, t, J=4.6 Hz), 3.01 (3H, s), 3.44 (2H, s), 3.47 (2H, brs), 3.64 (2H, brs), 4.07 (2H, s), 5.95 (2H, s), 6.33-6.44 (2H, m), 6.71-6.78 (2H, m), 6.84-6.87 (2H, m), 6.98 (1H, t, J=9.1 Hz), 7.47 (1H, dd, J=8.4 Hz, 2.0 Hz), 7.51 (2H, dd, J=8.4 Hz, 2.8 Hz), 7.68 (1H, d, J=2.1 Hz), 7.83 (1H, d, J=1.8 Hz); MS 701 (M + ). 
         [1117]    The following compounds were produced in the same manner as in Example 1615. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 293 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 892   
                 R 893   
                 R 894   
                 R 895   
                 M 
                   1 H NMR (solvent) δppm 
               
               
                   
               
               
                 1616 
                 —CH 3   
                 —H 
                 —H 
                 benzyl 
                 2 
                 (CDCl 3 ) 2.29-2.37(2 H, m), 2.37-2.45(5 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 2.61(2 H, t, J = 7.9 Hz), 2.95(2 H, t, J = 7.9 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 3.35-3.42(2 H, m), 3.50(2 H, s), 3.59- 
               
               
                   
                   
                   
                   
                   
                   
                 3.68(2 H, m), 6.58(1 H, brs), 6.83(1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.8 Hz), 7.00(2 H, d, J = 8.4 Hz), 7.18- 
               
               
                   
                   
                   
                   
                   
                   
                 7.38(9 H, m), .755-7.63(3 H, m), 7.68(1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 2.8 Hz). 
               
               
                 1617 
                 —CF 3   
                 —H 
                 —H 
                 benzyl 
                 0 
                 (CDCl 3 ) 2.46(4 H, brs), 3.54(2 H, s), 3.54(2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs), 3.79(2 H, brs), 6.88(1 H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.10(2 H, d, J = 8.6 Hz), 7.28-7.33(5 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.42(2 H, d, J = 8.6 Hz), 7.59(1 H, dd, J = 8.7 
               
               
                   
                   
                   
                   
                   
                   
                 Hz, 2.8 Hz), 7.73(2 H, d, J = 8.4 Hz), 7.74(1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 s), 7.86(2 H, d, J = 8.4 Hz). 
               
               
                 1618 
                 —CF 3   
                 —H 
                 —CH 3   
                 piperonyl 
                 2 
                 (DMSO-d 6 ) 1.96(3 H, s), 2.20-2.40(4 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 2.56-2.62(2 H, m), 2.73-2.78(2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 3.32(2 H, s), 3.37-3.43(4 H, m), 5.99(2 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 6.74(1 H, dd, J = 7.9 Hz, 1.3 Hz), 6.82- 
               
               
                   
                   
                   
                   
                   
                   
                 6.93(4 H, m), 7.05(1 H, dd, J = 8.2 Hz, 1.9 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.12(1 H, s), 7.52(1 H, dd, J = 8.8 Hz, 2.7 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.73(1 H, d, J = 2.7 Hz), 7.89-7.98(4 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 10.45(1 H, brs). 
               
               
                 1619 
                 —Cl 
                 —Cl 
                 —OCH 3   
                 piperonyl 
                 2 
                 (DMSO-d 6 ) 2.20-2.40(4 H, m), 2.58-2.64(2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 2.75-2.81(2 H, m), 3.37-3.43(6 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 3.60(3 H, s), 5.97(2 H, s), 6.70-7.00(7 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.47(1 H, dd, J = 8.8 Hz, 2.8 Hz), 7.61(1 H, dd, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.5 Hz, 2.1 Hz), 7.68(1 H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.82-7.86(2 H, m), 10.32(1 H, brs). 
               
               
                 1620 
                 —CF 3   
                 —H 
                 —OCH 3   
                 piperonyl 
                 2 
                 (DMSO-d 6 ) 2.20-2.40(4 H, m), 2.55-2.70(2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 2.75-2.85(2 H, m), 3.30-3.50(6 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 3.58(3 H, s), 5.97(2 H, s), 6.71-7.00(7 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.47(1 H, dd, J = 8.8 Hz, 2.7 Hz), 7.67(1 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 2.7 Hz), 7.87-7.98(4 H, m), 10.40(1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs). 
               
               
                 1621 
                 —Cl 
                 —Cl 
                 —CH 3   
                 piperonyl 
                 2 
                 (DMSO-d 6 ) 1.97(3 H, s), 2.20-2.35(4 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 2.56-2.62(2 H, m), 2.73-2.79(2 H, m), 3.37- 
               
               
                   
                   
                   
                   
                   
                   
                 3.50(6 H, m), 5.98(2 H, s), 6.72-6.76(1 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 6.82-6.94(4 H, m), 7.00-7.13(2 H, m), 7.52(1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 dd, J = 8.8 Hz, 2.8 Hz), 7.62(1 H, dd, J = 8.4 
               
               
                   
                   
                   
                   
                   
                   
                 Hz, 2.1 Hz), 7.72(1 H, d, J = 2.6 Hz), 7.83(1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 2.1 Hz), 7.85(1 H, d, J = 8.5 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 10.36(1 H, brs). 
               
               
                 1622 
                 —CF 3   
                 —H 
                 —F 
                 piperonyl 
                 2 
                 (DMSO-d 6 ) 2.20-2.35(4 H, m), 2.60-2.66(2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 2.78-2.84(2 H, m), 3.39(2 H, s), 3.42- 
               
               
                   
                   
                   
                   
                   
                   
                 3.50(4 H, m), 5.99(2 H, s), 6.72-6.76(1 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 6.83-6.86(2 H, m), 7.03-7.24(4 H, m), 7.55(1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 dd, J = 8.8 Hz, 2.7 Hz), 7.75(1 H, d, J = 2.7 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.90-7.99(4 H, m), 10.52(1 H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 294 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                 mp (° C.) or  1 H NMR (solvent) 
               
               
                 No. 
                 R 896   
                 R 897   
                 R 898   
                 δppm 
               
               
                   
               
               
                 1623 
                 —CF 3   
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 mp 208.0-209.0 
               
               
                   
               
               
                 1624 
                 —Cl 
                 —Cl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (CDCl 3 ) 1.70(1 H, brs), 2.42(4 H, t, J = 5.1 Hz), 3.39(4 H, t, J = 5.1 Hz), 3.43(2 H, s), 4.38(2 H, d, J = 5.4 Hz), 4.80(1 H, t, J = 5.4 Hz), 5.94(2 H, s), 6.73(2 H, s), 6.84(1 H, s), 6.86(1 H, d, J = 8.5 Hz), 7.00(2 H, d, J = 8.6 Hz), 7.27(2 H, d, J = 8.6 Hz), 7.51(2 H, d, J = 2.5 Hz), 7.58(1 H, dd, J = 8.7 Hz, 2.7 Hz), 7.73(1 H, dd, J = 2.7 Hz, 0.7 Hz), 7.83(1 H, t, J = 2.5 Hz). 
               
               
                   
               
               
                 1625 
                 —Cl 
                 —Cl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (DMSO-d 6 ) 2.20- 2.35(4 H, m), 2.56-2.62(2 H, m), 2.77-2.82(2 H, m), 3.30-3.50(6 H, m), 5.98(2 H, s), 6.70-6.80(1 H, m), 6.82-6.90(3 H, m), 6.93- 6.97(2 H, m), 7.05-7.10(1 H, m), 7.24-7.35(1 H, m), 7.54(1 H, dd, J = 8.8 Hz, 2.8 Hz), 7.64(1 H, dd, J = 8.5 Hz, 2.0 Hz), 7.80(1 H, d, J = 2.8 Hz), 7.86(1 H, d, J = 8.4 Hz), 7.89(1 H, d, J = 2.0 Hz), 10.43(1 H, brs). 
               
               
                   
               
               
                 1626 
                 —CF 3   
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (DMSO-d 6 ) 2.20- 2.30(4 H, m), 2.55-2.61(2 H, m), 2.76-2.82(2 H, m), 3.30-3.40(6 H, m), 5.98(2 H, s), 6.70-6.80(1 H, m), 6.82-6.95(5 H, m), 7.05(1 H, d, J = 7.7 Hz), 7.23-7.30(1 H, m), 7.54(1 H, dd, J = 8.8 Hz, 2.8 Hz), 7.80(1 H, d, J = 2.8 Hz), 7.90- 7.99(4 H, m), 10.52(1 H, brs). 
               
               
                   
               
               
                 1627 
                 —Cl 
                 —Cl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (DMSO-d 6 ) 2.25- 2.45(4 H, m), 3.42(2 H, s), 3.50- 3.75(4 H, m), 5.99(2 H, s), 6.75- 6.80(1 H, m), 6.83-6.88(2 H, m), 7.00(1 H, d, J = 8.8 Hz), 7.05- 7.10(1 H, m), 7.25-7.29(1 H, m), 7.35-7.65(6 H, m), 7.80(1 H, d, J = 2.7 Hz), 7.86(1 H, d, J = 8.4 Hz), 7.90(1 H, d, J = 2.1 Hz), 10.44 (1 H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 295 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 899   
                 R 900   
                 M 
                 mp (° C.) or  1 H NMR (DMSO-d 6 ) δppm 
               
               
                   
               
               
                 1628 
                 4-CF 3 Ph- 
                 piperonyl 
                 2 
                   1 H NMR 1.89-2.06(5 H, m), 3.17-3.31(2 H, 
               
               
                   
                   
                   
                   
                 m), 3.52-3.71(2 H, m), 4.39(2 H, s), 5.98(2 H, 
               
               
                   
                   
                   
                   
                 m), 6.75(1 H, dd, J = 1.2 Hz, 7.9 Hz), 
               
               
                   
                   
                   
                   
                 6.83(1 H, d, J = 1.2 Hz), 6.86(1 H, d, J = 7.9 
               
               
                   
                   
                   
                   
                 Hz), 6.92(1 H, d, J = 8.6 Hz), 6.95(1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.8 Hz), 7.09(1 H, dd, J = 2.5 Hz, 8.6 Hz), 
               
               
                   
                   
                   
                   
                 7.18(1 H, d, J = 2.5 Hz), 7.53(1 H, dd, J = 2.8 
               
               
                   
                   
                   
                   
                 Hz, 8.8 Hz), 7.75(1 , d, J = 2.8 Hz), 
               
               
                   
                   
                   
                   
                 7.90(2 H, d, J = 8.4 Hz), 7.96(2 H, d, J = 8.4 
               
               
                   
                   
                   
                   
                 Hz), 10.47(1 H, s). 
               
               
                 1629 
                 3,4-Cl 2 Ph- 
                 piperonyl 
                 2 
                   1 H NMR (1.89-2.09(5 H, m), 3.19-3.33(2 H, 
               
               
                   
                   
                   
                   
                 m), 3.50-3.71(2 H, m), 4.39(2 H, s), 5.98(2 H, 
               
               
                   
                   
                   
                   
                 s), 6.73-6.78(1 H, m), 6.83(1 H, d, J = 1.3 
               
               
                   
                   
                   
                   
                 Hz), 6.86(1 H, d, J = 7.9 Hz), 6.93(1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.6 Hz), 6.97(1 H, d, J = 8.8 Hz), 7.10(1 H, d, 
               
               
                   
                   
                   
                   
                 J = 2.4 Hz, 8.6 Hz), 7.19(1 H, d, J = 2.4 Hz), 
               
               
                   
                   
                   
                   
                 7.53(1 H, dd, J = 2.7 Hz, 8.8 Hz), 7.62(1 H, 
               
               
                   
                   
                   
                   
                 dd, J = 2.1 Hz, 8.4 Hz), 7.75(1 H, d, J = 2.7 
               
               
                   
                   
                   
                   
                 Hz), 7.83(1 H, d, J = 2.1 Hz), 7.85(1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.4 Hz), 10.37(1 H, s). 
               
               
                 1630 
                 4-CF 3 Ph- 
                 piperonyl 
                 1 
                 mp 163.0-164.0 
               
               
                 1631 
                 3,4-Cl 2 Ph- 
                 piperonyl 
                 1 
                 mp 190.5-191.0 
               
               
                 1632 
                 4-CF 3 Ph- 
                 3,4-(CH 3 O) 2 PhCH 2 — 
                 2 
                 mp 141.0-143.0 
               
               
                 1633 
                 3,4-Cl 2 Ph- 
                 3,4-(CH 3 O) 2 PhCH 2 — 
                 2 
                 mp 135.0-136.0 
               
               
                   
               
               
                 1634 
                 3,4-Cl 2 Ph- 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2 
                 mp 181.0-183.0 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 296 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                 R 901   
                 R 902   
                 M 
                   1 H NMR (CDCl 3 ) δppm 
               
               
                   
               
               
                 1635 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 0 
                 1.27(3 H, t, J = 7.1 Hz), 1.84-2.05(4 H, m), 2.06(3 H, s), 
               
               
                   
                   
                   
                   
                 2.40-2.48(1 H, m), 2.71-2.81(2 H, m), 3.56-3.61(2 H, m), 
               
               
                   
                   
                   
                   
                 4.16(2 H, q, J = 7.1 Hz), 6.74-6.79(3 H, m), 6.89(1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.6 Hz), 7.47-7.57(4 H, m), 7.76-7.79(2 H, m). 
               
               
                 1636 
                 4-CF 3 Ph- 
                 —CH 3   
                 0 
                 1.27(3 H, t, J = 7.1 Hz), 1.84-2.00(4 H, m), 2.03(3 H, s), 
               
               
                   
                   
                   
                   
                 2.42-2.51(1 H, m), 2.70-2.79(2 H, m), 3.55-3.60(2 H, m), 
               
               
                   
                   
                   
                   
                 4.16(2 H, q, J = 7.1 Hz), 6.68-6.78(3 H, m), 6.87(1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.6 Hz), 7.55(1 H, dd, J = 8.7 Hz, 2.6 Hz), 7.67(2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.2 Hz), 7.79-7.84(3 H, m), 8.10(1 H, s). 
               
               
                 1637 
                 3,4-Cl 2 Ph- 
                 —H 
                 1 
                 1.27(3 H, t, J = 7.1 Hz), 1.39-1.48(2 H, m), 1.81-1.92(3 H, 
               
               
                   
                   
                   
                   
                 m), 2.29(2 H, d, J = 6.9 Hz), 2.71(2 H, dd, J = 12.2 Hz, 9.9 
               
               
                   
                   
                   
                   
                 Hz), 3.59(2 H, d, J = 12.4 Hz), 4.15(2 H, q, J = 7.3 Hz), 
               
               
                   
                   
                   
                   
                 6.78(1 H, d, J = 8.7 Hz), 6.90-6.98(4 H, m), 7.50(2 H, d, J = 
               
               
                   
                   
                   
                   
                 1.2 Hz), 7.55(1 H, dd, J = 8.7 Hz, 2.6 Hz), 7.78-7.81(3 H, 
               
               
                   
                   
                   
                   
                 m). 
               
               
                 1638 
                 4-CF 3 Ph- 
                 —H 
                 1 
                 1.27(3 H, t, J = 7.1 Hz), 1.36-1.48(2 H, m), 1.81-1.92(3 H, 
               
               
                   
                   
                   
                   
                 m), 2.29(2 H, d, J = 6.9 Hz), 2.70(2 H, dd, J = 12.2 Hz, 9.9 
               
               
                   
                   
                   
                   
                 Hz), 3.59(2 H, d, J = 12.2 Hz), 4.15(2 H, q, J = 7.3 Hz), 
               
               
                   
                   
                   
                   
                 6.75(1 H, d, J = 8.9 Hz), 6.89-6.97(4 H, m), 7.55(1 H, dd, J = 
               
               
                   
                   
                   
                   
                 8.7 Hz, 2.6 Hz), 7.68(2 H, d, J = 8.7 Hz), 7.79-7.85(4 H, 
               
               
                   
                   
                   
                   
                 m). 
               
               
                 1639 
                 4-CF 3 Ph- 
                 —OCH 3   
                 1 
                 1.27(3 H, t, J = 7.1 Hz), 1.30-1.48(2 H, m), 1.82-2.05(3 H, 
               
               
                   
                   
                   
                   
                 m), 2.29(2 H, d, J = 6.9 Hz), 2.69-2.77(2 H, m), 3.60(2 H, d, 
               
               
                   
                   
                   
                   
                 J = 12.2 Hz), 3.68(3 H, s), 4.15(2 H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 6.48(1 H, dd, J = 8.6 Hz, 2.5 Hz), 6.56(1 H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                 6.76(1 H, d, J = 8.7 Hz), 6.94(1 H, d, J = 8.7 Hz), 7.54(1 H, 
               
               
                   
                   
                   
                   
                 dd, J = 8.7 Hz, 2.8 z), 7.66-7.73(4 H, m), 7.83(2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.2 Hz). 
               
               
                 1640 
                 3,4-Cl 2 Ph- 
                 —OCH 3   
                 1 
                 1.28(3 H, t, J = 7.1 Hz), 1.30-1.48(2 H, m), 1.82-2.05(3 H, 
               
               
                   
                   
                   
                   
                 m), 2.29(2 H, d, J = 6.9 Hz), 2.73(2 H, t, J = 12.0 Hz), 
               
               
                   
                   
                   
                   
                 3.60(2 H, d, J = 12.2 Hz), 3.69(3 H, s), 4.16(2 H, q, J = 7.1 
               
               
                   
                   
                   
                   
                 Hz), 5.29(2 H, s), 6.48(1 H, dd, J = 8.7 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                   
                 6.56(1 H, d, J = 2.6 Hz), 6.77(1 H, d, J = 8.7 Hz), 6.94(1 H, 
               
               
                   
                   
                   
                   
                 d, J = 8.6 Hz), 7.46-7.75(3 H, m), 7.79-7.80(3 H, m). 
               
               
                 1641 
                 4-CF 3 Ph- 
                 —H 
                 0 
                 1.27(3 H, t, J = 7.1 Hz), 1.81-1.94(2 H, m), 2.00-2.05(2 H, 
               
               
                   
                   
                   
                   
                 m), 2.40-2.54(1 H, m), 2.71-2.82(2 H, m), 3.56-3.60(2 H, m), 
               
               
                   
                   
                   
                   
                 4.16(2 H, q, J = 7.1 Hz), 6.78(1 H, d, J = 8.9 Hz), 6.90- 
               
               
                   
                   
                   
                   
                 6.99(5 H, m), 7.56(1 H, dd, J = 8.9 Hz, 2.8 z), 7.70(2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.4 Hz), 7.77(1 H, d, J = 2.8 Hz), 7.84(2 H, d, J = 8.2 Hz). 
               
               
                 1642 
                 3,4-Cl 2 Ph- 
                 —H 
                 0 
                 1.27(3 H, t, J = 7.3 Hz), 1.89-1.94(2 H, m), 2.01-2.05(2 H, 
               
               
                   
                   
                   
                   
                 m), 2.38-2.54(1 H, m), 2.72-2.82(2 H, m), 3.56-3.61(2 H, m), 
               
               
                   
                   
                   
                   
                 4.16(2 H, q, J = 7.1 Hz), 6.80(1 H, d, J = 8.7 Hz), 6.91- 
               
               
                   
                   
                   
                   
                 7.00(4 H, m), 7.26(1 H, brs), 7.51-7.58(3 H, m), 7.77(1 H, d, 
               
               
                   
                   
                   
                   
                 J = 2.8 Hz), 7.82(1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 297 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 903   
                 R 904   
                 M 
                   1 H NMR (CDCl 3 ) δppm 
               
               
                   
               
               
                 1643 
                 4-CF 3 Ph- 
                 —CH 3   
                 1 
                 1.27(3 H, t, J = 7.1 Hz), 1.38-1.43(2 H, m), 1.80- 
               
               
                   
                   
                   
                   
                 2.01(3 H, m), 2.02(3 H, s), 2.29(2 H, d, J = 6.9 Hz), 
               
               
                   
                   
                   
                   
                 2.69(2 H, t, J = 12.0 Hz), 3.58(2 H, d, J = 12.0 Hz), 
               
               
                   
                   
                   
                   
                 4.15(2 H, q, J = 7.3 Hz), 6.67-6.87(4 H, m), 7.53- 
               
               
                   
                   
                   
                   
                 7.68(3 H, m), 7.79-7.84(4 H, m). 
               
               
                 1644 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 1 
                 1.27(3 H, t, J = 7.1 Hz), 1.30-1.48(2 H, m), 1.80- 
               
               
                   
                   
                   
                   
                 2.04(3 H, m), 2.05(3 H, s), 2.29(2 H, d, J = 6.9 Hz), 
               
               
                   
                   
                   
                   
                 2.69(2 H, t, J = 12.0 Hz), 3.58(2 H, d, J = 12.0 Hz), 
               
               
                   
                   
                   
                   
                 4.15(2 H, q, J = 7.1 Hz), 6.71-6.79(3 H, m), 6.88(1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.6 Hz), 7.49-7.57(4 H, m), 7.77(2 H, d, J = 2.8 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 298 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 905   
                 R 906   
                 R 907   
                 Form 
                 mp (° C.) 
               
               
                   
               
               
                 1645 
                 4-CF 3 Ph- 
                 —H 
                 —CH 3   
                 hydrochloride 
                 189.0-191.0 
               
               
                 1646 
                 3,4-Cl 2 Ph- 
                 —H 
                 —CH 3   
                 free 
                 180.0-182.0 
               
               
                 1647 
                 4-CF 3 Ph- 
                 —CH 3   
                 —H 
                 free 
                 129.5-131.0 
               
               
                 1648 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 —H 
                 free 
                 129.0-130.0 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 299 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 908   
                 R 909   
                   1 H NMR (DMSO-d 6 ) δppm 
               
               
                   
               
               
                 1649 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 2.20-2.35(4 H, m), 2.60-2.66(2 H, m), 2.77-2.83(2 H, m), 3.39(2 H, s), 3.39-3.50(4 H, m), 5.99(2 H, s), 6.65-6.76(1 H, m), 6.83-6.86(2 H, m), 7.01-7.25(4 H, m), 7.30-7.40(1 H, m), 7.55(1 H, dd, J = 8.8 Hz, 2.8 Hz), 7.72(1 H, dd, J = 8.7 Hz, 2.6 Hz), 7.78(1 H, d, J = 2.3 Hz), 8.00-8.05(1 H, m), 10.65(1 H, brs). 
               
               
                   
               
               
                 1650 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 1.94(3 H, s), 2.20-2.35(4 H, m), 2.56-2.61(2 H, m), 2.72- 2.78(2 H, m), 3.38(2 H, s), 3.38-3.50(4 H, m), 5.98(2 H, s), 6.72-6.75(1 H, m), 6.82-6.91(4 H, m), 7.03-7.12(2 H m), 7.30-7.45(1 H, m), 7.52(1 H, dd, J = 8.8 Hz, 2.2 Hz), 7.71(1 H, dd, J = 8.7 Hz, 2.1 Hz), 7.78(1 H, d, J = 2.7 Hz), 7.98-8.04(1 H, m), 10.58(1 H, brs). 
               
               
                   
               
               
                 1651 
                 3,4-Cl 2 Ph- 
                 —H 
                 2.20-2.35(4 H, m), 2.57-2.63(2 H, m), 2.76-2.82(2 H, m), 
               
               
                   
                   
                   
                 3.39(2 H, s), 3.39-3.43(4 H, m), 5.99(2 H, s), 6.70-6.76(1 H, 
               
               
                   
                   
                   
                 m), 6.82-6.86(2 H, m), 6.93-6.98(3 H, m), 7.22-7.26(2 H, m), 
               
               
                   
                   
                   
                 7.51-7.55(1 H, m), 7.63(1 H, dd, J = 8.5 Hz, 2.0 Hz), 
               
               
                   
                   
                   
                 7.79(1 H, d, J = 2.7 Hz), 7.86(1 H, d, J = 8.5 Hz), 7.88(1 H, 
               
               
                   
                   
                   
                 d, J = 2.1 Hz), 10.41(1 H, brs). 
               
               
                 1652 
                 4-CF 3 Ph- 
                 —H 
                 2.20-2.35(4 H, m), 2.57-2.63(2 H, m), 2.76-2.82(2 H, m), 
               
               
                   
                   
                   
                 3.32(2 H, s), 3.32-3.50(4 H, m), 5.98(2 H, s), 6.70-6.76(1 H, 
               
               
                   
                   
                   
                 m), 6.82-6.86(2 H, m), 6.92-6.98(3 H, m), 7.22-7.25(2 H, m), 
               
               
                   
                   
                   
                 7.52(1 H, dd, J = 8.8 Hz, 2.8 Hz), 7.78(1 H, d, J = 2.7 Hz), 
               
               
                   
                   
                   
                 7.90-7.99(4 H, m), 10.50(1 H, brs). 
               
               
                 1653 
                 3,4-Cl 2 Ph- 
                 —F 
                 2.20-2.35(4 H, m), 2.60-2.66(2 H, m), 2.78-2.84(2 H, m), 
               
               
                   
                   
                   
                 3.39(2 H, s), 3.42-3.50(4 H, m), 5.99(2 H, s), 6.70-6.7(1 H, 
               
               
                   
                   
                   
                 m), 6.82-6.86(2 H, m), 7.04-7.30(4 H, m), 7.55(1 H, dd, J = 
               
               
                   
                   
                   
                 8.8 Hz, 2.8 Hz), 7.63(1 H, dd, J = 8.5 Hz, 2.2 Hz), 7.75(1 H, 
               
               
                   
                   
                   
                 d, J = 2.6 Hz), 7.85(1 H, d, J = 8.5 Hz), 7.88(1 H, d, J = 2.1 
               
               
                   
                   
                   
                 Hz), 10.43(1 H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 300 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 910   
                 R 911   
                 R 912   
                 R 913   
                 mp (° C.) or  1 H NMR (solvent) δppm 
               
               
                   
               
               
                 1654 
                 4-CF 3 Ph- 
                 —F 
                 —H 
                 —CH 3   
                 mp 186.0-188.0 
               
               
                 1655 
                 3,4-Cl 2 Ph- 
                 —F 
                 —H 
                 —C 2 H 5   
                 mp 157.3-160.1 
               
               
                 1656 
                 4-CF 3 Ph- 
                 —F 
                 —H 
                 —C 2 H 5   
                 mp 173.0-176.8 
               
               
                 1657 
                 4-CF 3 Ph- 
                 —OCH 3   
                 —H 
                 —C 2 H 5   
                 mp 179.0-181.0 
               
               
                 1658 
                 3,4-Cl 2 Ph- 
                 —OCH 3   
                 —H 
                 —C 2 H 5   
                 mp 175.0-176.0 
               
               
                 1659 
                 4-CF 3 Ph- 
                 —CH 3   
                 —H 
                 —CH 3   
                 mp 170.0-172.0 
               
               
                 1660 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 —H 
                 —CH 3   
                 mp 170.0-173.0 
               
               
                 1661 
                 3,4-Cl 2 Ph- 
                 —H 
                 —H 
                 —CH 3   
                 mp 135.0-137.0 
               
               
                 1662 
                 4-CF 3 Ph- 
                 —H 
                 —H 
                 —CH 3   
                 mp 189.0-190.0 
               
               
                 1663 
                 4-CF 3 Ph- 
                 —F 
                 —F 
                 —CH 3   
                 mp 159.5-160.0 
               
               
                 1664 
                 3,4-Cl 2 Ph- 
                 —F 
                 —F 
                 —CH 3   
                 mp 136.0-137.0 
               
               
                 1665 
                 Ph- 
                 —H 
                 —H 
                 —CH 3   
                   1 H NMR (CDCl 3 ) 2.41-2.45(4 H, m), 3.01(3 H, 
               
               
                   
                   
                   
                   
                   
                 s), 3.43(2 H, s), 3.47-3.49(2 H, m), 3.63(2 H, 
               
               
                   
                   
                   
                   
                   
                 brs), 4.07(2 H, s), 5.95(2 H, s), 6.63(1 H, brs), 
               
               
                   
                   
                   
                   
                   
                 6.66(2 H, d, J = 9.1 Hz), 6.71-6.77(3 H, m), 
               
               
                   
                   
                   
                   
                   
                 6.85(1 H, brs), 6.93(2 H, d, J = 9.1 Hz), 7.42- 
               
               
                   
                   
                   
                   
                   
                 7.59(4 H, m), 7.68-7.73(3 H, m). 
               
               
                 1666 
                 —(CH 2 ) 3 CH 3   
                 —H 
                 —H 
                 —CH 3   
                   1 H NMR (CDCl 3 ) 0.93(3 H, t, J = 7.3 Hz), 
               
               
                   
                   
                   
                   
                   
                 1.36-1.50(2 H, m), 1.75-1.87(2 H, m), 2.41- 
               
               
                   
                   
                   
                   
                   
                 2.45(4 H, m), 3.01-3.06(5 H, m), 3.44(2 H, s), 
               
               
                   
                   
                   
                   
                   
                 3.47-3.49(2 H, m), 3.63(2 H, brs), 4.09(2 H, s), 
               
               
                   
                   
                   
                   
                   
                 5.95(2 H, s), 6.37(1 H, brs), 6.69(2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 9.1 Hz), 6.72-6.77(2 H, m), 6.82-6.96(2 H, m), 
               
               
                   
                   
                   
                   
                   
                 6.99(2 H, d, J = 9.1 Hz), 7.65(1 H, dd, J = 8.7 
               
               
                   
                   
                   
                   
                   
                 Hz, 2.8 H), 8.00(1 H, d, J = 2.8 Hz). 
               
               
                 1667 
                 4-CH 3 Ph- 
                 —H 
                 —H 
                 —CH 3   
                   1 H NMR (CDCl 3 ) 2.39(3 H, s), 2.41-2.44(4 H, 
               
               
                   
                   
                   
                   
                   
                 m), 3.01(3 H, s), 3.43(2 H, s), 3.47-3.49(2 H, 
               
               
                   
                   
                   
                   
                   
                 m), 3.62(2 H, brs), 4.07(2 H, s), 5.95(2 H, s), 
               
               
                   
                   
                   
                   
                   
                 6.46-6.51(1 H, m), 6.66(2 H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.70-6.77(3 H, m), 6.85(1 H, brs), 6.94(2 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.9 Hz), 7.23(2 H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.50(1 H, dd, J = 8.2 Hz, 2.8 Hz), 7.58(2 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.4 Hz), 7.66(1 H, d, J = 2.6 Hz). 
               
               
                   
               
               
                 1668 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 —H 
                 —CH 3   
                   1 H NMR (DMSO-d 6 ) 2.25-2.45(4 H, m), 2.91(3 H, s), 3.42(6 H, brs), 4.26(2 H, s), 5.99(2 H, s), 6.30-6.40(1 H, m), 6.45-6.55(1 H, m), 6.74-6.77(1 H, m), 6.83-7.05(4 H, m), 7.30-7.45(1 H, m), 7.51(1 H, dd, J = 8.9 Hz, 2.8 Hz), 7.71(1 H, dd, J = 8.7 Hz, 2.5 Hz), 7.79(1 H, d, J = 2.7 Hz), 8.02(1 H, dd, J = 8.9 Hz, 5.9 Hz), 10.60(1 H, brs). 
               
               
                   
               
               
                 1669 
                 3,4-Cl 2 Ph- 
                 —COOCH 3   
                 —H 
                 —C 2 H 5   
                   1 H NMR (DMSO-d 6 ) 1.11(3 H, t, J = 7.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 2.20-2.5(4 H, m), 3.30-3.50(11 H, m), 
               
               
                   
                   
                   
                   
                   
                 4.22(2 H, s), 5.99(2 H, s), 6.75-7.00(7 H, m), 
               
               
                   
                   
                   
                   
                   
                 7.45-7.55(1 H, m), 7.60-7.70(2 H, m), 7.83- 
               
               
                   
                   
                   
                   
                   
                 7.87(2 H, m), 10.31(1 H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 301 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 914   
                 R 915   
                 R 916   
                 R 917   
                   1 H NMR (solvent) δppm 
               
               
                   
               
               
                 1670 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 —CH 3   
                 —H 
                 (DMSO-d 6 ) 2.23(3 H, s), 2.25-2.45(4 H, m), 2.91(3 H, s), 3.41(6 H, brs), 3.83(3 H, s), 4.25(2 H, s), 5.99(2 H, s), 6.30-6.40(1 H, m), 6.45-6.55(1 H, m), 6.75-6.77(1 H, m), 6.83- 6.99(4 H, m), 7.07(1 H, d, J = 8.5 Hz), 7.30- 7.40(1 H, m), 7.48(1 H, d, J = 1.9 Hz), 7.51(1 H, dd, J = 8.8 Hz, 2.7 Hz), 7.74(1 H, d, J = 2.6 Hz), 9.85(1 H, brs). 
               
               
                   
               
               
                 1671 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 —CH 3   
                 —CH 3   
                 (CDCl 3 ) 1.28(3 H, d, J = 6.6 Hz), 2.05(3 H, 
               
               
                   
                   
                   
                   
                   
                 s), 2.08-2.21(1 H, m), 2.33(2 H, brs), 
               
               
                   
                   
                   
                   
                   
                 2.50(1 H, brs), 2.75(3 H, s), 3.29-3.57(3 H, 
               
               
                   
                   
                   
                   
                   
                 m), 3.38(2 H, s), 3.77(1 H, brs), 4.55(1 H, q, J = 
               
               
                   
                   
                   
                   
                   
                 6.6 Hz), 5.94(2 H, s), 6.56-6.59(2 H, m), 
               
               
                   
                   
                   
                   
                   
                 6.68-6.75(2 H, m), 6.79-6.82(2 H, m), 6.89- 
               
               
                   
                   
                   
                   
                   
                 6.93(1 H, m), 7.51-7.52(2 H, m), 7.57(1 H, dd, 
               
               
                   
                   
                   
                   
                   
                 J = 8.9 Hz, 2.8 Hz), 7.71(1 H, dd, J = 2.8 Hz, 
               
               
                   
                   
                   
                   
                   
                 0.5 Hz), 7.79(1 H, dd, J = 1.7 Hz, 0.8 Hz). 
               
               
                 1672 
                 4-CF 3 Ph- 
                 —CH 3   
                 —CH 3   
                 —CH 3   
                 (CDCl 3 ) 1.28(3 H, d, J = 6.4 Hz), 2.07(3 H, 
               
               
                   
                   
                   
                   
                   
                 s), 2.17-2.20(1 H, m), 2.33-2.36(2 H, m), 
               
               
                   
                   
                   
                   
                   
                 2.47-2.49(1 H, m), 2.75(3 H, s), 3.28- 
               
               
                   
                   
                   
                   
                   
                 3.30(1 H, m), 3.38(2 H, s), 3.38-3.50(1 H, m), 
               
               
                   
                   
                   
                   
                   
                 3.52-3.56(1 H, m), 3.77-3.82(1 H, m), 
               
               
                   
                   
                   
                   
                   
                 4.55(1 H, q, J = 6.6 Hz), 5.94(2 H, s), 6.55- 
               
               
                   
                   
                   
                   
                   
                 6.59(2 H, m), 6.68-6.75(2 H, m), 6.78- 
               
               
                   
                   
                   
                   
                   
                 6.82(2 H, m), 6.89-6.92(1 H, m), 7.57(1 H, dd, 
               
               
                   
                   
                   
                   
                   
                 J = 8.7 Hz, 2.8 Hz), 7.70(1 H, dd, J = 2.8 Hz, 
               
               
                   
                   
                   
                   
                   
                 0.5 Hz), 7.73(2 H, d, J = 8.3 Hz), 7.85(2 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.3 Hz). 
               
               
                   
               
               
                 1673 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 —CH 3   
                 —H 
                 (DMSO-d 6 ) 2.20-2.50(4 H, m), 2.91(3 H, s), 3.35-3.50(6 H, m), 4.26(2 H, s), 5.99(2 H, s), 6.20-6.30(1 H, m), 6.45-6.55(1 H, m), 6.75- 6.80(1 H, m), 6.84-7.01(4 H, m), 7.52(1 H, dd, J = 8.8 Hz, 2.7 Hz), 7.79(1 H, d, J = 2.8 Hz), 7.97(1 H, dd, J = 8.2 Hz, 1.5 Hz), 8.09(1 H, d, J = 8.2 Hz), 8.29(1 H, d, J = 1.5 Hz), 10.80(1 H, brs). 
               
               
                   
               
               
                 1674 
                 4-PhOPh- 
                 —F 
                 —CH 3   
                 —H 
                 (DMSO-d 6 ) 2.20-2.45(4 H, m), 2.92(3 H, s), 
               
               
                   
                   
                   
                   
                   
                 3.35-3.50(6 H, m), 4.26(2 H, s), 5.99(2 H, s), 
               
               
                   
                   
                   
                   
                   
                 6.35-6.45(1 H, m), 6.45-6.60(1 H, m), 
               
               
                   
                   
                   
                   
                   
                 6.76(1 H, d, J = 7.9 Hz), 6.83-6.87(2 H, m), 
               
               
                   
                   
                   
                   
                   
                 6.93-7.14(6 H, m), 7.20-7.30(1 H, m), 7.43- 
               
               
                   
                   
                   
                   
                   
                 7.55(3 H, m), 7.68-7.74(3 H, m), 10.17(1 H, 
               
               
                   
                   
                   
                   
                   
                 brs). 
               
               
                 1675 
                 3,4-Cl 2 Ph- 
                 —CF 3   
                 —C 2 H 5   
                 —H 
                 (DMSO-d 6 ) 1.11(3 H, t, J = 6.9 Hz), 2.25- 
               
               
                   
                   
                   
                   
                   
                 2.45(4 H, m), 3.35-3.55(8 H, m), 4.27(2 H, s), 
               
               
                   
                   
                   
                   
                   
                 5.99(2 H, s), 6.67-6.88(5 H, m), 6.94- 
               
               
                   
                   
                   
                   
                   
                 7.05(2 H, m), 7.52(1 H, dd, J = 8.8 Hz, 2.8 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.63(1 H, dd, J = 8.4 Hz, 2.2 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.75(1 H, d, J = 2.7 Hz), 7.83-7.87(2 H, m), 
               
               
                   
                   
                   
                   
                   
                 10.38(1 H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 302 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 918   
                 R 919   
                 R 920   
                 R 921   
                 R 922   
                 Form 
                 Property 
               
               
                   
               
               
                 1676 
                 4-CF 3 Ph- 
                 —F 
                 —F 
                 —H 
                 —CH 3   
                 free 
                 mp 199.0-200.0° C. 
               
               
                 1677 
                 3,4-Cl 2 Ph- 
                 —F 
                 —F 
                 —H 
                 —CH 3   
                 free 
                 mp 198.0-199.0° C. 
               
               
                 1678 
                 4-CF 3 Ph- 
                 —F 
                 —H 
                 —F 
                 —CH 3   
                 free 
                 mp 176.0-177.0° C. 
               
               
                 1679 
                 3,4-Cl 2 Ph- 
                 —F 
                 —H 
                 —F 
                 —CH 3   
                 free 
                 mp 115.0-116.0° C. 
               
               
                 1680 
                 4-CF 3 Ph- 
                 —F 
                 —H 
                 —F 
                 —C 2 H 5   
                 free 
                 mp 173.0-174.0° C. 
               
               
                 1681 
                 3,4-Cl 2 Ph- 
                 —F 
                 —H 
                 —F 
                 —C 2 H 5   
                 free 
                 mp 156.0-157.0° C. 
               
               
                 1682 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 —H 
                 —CH 3   
                 —C 2 H 5   
                 hydro- 
                   1 H NMR (DMSO-d 6 ) δ 0.95(3 H, t, 
               
               
                   
                   
                   
                   
                   
                   
                 chloride 
                 J = 7.0 Hz), 1.97(3 H, s), 2.28(3 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 s), 2.70-4.40(14 H, m), 6.07(2 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.86(1 H, brs), 6.93-7.10(3 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.20-7.40(2 H, m), 7.56(1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.8 Hz, 2.7 Hz), 7.66(1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 8.5 Hz, 2.1 Hz), 7.78(1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 2.6 Hz), 7.85-7.88(2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 10.55(1 H, brs), 11.47(1 H, brs). 
               
               
                 1683 
                 4-CF 3 Ph- 
                 —CH 3   
                 —H 
                 —CH 3   
                 —C 2 H 5   
                 free 
                   1 H NMR (DMSO-d 6 ) δ 0.92(3 H, t, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 J = 7.0 Hz), 1.91(3 H, s), 2.16(3 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 s), 2.20-2.40(4 H, m), 2.98(2 H, q, J = 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.0 Hz), 3.30-3.50(6 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 3.77(2 H, s), 5.98(2 H, s), 6.72- 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.76(2 H, m), 6.82-6.90(3 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.01(1 H, s), 7.51(1 H, dd, J = 8.8 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz, 2.8 Hz), 7.75(1 H, d, J = 2.7 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz), 7.89-7.99(4 H, m), 10.45(1 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 brs). 
               
               
                 1684 
                 3,4-Cl 2 Ph- 
                 —F 
                 —H 
                 —H 
                 —H 
                 hydro- 
                   1 H NMR (DMSO-d 6 ) δ 2.75- 
               
               
                   
                   
                   
                   
                   
                   
                 chloride 
                 3.65(7 H, m), 3.85-4.55(6 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.08(2 H, s), 6.47-6.50(1 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.59(1 H, dd, J = 13.5 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 6.92-7.01(4 H, m), 7.20(1 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.52(1 H, dd, J = 8.7 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.64(1 H, dd ,J = 8.4 Hz, 2.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                   
                 7.76(1 H, d, J = 2.5 Hz), 7.86(1 H, 
               
               
                   
                   
                   
                   
                   
                   
                   
                 d, J = 8.6 Hz), 7.89(1 H, d, J = 2.2 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Hz), 10.45(1 H, s), 10.90(1 H, brs). 
               
               
                 1685 
                 4- 
                 —H 
                 —H 
                 —H 
                 —CH 3   
                 free 
                 MS 646(M +  + H) 
               
               
                   
                 CH 3 OPh- 
               
               
                 1686 
                 1-naphthyl 
                 —H 
                 —H 
                 —H 
                 —CH 3   
                 free 
                 MS 666(M +  + H) 
               
               
                 1687 
                 2-naphthyl 
                 —H 
                 —H 
                 —H 
                 —CH 3   
                 free 
                 MS 666(M +  + H) 
               
               
                 1688 
                 2-CH 3 Ph- 
                 —H 
                 —H 
                 —H 
                 —CH 3   
                 free 
                 MS 630(M +  + H) 
               
               
                 1689 
                 4-FPh- 
                 —H 
                 —H 
                 —H 
                 —CH 3   
                 free 
                 MS 634(M +  + H) 
               
               
                 1690 
                 2-CF 3 Ph- 
                 —H 
                 —H 
                 —H 
                 —CH 3   
                 free 
                 MS 684(M +  + H) 
               
               
                 1691 
                 2-ClPh- 
                 —H 
                 —H 
                 —H 
                 —CH 3   
                 free 
                 MS 650(M +  + H) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 303 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                   
                 Example 
                   
                   
                   
               
               
                   
                 No. 
                 R 923   
                 R 924   
                 MS (M +  + H) 
               
               
                   
                   
               
               
                   
                 1692 
                 2-thienyl 
                 —H 
                 622 
               
               
                   
                 1693 
                 2-CF 3 OPh- 
                 —H 
                 700 
               
               
                   
                 1694 
                 3-CF 3 OPh- 
                 —H 
                 700 
               
               
                   
                 1695 
                 3-CH 3 OPh- 
                 —H 
                 646 
               
               
                   
                 1696 
                 3-FPh- 
                 —H 
                 634 
               
               
                   
                 1697 
                 2,3-Cl 2 Ph- 
                 —H 
                 684 
               
               
                   
                 1698 
                 3-CF 3 Ph- 
                 —H 
                 684 
               
               
                   
                 1699 
                 4-CF 3 OPh- 
                 —H 
                 700 
               
               
                   
                 1700 
                 4-biphenylyl 
                 —H 
                 692 
               
               
                   
                 1701 
                 3,4-(CH 3 O) 2 Ph- 
                 —H 
                 676 
               
               
                   
                 1702 
                 2,5-(CH 3 O) 2 Ph- 
                 —H 
                 676 
               
               
                   
                 1703 
                 3-CH 3 Ph- 
                 —H 
                 630 
               
               
                   
                 1704 
                 2,5-Cl 2 Ph- 
                 —H 
                 684 
               
               
                   
                 1705 
                 3-ClPh- 
                 —H 
                 650 
               
               
                   
                 1706 
                 2,4-Cl 2 Ph- 
                 —H 
                 684 
               
               
                   
                 1707 
                 2,3,4-Cl 3 Ph- 
                 —H 
                 720 
               
               
                   
                 1708 
                 —C 2 H 5   
                 —H 
                 568 
               
               
                   
                 1709 
                 2,6-Cl 2 Ph- 
                 —H 
                 684 
               
               
                   
                 1710 
                 4-CH 3 OOPh- 
                 —F 
                 664 
               
               
                   
                 1711 
                 4-ClPh- 
                 —F 
                 668 
               
               
                   
                 1712 
                 1-naphthyl 
                 —F 
                 684 
               
               
                   
                 1713 
                 2-naphthyl 
                 —F 
                 684 
               
               
                   
                 1714 
                 2-CH 3 Ph- 
                 —F 
                 648 
               
               
                   
                 1715 
                 4-FPh- 
                 —F 
                 652 
               
               
                   
                 1716 
                 2-CF 3 Ph- 
                 —F 
                 702 
               
               
                   
                 1717 
                 2-thienyl 
                 —F 
                 640 
               
               
                   
                 1718 
                 2-ClPh- 
                 —F 
                 668 
               
               
                   
                 1719 
                 2-CF 3 OPh- 
                 —F 
                 718 
               
               
                   
                 1720 
                 3-CF 3 OPh- 
                 —F 
                 718 
               
               
                   
                 1721 
                 2-CNPh- 
                 —F 
                 660 
               
               
                   
                 1722 
                 3-CH 3 OPh- 
                 —F 
                 664 
               
               
                   
                 1723 
                 3-FPh- 
                 —F 
                 652 
               
               
                   
                 1724 
                 2,3-Cl 2 Ph- 
                 —F 
                 702 
               
               
                   
                 1725 
                 3-CF 3 Ph- 
                 —F 
                 702 
               
               
                   
                 1726 
                 4-CF 3 OPh- 
                 —F 
                 718 
               
               
                   
                 1727 
                 4-biphenylyl 
                 —F 
                 710 
               
               
                   
                 1728 
                 3,4-(CH 3 O) 2 Ph- 
                 —F 
                 694 
               
               
                   
                 1729 
                 2,5-(CH 3 O) 2 Ph- 
                 —F 
                 694 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 304 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                   
                 Example 
                   
                   
                   
               
               
                   
                 No. 
                 R 925   
                 R 926   
                 MS (M +  + H) 
               
               
                   
                   
               
               
                   
                 1730 
                 3-CH 3 Ph- 
                 —F 
                 648 
               
               
                   
                 1731 
                 2,5-Cl 2 Ph- 
                 —F 
                 702 
               
               
                   
                 1732 
                 3-ClPh- 
                 —F 
                 668 
               
               
                   
                 1733 
                 2,4-Cl 2 Ph- 
                 —F 
                 702 
               
               
                   
                 1734 
                 —CH 3   
                 —F 
                 572 
               
               
                   
                 1735 
                 2,3,4-Cl 3 Ph- 
                 —F 
                 738 
               
               
                   
                 1736 
                 —(CH 2 ) 3 CH 3   
                 —F 
                 614 
               
               
                   
                 1737 
                 —C 2 H 5   
                 —F 
                 586 
               
               
                   
                 1738 
                 2,6-Cl 2 Ph- 
                 —F 
                 702 
               
               
                   
                 1739 
                 4-CH 3 OPh- 
                 —CH 3   
                 660 
               
               
                   
                 1740 
                 4-ClPh- 
                 —CH 3   
                 664 
               
               
                   
                 1741 
                 1-naphthyl 
                 —CH 3   
                 680 
               
               
                   
                 1742 
                 2-naphthyl 
                 —CH 3   
                 680 
               
               
                   
                 1743 
                 2-CH 3 Ph- 
                 —CH 3   
                 644 
               
               
                   
                 1744 
                 4-FPh- 
                 —CH 3   
                 648 
               
               
                   
                 1745 
                 2-CF 3 Ph- 
                 —CH 3   
                 698 
               
               
                   
                 1746 
                 2-thienyl 
                 —CH 3   
                 636 
               
               
                   
                 1747 
                 2-ClPh- 
                 —CH 3   
                 664 
               
               
                   
                 1748 
                 2-CF 3 OPh- 
                 —CH 3   
                 714 
               
               
                   
                 1749 
                 2-CNPh- 
                 —CH 3   
                 656 
               
               
                   
                 1750 
                 3-CH 3 OPh- 
                 —CH 3   
                 660 
               
               
                   
                 1751 
                 3-FPh- 
                 —CH 3   
                 648 
               
               
                   
                 1752 
                 2,3-Cl 2 Ph- 
                 —CH 3   
                 698 
               
               
                   
                 1753 
                 3-CF 3 Ph- 
                 —CH 3   
                 698 
               
               
                   
                 1754 
                 4-CF 3 OPh- 
                 —CH 3   
                 714 
               
               
                   
                 1755 
                 4-biphenylyl 
                 —CH 3   
                 706 
               
               
                   
                 1756 
                 3,4-(CH 3 O) 2 Ph- 
                 —CH 3   
                 690 
               
               
                   
                 1757 
                 2,5-(CH 3 O) 2 Ph- 
                 —CH 3   
                 690 
               
               
                   
                 1758 
                 3-CH 3 Ph- 
                 —CH 3   
                 644 
               
               
                   
                 1759 
                 2,5-Cl 2 Ph- 
                 —CH 3   
                 698 
               
               
                   
                 1760 
                 3-ClPh- 
                 —CH 3   
                 664 
               
               
                   
                 1761 
                 2,4-Cl 2 Ph- 
                 —CH 3   
                 698 
               
               
                   
                 1762 
                 —CH 3   
                 —CH 3   
                 568 
               
               
                   
                 1763 
                 2,3,4-Cl 3 Ph- 
                 —CH 3   
                 734 
               
               
                   
                 1764 
                 —(CH 2 ) 3 CH 3   
                 —CH 3   
                 610 
               
               
                   
                 1765 
                 —C 2 H 5   
                 —CH 3   
                 582 
               
               
                   
                 1766 
                 2,6-Cl 2 Ph- 
                 —CH 3   
                 698 
               
               
                   
                 1767 
                 2,4,5-Cl 3 Ph- 
                 —H 
                 719 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 305 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                   
                 Example 
                   
                   
                   
               
               
                   
                 No. 
                 R 927   
                 R 928   
                 MS (M +  + H) 
               
               
                   
                   
               
               
                   
                 1768 
                 2,4,6-(CH 3 ) 3 Ph- 
                 —H 
                 658 
               
               
                   
                 1769 
                 4-C 2 H 5 Ph- 
                 —H 
                 644 
               
               
                   
                 1770 
                 2,5-(CH 3 ) 2 Ph- 
                 —H 
                 644 
               
               
                   
                 1771 
                 2-FPh- 
                 —H 
                 634 
               
               
                   
                 1772 
                 2,4,6-(CH 3 ) 3 Ph- 
                 —F 
                 676 
               
               
                   
                 1773 
                 4-CH 3 Ph- 
                 —F 
                 648 
               
               
                   
                 1774 
                 4-C 2 H 5 Ph- 
                 —F 
                 662 
               
               
                   
                 1775 
                 2,5-(CH 3 ) 2 Ph- 
                 —F 
                 662 
               
               
                   
                 1776 
                 2-FPh- 
                 —F 
                 652 
               
               
                   
                 1777 
                 2,4,5-Cl 3 Ph- 
                 —CH 3   
                 732 
               
               
                   
                 1778 
                 2,4,6-(CH 3 ) 3 Ph- 
                 —CH 3   
                 672 
               
               
                   
                 1779 
                 4-CH 3 Ph- 
                 —CH 3   
                 644 
               
               
                   
                 1780 
                 4-C 2 H 5 Ph- 
                 —CH 3   
                 658 
               
               
                   
                 1781 
                 2,5-(CH 3 ) 2 Ph- 
                 —CH 3   
                 658 
               
               
                   
                 1782 
                 2-FPh- 
                 —CH 3   
                 648 
               
               
                   
                 1783 
                 4-BrPh- 
                 —H 
                 696 
               
               
                   
                 1784 
                 —CH(CH 3 ) 2   
                 —H 
                 582 
               
               
                   
                 1785 
                 8-quinolyl 
                 —H 
                 667 
               
               
                   
                 1786 
                 3-CNPh- 
                 —H 
                 641 
               
               
                   
                 1787 
                 4-PhOPh- 
                 —H 
                 708 
               
               
                   
                 1788 
                 3-BrPh- 
                 —H 
                 696 
               
               
                   
                 1789 
                 4-CNPh- 
                 —H 
                 641 
               
               
                   
                 1790 
                 2,4-F 2 Ph- 
                 —H 
                 652 
               
               
                   
                 1791 
                 4-BrPh- 
                 —F 
                 714 
               
               
                   
                 1792 
                 —CH(CH 3 ) 2   
                 —F 
                 600 
               
               
                   
                 1793 
                 8-quinolyl 
                 —F 
                 685 
               
               
                   
                 1794 
                 3-CNPh- 
                 —F 
                 659 
               
               
                   
                 1795 
                 4-CNPh- 
                 —F 
                 659 
               
               
                   
                 1796 
                 2,4-F 2 Ph- 
                 —F 
                 670 
               
               
                   
                 1797 
                 4-BrPh- 
                 —CH 3   
                 710 
               
               
                   
                 1798 
                 —CH(CH 3 ) 2   
                 —CH 3   
                 596 
               
               
                   
                 1799 
                 8-quinolyl 
                 —CH 3   
                 681 
               
               
                   
                 1800 
                 3-CNPh- 
                 —CH 3   
                 655 
               
               
                   
                 1801 
                 3-BrPh- 
                 —CH 3   
                 710 
               
               
                   
                 1802 
                 4-CNPh- 
                 —CH 3   
                 655 
               
               
                   
                 1803 
                 2,4-F 2 ph- 
                 —CH 3   
                 666 
               
               
                   
                 1804 
                 2,4,6-Cl 3 Ph- 
                 —H 
                 720 
               
               
                   
                 1805 
                 2,4,6-Cl 3 Ph- 
                 —F 
                 738 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 306 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                   
                 Example 
                   
                   
                   
               
               
                   
                 No. 
                 R 929   
                 R 930   
                 MS (M +  + H) 
               
               
                   
                   
               
               
                   
                 1806 
                 2,4,5-Cl 3 Ph- 
                 —F 
                 738 
               
               
                   
                 1807 
                 2,4,6-Cl 3 Ph- 
                 —CH 3   
                 734 
               
               
                   
                 1808 
                 Ph- 
                 —F 
                 634 
               
               
                   
                 1809 
                 Ph- 
                 —CH 3   
                 630 
               
               
                   
                 1810 
                 2,5-F 2 Ph- 
                 —F 
                 670 
               
               
                   
                 1811 
                 2,5-F 2 Ph- 
                 —CH 3   
                 666 
               
               
                   
                 1812 
                 2,6-F 2 Ph- 
                 —CH 3   
                 666 
               
               
                   
                 1813 
                 3,4-F 2 Ph- 
                 —CH 3   
                 666 
               
               
                   
                 1814 
                 2,6-F 2 Ph- 
                 —H 
                 652 
               
               
                   
                 1815 
                 3,4-F 2 Ph- 
                 —H 
                 652 
               
               
                   
                 1816 
                 2,6-F 2 Ph- 
                 —F 
                 670 
               
               
                   
                 1817 
                 3,4-F 2 Ph- 
                 —F 
                 670 
               
               
                   
                 1818 
                 —CH 3   
                 —H 
                 554 
               
               
                   
                   
               
               
                   
                 1819 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 680 
               
               
                   
                   
               
               
                   
                 1820 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 660 
               
               
                   
                   
               
               
                   
                 1821 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 698 
               
               
                   
                   
               
               
                   
                 1822 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 694 
               
               
                   
                   
               
               
                   
                 1823 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 674 
               
               
                   
                   
               
               
                   
                 1824 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 718 
               
               
                   
                   
               
               
                   
                 1825 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 668 
               
               
                   
                   
               
               
                   
                 1826 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 698 
               
               
                   
                   
               
               
                   
                 1827 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 718 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 307 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
             
          
           
               
                   
                 Example 
                   
                   
                   
               
               
                   
                 No. 
                 R 931   
                 R 932   
                 MS (M +  + H) 
               
               
                   
                   
               
               
                   
                 1828 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 675 
               
               
                   
                   
               
               
                   
                 1829 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 686 
               
               
                   
                   
               
               
                   
                 1830 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 742 
               
               
                   
                   
               
               
                   
                 1831 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 672 
               
               
                   
                   
               
               
                   
                 1832 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 660 
               
               
                   
                   
               
               
                   
                 1833 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 688 
               
               
                   
                   
               
               
                   
                 1834 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 716 
               
               
                   
                   
               
               
                   
                 1835 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 736 
               
               
                   
                   
               
               
                   
                 1836 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 718 
               
               
                   
                   
               
               
                   
                 1837 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 678 
               
               
                   
                   
               
               
                   
                 1838 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 747 
               
               
                   
                   
               
               
                   
                 1839 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 706 
               
               
                   
                   
               
               
                   
                 1840 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 712 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 308 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                   
                 Example 
                   
                   
                   
               
               
                   
                 No. 
                 R 933   
                 R 934   
                 MS (M +  + H) 
               
               
                   
                   
               
               
                   
                 1841 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 732 
               
               
                   
                   
               
               
                   
                 1842 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 689 
               
               
                   
                   
               
               
                   
                 1843 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 700 
               
               
                   
                   
               
               
                   
                 1844 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 714 
               
               
                   
                   
               
               
                   
                 1845 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 674 
               
               
                   
                   
               
               
                   
                 1846 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 743 
               
               
                   
                   
               
               
                   
                 1847 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 702 
               
               
                   
                   
               
               
                   
                 1848 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 700 
               
               
                   
                   
               
               
                   
                 1849 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 709 
               
               
                   
                   
               
               
                   
                 1850 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 680 
               
               
                   
                   
               
               
                   
                 1851 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 674 
               
               
                   
                   
               
               
                   
                 1852 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 698 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 309 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                   
                 Example 
                   
                   
                   
               
               
                   
                 No. 
                 R 935   
                 R 936   
                 MS (M +  + H) 
               
               
                   
                   
               
               
                   
                 1853 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 682 
               
               
                   
                   
               
               
                   
                 1854 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 710 
               
               
                   
                   
               
               
                   
                 1855 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 707 
               
               
                   
                   
               
               
                   
                 1856 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 727 
               
               
                   
                   
               
               
                   
                 1857 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 698 
               
               
                   
                   
               
               
                   
                 1858 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 692 
               
               
                   
                   
               
               
                   
                 1859 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 716 
               
               
                   
                   
               
               
                   
                 1860 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 700 
               
               
                   
                   
               
               
                   
                 1861 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 728 
               
               
                   
                   
               
               
                   
                 1862 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 725 
               
               
                   
                   
               
               
                   
                 1863 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 723 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 310 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                   
                 Example 
                   
                   
                   
               
               
                   
                 No. 
                 R 937   
                 R 938   
                 MS (M +  + H) 
               
               
                   
                   
               
               
                   
                 1864 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 694 
               
               
                   
                   
               
               
                   
                 1865 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 688 
               
               
                   
                   
               
               
                   
                 1866 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 712 
               
               
                   
                   
               
               
                   
                 1867 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 696 
               
               
                   
                   
               
               
                   
                 1868 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 724 
               
               
                   
                   
               
               
                   
                 1869 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 721 
               
               
                   
                   
               
               
                   
                 1870 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 730 
               
               
                   
                   
               
               
                   
                 1871 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 736 
               
               
                   
                   
               
               
                   
                 1872 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 704 
               
               
                   
                   
               
               
                   
                 1873 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 732 
               
               
                   
                   
               
               
                   
                 1874 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 682 
               
               
                   
                   
               
               
                   
                 1875 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 668 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 311 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                   
                 Example 
                   
                   
                   
               
               
                   
                 No. 
                 R 939   
                 R 940   
                 MS (M +  + H) 
               
               
                   
                   
               
               
                   
                 1876 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 660 
               
               
                   
                   
               
               
                   
                 1877 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 664 
               
               
                   
                   
               
               
                   
                 1878 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 648 
               
               
                   
                   
               
               
                   
                 1879 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 664 
               
               
                   
                   
               
               
                   
                 1880 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 714 
               
               
                   
                   
               
               
                   
                 1881 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 664 
               
               
                   
                   
               
               
                   
                 1882 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 678 
               
               
                   
                   
               
               
                   
                 1883 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 682 
               
               
                   
                   
               
               
                   
                 1884 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 666 
               
               
                   
                   
               
               
                   
                 1885 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 682 
               
               
                   
                   
               
               
                   
                 1886 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 686 
               
               
                   
                   
               
               
                   
                 1887 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 682 
               
               
                   
                   
               
               
                   
                 1888 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 682 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 312 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                   
                 Example 
                   
                   
                   
               
               
                   
                 No. 
                 R 941   
                 R 942   
                 MS (M +  + H) 
               
               
                   
                   
               
               
                   
                 1889 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 674 
               
               
                   
                   
               
               
                   
                 1890 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 678 
               
               
                   
                   
               
               
                   
                 1891 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 662 
               
               
                   
                   
               
               
                   
                 1892 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 678 
               
               
                   
                   
               
               
                   
                 1893 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 728 
               
               
                   
                   
               
               
                   
                 1894 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 678 
               
               
                   
                   
               
               
                   
                 1895 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 732 
               
               
                   
                   
               
               
                   
                 1896 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 760 
               
               
                   
                   
               
               
                   
                 1897 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 756 
               
               
                   
                   
               
               
                   
                 1898 
                 3-BrPh- 
                 —F 
                 714 
               
               
                   
                 1899 
                 4-PhOPh- 
                 —CH 3   
                 722 
               
               
                   
                   
               
               
                   
                 1900 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 690 
               
               
                   
                   
               
               
                   
                 1901 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 686 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 313 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                   
                 Example 
                   
                   
                   
               
               
                   
                 No. 
                 R 943   
                 R 944   
                 MS (M +  + H) 
               
               
                   
                   
               
               
                   
                 1902 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 678 
               
               
                   
                   
               
               
                   
                 1903 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 658 
               
               
                   
                   
               
               
                   
                 1904 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 700 
               
               
                   
                   
               
               
                   
                 1905 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 700 
               
               
                   
                   
               
               
                   
                 1906 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 674 
               
               
                   
                   
               
               
                   
                 1907 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 620 
               
               
                   
                   
               
               
                   
                 1908 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 696 
               
               
                   
                   
               
               
                   
                 1909 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 676 
               
               
                   
                   
               
               
                   
                 1910 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 718 
               
               
                   
                   
               
               
                   
                 1911 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 718 
               
               
                   
                   
               
               
                   
                 1912 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 692 
               
               
                   
                   
               
               
                   
                 1913 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 638 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 314 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                   
                 Example 
                   
                   
                   
               
               
                   
                 No. 
                 R 945   
                 R 946   
                 MS (M +  + H) 
               
               
                   
                   
               
               
                   
                 1914 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 692 
               
               
                   
                   
               
               
                   
                 1915 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 672 
               
               
                   
                   
               
               
                   
                 1916 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 714 
               
               
                   
                   
               
               
                   
                 1917 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 714 
               
               
                   
                   
               
               
                   
                 1918 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 688 
               
               
                   
                   
               
               
                   
                 1919 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 634 
               
               
                   
                   
               
               
                   
                 1920 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 673 
               
               
                   
                   
               
               
                   
                 1921 
                 vinyl 
                 —H 
                 566 
               
               
                   
                 1922 
                 —(CH 2 ) 3 Cl 
                 —H 
                 616 
               
               
                   
                 1923 
                 cyclohexylmethyl 
                 —H 
                 636 
               
               
                   
                   
               
               
                   
                 1924 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 691 
               
               
                   
                   
               
               
                   
                 1925 
                 vinyl 
                 —F 
                 584 
               
               
                   
                 1926 
                 —(CH 2 ) 3 Cl 
                 —F 
                 634 
               
               
                   
                 1927 
                 cyclohexylmethyl 
                 —F 
                 654 
               
               
                   
                   
               
               
                   
                 1928 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 687 
               
               
                   
                   
               
               
                   
                 1929 
                 vinyl 
                 —CH 3   
                 580 
               
               
                   
                 1930 
                 —(CH 2 ) 3 Cl 
                 —CH 3   
                 630 
               
               
                   
                 1931 
                 cyclohexylmethyl 
                 —CH 3   
                 650 
               
               
                   
                 1932 
                 2-BrPh- 
                 —H 
                 696 
               
               
                   
                   
               
               
                   
                 1933 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 656 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 315 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 947   
                 MS (M +  + H) 
               
               
                   
               
               
                 1934 
                 3,5-Cl 2 Ph 
                 684 
               
               
                   
               
               
                 1935 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 683 
               
               
                   
               
               
                 1936 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 682 
               
               
                   
               
               
                 1937 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 702 
               
               
                   
               
               
                 1938 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 687 
               
               
                   
               
               
                 1939 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 681 
               
               
                   
               
               
                 1940 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 723 
               
               
                   
               
               
                 1941 
                 5-isoquinolyl 
                 667 
               
               
                 1942 
                 —CH 2 CF 3   
                 622 
               
               
                   
               
               
                 1943 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 688 
               
               
                   
               
               
                 1944 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 668 
               
               
                   
               
               
                 1945 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 635 
               
               
                   
               
               
                 1946 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 690 
               
               
                   
               
               
                 1947 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 690 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 316 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                   
                 Example 
                   
                   
                   
               
               
                   
                 No. 
                 R 948   
                 R 949   
                 MS (M +  + H) 
               
               
                   
                   
               
               
                   
                 1948 
                 —CH 2 Cl 
                 —H 
                 588 
               
               
                   
                   
               
               
                   
                 1949 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 702 
               
               
                   
                   
               
               
                   
                 1950 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 660 
               
               
                   
                   
               
               
                   
                 1951 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 694 
               
               
                   
                   
               
               
                   
                 1952 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 680 
               
               
                   
                   
               
               
                   
                 1953 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 726 
               
               
                   
                   
               
               
                   
                 1954 
                 benzyl 
                 —H 
                 630 
               
               
                   
                 1955 
                 PhCH═CH— 
                 —H 
                 642 
               
               
                   
                 1956 
                 —(CH 2 ) 2 CH 3   
                 —H 
                 582 
               
               
                   
                 1957 
                 2-BrPh- 
                 —F 
                 714 
               
               
                   
                   
               
               
                   
                 1958 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 674 
               
               
                   
                   
               
               
                   
                 1959 
                 3,5-Cl 2 Ph 
                 —F 
                 702 
               
               
                   
                   
               
               
                   
                 1960 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 701 
               
               
                   
                   
               
               
                   
                 1961 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 700 
               
               
                   
                   
               
               
                   
                 1962 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 720 
               
               
                   
                   
               
               
                   
                 1963 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 705 
               
               
                   
                   
               
               
                   
                 1964 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 699 
               
               
                   
                   
               
               
                   
                 1965 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —F 
                 741 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 317 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 950   
                 MS (M +  + H) 
               
               
                   
               
               
                 1966 
                 5-isoquinolyl 
                 685 
               
               
                 1967 
                 —CH 2 CF 3   
                 640 
               
               
                   
               
               
                 1968 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 706 
               
               
                   
               
               
                 1969 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 686 
               
               
                   
               
               
                 1970 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 653 
               
               
                   
               
               
                 1971 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 694 
               
               
                   
               
               
                 1972 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 708 
               
               
                   
               
               
                 1973 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 708 
               
               
                   
               
               
                 1974 
                 —CH 2 Cl 
                 606 
               
               
                   
               
               
                 1975 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 720 
               
               
                   
               
               
                 1976 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 678 
               
               
                   
               
               
                 1977 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 712 
               
               
                   
               
               
                 1978 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 698 
               
               
                   
               
               
                 1979 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 744 
               
               
                   
               
               
                 1980 
                 benzyl 
                 648 
               
               
                 1981 
                 PhCH═CH— 
                 660 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 318 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                   
                 Example 
                   
                   
                   
               
               
                   
                 No. 
                 R 951   
                 R 952   
                 MS (M +  + H) 
               
               
                   
                   
               
               
                   
                 1982 
                 —(CH 2 ) 2 CH 3   
                 —F 
                 600 
               
               
                   
                 1983 
                 2-BrPh- 
                 —CH 3   
                 710 
               
               
                   
                   
               
               
                   
                 1984 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 670 
               
               
                   
                   
               
               
                   
                 1985 
                 3,5-Cl 2 Ph 
                 —CH 3   
                 698 
               
               
                   
                   
               
               
                   
                 1986 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 697 
               
               
                   
                   
               
               
                   
                 1987 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 696 
               
               
                   
                   
               
               
                   
                 1988 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 716 
               
               
                   
                   
               
               
                   
                 1989 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 701 
               
               
                   
                   
               
               
                   
                 1990 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 695 
               
               
                   
                   
               
               
                   
                 1991 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 737 
               
               
                   
                   
               
               
                   
                 1992 
                 5-isoquinolyl 
                 —CH 3   
                 681 
               
               
                   
                 1993 
                 —CH 2 CF 3   
                 —CH 3   
                 636 
               
               
                   
                   
               
               
                   
                 1994 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 702 
               
               
                   
                   
               
               
                   
                 1995 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 682 
               
               
                   
                   
               
               
                   
                 1996 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 649 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 319 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                   
                 Example 
                   
                   
                   
               
               
                   
                 No. 
                 R 953   
                 R 954   
                 MS (M +  + H) 
               
               
                   
                   
               
               
                   
                 1997 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 690 
               
               
                   
                   
               
               
                   
                 1998 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 704 
               
               
                   
                   
               
               
                   
                 1999 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 704 
               
               
                   
                   
               
               
                   
                 2000 
                 —CH 2 Cl 
                 —CH 3   
                 602 
               
               
                   
                   
               
               
                   
                 2001 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 716 
               
               
                   
                   
               
               
                   
                 2002 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 674 
               
               
                   
                   
               
               
                   
                 2003 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 708 
               
               
                   
                   
               
               
                   
                 2004 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 694 
               
               
                   
                   
               
               
                   
                 2005 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 740 
               
               
                   
                   
               
               
                   
                 2006 
                 benzyl 
                 —CH 3   
                 644 
               
               
                   
                 2007 
                 —CHCl 2   
                 —CH 3   
                 636 
               
               
                   
                 2008 
                 PhCH═CH— 
                 —CH 3   
                 656 
               
               
                   
                 2009 
                 —(CH 2 ) 2 CH 3   
                 —CH 3   
                 596 
               
               
                   
                 2010 
                 2,3,4-F 3 Ph- 
                 —H 
                 670 
               
               
                   
                 2011 
                 2,3,4-F 3 Ph- 
                 —F 
                 688 
               
               
                   
                 2012 
                 2,3,4-F 3 Ph- 
                 —CH 3   
                 684 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 320 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 955   
                 R 956   
                 R 957   
                 Xb 29   
                   1 H NMR (solvent) δppm 
               
               
                   
               
               
                 2013 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 —H 
                 —CO— 
                 (CDCl 3 ) 2.12 (3 H, s), 2.50-2.52 (4 H, m), 
               
               
                   
                   
                   
                   
                   
                 3.45 (2 H, s), 3.72 (2 H, brs), 4.24 (2 H, brs), 
               
               
                   
                   
                   
                   
                   
                 5.95 (2 H, s), 6.71-6.78 (2 H, m), 6.85-6.89 (2 H, 
               
               
                   
                   
                   
                   
                   
                 m), 7.00 (1 H, d, J = 8.6 Hz), 7.42 (1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 8.6 Hz, 2.5 Hz), 7.52-7.55 (3 H, m), 7.60 (1 H, 
               
               
                   
                   
                   
                   
                   
                 dd, J = 8.7 Hz, 2.8 Hz), 7.70 (1 H, d, J = 2.6 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.79 (1 H, brs), 9.17 (1 H, brs). 
               
               
                 2014 
                 4-CF 3 Ph- 
                 —CH 3   
                 —H 
                 —CO— 
                 (CDCl 3 ) 2.10 (3 H, s), 2.50-2.54 (4 H, m), 
               
               
                   
                   
                   
                   
                   
                 3.45 (2 H, s), 3.70-3.73 (2 H, m), 4.23 (2 H, brs), 
               
               
                   
                   
                   
                   
                   
                 5.95 (2 H, s), 6.71-6.78 (2 H, m), 6.83-6.87 (2 H, 
               
               
                   
                   
                   
                   
                   
                 m), 6.99 (1 H, d, J = 8.6 Hz), 7.42(1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 8.6 Hz, 2.6 Hz), 7.54 (1 H, d, J = 2.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.60 (1 H, dd, J = 8.7 Hz, 3.3 Hz), 7.70 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 3.3 Hz), 7.72 (2 H, d, J = 8.9 Hz), 7.85(2 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.3 Hz), 9.18 (1 H, brs). 
               
               
                 2015 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 —CH 3   
                 —CO— 
                 (CDCl 3 ) 2.12 (3 H, brs), 2.20-2.50 (4 H, m), 
               
               
                   
                   
                   
                   
                   
                 3.27-3.46 (9 H, m), 5.95-5.96 (2 H, m), 6.66- 
               
               
                   
                   
                   
                   
                   
                 6.77 (3 H, m), 6.85-7.04 (2 H, m), 7.08-7.22 
               
               
                   
                   
                   
                   
                   
                 (2 H, m), 7.51-7.53 (2 H, m), 7.55-7.72 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                 7.78-7.80 (1 H, m). 
               
               
                 2016 
                 4-CF 3 Ph- 
                 —CH 3   
                 —CH 3   
                 —CO— 
                 (DMSO-d 6 ) 2.11 (3 H, s), 2.19-2.51 (4 H, m), 
               
               
                   
                   
                   
                   
                   
                 3.28-3.71 (9 H, m), 5.96 (2 H, s), 6.65-6.78 (3 H, 
               
               
                   
                   
                   
                   
                   
                 m), 6.85-7.04 (2 H, m), 7.08-7.22 (2 H, m), 7.57- 
               
               
                   
                   
                   
                   
                   
                 7.65 (1 H, m), 7.70-7.73 (3 H, m), 7.84-7.87 (2 H, 
               
               
                   
                   
                   
                   
                   
                 m). 
               
               
                 2017 
                 3,4-Cl 2 Ph- 
                 —H 
                 —SO 2 CH 3   
                 —CH 2 — 
                 (CDCl 3 ) 2.42 (4 H, brs), 3.20 (3 H, s), 3.37- 
               
               
                   
                   
                   
                   
                   
                 3.39 (2 H, m), 3.42 (2 H, s), 3.61 (2 H, brs), 
               
               
                   
                   
                   
                   
                   
                 4.54 (2 H, s), 5.95 (2 H, s), 6.70-6.77 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                 6.83 (1 H, brs), 6.93 (1 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.08 (2 H, d, J = 8.9 Hz), 7.53-7.54 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                 7.58-7.63 (3 H, m), 7.77 (1 H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.88 (1 H, d, J = 1.0 Hz). 
               
               
                 2018 
                 4-CF 3 Ph- 
                 —H 
                 —SO 2 CH 3   
                 —CH 2 — 
                 (CDCl 3 ) 2.42 (4 H, brs), 3.19 (3 H, s), 3.37 (2 H, 
               
               
                   
                   
                   
                   
                   
                 brs), 3.42 (2 H, s), 3.61 (2 H, brs), 4.53 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                 5.95 (2 H, s), 6.73-6.77 (2 H, m), 6.83 (1 H, brs), 
               
               
                   
                   
                   
                   
                   
                 6.92 (1 H, d, J = 8.7 Hz), 7.08(2 H, d, J = 8.7 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.59 (2 H, d, J = 8.7 Hz), 7.61 (1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 8.7 Hz, 2.8 Hz), 7.73-7.76 (3 H, m), 7.87 (2 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.6 Hz). 
               
               
                 2019 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 —SO 2 CH 3   
                 —CH 2 — 
                 (CDCl 3 ) 2.12 (3 H, s), 2.42 (4 H, brs), 3.21 (3 H, 
               
               
                   
                   
                   
                   
                   
                 s), 3.83 (2 H, brs), 3.42 (2 H, s), 3.61 (2 H, brs), 
               
               
                   
                   
                   
                   
                   
                 4.53 (2 H, s), 5.95 (2 H, s), 6.70-6.77 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                 6.83 (1 H, brs), 6.91 (1 H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.98 (1 H, d, J = 8.4 Hz), 7.40-7.50 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                 7.53-7.56 (2 H, m), 7.60 (1 H, dd, J = 8.7 Hz, 
               
               
                   
                   
                   
                   
                   
                 2.8 Hz), 7.71 (1 H, d, J = 2.3 Hz), 7.80 (1 H, dd, 
               
               
                   
                   
                   
                   
                   
                 J = 1.7 Hz, 0.8 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 321 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 958   
                 R 959   
                 R 960   
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 2020 
                 4-CF 3 Ph- 
                 —CH 3   
                 —SO 2 CH 3   
                 (CDCl 3 ) 2.10 (3 H, s), 2.40-2.42 (4 H, m), 3.20 (3 H, s), 
               
               
                   
                   
                   
                   
                 3.37 (2 H, brs), 3.42 (2 H, s), 3.60 (2 H, brs), 4.53 (2 H, 
               
               
                   
                   
                   
                   
                 s), 5.94 (2 H, s), 6.69-6.76 (2 H, m), 6.83 (1 H, brs), 
               
               
                   
                   
                   
                   
                 6.87 (1 H, d, J = 8.7 Hz), 6.96 (1 H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                 7.40 (1 H, d, J = 8.6 Hz), 7.44 (1 H, brs), 7.59 (1 H, dd, 
               
               
                   
                   
                   
                   
                 J = 8.7 Hz, 2.8 Hz), 7.72 (2 H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                 7.73 (1 H, d, J = 2.8 Hz), 7.86 (2 H, d, J = 8.2 Hz). 
               
               
                 2021 
                 4-CF 3 Ph- 
                 —CF 3   
                 —C 2 H 5   
                 (DMSO-d 6 ) 1.11 (3 H, t, J = 6.9 Hz), 2.25-2.45 (4 H, 
               
               
                   
                   
                   
                   
                 m), 3.35-3.55 (8 H, m), 4.26 (2 H, s), 5.99 (2 H, s), 6.67- 
               
               
                   
                   
                   
                   
                 7.04 (7 H, m), 7.52 (1 H, dd, J = 8.8 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                   
                 7.74 (1 H, d, J = 2.6 Hz), 7.88-7.98 (4 H, m), 10.48 (1 H, 
               
               
                   
                   
                   
                   
                 brs). 
               
               
                   
               
               
                 2022 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CF 3   
                 —C 2 H 5   
                 (DMSO-d 6 ) 1.11 (3 H, t, J = 6.9 Hz), 2.25-2.45 (4 H, m), 3.35-3.55 (8 H, m), 4.26 (2 H, s), 5.99 (2 H, s), 6.67- 7.03 (7 H, m), 7.30-7.45 (1 H, m), 7.52 (1 H, dd, J = 8.8 Hz, 2.6 Hz), 7.71 (1 H, dd, J = 8.7 Hz, 2.5 Hz), 7.79 (1 H, d, J = 2.7 Hz), 7.99-8.05 (1 H, m), 10.61 (1 H, brs). 
               
               
                   
               
               
                 2023 
                 3,4-Cl 2 Ph- 
                 —CF 3   
                 —CH 3   
                 (DMSO-d 6 ) 2.20-2.45 (4 H, m), 2.97 (3 H, s), 3.40- 
               
               
                   
                   
                   
                   
                 3.55 (6 H, m), 4.34 (2 H, s), 5.99 (2 H, s), 6.70-6.80 (2 H, 
               
               
                   
                   
                   
                   
                 m), 6.83-6.88 (3 H, m), 6.97 (1 H, d, J = 8.8 Hz), 7.03- 
               
               
                   
                   
                   
                   
                 7.07 (1 H, m), 7.52 (1 H, dd, J = 8.8 Hz, 2.8 Hz), 
               
               
                   
               
               
                 2024 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CF 3   
                 —CH 3   
                 (DMSO-d 6 ) 2.25-2.50 (4 H, m), 2.97 (3 H, s), 3.35- 3.55 (6 H, m), 4.34 (2 H, s), 5.99 (2 H, s), 6.74-7.05 (7 H, m), 7.30-7.45 (1 H, m), 7.52 (1 H, dd, J = 8.8 Hz, 2.7 Hz), 7.71 (1 H, dd, J = 8.7 Hz, 2.5 Hz), 7.80 (1 H, d, J = 2.7 Hz), 8.00-8.06 (1 H, m), 10.61 (1 H, brs). 
               
               
                   
               
               
                 2025 
                 3,4-Cl 2 Ph- 
                 —CN 
                 —CH 3   
                 (DMSO-d 6 ) 2.25-2.50 (4 H, m), 2.94 (3 H, s), 3.35- 
               
               
                   
                   
                   
                   
                 3.50 (6 H, m), 4.33 (2 H, s), 5.99 (2 H, s), 6.74-7.11 (7 H, 
               
               
                   
                   
                   
                   
                 m), 7.50-7.65 (2 H, m), 7.78 (1 H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                 7.83 (1 H, d, J = 8.5 Hz), 7.89 (1 H, d, J = 1.5 Hz), 
               
               
                   
                   
                   
                   
                 10.45 (1 H, brs). 
               
               
                 2026 
                 4-CF 3 Ph- 
                 —OCH 3   
                 —SO 2 CH 3   
                 (CDCl 3 ) 2.43 (4 H, brs), 3.20 (3 H, s), 3.38 (2 H, brs), 
               
               
                   
                   
                   
                   
                 3.43 (2 H, s), 3.61 (2 H, brs), 3.68 (3 H, s), 4.54 (2 H, s), 
               
               
                   
                   
                   
                   
                 5.94 (2 H, s), 6.73-6.76 (2 H, m), 6.80-6.90 (2 H, m), 
               
               
                   
                   
                   
                   
                 7.04 (1 H, d, J = 8.4 Hz), 7.15-7.19 (1 H, m), 7.24- 
               
               
                   
                   
                   
                   
                 7.26 (1 H, m), 7.57 (1 H, dd, J = 8.7 Hz, 2.8 Hz), 7.70- 
               
               
                   
                   
                   
                   
                 7.72 (4 H, m), 7.85 (2 H, d, J = 8.2 Hz). 
               
               
                 2027 
                 3,4-Cl 2 Ph- 
                 —OCH 3   
                 —SO 3 CH 3   
                 (CDCl 3 ) 2.43 (4 H, brs), 3.21 (3 H, s), 3.37 (2 H, brs), 
               
               
                   
                   
                   
                   
                 3.43 (2 H, s), 3.61 (2 H, brs), 3.71 (3 H, s), 4.54 (2 H, s), 
               
               
                   
                   
                   
                   
                 5.95 (2 H, s), 6.73-6.77 (2 H, m), 6.83 (1 H, s), 6.92 (1 H, 
               
               
                   
                   
                   
                   
                 d, J = 8.7 Hz), 7.06 (1 H, d, J = 8.6 Hz), 7.18 (1 H, dd, 
               
               
                   
                   
                   
                   
                 J = 8.4 Hz, 2.3 Hz), 7.25 (2 H, s), 7.52 (2 H, s), 
               
               
                   
                   
                   
                   
                 7.57 (1 H, dd, J = 8.7 Hz, 2.8 Hz), 7.70 (1 H, d, J = 2.6 
               
               
                   
                   
                   
                   
                 Hz), 7.81 (1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 322 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 961   
                 R 962   
                 R 963   
                 R 964   
                 R 965   
                   1 H NMR (DMSO-d 6 ) δ ppm 
               
               
                   
               
               
                 2028 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 —H 
                 —CH 3   
                 —CH 3   
                 1.93 (3 H, s), 2.16 (3 H, s), 2.20-2.40 (4 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 2.63 (3 H, s), 3.39 (2 H, s), 3.39- 
               
               
                   
                   
                   
                   
                   
                   
                 3.50 (4 H, m), 3.74 (2 H, s), 5.99 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 s), 6.72-6.92 (5 H, m), 6.98 (1 H, s), 7.51 (1  
               
               
                   
                   
                   
                   
                   
                   
                 H, dd, J = 8.8 Hz, 2.4 Hz), 7.63 (1 H, dd, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.5 Hz, 1.4 Hz), 7.73 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 2.6 Hz), 7.82-7.87 (2 H, m), 10.35 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs). 
               
               
                   
               
               
                 2029 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 3   
                 —H 
                 —CH 3   
                 —CH 3   
                 1.90 (3 H, s), 2.15 (3 H, s), 2.25-2.40 (4 H, m), 2.62 (3 H, s), 3.38 (2 H, s), 3.38- 3.50 (4 H, m), 3.73 (2 H,s ), 5.98 (2 H, s), 6.72-6.76 (2 H, m), 6.82-6.88 (3 H, m), 6.97 (1 H, s), 7.30-7.45 (1 H, m), 7.51 (1 H, dd, J = 8.8 Hz, 2.7 Hz), 7.72 (1 H, dd, J = 8.7 Hz, 2.6 Hz), 7.78 (1 H, d, J = 2.8 Hz), 7.98-8.04 (1 H, m), 10.56 (1 H, brs). 
               
               
                   
               
               
                 2030 
                 3,4-Cl 2 Ph- 
                 —H 
                 —CF 3   
                 —H 
                 —C 2 H 5   
                 0.92 (3 H, t, J = 7.1 Hz), 2.20-2.40 (4 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 3.11 (2 H, q, J = 7.1 Hz), 3.35- 
               
               
                   
                   
                   
                   
                   
                   
                 3.50 (6 H, m), 3.83 (2 H, s), 5.98 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 6.70-6.90 (3 H, m), 7.05 (1 H, d, J = 8.8 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.32-7.36 (2 H, m), 7.56-7.75 (3 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.81-7.91 (3 H, m), 10.48 (1 H, brs). 
               
               
                   
               
             
          
         
       
     
       Example 2031 
     N-{4-[4-(4-benzenesulfonylpiperazin-1-yl)phenoxy]phenyl}-3,4-dichlorobenzamide 
       [1118]    Melting point: 191-192° C. 
         [1119]    The following compounds were produced in the same manner as in Reference Example 292. 
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 323 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example No. 
                 R 966   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 2032 
                 —CH 3   
                 2.41 (4H, brs), 3.20 (3H, s), 3.36 (2H, brs), 3.42 (2H, s), 3.59 (2H, brs), 3.66 (3H, s), 4.50 
               
               
                   
                   
                 (2H, s), 5.94 (2H, s), 6.70-6.76 (2H, m), 6.83 (1H, s), 6.93 (1H, d, J = 8.7 Hz), 6.99-7.04 
               
               
                   
                   
                 (2H, m), 7.13 (1H, dd, J = 8.4 Hz, 2.1 Hz), 7.51 (1H, d, J = 2.3 Hz), 7.69 (1H, dd, J = 8.4 
               
               
                   
                   
                 Hz, 2.1 Hz), 7.95 (1H, d, J = 2.1 Hz), 8.12 (1H, dd, J = 8.7 Hz, 2.6 Hz), 8.23 (1H, d, J = 2.6 
               
               
                   
                   
                 Hz), 8.53 (1H, s). 
               
               
                 2033 
                 —C 2 H 5   
                 1.37 (3H, t, J = 7.4 Hz), 2.42 (4H, brs), 3.38-3.46 (6H, m), 3.60 (2H, brs), 3.71 (3H, s), 4.53 
               
               
                   
                   
                 (2H, s), 5.94 (2H, s), 6.70-6.77 (2H, m), 6.84 (1H, s), 6.97 (1H, d, J = 8.7 Hz), 7.06 (1H, d, 
               
               
                   
                   
                 J = 8.6 Hz), 7.14-7.18 (1H, m), 7.26 (1H, s), 7.55 (1H, d, J = 8.4 Hz), 7.71 (1H, dd, J = 8.4 
               
               
                   
                   
                 Hz, 2.1 Hz), 7.98 (1H, d, J = 2.1 Hz), 8.16-8.23 (3H, m). 
               
               
                   
               
             
          
         
       
     
       Example 2034 
     Production of t-butyl 4-{4-[5-(3,4-dichlorobenzoyl-amino)pyridin-2-yloxy]phenylcarbamoyl}piperidine-1-carboxylate 
       [1120]    To a solution of N-[6-(4-aminophenoxy)pyridin-3-yl]-3,4-dichlorobenzamide dihydrochloride (1.0 g, 2.24 mmol) in DMF (15 mL) were added, piperidine-1,4-dicarboxylic acid mono-t-butyl ester (510 mg, 2.22 mmol), triethylamine (0.94 mL, 6.74 mmol), 1-hydroxybenzotriazole monohydrate (350 mg, 2.29 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (514 mg, 2.68 mmol) under ice cooling. The resulting solution was then stirred under ice cooling for 1 hour, and at room temperature for 17 hours. This reaction solution was concentrated under reduced pressure. The residue was diluted with water and ethyl acetate, whereupon a white powder was precipitated. The white powder was filtered, then washed with water, and subsequently washed with ethyl acetate, to thereby yield 1.04 g of the title compound. 
         [1121]    Appearance: White powder 
         [1122]      1 H NMR (DMSO-d 6 ) δ 1.41 (9H, s), 1.35-1.50 (2H, m), 1.70-1.85 (2H, m), 2.40-2.60 (1H, m), 2.65-2.90 (2H, m), 3.90-4.11 (2H, m), 7.03 (1H, d, J=8.9 Hz), 7.06 (2H, d, J=8.9 Hz), 7.62 (2H, d, J=8.9 Hz), 7.84 (1H, d, J=8.5 Hz), 7.94 (1H, dd, J=8.5 Hz, 2.0 Hz), 8.17 (1H, dd, J=8.9 Hz, 2.6 Hz), 8.22 (1H, d, J=2.0 Hz), 8.46 (1H, d, J=2.6 Hz), 9.96 (1H, s), 10.54 (1H, s). 
         [1123]    The following compound was produced in the same manner as in Example 2034. 
       Example 2035 
     3,4-Dichloro-N-(6-{4-[2-(2,4-dioxothiazolidine-5-yl)-acetylamino]phenoxy}pyridin-3-yl)benzamide 
       [1124]      1 H NMR (DMSO-d 6 ) δ 3.07 (1H, dd, J=16.5 Hz, 8.9 Hz), 3.24 (1H, dd, J=16.5 Hz, 4.0 Hz), 4.73 (1H, dd, J=9.0 Hz, 4.0 Hz), 7.04 (1H, d, J=8.9 Hz), 7.08 (2H, d, J=8.9 Hz), 7.58 (2H, d, J=8.9 Hz), 7.84 (1H, d, J=8.2 Hz), 7.94 (1H, dd, J=8.2 Hz, 2.0 Hz), 8.18 (1H, dd, J=8.9 Hz, 2.6 Hz), 8.22 (1H, d, J=2.0 Hz), 8.46 (1H, d, J=2.6 Hz), 10.21 (1H, s), 10.53 (1H, s), 12.00 (1H, s). 
       Example 2036 
     Production of 3,4-dichloro-N-(6-{4-[4-piperonyl-piperazin-1-ylmethyl]phenoxy}pyridin-3-yl)benzamide 
       [1125]    To a solution of 3,4-dichloro-N-[6-(4-piperazin-1-ylmethylphenoxy)pyridin-3-yl]benzamide (300 mg, 0.66 mmol) in DMF (10 mL) were added piperonylic acid (120 mg, 0.72 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (140 mg, 0.73 mmol) and 1-hydroxybenzotriazole monohydrate (100 mg, 0.74 mmol) under ice cooling. The resulting reaction solution was stirred overnight at room temperature. To the residue was added a saturated sodium bicarbonate solution, and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and evaporated, to thereby yield 110 mg of the title compound. 
         [1126]    Appearance: White powder 
         [1127]      1 H NMR (CDCl 3 ) δ 2.46 (4H, brs), 3.53 (2H, s), 3.60 (4H, brs), 5.99 (2H, s), 6.79 (1H, d, J=7.9 Hz), 6.85-6.96 (3H, m), 7.08 (2H, d, J=8.6 Hz), 7.33 (2H, d, J=8.3 Hz), 7.54 (1H, d, J=8.3 Hz), 7.69-7.73 (1H, m), 7.99 (1H, d, J=2.3 Hz), 8.16-8.21 (1H, m), 8.27-8.30 (2H, m). 
         [1128]    The following compounds were produced in the same manner as in Example 2036. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 324 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 967   
                 R 968   
                 Xb 30   
                 R 969   
                 mp (° C. ) or  1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 2037 
                 —CF 3   
                 —H 
                 —CO— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (DMSO-d 6 ) 3.52 (4 H, brs), 3.60 (4 H, brs), 5.57 (1 H, s), 7.17 (1 H, d, J = 8.9 Hz), 7.20 (2 H, d, J = 8.9 Hz), 7.51 (2 H, d, J = 8.4 Hz), 7.95 (2 H, d, J = 8.1 Hz), 8.17 (2 H, d, J = 8.1 Hz), 8.27 (1 H, dd, J = 8.9 Hz, 2.6 Hz), 8.55 (1 H, d, J = 2.6 Hz), 10.69 (1 H, brs), 11.18(1 H, brs), 11.32 (1 H, brs). 
               
               
                   
               
               
                 2038 
                 —Cl 
                 —Cl 
                 —CH 2 — 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 mp 250-251 
               
               
                   
               
               
                 2039 
                 —CF 3   
                 —H 
                 —CH 2 — 
                 2-CNPh- 
                 mp 189-192 
               
               
                 2040 
                 —CF 3   
                 —H 
                 —CH 2 — 
                 4-pyridyl 
                 mp 122-124 
               
               
                 2041 
                 —CF 3   
                 —H 
                 —CH 2 — 
                 3-pyridyl 
                 mp 167-168 
               
               
                 2042 
                 —CF 3   
                 —H 
                 —CH 2 — 
                 2-pyridyl 
                 mp 189-191 
               
               
                   
               
               
                 2043 
                 —CF 3   
                 —H 
                 —CH 2 — 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (DMSO-d 6 ) 2.45 (4 H, brs), 3.36 (2 H, s), 3.54-4.18 (4 H, m), 7.09 (3 H, d, J = 8.9 Hz), 7.36 (2 H, d, J = 8.4 Hz), 7.59 (1 H, brs), 7.72 (1 H, s), 7.94 (2 H, d, J = 8.4 Hz), 8.18 (2 H, d, J = 8.4 Hz), 8.24 (1 H, dd, J = 8.9 Hz, 2.6 Hz), 8.53 (1 H, d, J = 2.6 Hz), 10.67 (1 H, s), 12.48 (1 H, brs). 
               
               
                   
               
               
                 2044 
                 —CF 3   
                 —H 
                 —CH 2 — 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (CDCl 3  + CD 3 OD) 2.98- 3.15 (5 H, m), 3.34-3.47 (1 H, m), 3.61- 3.76 (4 H, m), 4.18 (2 H, s), 4.57 (1 H, dd, J = 10.2 Hz, 3.1 Hz), 7.04 (1 H, d, J = 8.7 Hz), 7.19 (2 H, d, J = 8.6 Hz), 7.49 (2 H, d, J = 8.6 Hz), 7.79 (2 H, d, J = 8.3 Hz), 8.11 (2 H, d, J = 8.1 Hz), 8.25 (1 H, dd, J = 8.9 Hz, 2.8 Hz), 8.52 (1 H, d, J = 2.3 Hz). 
               
               
                   
               
               
                 2045 
                 —CF 3   
                 —H 
                 —(CH 2 ) 3 — 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (CDCl 3 ) 1.81-1.89 (2 H, m), 2.40-2.45 (6 H, m), 2.62-2.68 (2 H, m), 3.61 (4 H, brs), 5.98 (2 H, s), 6.76-6.93 (4 H, m), 7.03 (2 H, d, J = 8.4 Hz), 7.19 (2 H, d, J = 8.4 Hz), 7.68 (2 H, d, J = 8.4 Hz), 7.99 (2 H, d, J = 8.3 Hz), 8.18-8.23 (1 H, m), 8.30 (1 H, d, J = 2.6 Hz), 8.73 (1 H, s). 
               
               
                   
               
               
                 2046 
                 —CF 3   
                 —H 
                 —(CH 2 ) 3 — 
                 3,4-(CH 3 O) 2 Ph- 
                   1 H NMR (CDCl 3 ) 1.78-1.89 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                 2.39-2.45 (6 H, m), 2.63-2.68 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                 3.62 (4 H, brs), 3.85 (3 H, s), 3.89 (3 H, s), 
               
               
                   
                   
                   
                   
                   
                 6.82-6.85 (1 H, m), 6.91-6.95 (3 H, m), 
               
               
                   
                   
                   
                   
                   
                 7.01-7.06 (2 H, m), 7.18-7.23 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                 7.70 (2 H, d, J = 8.2 Hz), 7.99 (2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.2 Hz), 8.20-8.24 (1 H, m), 8.29 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 2.6 Hz), 8.51 (1 H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 325 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 970   
                 R 971   
                 R 972   
                 M 
                 Form 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 2047 
                 —CF 3   
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1 
                 free 
                 (DMSO-d 6 ) 1.94 (6 H, s), 2.49- 2.51 (4 H, m), 2.76-2.93 (1 H, m), 3.17-3.51 (7 H, m), 4.20 (1 H, dd, J = 10.4 Hz, 3.0 Hz), 7.09-7.13 (3 H, m), 7.42 (2 H, brs), 7.94 (2 H, d, J = 8.4 Hz), 8.16-8.26 (3 H, m), 8.54 (1 H, d, J = 2.5 Hz), 10.67 (1 H, s), 11.68 (1 H, brs). 
               
               
                   
               
               
                 2048 
                 —CF 3   
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1 
                 free 
                 (CDCl 3  + CD 3 OD) 2.46-2.59 (4 H, m), 3.16 (1 H, dd, J = 14.2 Hz, 9.4 Hz), 3.32 (4 H, brs), 3.51 (1 H, dd, J = 14.0 Hz, 3.8 Hz), 3.79 (2 H, brs), 4.50 (1 H, dd, J = 9.4 Hz, 4.0 Hz), 6.93 (1 H, d, J = 8.9 Hz), 7.06 (2 H, d, J = 8.4 Hz), 7.26-7.46 (6 H, m), 7.72 (2 H, d, J = 8.3 Hz), 8.05 (2 H, d, J = 8.1 Hz), 8.27 (1 H, d, J = 2.1 Hz), 8.33 (1 H, dd, J = 8.9 Hz, 2.8 Hz). 
               
               
                   
               
               
                 2049 
                 —CF 3   
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1 
                 free 
                 (DMSO-d 6 ) 2.49-2.52 (4 H, m), 3.34-3.40 (4 H, m), 3.57 (2 H, s), 7.06-7.10 (3 H, m), 7.36 (2 H, d, J = 8.6 Hz), 7.54 (2 H, d, J = 8.1 Hz), 7.67 (2 H, d, J = 8.4 Hz), 7.79 (1 H, s), 7.94 (2 H, d, J = 8.6 Hz), 8.15- 8.25 (3 H, m), 8.51 (1 H, d, J = 2.8 Hz), 10.64 (1 H, s). 
               
               
                   
               
               
                 2050 
                 —CF 3   
                 —H 
                 4-pyridyl 
                 3 
                 hydro- 
                 (DMSO-d 6 ) 2.04 (2 H, brs), 2.63- 
               
               
                   
                   
                   
                   
                   
                 chloride 
                 2.69 (2 H, m), 3.10-3.59 (9 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 4.54 (1 H, brs), 7.05-7.08 (3 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.28 (2 H, d, J = 8.2 Hz), 7.45 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 4.9 Hz), 7.94 (2 H, d, J = 8.2 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 8.18-8.26 (3 H, m), 8.53 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 2.3 Hz), 8.70 (2 H, d, J = 5.4 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 10.72 (1 H, s), 11.27 (1 H, brs). 
               
               
                 2051 
                 —Cl 
                 —Cl 
                 3,4-F 2 Ph- 
                 1 
                 free 
                 (CDCl 3 ) 2.46 (4 H, brs), 3.47- 
               
               
                   
                   
                   
                   
                   
                   
                 3.72 (6 H, m), 6.91 (1 H, d, J = 8.9 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.05-7.33 (7 H, m), 7.50 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.4 Hz), 7.71 (1 H, dd, J = 8.4 
               
               
                   
                   
                   
                   
                   
                   
                 Hz, 2.1 Hz), 7.97 (1 H, d, J = 2.1 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 8.14-8.18 (1 H, m), 8.28 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 2.6 Hz), 8.68 (1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
           
               
                 TABLE 326 
               
               
                   
               
               
                 Ex- 
                   
                   
               
               
                 am- 
                   
                   
               
               
                 ple 
                   
                   
               
               
                 No. 
                 Chemical stracture 
                 mp (° C.) or  1 H NMR 
               
               
                   
               
             
             
               
                 2052 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 mp 171-173 
               
               
                   
               
               
                 2053 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 mp 116-118 
               
               
                   
               
               
                 2054 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 mp 133-135 
               
               
                   
               
               
                 2055 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (CDCl 3 ) δ 2.39 (2 H, brs), 2.55 (2 H, brs), 3.00 (3 H, s), 3.35 (2 H, brs), 3.51 (2 H, s), 3.79 (2 H, brs), 4.40 (2 H, s), 6.82 (1 H, d, J = 8.9 Hz), 6.99-7.13 (4 H, m), 7.25-7.29 (5 H, m), 7.32 (1 H, d, J = 1.8 Hz), 7.39 (1 H, d, J = 3.3 Hz), 8.68-8.70 (2 H, m). 
               
               
                   
               
             
          
         
       
     
       Example 2056 
     Production of N-{6-[4-(4-chloroacetylpiperazino)phenoxy]-3-pyridyl}-4-(trifluoromethyl)benzamide 
       [1129]    To a solution of N-[6-(4-piperazinophenoxy)-3-pyridyl]-4-(trifluoromethyl)benzamide (885 mg, 2.00 mmol) in DMF (20 mL) were added triethylamine (0.418 mL, 3.00 mmol) and chloroacetyl chloride (0.191 g, 2.40 mmol), and the resulting reaction solution was stirred for 10 minutes at room temperature. To this reaction solution was added ethyl acetate. The resulting solution was washed with water, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, to thereby yield 1.00 g of the title compound. 
         [1130]    Appearance: White powder 
         [1131]      1 H NMR (CDCl 3 ) δ 3.17 (2H, t, J=5.0 Hz), 3.22 (2H, t, J=5.0 Hz), 3.70 (2H, t, J=5.0 Hz), 3.80 (2H, t, J=5.0 Hz), 6.95 (1H, d, J=9.0 Hz), 6.97 (2H, d, J=9.0 Hz), 7.08 (2H, d, J=9.0 Hz), 7.77 (1H, brs), 7.78 (2H, d, J=8.0 Hz), 7.99 (2H, d, J=8.0 Hz), 8.20 (1H, dd, J=9.0 Hz, 2.5 Hz), 8.26 (1H, d, J=2.5 Hz). 
         [1132]    The following compounds were produced in the same manner as in Example 2056. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 327 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 973   
                 R 974   
                 Xb 31   
                 R 975   
                 mp (° C.) or  1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 2057 
                 —CF 3   
                 —H 
                 —CO— 
                 4-CNPh- 
                   1 H NMR (DMSO-d 6 ) 3.29-3.69 (8 H, m), 7.14- 
               
               
                   
                   
                   
                   
                   
                 7.20 (3 H, m), 7.49 (2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.63 (2 H, d, J = 8.1 Hz), 7.93-7.95 (4 H, m), 
               
               
                   
                   
                   
                   
                   
                 8.17 (2 H, d, J = 8.1 Hz), 8.27 (1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 8.9 Hz, 2.4 Hz), 8.55 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 2.4 Hz), 10.66 (1 H, s). 
               
               
                 2058 
                 —CF 3   
                 —H 
                 —CO— 
                 —CH 3   
                   1 H NMR (CDCl 3 ) 2.13 (3 H, s), 3.35-3.90 (8 H, 
               
               
                   
                   
                   
                   
                   
                 m), 7.02 (1 H, d, J = 8.8 Hz), 7.17 (2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.6 Hz), 7.44 (2 H, d, J = 8.6 Hz), 7.75 (2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.1 Hz), 8.02 (2 H, d, J = 8.1 Hz), 8.25 (1 H, 
               
               
                   
                   
                   
                   
                   
                 dd, J = 8.8 Hz, 2.5 Hz), 8.33 (1 H, d, J = 2.5 
               
               
                   
                   
                   
                   
                   
                 Hz), 8.38 (1 H, brs). 
               
               
                 2059 
                 —Cl 
                 —Cl 
                 —CH 2 — 
                 -Ph 
                   1 H NMR (CDCl 3 ) 2.08-2.55 (4 H, m), 3.43- 
               
               
                   
                   
                   
                   
                   
                 3.45 (2 H, m), 3.55 (2 H, s), 3.79-3.81 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                 6.96 (1 H, d, J = 8.9 Hz), 7.07-7.12 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                 7.33-7.46 (7 H, m), 7.57 (1 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.69-7.73 (1 H, m), 7.94-7.99 (2 H, m), 8.17- 
               
               
                   
                   
                   
                   
                   
                 8.21 (1 H, m), 8.27 (1 H, d, J = 2.6 Hz). 
               
               
                 2060 
                 —Cl 
                 —Cl 
                 —CH 2 — 
                 4-CNPh- 
                   1 H NMR (CDCl 3 ) 2.44 (2 H, brs), 2.58 (2 H, 
               
               
                   
                   
                   
                   
                   
                 brs), 3.39 (2 H, brs), 3.56 (2 H, s), 3.81 (2 H, 
               
               
                   
                   
                   
                   
                   
                 brs), 6.96 (1 H, d, J = 8.9 Hz), 7.08-7.12 (2 H, 
               
               
                   
                   
                   
                   
                   
                 m), 7.34 (2 H, d, J = 8.4 Hz), 7.48-7.51 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                 7.57 (1 H, d, J = 8.4 Hz), 7.69-7.77 (3 H, m), 
               
               
                   
                   
                   
                   
                   
                 7.95 (1 H, brs), 7.98 (1 H, d, J = 2.0 Hz), 8.14- 
               
               
                   
                   
                   
                   
                   
                 8.21 (1 H, m), 8.27 (1 H, d, J = 2.3 Hz), 
               
               
                 2061 
                 —CF 3   
                 —H 
                 —CH 2 — 
                 4-CNPh- 
                 mp 167-168 
               
               
                 2062 
                 —CF 3   
                 —H 
                 —CH 2 — 
                 -Ph 
                   1 H NMR (CDCl 3 ) 2.41-2.53 (4 H, m), 3.43 (2 H, 
               
               
                   
                   
                   
                   
                   
                 brs), 3.53 (2 H, s), 3.78 (2 H, brs), 6.95 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.9 Hz), 7.06-7.11 (2 H, m), 7.33-7.41 (7 H, 
               
               
                   
                   
                   
                   
                   
                 m), 7.71 (2 H, d, J = 8.4 Hz), 7.99 (2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.4 Hz), 8.23 (1 H, dd, J = 8.9 Hz, 2.7 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.31 (1 H, d, J = 2.7 Hz), 8.39 (1 H, s). 
               
               
                 2063 
                 —CF 3   
                 —H 
                 —CH 2 — 
                 3,4-F 2 Ph- 
                 mp 130-133 
               
               
                 2064 
                 —CF 3   
                 —H 
                 —CH 2 — 
                 3-CNPh- 
                   1 H NMR (CDCl 3 ) 2.43 (2 H, brs), 2.56 (2 H, 
               
               
                   
                   
                   
                   
                   
                 brs), 3.39 (2 H, brs), 3.55 (2 H, s), 3.79 (2 H, 
               
               
                   
                   
                   
                   
                   
                 brs), 6.97 (1 H, d, J = 8.9 Hz), 7.07-7.12 (2 H, 
               
               
                   
                   
                   
                   
                   
                 m), 7.32-7.37 (2 H, m), 7.50-7.77 (6 H, m), 
               
               
                   
                   
                   
                   
                   
                 8.00 (2 H, d, J = 8.1 Hz), 8.07 (1 H, brs), 
               
               
                   
                   
                   
                   
                   
                 8.23 (1 H, dd, J = 8.9 Hz, 2.7 Hz), 8.28 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 2.7 Hz). 
               
               
                 2065 
                 —CF 3   
                 —H 
                 —CH 2 — 
                 4-CH 3 Ph- 
                 mp 193-194 
               
               
                 2066 
                 —CF 3   
                 —H 
                 —CH 2 — 
                 4-ClPh- 
                 mp 176-178 
               
               
                 2067 
                 —CF 3   
                 —H 
                 —CH 2 — 
                 4-CH 3 OPh- 
                 mp 190-191 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 328 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 976   
                 R 977   
                 M 
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 2068 
                 3,4- 
                 -Ph 
                 1 
                 2.38 (2 H, brs), 2.53 (2 H, brs), 2.99 (3 H, s), 
               
               
                   
                 Cl 2 PhCH 2 N(CH 3 )— 
                   
                   
                 3.42 (2 H, brs), 3.50 (2 H, s), 3.79 (2 H, brs), 
               
               
                   
                   
                   
                   
                 4.39 (2 H, s), 6.81 (1 H, d, J = 8.9 Hz), 6.99- 
               
               
                   
                   
                   
                   
                 7.12 (4 H, m), 7.26-7.39 (9 H, m), 7.69 (1 H, d, 
               
               
                   
                   
                   
                   
                 J = 3.1 Hz). 
               
               
                 2069 
                 3,4- 
                 4-CNPh- 
                 1 
                 2.39 (2 H, brs), 2.55 (2 H, brs), 3.01 (3 H, s), 
               
               
                   
                 Cl 2 PhCH 2 N(CH 3 )— 
                   
                   
                 3.35 (2 H, brs), 3.51 (2 H, s), 3.79 (2 H, brs), 
               
               
                   
                   
                   
                   
                 4.40 (2 H, s), 6.82 (1 H, d, J = 8.9 Hz), 6.99- 
               
               
                   
                   
                   
                   
                 7.13 (4 H, m), 7.25-7.33 (3 H, m), 7.39 (1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.1 Hz), 7.48-7.52 (2 H, m), 7.69-7.73 (3 H, 
               
               
                   
                   
                   
                   
                 m). 
               
               
                 2070 
                 3,4- 
                 4-ClPh 
                 1 
                 2.34-2.59 (4 H, m), 3.00 (3 H, s), 3.36 (2 H, brs), 
               
               
                   
                 Cl 2 PhCH 2 N(CH 3 )— 
                   
                   
                 3.52 (2 H, s), 3.83 (2 H, brs), 4.40 (2 H, s), 
               
               
                   
                   
                   
                   
                 6.82 (1 H, d, J = 8.9 Hz), 6.98-7.13 (4 H, m), 
               
               
                   
                   
                   
                   
                 7.25-7.41 (8 H, m), 7.70 (1 H, d, J = 3.3 Hz). 
               
               
                 2071 
                 3,4- 
                 3,4-F 2 Ph- 
                 1 
                 2.33-2.57 (4 H, m), 3.00 (3 H, s), 3.37-3.51 (4 H, 
               
               
                   
                 Cl 2 PhCH 2 N(CH 3 )— 
                   
                   
                 m), 3.75 (2 H, brs), 4.40 (2 H, s), 6.82 (1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.9 Hz), 7.00-7.32 (10 H, m), 7.39 (1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.1 Hz), 7.69 (1 H, d, J = 3.1 Hz). 
               
               
                 2072 
                 4-CF 3 PhCONH— 
                 -Ph 
                 3 
                 1.78-1.89 (2 H, m), 2.39-2.49 (6 H, m), 
               
               
                   
                   
                   
                   
                 2.66 (2 H, t, J = 7.6 Hz), 3.44 (2 H, brs), 
               
               
                   
                   
                   
                   
                 3.79 (2 H, brs), 6.94 (1 H, d, J = 8.7 Hz), 7.02- 
               
               
                   
                   
                   
                   
                 7.07 (2 H, m), 7.18-7.23 (2 H, m), 7.35- 
               
               
                   
                   
                   
                   
                 7.42 (5 H, m), 7.72 (2 H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                 7.99 (2 H, d, J = 8.1 Hz), 8.19-8.29 (3 H, m). 
               
               
                 2073 
                 4-CF 3 PhCONH— 
                 4-CNPh- 
                 3 
                 1.79-1.90 (2 H, m), 2.41-2.69 (8 H, m), 
               
               
                   
                   
                   
                   
                 3.39 (2 H, brs), 3.81 (2 H, brs), 6.95 (1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.9 Hz), 7.02-7.07 (2 H, m), 7.18-7.23 (2 H, m), 
               
               
                   
                   
                   
                   
                 7.49 (2 H, d, J = 7.9 Hz), 7.69-7.77 (4 H, m), 
               
               
                   
                   
                   
                   
                 8.00 (2 H, d, J = 8.1 Hz), 8.06 (1 H, brs), 
               
               
                   
                   
                   
                   
                 8.21 (1 H, dd, J = 8.9 Hz, 2.6 Hz), 8.28 (1 H, d, 
               
               
                   
                   
                   
                   
                 J = 2.6 Hz). 
               
               
                 2074 
                 4-CF 3 PhCONH— 
                 3,4-F 2 Ph- 
                 3 
                 1.81-1.87 (2 H, m), 2.41-2.69 (8 H, m), 3.47- 
               
               
                   
                   
                   
                   
                 3.76 (4 H, m), 6.95 (1 H, d, J = 8.7 Hz), 7.02- 
               
               
                   
                   
                   
                   
                 7.07 (2 H, m), 7.11-7.28 (5 H, m), 7.75 (2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.4 Hz), 7.99-8.06 (3 H, m), 8.19-8.23 (1 H, 
               
               
                   
                   
                   
                   
                 m), 8.28 (1 H, d, J = 2.6 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 329 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 Xb 32   
                 Xb 33   
                 R 978   
                 mp (° C.) or  1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 2075 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —COPh 
                 mp 136-138 
               
               
                   
               
               
                 2076 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 4-CH 3 OPhCO— 
                 mp 161-162 
               
               
                   
               
               
                 2077 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 4-CF 3 PhCO— 
                 mp 143-144 
               
               
                   
               
               
                 2078 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 mp 163-165 
               
               
                   
               
               
                 2079 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 4-ClPhCO— 
                 mp 147-151 
               
               
                   
               
               
                 2080 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —N(CH 3 )COPh 
                 mp 231-232 
               
               
                   
               
               
                 2081 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —N(CH 3 )COCH 2 Cl 
                   1 H NMR (CDCl 3 ) 1.70-1.76 (2 H, m), 1.80- 1.90 (2 H, m), 2.80-2.88 (2 H, m), 2.98 (3 H, s), 3.56-3.68 (2 H, m), 4.10 (2 H, s), 4.57 (1 H, m), 6.94-6.99 (6 H, m), 7.53-7.58 (3 H, m), 7.69-7.71 (2 H, m), 7.97 (1 H, d, J = 2.0 Hz). 
               
               
                   
               
               
                 2082 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —COCH 2 Cl 
                   1 H NMR (DMSO-d 6 ) 3.08 (2 H, m), 3.14 (2 H, m), 3.61 (4 H, m), 4.44 (2 H, s), 6.93- 7.02 (6 H, m), 7.71 (2 H, d, J = 9.0 Hz), 7.82 (1 H, d, J = 8.5 Hz), 7.93 (1 H, dd, J = 8.5 Hz, 2.0 Hz), 8.21 (1 H, d, J = 2.0 Hz), 10.39 (1 H, s). 
               
               
                   
               
               
                 2083 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —COCH 2 Cl 
                   1 H NMR (CDCl 3 ) 1.66 (1 H, m), 1.74 (1 H, m), 1.91-1.98 (2 H, m), 2.72-2.77 (2 H, m), 3.24 (1 H, m), 3.99 (1 H, brd, J = 13.0 Hz), 4.11 (2 H, s), 4.73 (1 H, brd, J = 13.0 Hz), 6.96 (2 H, d, J = 8.5 Hz), 7.02 (2 H, d, J = 9.0 Hz), 7.15 (2 H, d, J = 8.5 Hz), 7.56- 7.79 (3 H, m), 7.71 (1 H, dd, J = 8.5 Hz, 2.0 Hz), 7.90 (1 H, brs), 7.98 (1 H, d, J = 2.0 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 330 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
                 mp (° C.) or 
               
               
                 No. 
                 R 979   
                 R 980   
                 Xb 34   
                 Xb 35   
                 Xb 36   
                 R 981   
                 MS 
               
               
                   
               
               
                 2084 
                 3,4- Cl 2 Ph- 
                 —H 
                 none 
                 none 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —N(CH 3 )COCH 2 Ph 
                 MS 616 (M + ) 
               
               
                   
               
               
                 2085 
                 4-CF 3 Ph- 
                 —CH 3   
                 —N(CH 3 )— 
                 —CH 2 — 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 4-CNPhCO— 
                 mp 131-132 
               
               
                   
               
               
                 2086 
                 4-CF 3 Ph- 
                 —CH 3   
                 —N(CH 3 )— 
                 —CH 2 — 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 mp 143-145 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 331 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 982   
                 Xb 37   
                 R 983   
                 Property 
               
               
                   
               
               
                 2087 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —Ac 
                 mp 138-140° C. 
               
               
                   
               
               
                 2088 
                 —F 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —N(CH 3 )COCH 2 Ph 
                 MS 661 (M + ) 
               
               
                   
               
               
                 2089 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —COCH 2 Cl 
                   1 H NMR (CDCl 3 ) δ 2.62 (2 H, t, J = 7.6 Hz), 2.95 (2 H, t, J = 7.6 Hz), 3.31-3.73 (8 H, m), 4.05 (2 H, s), 6.91 (2 H, d, J = 8.5 Hz), 6.97 (2 H, d, J = 8.9 Hz), 7.15 (2 H, d, J = 8.5 Hz), 7.49-7.60 (3 H, m), 7.68 (1 H, dd, J = 8.3 Hz, 2.1 Hz), 7.91 (1 H, brs), 7.95 (1 H, d, J = 2.1 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 332 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 984   
                 mp (° C.) 
               
               
                   
               
               
                 2090 
                 2-pyridyl 
                 217-218 
               
               
                 2091 
                 3-pyridyl 
                 191-192 
               
               
                 2092 
                 4-pyridyl 
                 204-205 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 333 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 985   
                 mp (° C) or  1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 2093 
                 -Ph 
                 mp 185-186 
               
               
                 2094 
                 —CH 2 Cl 
                 a mixture of the rotational isomers  1 H NMR 2.57 (0.4 H, brs), 2.65 (0.6 H, brs), 3.74 (0.6 H, t, J = 6.0 Hz), 3.85 (0.4 H, t, J = 6.0 Hz), 4.13 (0.8 H, s), 4.15 (1.2 H, s), 4.22 (1.2 H, m), 4.25 (0.8 H, m), 5.89 (0.4 H, brs), 6.04 (0.6 H, brs), 6.98 (2 H, d, J = 8.5 Hz), 7.04 (2 H, d, J = 9.0 Hz), 7.34 (2 H, dd, J = 8.5 Hz, 4.0 Hz), 7.56- 7.60 (3 H, m), 7.71 (1 H, dd, J = 8.5 Hz, 2.0 Hz), 7.89 (1 H, brs), 7.89 (1 H, d, J = 2.0 Hz). 
               
               
                   
               
             
          
         
       
     
       Example 2095 
     Production of 1-{4-[4-(3,4-dichlorobenzoylamino)-phenoxy]phenyl}-4-benzoyloxypiperidine 
       [1133]    To a solution of 1-{4-[4-(3,4-dichlorobenzoylamino)phenoxy]phenyl}-4-hydroxypiperidine (200 mg, 0.44 mmol) in dichloromethane (8 mL) were added with triethylamine (0.091 mL, 0.65 mmol), benzoyl chloride (74 mg, 0.53 mmol) and 4-(dimethylamino)pyridine (3 mg, 0.025 mmol), and the resulting solution was stirred for 2.5 days at room temperature. This reaction solution was purified by silica gel column chromatography (methanol:dichloromethane=7:93), to thereby yield 80 mg of the title compound. 
         [1134]    Appearance: White powder 
         [1135]    Melting point: 188-190° C. 
       Example 2096 
     Production of 3,4-dichloro-N-(6-{4-[[2-oxo-2-(4-piperonylpiperazin-1-yl)ethyl](2,2,2-trifluoroacetyl)amino]phenoxy}pyridin-3-yl)benzamide 
       [1136]    To a solution of 3,4-dichloro-N-(6-{4-[2-oxo-2-(4-piperonylpiperazin-1-yl)ethylamino]phenoxy}pyridin-3-yl)benzamide (0.152 g, 0.239 mmol) in THF (5 mL) were added triethylamine (0.0500 mL, 0.359 mmol) and trifluoroacetic anhydride (0.0410 mL, 0.2.87 mmol), and the resulting solution was stirred for 6 hours. Water was added to the resulting reaction solution, and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatography (dichloromethane:methanol=20:1) to yield a solid. This solid was recrystallized from methanol, to thereby yield 28.8 mg of the title compound. 
         [1137]    Appearance: White powder 
         [1138]    Melting point: 211-213° C. 
         [1139]    The following compound was produced in the same manner as in Example 2096. 
       Example 2097 
     N-[6-(4-Acetyl[2-oxo-2-(4-piperonylpiperazin-1-yl)ethyl]amino}-2-methoxyphenoxy)pyridin-3-yl]-3,4-dichlorobenzamide 
       [1140]      1 H NMR (CDCl 3 ) δ 1.90 (3H, s), 2.28 (2H, brs), 2.38 (2H, brs), 3.37 (4H, brs), 3.49 (2H, brs), 3.67 (3H, s), 4.43 (2H, s), 5.93 (2H, s), 6.68-6.75 (2H, m), 6.82 (1H, s), 6.91-6.97 (2H, m), 7.07-7.10 (2H, m), 7.53 (1H, d, J=8.4 Hz), 7.76 (1H, dd, J=8.4 Hz, 2.0 Hz), 8.05 (1H, d, J=2.0 Hz), 8.20 (1H, dd, J=8.9 Hz, 2.8 Hz), 8.37 (1H, d, J=2.6 Hz), 9.26 (1H, s). 
       Example 2098 
     Production of N-[6-(benzoyl{4-[3-oxo-3-(4-piperonylpiperazin-1-yl)propyl]phenyl}amino)pyridin-3-yl]-3,4-dichlorobenzamide monooxalate 
       [1141]    To a solution of 3,4-dichloro-N-(6-{4-[3-oxo-3-(4-piperonylpiperazin-1-yl)propyl]phenylamino}-pyridin-3-yl)benzamide (250 mg, 0.395 mmol) in THF (5 mL) were added triethylamine (0.132 mL, 0.949 mmol) and benzoyl chloride (0.0550 mL, 0.474 mmol), and the resulting solution was stirred for 7 hours at room temperature. Water was added to the resulting reaction solution, and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatography (dichloromethane:methanol 10:1) to yield 0.300 g of a free form. To this free form were added isopropanol (5 mL) and oxalic acid dihydrate (100 mg, 0.793 mmol), and the resulting solution was dissolved under heat. The solvent was evaporated, and the resulting solid was recrystallized from isopropanol, to thereby yield 80.0 mg of the title compound. 
         [1142]    Appearance: Yellow powder 
         [1143]    Melting point: 140-143° C. 
         [1144]    The following compound was produced in the same manner as in Example 2098. 
       Example 2099 
     N-[6-(Acetyl{4-[3-oxo-3-(4-piperonylpiperazin-1-yl)propyl]phenyl}amino)pyridin-3-yl]-3,4-dichlorobenzamide 
       [1145]    Melting point: 150-165° C. 
         [1146]      1 H NMR (DMSO-d 6 ) δ 1.98 (3H, s), 2.62-2.98 (7H, m), 3.04 (1H, t, J=12.1 Hz), 3.26 (2H, t, J=14.7 Hz), 3.35-3.50 (2H, m), 4.06 (1H, d, J=13.8 Hz), 4.13-4.26 (2H, m), 4.44 (1H, d, J=13.8 Hz), 6.07 (2H, s), 6.95-7.02 (2H, m), 7.20-7.24 (3H, m), 7.28 (2H, d, J=8.3 Hz), 7.52 (1H, d, J=8.9 Hz), 7.85 (1H, d, J=8.4 Hz), 7.96 (1H, dd, J=2.0 Hz, 8.4 Hz), 8.23-8.26 (2H, m), 8.77 (1H, s), 10.77 (1H, s), 11.10 (1H, brs). 
       Example 2100 
     Production of 6-{4-[3-(4-piperonylpiperazin-1-yl)-3-oxopropyl]phenoxy}-N-(3,4-dichlorophenyl)nicotinamide 
       [1147]    To a solution of 6-{4-[3-(4-piperonylpiperazin-1-yl)-3-oxopropyl]phenoxy}nicotinic acid (1.23 g, 2.5 mmol) in THF (35 mL) was added N,N′-carbonyldiimidazole (540 mg, 3.3 mmol), and the resulting solution was stirred for 30 minutes at room temperature. The resulting reaction solution was concentrated under reduced pressure, and to the residue was added 3,4-dichloroaniline (4.07 g, 25 mmol). The resulting solution was stirred for 3 days at room temperature. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate), and the resulting product was recrystallized from diethyl ether, to thereby yield 510 mg of the title compound. 
         [1148]    Appearance: White powder 
         [1149]      1 H NMR (CDCl 3 ) δ 2.33 (4H, brs), 2.59-2.65 (2H, m), 2.91-2.97 (2H, m), 3.40 (4H, brs), 3.59 (2H, s), 5.94 (2H, s), 6.70-6.76 (2H, m), 6.83 (1H, s), 6.96-7.06 (3H, m), 7.20-7.26 (2H, m), 7.40 (1H, d, J=8.6 Hz), 7.50-7.54 (1H, m), 7.86 (1H, d, J=1.8 Hz), 8.18-8.22 (1H, m), 8.44 (1H, brs), 8.66 (1H, brs). 
         [1150]    The following compounds were produced in the same manner as in Example 2100. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 334 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example No. 
                 R 986   
                 Xb 38   
                 Xb 39   
                 R 987   
                 mp (° C.) or  1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 2101 
                 3,4-Cl 2 Ph- 
                 none 
                 none 
                 benzyl 
                 mp 206-207 
               
               
                 2102 
                 4-CF 3 Ph- 
                 none 
                 none 
                 benzyl 
                   1 H NMR 2.44 (4H, brs), 3.53-3.70 (6H, 
               
               
                   
                   
                   
                   
                   
                 m), 6.93 (1H, d, J = 8.4 Hz), 7.11- 
               
               
                   
                   
                   
                   
                   
                 7.14 (2H, m), 7.27-7.40 (7H, m), 
               
               
                   
                   
                   
                   
                   
                 7.56 (2H, d, J = 8.9 Hz), 7.83 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.4 Hz), 8.23-8.27 (1H, m), 8.71 (1H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 2.4 Hz), 9.39 (1H, brs). 
               
               
                 2103 
                 4-CF 3 Ph- 
                 —N(CH 3 )— 
                 —CH 2 — 
                 piperonyl 
                   1 H NMR 2.42 (4H, brs), 3.03 (3H, s), 
               
               
                   
                   
                   
                   
                   
                 3.43-3.52 (4H, m), 3.60 (2H, brs), 
               
               
                   
                   
                   
                   
                   
                 4.10 (2H, s), 5.95 (2H, s), 6.66-6.77 (4H, 
               
               
                   
                   
                   
                   
                   
                 m), 6.85 (1H, brs), 6.89 (1H, d, J = 8.6 
               
               
                   
                   
                   
                   
                   
                 Hz), 6.98 (2H, d, J = 6.6 Hz), 7.60 (2H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.4 Hz), 7.76 (2H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.14 (1H, dd, J = 8.6 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.33 (1H, brs), 8.63 (1H, brs). 
               
               
                 2104 
                 3,4-Cl 2 Ph- 
                 —N(CH 3 )— 
                 —CH 2 — 
                 piperonyl 
                   1 H NMR 2.42-2.44 (4H, m), 3.05 (3H, 
               
               
                   
                   
                   
                   
                   
                 s), 3.44 (2H, brs), 3.47-3.57 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 3.63 (2H, brs), 4.11 (2H, s), 5.95 (2H, s), 
               
               
                   
                   
                   
                   
                   
                 6.68-6.74 (4H, m), 6.85 (1H, brs), 6.92 
               
               
                   
                   
                   
                   
                   
                 (1H, d, J = 8.9 Hz), 7.00 (2H, d, J = 8.7 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.42-7.44 (2H, m), 7.80-7.86 (1H, 
               
               
                   
                   
                   
                   
                   
                 m), 7.87 (1H, d, J = 2.1 Hz), 8.13 (1H, 
               
               
                   
                   
                   
                   
                   
                 dd, J = 8.7 Hz, 2.6 Hz), 8.63 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 2.1 Hz). 
               
               
                 2105 
                 4-CF 3 Ph- 
                 none 
                 none 
                 piperonyl 
                   1 H NMR 2.71 (4H, brs), 3.46-3.92 (6H, 
               
               
                   
                   
                   
                   
                   
                 m), 5.91 (2H, s), 6.65-6.73 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 6.81 (1H, d, J = 1.5 Hz), 7.01 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 9.1 Hz), 7.14 (2H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.43 (2H, d, J = 8.7 Hz), 7.60 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.6 Hz), 7.82 (2H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.29 (1H, dd, J = 2.6 Hz, 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.71 (1H, d, J = 2.1 Hz), 8.87 (1H, brs). 
               
               
                   
               
             
          
         
       
     
       Example 2106 
     Production of (4-benzylpiperazin-1-yl){4-[5-(3,4-dichlorophenylsulfanyl)pyridin-2-yloxy]phenyl}methanone 
       [1151]    To a solution of [4-(5-aminopyridin-2-yloxy)phenyl](4-benzylpiperazin-1-yl)methanone (0.73 g, 1.88 mmol) in concentrated sulfuric acid (0.38 mL)-water. (1.1 mL) were added dropwise a solution of sodium nitrate (0.13 g, 1.88 mmol) in water (0.6 mL) under ice cooling. The reaction mixture was stirred for 10 minutes. This reaction mixture was added to a solution of 3,4-dichlorobenzenethiol (0.24 mL, 1.88 mmol) in 2 N aqueous sodium hydroxide (2 mL) under cooling with ice. Water was added to the resulting reaction solution, and extracted with dichloromethane. The dichloromethane layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel chromatography (dichloromethane:methanol=80:1), to thereby yield 0.1 g of the title compound. 
         [1152]    Appearance: Yellow oil 
         [1153]      1 H NMR (CDCl 3 ) δ 2.49 (4H, brs), 3.56 (2H, s), 3.56 (2H, brs), 3.78 (2H, brs), 6.99 (1H, d, J=8.9 Hz), 7.20 (2H, d, J=8.7 Hz), 7.25-7.39 (5H, m), 7.46 (1H, dd, J=8.2 Hz, 2.0 Hz), 7.47 (2H, d, J=8.7 Hz), 7.56 (1H, d, J=8.2 Hz), 7.76 (1H, d, J=2.0 Hz), 7.86 (1H, dd, J=8.9 Hz, 2.5 Hz), 8.50 (1H, d, J=2.5 Hz). 
         [1154]    The following compound was produced in the same manner as in Example 2106. 
       Example 2107 
     2-({4-[5-(3,4-Dichlorophenylsulfanyl)pyridin-2-yloxy]-3-methoxyphenyl}ethylamino)-1-(4-piperonylpiperazin-1-yl)ethanone 
       [1155]      1 H NMR (CDCl 3 ) δ 1.20 (3H, t, J=7.0 Hz), 2.43 (4H, t, J=4.9 Hz), 3.43 (2H, s), 3.35-3.50 (2H, m), 3.49-3.60 (2H, m), 3.60-3.70 (2H, m), 3.73 (3H, s), 4.05 (2H, s), 5.95 (2H, s), 6.22 (1H, dd, J=8.9 Hz, 2.7 Hz), 6.35 (1H, d, J=2.7 Hz), 6.70-6.76 (2H, m), 6.85 (1H, s), 6.90 (1H, d, J=9.0 Hz), 6.98 (1H, d, J=8.8 Hz), 7.46 (1H, dd, J=8.2 Hz, 2.0 Hz), 7.55 (1H, d, J=8.2 Hz), 7.75 (1H, d, J=2.0 Hz), 7.78 (1H, dd, J=9.0 Hz, 2.5 Hz), 8.49 (1H, d, J=2.5 Hz). 
       Example 2108 
     Production of 1-(6-{4-[3-(4-piperonylpiperazin-1-yl)-3-oxopropyl]phenoxy}pyridin-3-yl)-3-(3,4-dichlorophenyl)urea 
       [1156]    To a solution of 3-[4-(5-aminopyridin-2-yloxy)phenyl]-1-(4-piperonylpiperazin-1-yl)propane-1-one (600 mg, 1.3 mmol) in toluene (20 mL) were added ethyldiisopropylamine (0.454 mL, 2.6 mmol) and 3,4-dichlorophenylisocyanate (270 mg, 1.4 mmol), and the resulting solution was stirred for 1 day under reflux. The reaction solution was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (methanol:chloroform=1:19), and then recrystallized from ethyl acetate to thereby yield 280 mg of the title compound. 
         [1157]    Appearance: Pale yellow powder 
         [1158]      1 H NMR (CDCl 3 ) δ 2.37-2.39 (4H, m), 2.61-2.67 (2H, m), 2.89-2.94 (2H, m), 3.41-3.47 (4H, m), 3.61-3.65 (2H, m), 5.94 (2H, s), 6.69-6.83 (4H, m), 6.95 (2H, d, J=8.4 Hz), 7.10-7.26 (4H, m), 7.49 (1H, d, J=2.3 Hz), 7.93-7.96 (2H, m), 8.1-5 (1H, s), 8.21 (1H, s). 
         [1159]    The following compounds were produced in the same manner as in Example 2108. 
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 335 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example No. 
                 R 988   
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 2109 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (DMSO-d 6 ) 1.13 (3H, t, J = 6.9 Hz), 2.20-2.60 (1H, m), 2.75-3.20 (2H, m), 3.20-3.65 (7H, m), 3.64 (3H, s), 4.05- 4.52 (4H, m), 6.07 (2H, brs), 6.10 (1H, dd, J = 8.8 Hz, 2.7 Hz), 6.27 (1H, brs), 6.80 (1H, d, J = 8.6 Hz), 6.84 (1H, d, J = 8.6 Hz), 7.01 (2H, brs), 7.19 (1H, brs), 7.33 (1H, dd, J = 8.9 Hz, 2.6 Hz), 7.51 (1H, d, J = 8.9 Hz), 7.85 (1H, dd, J = 8.9 Hz, 2.6 Hz), 7.86 (1H, d, J = 2.6 Hz), 8.07 (1H, d, J = 2.6 Hz), 8.94 (1H, s), 9.28 (1H, s). 
               
               
                   
               
               
                 2110 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 1.14 (3H, t, J = 7.0 Hz), 2.35- 2.55 (4H, m), 3.38 (2H, q, J = 7.0 Hz), 3.44 (2H, s), 3.45-3.55 (2H, m), 3.60 (3H, s), 3.60-3.75 (2H, m), 4.02 (2H, s), 5.95 (2H, s), 6.60-6.80 (4H, m), 6.85 (1H, s), 6.92 (1H, d, J = 8.9 Hz), 7.00- 7.15 (2H, m), 7.22 (1H, d, J = 8.7 Hz), 7.45 (1H, d, J = 2.3 Hz), 7.75-7.85 (2H, m), 7.95 (1H, s), 7.97 (1H, s). 
               
               
                   
               
               
                 2111 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 1.09 (3H, t, J = 7.1 Hz), 2.35- 2.45 (4H, m), 3.10 (2H, q, J = 7.1 Hz), 3.43 (2H, s), 3.55-3.65 (4H, m), 3.85 (2H, s), 5.95 (2H, s), 6.70-6.80 (2H, m), 6.85 (1H, s), 6.90 (1H, d, J = 8.8 Hz), 7.05-7.35 (4H, m), 7.46 (1H, d, J = 8.8 Hz), 7.53 (1H, d, J = 2.4 Hz), 7.79 (1H, brs), 7.85 (1H, brs), 7.93 (1H, d, J = 2.6 Hz), 7.99 (1H, dd, J = 8.8 Hz, 2.8 Hz). 
               
               
                   
               
               
                 2112 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 1.44 (9H, s), 1.96 (3H, s), 2.10- 2.30 (2H, m), 3.42-3.61 (2H, m), 3.62- 3.78 (2H, m), 4.04 (2H, s), 6.58 (1H, d, J = 8.8 Hz), 6.60 (1H, d, J = 8.5 Hz), 6.91 (1H, dd, J = 2.6 Hz, 8.5 Hz), 7.00 (1H, d, J = 2.6 Hz), 7.31 (1H, d, J = 8.8 Hz), 7.36 (1H, dd, J = 2.3 Hz, 8.8 Hz), 7.69 (1H, d, J = 2.3 Hz), 7.79 (1H, dd, J = 2.8 Hz, 8.8 Hz), 7.91 (1H, d, J = 2.8 Hz), 7.93 (1H, s), 8.05 (1H, s). 
               
               
                   
               
             
          
         
       
     
       Example 2113 
     Production of 4-piperonylpiperazine-1-carboxylic acid {(4-[5-(3,4-dichlorobenzoylamino)pyridin-2-yloxy]phenyl}amide hydrochloride 
       [1160]    To a solution of {4-[5-(3,4-dichlorobenzoyl-amino)pyridin-2-yloxy]phenyl}-carbamic acid phenyl ester (320 mg, 0.65 mmol) in DMF (4 mL) was added 1-piperonylpiperazine (285 mg, 1.29 mmol), and the resulting solution was stirred for 17 hours at room temperature. This reaction solution was concentrated under reduced pressure. Water was added to the residue, and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was then purified by silica gel column chromatography (dichloromethane:methanol=25:1). The obtained residue was dissolved in a mixed solvent of ethanol-ethyl acetate. To the resulting solution was added a solution of 4 N hydrogen chloride in ethyl acetate to bring the pH to 3. The precipitated white powder was then filtered off and washed with ethanol, to thereby yield 330 mg of the title compound. 
         [1161]    Appearance: White powder 
         [1162]      1 H NMR (DMSO-d 6 ) δ 2.85-3.09 (2H, m), 3.20-3.50 (4H, m), 4.12-4.38 (4H, m), 6.08 (2H, s), 7.02 (2H, d, J=9.0 Hz), 6.93-7.12 (3H, m), 7.28 (1H, d, J=1.5 Hz), 7.49 (2H, d, J=9.0 Hz), 7.83 (1H, d, J=8.5 Hz), 7.97 (1H, dd, J=8.5 Hz, 2.0 Hz), 8.19 (1H, dd, J=8.8 Hz, 2.6 Hz), 8.25 (1H, d, J=2.0 Hz), 8.50 (1H, d, J=2.6 Hz), 8.92 (1H, s), 10.63 (1H, s) 
         [1163]    The following compound was produced in the same manner as in Example 2113. 
       Example 2114 
     4-Benzylpiperazine-1-carboxylic acid {4-[5-(3,4-dichlorobenzoylamino)pyridin-2-yloxy]phenyl}amide hydrochloride 
       [1164]      1 H NMR (DMSO-d 6 ) δ 2.90-3.20 (2H, m), 3.22-3.45 (4H, m), 4.27 (2H, d, J=13.6 Hz), 4.35 (2H, d, J=5.0 Hz), 7.02 (1H, d, J=8.9 Hz), 7.03 (2H, d, J=8.9 Hz), 7.41-7.52 (3H, m), 7.48 (2H, d, J=8.9 Hz), 7.55-7.69 (2H, m), 7.84 (1H, d, J=8.4 Hz), 7.97 (1H, dd, J=8.4 Hz, 2.0 Hz), 8.19 (1H, dd, J=8.9 Hz, 2.6 Hz), 8.25 (1H, d, J=2.0 Hz), 8.49 (1H, d, J=2.6 Hz), 8.90 (1H, s), 10.62 (1H, s). 
       Example 2115 
     Production of 2-[(4-{5-[(3,4-dichlorobenzylidene)-amino]pyridin-2-yloxy}phenyl)methylamino]-1-(4-piperonylpiperazin-1-yl)ethanone 
       [1165]    2-{[(4-(5-aminopyridin-2-yloxy)phenyl]methylamino}-1-(4-piperonylpiperazin-1-yl)ethanone (7.80 g, 16.4 mmol) was dissolved in methanol (400 mL), and to the resulting solution was added 3,4-dichlorobenzaldehyde (2.87 g, 16.4 mmol). This solution was refluxed for 16 hours. The resulting reaction solution was concentrated under reduced pressure, to thereby yield 10.4 g of the title compound. 
         [1166]    Appearance: Brown oil 
         [1167]      1 H NMR (CDCl 3 ) δ 2.44 (4H, brs), 3.03 (3H, s), 3.44-3.45 (2H, m), 3.50 (2H, brs), 3.63 (2H, brs), 4.09 (2H, s), 5.94 (2H, s), 6.65-6.77 (4H, m), 6.84-6.88 (2H, m), 7.03 (2H, d, J=9.1 Hz), 7.54 (1H, d, J=8.3 Hz), 7.58 (1H, dd, J=8.9 Hz, 2.8 Hz), 7.70 (1H, dd, J=8.4 Hz, 2.0 Hz), 8.00 (1H, d, J=2.0 Hz), 8.10 (1H, d, J=2.8 Hz), 8.39 (1H, s). 
         [1168]    The following compounds were produced in the same manner as in Example 2115. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 336 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 989   
                 R 990   
                 R 991   
                 Xb 40   
                 M 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 2116 
                 3,4- 
                 —H 
                 benzyl 
                 none 
                 0 
                 (DMSO-d 6 ) 2.41 (4 H, brs), 3.34-3.51 (6 H, m), 
               
               
                   
                 Cl 2 Ph 
                   
                   
                   
                   
                 7.19 (1 H, d, J = 8.7 Hz), 7.20 (2 H, d, J = 7.9 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.29-7.33 (5 H, m), 7.45 (2 H, d, J = 7.9 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.81 (1 H, d, J = 8.3 Hz), 7.91-7.96 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 8.15 (1 H, brs), 8.18 (1 H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 8.75 (1 H, s). 
               
               
                 2117 
                 3,4- 
                 —H 
                 benzyl 
                 none 
                 2 
                 (DMSO-d 6 ) 2.30 (4 H, brs), 2.60-2.62 (2 H, 
               
               
                   
                 Cl 2 Ph 
                   
                   
                   
                   
                 m), 2.79-2.85 (2 H, m), 3.44-3.48 (6 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.05 (2 H, d, J = 8.4 Hz), 7.09 (1 H, d, J = 8.7 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.25-7.36 (7 H, m), 7.81 (1 H, d, J = 8.2 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.88-7.93 (2 H, m), 8.13-8.14 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 8.74 (1 H, s). 
               
               
                 2118 
                 4- 
                 —H 
                 benzyl 
                 none 
                 0 
                 (CDCl 3 ) 2.47 (4 H, brs), 3.55 (2 H, brs), 
               
               
                   
                 CF 3 Ph- 
                   
                   
                   
                   
                 3.55 (2 H, s), 3.79 (2 H, brs), 7.00 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.7 Hz), 7.18 (2 H, d, J = 8.6 Hz), 7.22- 
               
               
                   
                   
                   
                   
                   
                   
                 7.40 (5 H, m), 7.47 (2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.67 (1 H, dd, J = 8.7 Hz, 2.6 Hz), 7.74 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 8.1 Hz), 8.03 (2 H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 8.14 (1 H, d, J = 2.6 Hz), 8.54 (1 H, s). 
               
               
                 2119 
                 4- 
                 —H 
                 piperonyl 
                 —N(CH 3 )— 
                 1 
                 (CDCl 3 ) 2.45 (4 H, brs), 3.04 (3 H, s), 3.45- 
               
               
                   
                 CF 3 Ph- 
                   
                   
                   
                   
                 3.51 (4 H, m), 3.65 (2 H, s), 4.09 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 5.95 (2 H, s), 6.71-6.74 (4 H, m), 6.86- 
               
               
                   
                   
                   
                   
                   
                   
                 6.89 (2 H, m), 7.04 (2 H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.61 (1 H, dd, J = 8.7 Hz, 2.6 Hz), 7.73 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 8.3 Hz), 8.01 (2 H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 8.14 (1 H, d, J = 2.6 Hz), 8.53 (1 H, s). 
               
               
                 2120 
                 4- 
                 —F 
                 benzyl 
                 none 
                 0 
                 (CDCl 3 ) 2.49 (4 H, brs), 3.43-3.75 (6 H, m), 
               
               
                   
                 CF 3 Ph- 
                   
                   
                   
                   
                 7.07 (1 H, d, J = 8.6 Hz), 7.29-7.34 (8 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.69 (1 H, dd, J = 8.7 Hz, 2.8 Hz), 7.74 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 8.3 Hz), 8.02 (2 H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 8.05 (1 H, d, J = 2.6 Hz), 8.53 (1 H, s). 
               
               
                 2121 
                 3,4- 
                 —H 
                 piperonyl 
                 —N(CH 3 )— 
                 2 
                 (CDCl 3 ) 2.34-2.41 (4 H, m), 2.55-2.61 (2 H, 
               
               
                   
                 Cl 2 Ph 
                   
                   
                   
                   
                 m), 2.95 (3 H, s), 3.41 (4 H, brs), 3.61- 
               
               
                   
                   
                   
                   
                   
                   
                 3.65 (2 H, m), 3.68-3.76 (2 H, m), 5.94 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 6.70-6.77 (4 H, m), 6.84 (1 H, d, J = 1.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 6.89 (1 H, dd, J = 8.7 Hz, 0.5 Hz), 7.04 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 9.2 Hz), 7.55 (1 H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.60 (1 H, dd, J = 8.7 Hz, 2.8 Hz), 7.71 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 dd, J = 8.3 Hz, 2.0 Hz), 8.01 (1 H, d, J = 1.8 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 8.11 (1 H, dd, J = 2.8 Hz, 0.5 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 8.40 (1 H, brs). 
               
               
                 2122 
                 4- 
                 —H 
                 piperonyl 
                 —N(CH 3 )— 
                 2 
                 (CDCl 3 ) 2.34-2.41 (4 H, m), 2.55-2.61 (2 H, 
               
               
                   
                 CF 3 Ph 
                   
                   
                   
                   
                 m), 2.95 (3 H, s), 3.39-3.42 (4 H, m), 3.61- 
               
               
                   
                   
                   
                   
                   
                   
                 3.64 (2 H, m), 3.68-3.76 (2 H, m), 5.94 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 6.70-6.77 (4 H, m), 6.84 (1 H, d, J = 0.8 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 6.90 (1 H, dd, J = 8.7 Hz, 0.7 Hz), 7.05 (2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 9.2 Hz), 7.63 (1 H, dd, J = 8.7 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.73 (2 H, d, J = 8.3 Hz), 8.01 (2 H, d, J = 8.6 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 8.13 (1 H, dd, J = 2.8 Hz, 0.7 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 8.53 (1 H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 337 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 992   
                 R 993   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 2123 
                 3,4-Cl 2 Ph- 
                 —H 
                 2.43 (4 H, brs), 3.22 (3 H, s), 3.38 (2 H, brs), 3.43 (2 H, s), 3.62 (2 H, 
               
               
                   
                   
                   
                 brs), 4.55 (2 H, s), 5.95 (2 H, s), 6.74 (2 H, brs), 6.84 (1 H, brs), 
               
               
                   
                   
                   
                 7.01 (1 H, d, J = 8.6 Hz), 7.15 (2 H, d, J = 8.7 Hz), 7.57 (1 H, d, J = 
               
               
                   
                   
                   
                 8.3 Hz), 7.61-7.68 (3 H, m), 7.72 (1 H, dd, J = 8.3 Hz, 1.8 Hz), 
               
               
                   
                   
                   
                 8.03 (1 H, d, J = 1.8 Hz), 8.11 (1 H, d, J = 2.8 Hz), 8.42 (1 H, brs). 
               
               
                 2124 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 2.20 (3 H, s), 2.42-2.43 (4 H, m), 3.23 (3 H, s), 3.38 (2 H, brs), 
               
               
                   
                   
                   
                 3.43 (2 H, s), 3.62 (2 H, brs), 4.54 (2 H, s), 5.94 (2 H, s), 6.70- 
               
               
                   
                   
                   
                 6.77 (2 H, m), 6.84 (1 H, brs), 6.97 (1 H, dd, J = 8.7 Hz, 0.5 Hz), 
               
               
                   
                   
                   
                 7.05 (1 H, d, J = 8.6 Hz), 7.43-7.49 (2 H, m), 7.55 (1 H, d, J = 8.2 
               
               
                   
                   
                   
                 Hz), 7.62-7.66 (1 H, m), 7.69-7.74 (1 H, m), 8.01 (1 H, d, J = 2.0 
               
               
                   
                   
                   
                 Hz), 8.07 (1 H, d, J = 2.1 Hz), 8.40 (1 H, brs). 
               
               
                 2125 
                 4-CF 3 Ph- 
                 —CH 3   
                 2.20 (3 H, s), 2.41-2.43 (4 H, m), 3.23 (3 H, s), 3.38 (2 H, brs), 
               
               
                   
                   
                   
                 3.43 (2 H, s), 3.60 (2 H, brs), 4.55 (2 H, s), 5.95 (2 H, s), 6.73- 
               
               
                   
                   
                   
                 6.74 (2 H, m), 6.84 (1 H, brs), 6.98 (1 H, d, J = 8.7 Hz), 7.05 (1 H, d, 
               
               
                   
                   
                   
                 J = 8.4 Hz), 7.43-7.49 (2 H, m), 7.65-7.75 (3 H, m), 8.00-8.10 (3 H, 
               
               
                   
                   
                   
                 m), 8.53 (1 H, brs). 
               
               
                 2126 
                 4-CF 3 Ph- 
                 —OCH 3   
                 2.43 (4 H, brs), 3.24 (3 H, s), 3.39 (2 H, brs), 3.43 (2 H, s), 3.63 (2 H, 
               
               
                   
                   
                   
                 brs), 3.77 (3 H, s), 4.57 (2 H, s), 5.94 (2 H, s), 6.73-6.77 (2 H, m), 
               
               
                   
                   
                   
                 6.84 (1 H, s), 7.02 (1 H, d, J = 8.6 Hz), 7.13 (1 H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                 7.22 (1 H, dd, J = 8.4 Hz, 2.3 Hz), 7.30 (1 H, d, J = 2.3 Hz), 
               
               
                   
                   
                   
                 7.66 (1 H, dd, J = 8.7 Hz, 2.8 Hz), 7.73 (2 H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                 8.01 (2 H, d, J = 8.1 Hz), 8.08 (1 H, d, J = 2.5 Hz), 8.53 (1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 338 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 994   
                 R 995   
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 2127 
                 3,4-Cl 2 Ph- 
                 —H 
                 (CDCl 3 ) 2.20 (3 H, s), 2.49-2.55 (4 H, m), 3.45 (2 H, s), 3.71- 
               
               
                   
                   
                   
                 3.75 (2 H, m), 4.25-4.29 (2 H, m), 5.95 (2 H, s), 6.75 (2 H, brs), 
               
               
                   
                   
                   
                 6.86 (1 H, brs), 6.92 (1 H, d, J = 8.6 Hz), 7.06 (1 H, d, J = 8.6 
               
               
                   
                   
                   
                 Hz), 7.44 (1 H, dd, J = 8.6 Hz, 2.6 Hz), 7.53-7.65 (3 H, m), 
               
               
                   
                   
                   
                 7.70 (1 H, dd, J = 8.2 Hz, 2.0 Hz), 8.01 (1 H, d, J = 1.8 Hz), 
               
               
                   
                   
                   
                 8.07 (1 H, d, J = 2.8 Hz), 8.40 (1 H, brs), 9.17 (1 H, brs). 
               
               
                 2128 
                 4-CF 3 Ph- 
                 —H 
                 (CDCl 3 ) 2.20 (3 H, s), 2.49-2.55 (4 H, m), 3.45 (2 H, s), 3.71- 
               
               
                   
                   
                   
                 3.75 (2 H, m), 4.25-4.28 (2 H, m), 5.95 (2 H, s), 6.75 (2 H, brs), 
               
               
                   
                   
                   
                 6.86 (1 H, brs), 6.93 (1 H, d, J = 8.7 Hz), 7.07 (1 H, d, J = 8.7 
               
               
                   
                   
                   
                 Hz), 7.45 (1 H, dd, J = 8.7 Hz, 2.6 Hz), 7.58 (1 H, d, J = 2.5 
               
               
                   
                   
                   
                 Hz), 7.65 (1 H, dd, J = 8.6 Hz, 2.6 Hz), 7.73 (2 H, d, J = 8.2 
               
               
                   
                   
                   
                 Hz), 8.01 (2 H, d, J = 8.1 Hz), 8.10 (1 H, d, J = 2.8 Hz), 
               
               
                   
                   
                   
                 8.53 (1 H, s), 9.19 (1 H, brs). 
               
               
                 2129 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 a mixture of the rotational isomers 
               
               
                   
                   
                   
                 (DMSO-d 6 ) 2.10-2.44 (7 H, m), 3.16-3.57 (9 H, m), 5.96- 
               
               
                   
                   
                   
                 5.99 (2 H, m), 6.67-6.89 (3 H, m), 7.09-7.26 (3 H, m), 7.29- 
               
               
                   
                   
                   
                 7.38 (1 H, m), 7.81 (1 H, d, J = 8.41 Hz), 7.89-7.96 (2 H, m), 
               
               
                   
                   
                   
                 8.10-8.15 (2 H, m), 8.74 (1 H, s). 
               
               
                 2130 
                 4-CF 3 Ph- 
                 —CH 3   
                 a mixture of rotational isomers 
               
               
                   
                   
                   
                 (DMSO-d 6 ) 2.11-2.44 (7 H, m), 3.18-3.57 (9 H, m), 5.96- 
               
               
                   
                   
                   
                 6.00 (2 H, m), 6.67-6.90 (3 H, m), 7.09-7.27 (3 H, m), 7.29- 
               
               
                   
                   
                   
                 7.38 (1 H, m), 7.90 (2 H, d, J = 8.24 Hz), 7.95-8.00 (1 H, m), 
               
               
                   
                   
                   
                 8.11-8.16 (3 H, m), 8.85 (1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 339 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 996   
                 R 997   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 2131 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.46 (9 H, s), 2.41-2.45 (4 H, m), 3.43-3.47 (4 H, m), 3.53 (2 H, s), 6.96 (1 H, d, J = 8.7 Hz), 7.08- 7.14 (2 H, m), 7.36 (2 H, d, J = 8.4 Hz), 7.55 (1 H, d, J = 8.2 Hz), 7.63 (1 H, dd, J = 8.7 Hz, 2.6 Hz), 7.71 (1 H, dd, J = 2.0 Hz), 8.01 (1 H, d, J = 1.8 Hz), 8.11-8.12 (1 H, m), 8.41 (1 H, s). 
               
               
                   
               
               
                 2132 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2.19 (3 H, s), 3.12 (1 H, dd, J = 14.0 Hz, 9.9 Hz), 3.55 (1 H, dd, J = 14.0 Hz, 3.8 Hz), 4.54 (1 H, dd, J = 9.9 Hz, 3.8 Hz), 6.95 (1 H, d, J = 8.7 Hz), 7.04 (1 H, d, J = 8.1 Hz), 7.12 (1 H, dd, J = 8.1 Hz, 2.1 Hz), 7.16 (1 H, d, J = 2.1 Hz), 7.56 (1 H, d, J = 8.4 Hz), 7.64 (1 H, dd, J = 8.7 Hz, 2.3 Hz), 7.71 (1 H, dd, J = 8.4 Hz, 1.8 Hz), 8.02 (1 H, d, J = 1.8 Hz), 8.08 (1 H, d, J = 2.3 Hz), 8.18 (1 H, brs), 8.41 (1 H, s). 
               
               
                   
               
             
          
         
       
     
       Example 2133 
     Production of 3-({4-[5-(3,4-dichlorobenzylamino)-pyridin-2-yloxy]phenyl}methylamino)-1-(4-piperonylpiperazin-1-yl)propane-1-one 
       [1169]    3-[(4-{5-(3,4-dichlorobenzylidene)pyridin-2-yloxy}phenyl)methylamino]-1-(4-piperonylpiperazin-1-yl)propane-1-one (3.88 g, 6.0 mmol) was dissolved in a mixed solvent of methanol (150 mL) and THF (50 mL). To the resulting solution was slowly added sodium borohydride (1.13 g, 30.0 mmol) and that resulting solution was stirred for 13 hours at room temperature. This reaction solution was concentrated under reduced pressure. The resulting residue was diluted with ethyl acetate, and washed with a saturated sodium bicarbonate solution and brine. The organic layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was then purified by silica gel column chromatography (dichloromethane:methanol=40:1), to thereby yield 3.60 g of the title compound. 
         [1170]    Appearance: White powder 
         [1171]      1 H NMR (CDCl 3 ) δ 2.32-2.39 (4H, m), 2.52-2.57 (2H, m), 2.91 (3H, s), 3.36-3.40 (4H, m), 3.59-3.63 (2H, m), 3.66-3.71 (2H, m), 3.97 (1H, brs), 4.27 (2H, d, J=5.0 Hz), 5.94 (2H, s), 6.65-6.76 (5H, m), 6.83 (1H, d, J=1.0 Hz), 6.94 (1H, dd, J=8.9 Hz, 3.0 Hz), 6.97 (2H, d, J=9.2 Hz), 7.18 (1H, dd, J=8.3 Hz, 2.0 Hz), 7.40 (1H, d, J=8.4 Hz), 7.45 (1H, d, J=2.0 Hz), 7.56 (1H, d, J=2.5 Hz); MS 647 (M + ). 
         [1172]    The following compounds were produced in the same manner as in Example 2133. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 340 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 998   
                 R 999   
                 Xb 41   
                 M 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 2134 
                 4-CF 3 Ph- 
                 piperonyl 
                 —N(CH 3 )— 
                 1 
                 (CDCl 3 ) 2.42 (4 H, brs), 2.99 (3 H, s), 3.43- 
               
               
                   
                   
                   
                   
                   
                 3.49 (4 H, m), 3.62 (2 H, brs), 4.04 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                 4.37 (2 H, s), 5.95 (2 H, s), 6.67-6.75 (5 H, m), 
               
               
                   
                   
                   
                   
                   
                 6.86 (1 H, brs), 6.92-6.97 (3 H, m), 7.47 (2 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 7.9 Hz), 7.58-7.61 (3 H, m). 
               
               
                 2135 
                 4-CF 3 Ph- 
                 piperonyl 
                 —N(CH 3 )— 
                 2 
                 (CDCl 3 ) 2.32-2.39 (4 H, m), 2.52-2.57 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                 2.91 (3 H, s), 3.36-3.39 (4 H, m), 3.59-3.63 (2 H, 
               
               
                   
                   
                   
                   
                   
                 m), 3.66-3.71 (2 H, m), 4.00 (1 H, brs), 
               
               
                   
                   
                   
                   
                   
                 4.37 (2 H, d, J = 4.3 Hz), 5.94 (2 H, s), 6.66- 
               
               
                   
                   
                   
                   
                   
                 6.76 (5 H, m), 6.83 (1 H, d, J = 1.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.95 (1 H, dd, J = 8.9 Hz, 3.0 Hz), 6.97 (2 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 9.1 Hz), 7.46 (2 H, d, J = 8.1 Hz), 7.57- 
               
               
                   
                   
                   
                   
                   
                 7.61 (3 H, m). 
               
               
                 2136 
                 3,4-Cl 2 Ph- 
                 piperonyl 
                 —N(CH 3 )— 
                 1 
                 (CDCl 3 ) 2.39-2.43 (4 H, m), 2.99 (3 H, s), 
               
               
                   
                   
                   
                   
                   
                 3.42 (2 H, brs), 3.46-3.50 (2 H, m), 3.60- 
               
               
                   
                   
                   
                   
                   
                 3.62 (2 H, m), 3.97 (1 H, t, J = 5.8 Hz), 
               
               
                   
                   
                   
                   
                   
                 4.05 (2 H, s), 4.26 (2 H, d, J = 5.8 Hz), 
               
               
                   
                   
                   
                   
                   
                 5.95 (2 H, s), 6.65-6.77 (5 H, m), 6.85 (1 H, brs), 
               
               
                   
                   
                   
                   
                   
                 6.93 (1 H, dd, J = 8.6 Hz, 3.1 Hz), 6.96 (2 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 9.1 Hz), 7.18 (1 H, dd, J = 8.3 Hz, 2.1 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.40 (1 H, d, J = 8.3 Hz), 7.45 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 2.1 Hz), 7.57 (1 H, d, J = 2.8 Hz) 
               
               
                 2137 
                 3,4-Cl 2 Ph- 
                 benzyl 
                 none 
                 2 
                 (DMSO-d 6 ) 2.26-2.28 (4 H, m), 2.57 (2 H, t, J = 
               
               
                   
                   
                   
                   
                   
                 7.9 Hz), 2.76 (2 H, t, J = 7.9 Hz), 3.40- 
               
               
                   
                   
                   
                   
                   
                 3.46 (6 H, m), 4.28 (2 H, d, J = 5.9 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.36 (1 H, t, J = 6.1 Hz), 6.77 (1 H, d, J = 8.7 
               
               
                   
                   
                   
                   
                   
                 Hz), 6.85 (2 H, d, J = 8.3 Hz), 7.09 (1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 8.7 Hz, 3.0 Hz), 7.17 (2 H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.24-7.37 (6 H, m), 7.50 (1 H, d, J = 3.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.58 (1 H, d, J = 8.3 Hz), 7.62 (1 H, d, J = 1.8 
               
               
                   
                   
                   
                   
                   
                 Hz). 
               
               
                 2138 
                 3,4-Cl 2 Ph- 
                 benzyl 
                 none 
                 0 
                 (DMSO-d 6 ) 2.38 (4 H, brs), 3.33-3.50 (6 H, m), 
               
               
                   
                   
                   
                   
                   
                 4.30 (2 H, d, J = 6.3 Hz), 6.47 (1 H, t, J = 6.3 
               
               
                   
                   
                   
                   
                   
                 Hz), 6.87 (1 H, d, J = 8.7 Hz), 6.97 (2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.6 Hz), 7.12 (1 H, dd, J = 8.7 Hz, 3.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.25-7.39 (8 H, m), 7.56 (1 H, d, J = 3.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.58-7.64 (2 H, m). 
               
               
                 2139 
                 4-CF 3 Ph- 
                 benzyl 
                 none 
                 0 
                 (CDCl 3 ) 2.45 (4 H, brs), 3.52 (2 H, brs), 
               
               
                   
                   
                   
                   
                   
                 3.53 (2 H, s), 3.73 (2 H, brs), 4.16 (1 H, brs), 
               
               
                   
                   
                   
                   
                   
                 4.41 (2 H, s), 6.80 (1 H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.99 (1 H, dd, J = 8.7 Hz, 3.0 Hz), 7.03 (2 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.5 Hz), 7.20-7.37 (5 H, m), 7.38 (2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.5 Hz), 7.48 (2 H, d, J = 8.1 Hz), 7.61 (2 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.1 Hz), 7.64 (1 H, d, J = 3.0 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 341 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 1000   
                 R 1001   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 2140 
                 3,4-Cl 2 Ph- 
                 —H 
                 2.41 (4 H, brs), 3.19 (3 H, s), 3.33-3.35 (2 H, m), 3.42 (2 H, s), 
               
               
                   
                   
                   
                 3.60 (2 H, brs), 4.08 (1 H, brs), 4.30 (2 H, d, J = 5.3 Hz), 
               
               
                   
                   
                   
                 4.50 (2 H, s), 5.95 (2 H, s), 6.73-6.74 (2 H, m), 6.80-6.84 (2 H, 
               
               
                   
                   
                   
                 m), 6.99 (1 H, dd, J = 8.6 Hz, 3.1 Hz), 7.02 (2 H, d, J = 8.7 
               
               
                   
                   
                   
                 Hz), 7.20 (1 H, dd, J = 8.3 Hz, 2.0 Hz), 7.42 (1 H, d, J = 8.3 
               
               
                   
                   
                   
                 Hz), 7.66 (1 H, d, J = 2.1 Hz), 7.54 (2 H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                 7.60 (1 H, d, J = 2.8 Hz). 
               
               
                 2141 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 2.19 (3 H, s), 2.41 (4 H, brs), 3.19 (3 H, s), 3.35 (2 H, brs), 
               
               
                   
                   
                   
                 3.41 (2 H, s), 3.60 (2 H, brs), 4.07-4.15 (1 H, m), 4.27 (2 H, s), 
               
               
                   
                   
                   
                 4.50 (2 H, s), 5.93 (2 H, s), 6.69-6.78 (3 H, m), 6.83 (1 H, brs), 
               
               
                   
                   
                   
                 6.88 (1 H, d, J = 8.6 Hz), 6.98 (1 H, dd, J = 8.7 Hz, 3.0 Hz), 
               
               
                   
                   
                   
                 7.17-7.20 (1 H, m), 7.34-7.44 (4 H, m), 7.53 (1 H, d, J = 3.0 
               
               
                   
                   
                   
                 Hz). 
               
               
                 2142 
                 4-CF 3 Ph- 
                 —CH 3   
                 2.20 (3 H, s), 2.41 (4 H, brs), 3.19 (3 H, s), 3.35-3.37 (2 H, m), 
               
               
                   
                   
                   
                 3.41 (2 H, s), 3.60-3.62 (2 H, m), 4.15 (1 H, brs), 4.38 (2 H, s), 
               
               
                   
                   
                   
                 4.50 (2 H, s), 5.94 (2 H, s), 6.73 (2 H, brs), 6.76 (1 H, d, J = 8.7 
               
               
                   
                   
                   
                 Hz), 6.83 (1 H, brs), 6.88 (1 H, d, J = 8.6 Hz), 7.00 (1 H, dd, J = 
               
               
                   
                   
                   
                 8.7 Hz, 3.0 Hz), 7.36 (1 H, dd, J= 8.6 Hz, 2.6 Hz), 7.42 (1 H, 
               
               
                   
                   
                   
                 d, J = 2.5 Hz), 7.47 (2 H, d, J = 8.1 Hz), 7.56 (1 H, d, J = 2.8 
               
               
                   
                   
                   
                 Hz), 7.59 (2 H, d, J = 8.1 Hz). 
               
               
                 2143 
                 4-CF 3 Ph- 
                 —OCH 3   
                 2.41 (4 H, brs), 3.21 (3 H, s), 3.36 (2 H, brs), 3.42 (2 H, s), 
               
               
                   
                   
                   
                 3.60 (2 H, brs), 3.76 (3 H, s), 4.09 (1 H, brs), 4.37 (2 H, s), 
               
               
                   
                   
                   
                 4.52 (2 H, s), 5.94 (2 H, s), 6.70-6.83 (4 H, m), 6.97-7.02 (2 H, 
               
               
                   
                   
                   
                 m), 7.12-7.16 (1 H, m), 7.23-7.26 (1 H, m), 7.44-7.60 (5 H, m). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 342 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 1002   
                 R 1003   
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 2144 
                 3,4-Cl 2 Ph- 
                 —H 
                 (CDCl 3 ) 2.17 (3 H, s), 2.48-2.53 (4 H, m), 3.44 (2 H, s), 3.69- 
               
               
                   
                   
                   
                 3.73 (2 H, m), 3.97 (1 H, brs), 4.23-4.27 (4 H, m), 5.95 (2 H, s), 6.70- 
               
               
                   
                   
                   
                 6.74 (3 H, m), 6.85 (1 H, brs), 6.94 (1 H, d, J = 8.7 Hz), 6.96 (1 H, 
               
               
                   
                   
                   
                 dd, J = 8.7 Hz, 3.1 Hz), 7.18 (1 H, dd, J = 8.2 Hz, 2.0 Hz), 
               
               
                   
                   
                   
                 7.36 (1 H, dd, J = 8.7 Hz, 2.5 Hz), 7.40 (1 H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                 7.45 (1 H, d, J = 2.1 Hz), 7.51 (1 H, d, J = 2.3 Hz), 7.55 (1 H, d, J = 
               
               
                   
                   
                   
                 3.0 Hz), 9.11 (1 H, brs). 
               
               
                 2145 
                 4-CF 3 Ph- 
                 —H 
                 (CDCl 3 ) 2.19 (3 H, s), 2.48-2.53 (4 H, m), 3.44 (2 H, s), 3.70- 
               
               
                   
                   
                   
                 3.73 (2 H, m), 4.00 (1 H, brs), 4.23-4.27 (2 H, m), 4.37 (2 H, s), 
               
               
                   
                   
                   
                 5.95 (2 H, s), 6.72 (1 H, d, J = 8.7 Hz), 6.74-6.77 (2 H, m), 6.85 (1 H, 
               
               
                   
                   
                   
                 brs), 6.94 (1 H, d, J = 8.7 Hz), 6.97 (1 H, dd, J = 8.7 Hz, 3.1 Hz), 
               
               
                   
                   
                   
                 7.37 (1 H, dd, J = 8.7 Hz, 2.6 Hz), 7.47 (2 H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                 7.51 (1 H, d, J = 2.5 Hz), 7.57 (1 H, d, J = 3.1 Hz), 7.60 (2 H, d, J = 
               
               
                   
                   
                   
                 8.1 Hz), 9.11 (1 H, brs). 
               
               
                 2146 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 a mixture of the rotational isomers 
               
               
                   
                   
                   
                 (DMSO-d 6 ) 2.25-2.42 (7 H, m), 3.22-3.55 (9 H, m), 4.27 (2 H, d, J = 
               
               
                   
                   
                   
                 6.27 Hz), 5.77-5.99 (2 H, m), 6.38 (1 H, t, J = 6.27 Hz), 6.65- 
               
               
                   
                   
                   
                 6.90 (5 H, m), 7.06-7.14 (2 H, m), 7.22-7.28 (1 H, m), 7.32-7.36 (1 H, 
               
               
                   
                   
                   
                 m), 7.46 (1 H, d, J = 2.80 Hz), 7.56-7.61 (2 H, m). 
               
               
                 2147 
                 4-CF 3 Ph- 
                 —CH 3   
                 a mixture of the rotational isomers 
               
               
                   
                   
                   
                 (DMSO-d 6 ) 2.24-2.41 (7 H, m), 3.20-3.54 (9 H, m), 4.34-4.36 (2 H, 
               
               
                   
                   
                   
                 m), 5.95-5.98 (2 H, m), 6.38-6.41 (1 H, m), 6.65-6.88 (5 H, m), 7.03- 
               
               
                   
                   
                   
                 7.13 (2 H, m), 7.21-7.27 (1 H, m), 7.45 (1 H, d, J = 2.64 Hz), 
               
               
                   
                   
                   
                 7.55 (2 H, d, J = 7.75 Hz), 7.67 (2 H, d, J = 7.75 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 343 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 1004   
                 R 1005   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 2148 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.45 (9 H, s), 2.37-2.40 (4 H, m), 3.40-3.44 (4 H, m), 3.47 (2 H, s), 4.28 (2 H, s), 6.77 (1 H, d, J = 8.7 Hz), 6.95-7.01 (3 H, m), 7.17-7.21 (1 H, m), 7.26- 7.29 (2 H, m), 7.41 (1 H, d, J = 8.1 Hz), 7.45 (1 H, d, J = 1.8 Hz), 7.60 (1 H, d, J = 3.0 Hz). 
               
               
                   
               
               
                 2149 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2.19 (3 H, s), 3.05 (1 H, dd, J = 14.0 Hz, 10.0 Hz), 3.50 (1 H, dd, J = 14.0 Hz, 3.8 Hz), 4.02 (1 H, brs), 4.27 (2 H, s), 4.49 (1 H, dd, J = 10.0 Hz, 3.8 Hz), 6.73 (1 H, d, J = 8.7 Hz), 6.99 (1 H, d, J = 8.2 Hz), 6.97 (1 H, dd, J = 8.7 Hz, 2.9 Hz), 7.02 (1 H, dd, J = 8.2 Hz, 2.0 Hz), 7.09 (1 H, d, J = 2.0 Hz), 7.18 (1 H, dd, J = 8.2 Hz, 2.0 Hz), 7.41 (1 H, d, J = 8.2 Hz), 7.45 (1 H, d, J = 2.0 Hz), 7.55 (1 H, d, J = 2.9 Hz), 8.61 (1 H, brs). 
               
               
                   
               
             
          
         
       
     
       Example 2150 
     Production of 1-(4-benzylpiperazin-1-yl)-3-(4-{5-(piperonylamino)pyridin-2-yloxy}phenyl)propane-1-one 
       [1173]    3-[4-(5-aminopyridin-2-yloxy)phenyl]-1-(4-piperonylpiperazin-1-yl)propane-1-one (1.04 g, 2.5 mmol) was dissolved in methanol (25 mL). To the resulting solution was added piperonal (0.39 g, 2.63 mmol), and this solution was refluxed overnight. The resulting reaction solution was cooled with ice, and then sodium borohydride (0.28 g, 7.50 mmol) was added. The resulting solution was stirred for 2 hours at room temperature. This reaction solution was concentrated under reduced pressure. The residue was diluted with ethyl acetate, and washed with water, saturated sodium bicarbonate solution and brine. The organic layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was then purified by silica gel column chromatography (ethyl acetate), to thereby yield 0.80 g of the title compound. 
         [1174]    Appearance: Yellow oil 
         [1175]      1 H NMR (DMSO-d 6 ) δ 2.28 (4H, brs), 2.57 (2H, t, J=7.9 Hz), 2.76 (2H, t, J=7.9 Hz), 3.40-3.46 (6H, m), 4.15 (2H, d, J=6.1 Hz), 5.97 (2H, s), 6.21 (1H, t, J=6.1 Hz), 6.76 (1H, d, J=8.6 Hz), 6.82-6.86 (4H, m), 6.92 (1H, brs), 7.08 (1H, dd, J=8.7 Hz, 3.0 Hz), 7.17 (2H, d, J=8.4 Hz), 7.24-7.32 (5H, m), 7.51 (1H, d, J=3.0 Hz). 
         [1176]    The following compounds were produced in the same manner as in Example 2150. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 344 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 1006   
                 R 1007   
                 R 1008    
                 Xb 42   
                 M 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 2151 
                 4-CF 3 Ph- 
                 —CH 3   
                 piperonyl 
                 —N(C 2 H 5 )— 
                 1 
                 (CDCl 3 ) 1.15 (3 H, t, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 2.11 (3 H, s), 2.30-2.50 (4 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 3.39 (2 H, q, J = 7.1 Hz), 3.42 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 3.42-3.55 (2 H, m) 3.56-3.70 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 3.80-4.05 (1 H, m), 3.99 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 4.36 (2 H, s), 5.94 (2 H, s), 6.44- 
               
               
                   
                   
                   
                   
                   
                   
                 6.55 (2 H, m), 6.58-6.64 (1 H, m), 6.69- 
               
               
                   
                   
                   
                   
                   
                   
                 6.78 (2 H, m), 6.80-6.89 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 6.94 (1 H, dd, J = 8.8 Hz, 3.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.46 (2 H, d, J = 8.0 Hz), 7.55- 
               
               
                   
                   
                   
                   
                   
                   
                 7.63 (3 H, m). 
               
               
                 2152 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 piperonyl 
                 —N(C 2 H 5 )— 
                 1 
                 (CDCl 3 ) 1.15 (3 H, t, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 2.11 (3 H, s), 2.32-2.49 (4 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 3.39 (2 H, q, J = 7.1 Hz), 3.42 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 3.44-3.55 (2 H, m), 3.56-3.69 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 3.79-3.94 (1 H, m), 3.99 (2 H, s), 4.15- 
               
               
                   
                   
                   
                   
                   
                   
                 4.30 (2 H, m), 5.94 (2 H, s), 6.50 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 dd, J = 8.5 Hz, 3.0 Hz), 6.54 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 3.0 Hz), 6.58-6.65 (1 H, m), 6.69- 
               
               
                   
                   
                   
                   
                   
                   
                 6.78 (2 H, m), 6.82-6.88 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 6.92 (1 H, dd, J = 8.8 Hz, 3.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.18 (1 H, dd, J = 8.2 Hz, 2.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.40 (1 H, d, J = 8.2 Hz), 7.45 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 2.0 Hz), 7.57 (1 H, d, J = 3.0 Hz). 
               
               
                 2153 
                 4-CF 3 Ph- 
                 —H 
                 benzyl 
                 none 
                 2 
                 (DMSO-d 6 ) 2.28 (4 H, brs), 2.54- 
               
               
                   
                   
                   
                   
                   
                   
                 2.60 (2 H, m), 2.73-2.79 (2 H, m), 3.42- 
               
               
                   
                   
                   
                   
                   
                   
                 3.46 (6 H, m), 4.37 (2 H, d, J = 5.9 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 6.41 (1 H, t, J = 6.1 Hz), 6.77 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.7 Hz), 6.84 (2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.08 (1 H, dd, J = 8.7 Hz, 3.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.17 (2 H, d, J = 8.6 Hz), 7.22- 
               
               
                   
                   
                   
                   
                   
                   
                 7.35 (5 H, m), 7.50 (1 H, d, J = 3.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.58 (2 H, d, J = 7.9 Hz), 7.69 (2 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 7.9 Hz). 
               
               
                 2154 
                 4-ClPh- 
                 —H 
                 benzyl 
                 none 
                 2 
                 (DMSO-d 6 ) 2.28 (4 H, t, J = 4.8 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 2.57 (2 H, t, J = 7.3 Hz), 2.76 (2 H, t, J = 
               
               
                   
                   
                   
                   
                   
                   
                 7.3 Hz), 3.38-3.46 (6 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 4.25 (2 H, d, J = 6.1 Hz), 6.32 (1 H, t, J = 
               
               
                   
                   
                   
                   
                   
                   
                 6.1 Hz), 6.76 (1 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 6.84 (2 H, d, J = 8.6 Hz), 7.07 (1 H, dd, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.7 Hz, 3.1 Hz), 7.17 (2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.6 Hz), 7.24-7.32 (5 H, m), 7.38 (4 H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs), 7.50 (1 H, d, J = 3.1 Hz). 
               
               
                 2155 
                 3,4-F 2 Ph- 
                 —H 
                 benzyl 
                 none 
                 2 
                 (DMSO-d 6 ) 2.26-2.28 (4 H, m), 2.57- 
               
               
                   
                   
                   
                   
                   
                   
                 2.60 (2 H, m), 2.73-2.79 (2 H, m), 3.37- 
               
               
                   
                   
                   
                   
                   
                   
                 3.46 (6 H, m), 4.25 (2 H, d, J = 5.8 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 6.32 (1 H, t, J = 5.8 Hz), 6.77 
               
               
                   
                   
                   
                   
                   
                   
                 (1 H, d, J = 8.6 Hz), 6.84 (2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.3 Hz), 7.08 (1 H, dd, J = 8.6 Hz, 3.0 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.17 (2 H, d, J = 8.4 Hz), 7.22- 
               
               
                   
                   
                   
                   
                   
                   
                 7.43 (8 H, m), 7.50 (1 H, d, J = 3.1 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 345 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                 mp (° C.) or  1 H NMR (solvent) 
               
               
                 No. 
                 R 1009   
                 R 1010   
                 R 1011   
                 Xb 43   
                 M 
                 δ ppm 
               
               
                   
               
               
                 2156 
                 4-CF 3 Ph- 
                 —CH 3   
                 piperonyl 
                 —N(CH 3 )— 
                 1 
                   1 H NMR (CDCl 3 ) 2.12 (3 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 2.42 (4 H, t, J = 5.0 Hz), 2.98 (3 H, 
               
               
                   
                   
                   
                   
                   
                   
                 s), 3.41-3.55 (4 H, m), 3.56- 
               
               
                   
                   
                   
                   
                   
                   
                 3.67 (2 H, m), 3.77-3.99 (1 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 4.04 (2 H, s), 4.36 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 5.94 (2 H, s), 6.52 (1 H, dd, J = 8.7 
               
               
                   
                   
                   
                   
                   
                   
                 Hz, 3.0 Hz), 6.56 (1 H, d, J = 3.0 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 6.59-6.64 (1 H, m), 6.69- 
               
               
                   
                   
                   
                   
                   
                   
                 6.78 (2 H, m), 6.85 (1 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 6.87 (1 H, d, J = 8.7 Hz), 6.93 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 dd, J = 8.8 Hz, 3.0 Hz), 7.46 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 8.0 Hz), 7.54-7.63 (3 H, m). 
               
               
                 2157 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 piperonyl 
                 —N(CH 3 )— 
                 1 
                 mp 132-134 
               
               
                 2158 
                 4-CF 3 Ph- 
                 —CH 3   
                 piperonyl 
                 —N(Ac)— 
                 1 
                   1 H NMR (CDCl 3 ) 1.94 (3 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 2.09 (3 H, s), 2.30-2.50 (4 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 3.29-3.51 (4 H, m), 3.52-3.69 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 3.92-4.17 (1 H, m), 4.29- 
               
               
                   
                   
                   
                   
                   
                   
                 4.51 (4 H, m), 5.94 (2 H, s), 6.69- 
               
               
                   
                   
                   
                   
                   
                   
                 6.77 (2 H, m), 6.78 (1 H, d, J = 8.7 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 6.81-6.86 (1 H, m), 6.91 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 8.5 Hz), 7.01 (1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.7 Hz, 3.1 Hz), 7.18 (1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.5 Hz, 2.5 Hz), 7.28 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 2.5 Hz), 7.48 (2 H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.56-7.64 (3 H, m). 
               
               
                 2159 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 piperonyl 
                 —N(Ac)— 
                 1 
                   1 H NMR (CDCl 3 ) 1.95 (3 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 2.07 (3 H, s), 2.30-2.51 (4 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 3.29-3.50 (4 H, m), 3.51-3.71 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 3.92-4.18 (1 H, m), 4.29 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 s), 4.42 (2 H, s), 5.94 (2 H, s), 6.69- 
               
               
                   
                   
                   
                   
                   
                   
                 6.78 (3 H, m), 6.82-6.87 (1 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 6.91 (1 H, d, J = 8.5 Hz), 7.00 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 dd, J = 8.7, 3.0 Hz), 7.14- 
               
               
                   
                   
                   
                   
                   
                   
                 7.23 (2 H, m), 7.26-7.31 (1 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.41 (1 H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.46 (1 H, d, J = 2.0 Hz), 7.57 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 3.0 Hz). 
               
               
                 2160 
                 Ph- 
                 —H 
                 benzyl 
                 none 
                 2 
                   1 H NMR (DMSO-d 6 ) 2.27 (4 H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs), 2.54-2.60 (2 H, m), 2.73- 
               
               
                   
                   
                   
                   
                   
                   
                 2.79 (2 H, m), 3.40-3.46 (6 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 4.25 (2 H, d, J = 5.9 Hz), 6.28 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 t, J = 5.9 Hz), 6.76 (1 H, d, J = 8.7 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 6.84 (2 H, d, J = 8.4 Hz), 7.09 
               
               
                   
                   
                   
                   
                   
                   
                 (1 H, dd, J = 8.7 Hz, 3.0 Hz), 7.17 
               
               
                   
                   
                   
                   
                   
                   
                 (2 H, d, J = 8.7 Hz), 7.23-7.38 
               
               
                   
                   
                   
                   
                   
                   
                 (10 H, m), 7.52 (1 H, d, J = 3.0 
               
               
                   
                   
                   
                   
                   
                   
                 Hz). 
               
               
                 2161 
                 4-CF 3 Ph- 
                 —OCH 3   
                 piperonyl 
                 —N(CH 3 )— 
                 1 
                 mp 102-103 
               
               
                 2162 
                 3,4-Cl 2 Ph- 
                 —OCH 3   
                 piperonyl 
                 —N(CH 3 )— 
                 1 
                 mp 145-146 
               
               
                 2163 
                 4-CF 3 Ph- 
                 —OCH 3   
                 piperonyl 
                 —N(C 2 H 5 )— 
                 1 
                 mp 160.0-160.5 
               
               
                 2164 
                 3,4-Cl 2 Ph- 
                 —OCH 3   
                 piperonyl 
                 —N(C 2 H 5 )— 
                 1 
                 mp 133-134 
               
               
                 2165 
                 3,4-Cl 2 Ph- 
                 —F 
                 piperonyl 
                 —N(CH 3 )— 
                 1 
                 mp 134-137 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 346 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 1012   
                 R 1013   
                 Xb 44   
                 M 
                 mp (° C.) or  1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 2166 
                 4-CF 3 Ph- 
                 —OCH 3   
                 none 
                 2 
                   1 H NMR 2.38-2.44 (4 H, m), 2.56-2.67 (2 H, 
               
               
                   
                   
                   
                   
                   
                 m), 2.88-2.99 (2 H, m), 3.31-3.45 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                 3.40 (2 H, s), 3.57-3.69 (2 H, m), 3.76 (3 H, 
               
               
                   
                   
                   
                   
                   
                 s), 3.80-4.06 (1 H, m), 4.37 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                 5.94 (2 H, s), 6.68-6.81 (4 H, m), 6.83- 
               
               
                   
                   
                   
                   
                   
                 6.87 (2 H, m), 6.96 (1 H, d, J = 8.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.98 (1 H, dd, J = 8.7 Hz, 3.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.46 (2 H, d, J = 8.0 Hz), 7.54 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 2.6 Hz), 7.59 (2 H, d, J = 8.0 Hz). 
               
               
                 2167 
                 4-CF 3 Ph- 
                 —F 
                 —N(C 2 H 5 )— 
                 1 
                 mp 106-107 
               
               
                 2168 
                 4-CF 3 Ph- 
                 —F 
                 —N(CH 3 )— 
                 1 
                 mp 163-164 
               
               
                 2169 
                 3,4-Cl 2 Ph- 
                 —F 
                 —N(C 2 H 5 )— 
                 1 
                 mp 107.5-109.0 
               
               
                 2170 
                 4-CF 3 Ph- 
                 —H 
                 —N(SO 2 CH 3 )— 
                 1 
                   1 H NMR 2.41 (4 H, brs), 3.18 (3 H, s), 
               
               
                   
                   
                   
                   
                   
                 3.35 (2 H, brs), 3.42 (2 H, s), 3.62 (2 H, brs), 
               
               
                   
                   
                   
                   
                   
                 4.14 (1 H, brs), 4.41 (2 H, brs), 4.50 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                 5.94 (2 H, s), 6.70-6.76 (2 H, m), 6.80- 
               
               
                   
                   
                   
                   
                   
                 6.83 (2 H, m), 6.98-7.04 (3 H, m), 7.47- 
               
               
                   
                   
                   
                   
                   
                 7.56 (4 H, m), 7.60-7.63 (3 H, m). 
               
               
                   
               
             
          
         
       
     
       Example 2171 
     Production of 1-(4-benzylpiperazin-1-yl)-3-[4-(5-dibenzylaminopyridin-2-yloxy)phenyl]propane-1-one 
       [1177]    3-[4-(5-aminopyridin-2-yloxy)phenyl]-1-(4-benzylpiperazin-1-yl)propane-1-one (1.0 g, 2.4 mmol) was dissolved in DMF (30 mL). To this solution were added potassium carbonate (0.73 g, 5.28 mmol), sodium iodide (0.76 g, 5.04 mmol) and benzyl bromide (0.60 mL, 5.04 mmol), and the resulting solution was stirred at room temperature overnight. This reaction solution was concentrated under reduced pressure. The residue was diluted with chloroform, and washed with water, saturated sodium bicarbonate solution and brine. The organic layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was then purified by silica gel column chromatography (chloroform methanol=80:1), to thereby yield 0.67 g of the title compound. 
         [1178]    Appearance: Yellow oil 
         [1179]      1 H NMR (DMSO-d 6 ) δ 2.27 (4H, brs), 2.50-2.59 (2H, m), 2.73-2.78 (2H, m), 3.37-3.45 (6H, m), 4.68 (4H, s), 6.78 (1H, d, J=8.9 Hz), 6.85 (2H, d, J=8.4 Hz), 7.17 (2H; d, J=8.6 Hz), 7.20-7.36 (16H, m), 7.54 (1H, d, J=3.1 Hz). 
       Example 2172 
     Production of 2-[(4-{5-[(3,4-dichlorobenzyl)-ethylamino]pyridin-2-yloxy}phenyl)methylamino]-1-(4-piperonylpiperazin-1-yl)ethanone 
       [1180]    2-({4-[5-(3,4-dichlorobenzylamino)pyridin-2-yloxy]phenyl}methylamino)-1-(4-piperonylpiperazin-1-yl)ethanone (1.59 g, 2.5 mmol) was dissolved in dichloroethane (80 mL). To this solution were added acetoaldehyde (1.40 mL, 25.0 mmol) and sodium triacetyloxy borohydride (1.59 mL, 7.5 mmol) under ice cooling. To the resulting solution was added dropwise acetic acid (0.43 mL, 7.5 mmol), and this solution was stirred at room temperature for 16 hours. The resulting reaction solution was washed with a saturated sodium bicarbonate solution and brine. The organic layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was then purified by silica gel column chromatography (chloroform:methanol=50:1). The obtained solid was recrystallized from ethanol, to thereby yield 0.65 g of the title compound. 
         [1181]    Appearance: White powder 
         [1182]      1 H NMR (CDCl 3 ) δ 1.17 (3H, t, J=7.1 Hz), 2.41 (4H, brs), 2.99 (3H, s), 3.36-3.44 (4H, m), 3.48 (2H, brs), 3.62 (2H, brs), 4.04 (2H, s), 4.35 (2H, s), 5.95 (2H, s), 6.67-6.77 (5H, m), 6.85 (1H, brs), 6.97 (2H, d, J=9.1 Hz), 7.01 (1H, dd, J=8.9 Hz, 3.1 Hz), 7.07 (1H, dd, J=8.2 Hz, 2.0 Hz), 7.32 (1H, d, J=2.0 Hz), 7.37 (1H, d, J=8.3 Hz), 7.63 (1H, d, J=3.0 Hz).; MS 661 (M + ). 
         [1183]    The following compounds were produced in the same manner as in Example 2172. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 347 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 1014   
                 R 1015   
                 R 1016   
                 Xb 45   
                 M 
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 2173 
                 4-CF 3 Ph- 
                 —H 
                 piperonyl 
                 —N(CH 3 )— 
                 1 
                 2.44 (4 H, brs), 2.99 (6 H, s), 3.39- 
               
               
                   
                   
                   
                   
                   
                   
                 3.62 (6 H, m), 4.04 (2 H, s), 4.48 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 s), 5.95 (2 H, s), 6.62-6.78 (5 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 6.86 (1 H, brs), 6.97 (2 H, d, J = 9.1 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.08 (1 H, dd, J = 8.9 Hz, 3.1 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.34 (2 H, d, J = 7.9 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.57 (2 H, d, J = 8.1 Hz), 7.69 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 3.1 Hz). 
               
               
                 2174 
                 3,4-Cl 2 Ph- 
                 —H 
                 piperonyl 
                 —N(CH 3 )— 
                 2 
                 2.32-2.40 (4 H, m), 2.53-2.58 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 2.92 (3 H, s), 2.97 (3 H, s), 3.37- 
               
               
                   
                   
                   
                   
                   
                   
                 3.40 (4 H, m), 3.59-3.63 (2 H, m), 3.66- 
               
               
                   
                   
                   
                   
                   
                   
                 3.72 (2 H, m), 4.37 (2 H, s), 5.94 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 s), 6.66-6.76 (5 H, m), 6.83 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 1.0 Hz), 6.98 (2 H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.04-7.11 (2 H, m), 7.32 (1 H, d, J = 2.0 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.38 (1 H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.67 (1 H, d, J = 3.1 Hz). 
               
               
                 2175 
                 4-CF 3 Ph- 
                 —H 
                 piperonyl 
                 —N(CH 3 )— 
                 2 
                 2.32-2.39 (4 H, m), 2.52-2.57 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 2.92 (3 H, s), 2.99 (3 H, s), 3.36- 
               
               
                   
                   
                   
                   
                   
                   
                 3.40 (4 H, m), 3.59-3.63 (2 H, m), 3.66- 
               
               
                   
                   
                   
                   
                   
                   
                 3.72 (2 H, m), 4.48 (2 H, s), 5.94 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 s), 6.67-6.76 (5 H, m), 6.83 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 1.0 Hz), 6.98 (2 H, d, J = 9.2 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.09 (1 H, dd, J = 9.1 Hz, 3.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.34 (2 H, d, J = 7.9 Hz), 7.57 (2 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.1 Hz), 7.68 (1 H, d, J = 2.8 Hz). 
               
               
                 2176 
                 3,4-Cl 2 Ph- 
                 —H 
                 piperonyl 
                 —N(CH 3 )— 
                 1 
                 2.40-2.44 (4 H, m), 2.96 (3 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 3.00 (3 H, s), 3.43 (2 H, brs), 3.49 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs), 3.62 (2 H, brs), 4.05 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 4.36 (2 H, s), 5.95 (2 H, s), 6.67- 
               
               
                   
                   
                   
                   
                   
                   
                 6.77 (5 H, m), 6.85 (1 H, brs), 6.97 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 9.1 Hz), 7.06 (1 H, dd, J = 8.3 
               
               
                   
                   
                   
                   
                   
                   
                 Hz, 1.7 Hz), 7.07 (1 H, dd, J = 8.9 Hz, 
               
               
                   
                   
                   
                   
                   
                   
                 3.1 Hz), 7.32 (1 H, d, J = 2.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.38 (1 H, d, J = 8.3 Hz), 7.69 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 3.1 Hz). 
               
               
                 2177 
                 4-CF 3 Ph- 
                 —F 
                 benzyl 
                 none 
                 0 
                 2.46 (4 H, brs), 3.02 (3 H, s), 3.54 (6 H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs), 4.52 (2 H, s), 6.89 (1 H, d, J = 8.9 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.14 (1 H, dd, J = 8.9 Hz, 3.1 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.17-7.21 (2 H, m), 7.28-7.35 
               
               
                   
                   
                   
                   
                   
                   
                 (8 H, m), 7.58 (2 H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.62 (1 H, d, J = 2.8 Hz). 
               
               
                 2178 
                 3,4-Cl 2 Ph- 
                 —F 
                 benzyl 
                 none 
                 0 
                 2.47 (4 H, brs), 3.00 (3 H, s), 3.55- 
               
               
                   
                   
                   
                   
                   
                   
                 3.73 (6 H, m), 4.40 (2 H, s), 6.89 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.9 Hz), 7.06 (1 H, dd, J = 8.2 Hz, 
               
               
                   
                   
                   
                   
                   
                   
                 1.7 Hz), 7.14 (1 H, dd, J = 8.9 Hz, 3.1 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.17-7.22 (3 H, m), 7.28-7.33 (6 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 7.39 (1 H, d, J = 8.3 Hz), 7.61 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 3.3 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 348 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                 mp (° C.) or  1 H NMR (DMSO-d 6 ) 
               
               
                 No. 
                 R 1017   
                 R 1018   
                 R 1019   
                 Form 
                 δ ppm 
               
               
                   
               
               
                 2179 
                 4-CF 3 Ph- 
                 —CH 3   
                 —C 2 H 5   
                 fumarate 
                 mp 157-159 dec 
               
               
                 2180 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 —C 2 H 5   
                 fumarate 
                 mp 148-151 dec 
               
               
                 2181 
                 4-CF 3 Ph- 
                 —CH 3   
                 —CH 3   
                 fumarate 
                 mp 151-154 
               
               
                 2182 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 —CH 3   
                 hydrochloride 
                 mp 139-142 
               
               
                 2183 
                 4-CF 3 Ph- 
                 —CH 3   
                 —Ac 
                 hydrochloride 
                 mp 199.5-201.5 
               
               
                 2184 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 —Ac 
                 hydrochloride 
                 mp 188.5-190.0 
               
               
                 2185 
                 4-CF 3 Ph- 
                 —OCH 3   
                 —CH 3   
                 oxalate 
                   1 H NMR 2.48-2.81 (4 H, m), 
               
               
                   
                   
                   
                   
                   
                 2.93 (3 H, s), 2.94 (3 H, s), 3.36- 
               
               
                   
                   
                   
                   
                   
                 3.85 (9 H, m), 4.25 (2 H, s), 4.56 
               
               
                   
                   
                   
                   
                   
                 (2 H, s), 6.01 (2 H, s), 6.12 (1 H, dd, 
               
               
                   
                   
                   
                   
                   
                 J = 8.8 Hz, 2.8 Hz), 6.29 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 2.8 Hz), 6.66 (1 H, d, J = 9.0 
               
               
                   
                   
                   
                   
                   
                 Hz), 6.77 (1 H, d, J = 8.8 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.79-6.98 (3 H, m), 7.22 (1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 9.0 Hz, 3.2 Hz), 7.42 (2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.1 Hz), 7.52 (1 H, d, J = 3.2 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.67 (2 H, d, J = 8.1 Hz). 
               
               
                 2186 
                 3,4-Cl 2 Ph- 
                 —OCH 3   
                 —CH 3   
                 hydrochloride 
                   1 H NMR 2.75-3.18 (8 H, m), 3.21- 
               
               
                   
                   
                   
                   
                   
                 3.42 (2 H, m), 3.63 (3 H, s), 3.83- 
               
               
                   
                   
                   
                   
                   
                 4.52 (10 H, m), 6.06 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                 6.16 (1 H, dd, J = 8.8 Hz, 2.7 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.34 (1 H, d, J = 2.7 Hz), 6.68 (1 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 9.0 Hz), 6.79 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.8 Hz), 6.94-7.06 (2 H, m), 7.16- 
               
               
                   
                   
                   
                   
                   
                 7.24 (2 H, m), 7.27 (1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 9.0 Hz, 3.2 Hz), 7.47 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 2.0 Hz), 7.53 (1 H, d, J = 3.2 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.56 (1 H, d, J = 8.2 Hz), 10.91- 
               
               
                   
                   
                   
                   
                   
                 11.26 (1 H, m). 
               
               
                 2187 
                 4-CF 3 Ph- 
                 —OCH 3   
                 —C 2 H 5   
                 fumarate 
                 mp 159-162 
               
               
                 2188 
                 3,4-Cl 2 Ph- 
                 —OCH 3   
                 —C 2 H 5   
                 fumarate 
                 mp 154-157 
               
               
                 2189 
                 4-CF 3 Ph- 
                 —F 
                 —CH 3   
                 hydrobromide 
                 mp 211-212 
               
               
                 2190 
                 3,4-Cl 2 Ph- 
                 —F 
                 —CH 3   
                 hydrobromide 
                 mp 206.5-207.0 
               
               
                 2191 
                 4-CF 3 Ph- 
                 —F 
                 —C 2 H 5   
                 hydrobromide 
                 mp 151.0-152.5 
               
               
                 2192 
                 3,4-Cl 2 Ph- 
                 —F 
                 —C 2 H 5   
                 hydrobromide 
                 mp 172.5-174.5 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 349 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 1020   
                 R 1021   
                 R 1022   
                 M 
                 Form 
                   1 H NMR (DMSO-d 6 ) δ ppm 
               
               
                   
               
               
                 2193 
                 Ph- 
                 —CH 3   
                 —H 
                 2 
                 dihydro- 
                 2.50-3.07 (10 H, m), 3.22-3.31 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                 chloride 
                 3.45-3.50 (1 H, m), 4.03-4.08 (1 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 4.30 (2 H, d, J = 3.8 Hz), 4.42-4.55 (3 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 6.85-6.92 (3 H, m), 7.19-7.26 (5 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.30-7.35 (3 H, m), 7.45-7.47 (3 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.58-7.60 (2 H, m), 7.66 (1 H, d, J = 2.8 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 11.33 (2 H, brs). 
               
               
                 2194 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 —H 
                 0 
                 dihydro- 
                 2.50-2.51 (2 H, m), 3.03 (3 H, s), 3.13- 
               
               
                   
                   
                   
                   
                   
                 chloride 
                 3.48 (6 H, m), 4.34-4.37 (2 H, m), 4.58 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 s), 6.97 (1 H, d, J = 8.9 Hz), 7.04 (2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.4 Hz), 7.23 (1 H, dd, J = 8.4 Hz, 1.5 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.34 (1 H, dd, J = 8.9 Hz, 3.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.44-7.47 (5 H, m), 7.51 (1 H, d, J = 1.5 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.58-7.61 (3 H, m), 7.70 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 3.3 Hz), 11.52 (2 H, brs). 
               
               
                 2195 
                 4-CF 3 Ph- 
                 —CH 3   
                 —H 
                 0 
                 dihydro- 
                 3.06 (3 H, s), 3.00-3.20 (2 H, m), 3.20- 
               
               
                   
                   
                   
                   
                   
                 chloride 
                 3.40 (2 H, m), 3.45 (2 H, brs), 4.20- 
               
               
                   
                   
                   
                   
                   
                   
                 4.50 (2 H, m), 4.34 (2 H, s), 4.69 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 6.97 (1 H, d, J = 8.9 Hz), 7.04 (2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.8 Hz), 7.33 (1 H, dd, J = 8.9 Hz, 3.1 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.41-7.49 (7 H, m), 7.55-7.68 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 7.70 (1 H, d, J = 3.1 Hz), 7.71 (2 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.0 Hz). 
               
               
                 2196 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 —H 
                 2 
                 dihydro- 
                 2.49-3.07 (10 H, m), 3.23-3.27 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                 chloride 
                 3.45-3.55 (1 H, m), 4.03-4.08 (1 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 4.30 (2 H, d, J = 4.3 Hz), 4.42-4.47 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 4.54 (2 H, s), 6.87 (1 H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 6.90 (2 H, d, J = 8.6 Hz), 7.19-7.23 (3 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 7.32 (1 H, dd, J = 8.9 Hz, 3.3 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.45-7.50 (4 H, m), 7.57-7.64 (4 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 11.33 (2 H, brs). 
               
               
                 2197 
                 4-CF 3 Ph- 
                 —C 2 H 5   
                 —F 
                 0 
                 hydro- 
                 1.21 (3 H, t, J = 6.9 Hz), 2.50-2.51 (2 H, 
               
               
                   
                   
                   
                   
                   
                 chloride 
                 m), 3.14-3.38 (6 H, m), 3.49 (2 H, q, J = 
               
               
                   
                   
                   
                   
                   
                   
                 6.9 Hz), 4.34 (2 H, brs), 4.61 (2 H, brs), 
               
               
                   
                   
                   
                   
                   
                   
                 6.98 (1 H, d, J = 8.9 Hz), 7.25-7.29 (3 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 7.42-7.50 (7 H, m), 7.58 (2 H, brs), 
               
               
                   
                   
                   
                   
                   
                   
                 7.69 (2 H, d, J = 8.1 Hz), 11.12 (1 H, brs). 
               
               
                 2198 
                 3,4-Cl 2 Ph- 
                 —C 2 H 5   
                 —F 
                 0 
                 hydro- 
                 1.10 (3 H, t, J = 7.0 Hz), 2.49-2.52 (2 H, 
               
               
                   
                   
                   
                   
                   
                 chloride 
                 m), 3.13 (2 H, brs), 3.32-3.58 (6 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 4.33 (2 H, brs), 4.50 (2 H, brs), 6.99 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 9.1 Hz), 7.20-7.31 (4 H, m), 7.42-7.57 
               
               
                   
                   
                   
                   
                   
                   
                 (6 H, m), 7.58-7.60 (3 H, m), 11.14 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 350 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 1023   
                 R 1024   
                 R 1025   
                 M 
                 Form 
                 mp (° C.) or  1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 2199 
                 3,4-Cl 2 Ph- 
                 —H 
                 —CH 3   
                 2 
                 free 
                   1 H NMR (CDCl 3 ) 1.17 (3 H, t, J = 
               
               
                   
                   
                   
                   
                   
                   
                 7.1 Hz), 2.32-2.39 (4 H, m), 2.52- 
               
               
                   
                   
                   
                   
                   
                   
                 2.57 (2 H, m), 2.91 (3 H, s), 3.36- 
               
               
                   
                   
                   
                   
                   
                   
                 3.44 (6 H, m), 3.59-3.63 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 3.66-3.71 (2 H, m), 4.35 (2 H, s), 5.95 
               
               
                   
                   
                   
                   
                   
                   
                 (2 H, s), 6.67-6.76 (5 H, m), 6.83 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 1.0 Hz), 6.98 (2 H, d, J = 9.1 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.03 (1 H, dd, J = 9.1 Hz, 3.3 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.07 (1 H, dd, J = 8.9 Hz, 2.1 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.32 (1 H, d, J = 2.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.47 (1 H, d, J = 8.3 Hz), 7.62 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 3.1 Hz). 
               
               
                 2200 
                 4-CF 3 Ph- 
                 —H 
                 —CH 3   
                 2 
                 free 
                   1 H NMR (CDCl 3 ) 1.19 (3 H, t, J = 
               
               
                   
                   
                   
                   
                   
                   
                 7.1 Hz), 2.32-2.38 (4 H, m), 2.52- 
               
               
                   
                   
                   
                   
                   
                   
                 2.57 (2 H, m), 2.91 (3 H, s), 3.36- 
               
               
                   
                   
                   
                   
                   
                   
                 3.47 (6 H, m), 3.59-3.63 (2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 3.66-3.71 (2 H, m), 4.47 (2 H, s), 5.94 
               
               
                   
                   
                   
                   
                   
                   
                 (2 H, s), 6.67-6.76 (5 H, m), 6.83 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 1.0 Hz), 6.97 (2 H, d, J = 9.2 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.03 (1 H, dd, J = 9.1 Hz, 3.1 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.35 (2 H, d, J = 7.9 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.56 (2 H, d, J = 7.9 Hz), 7.63 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 2.8 Hz). 
               
               
                 2201 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 —CH 3   
                 1 
                 hydrochloride 
                 mp 167-170 dec 
               
               
                 2202 
                 4-CF 3 Ph- 
                 —CH 3   
                 —Ac 
                 1 
                 hydrochloride 
                 mp 186-189 
               
               
                 2203 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 —Ac 
                 1 
                 hydrochloride 
                 mp 188.5-191.0 
               
               
                 2204 
                 4-CF 3 Ph- 
                 —OCH 3   
                 —CH 3   
                 1 
                 oxalate 
                   1 H NMR (DMSO-d 6 ) 1.08 (3 H, t, J = 
               
               
                   
                   
                   
                   
                   
                   
                 7.0 Hz), 2.50-2.81 (4 H, m), 2.93 (3 H, 
               
               
                   
                   
                   
                   
                   
                   
                 s), 3.41 (2 H, q, J = 7.0 Hz), 3.33- 
               
               
                   
                   
                   
                   
                   
                   
                 3.72 (7 H, m), 3.77 (2 H, s), 4.25 (2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 s), 4.52 (2 H, s), 6.01 (2 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 6.12 (1 H, dd, J = 8.8 Hz, 2.7 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 6.28 (1 H, d, J = 2.7 Hz), 6.64 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 9.0 Hz), 6.76 (1 H, d, J = 8.7 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 6.80-6.94 (2 H, m), 6.97 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs), 7.15 (1 H, dd, J = 9.0 Hz, 3.2 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.34-7.50 (3 H, m), 7.66 (2 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.1 Hz). 
               
               
                 2205 
                 3,4-Cl 2 Ph- 
                 —OCH 3   
                 —CH 3   
                 1 
                 hydrochloride 
                   1 H NMR (DMSO-d 6 ) 1.06 (3 H, t, J = 
               
               
                   
                   
                   
                   
                   
                   
                 6.9 Hz), 2.75-3.16 (5 H, m), 3.21- 
               
               
                   
                   
                   
                   
                   
                   
                 3.48 (4 H, m), 3.62 (3 H, s), 3.71- 
               
               
                   
                   
                   
                   
                   
                   
                 4.52 (10 H, m), 6.06 (2 H, s), 6.16 (1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 dd, J = 8.8 Hz, 2.7 Hz), 6.34 (1 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 2.7 Hz), 6.67 (1 H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 6.78 (1 H, d, J = 8.8 Hz), 6.94-7.06 
               
               
                   
                   
                   
                   
                   
                   
                 (2 H, m), 7.13-7.28 (3 H, m), 7.41- 
               
               
                   
                   
                   
                   
                   
                   
                 7.52 (2 H, m), 7.56 (1 H, d, J = 8.3 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 10.83-11.19 (1 H, m). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 351 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 1026    
                 R 1027    
                 R 1028    
                 Form 
                 mp (° C.) 
               
               
                   
               
               
                 2206 
                 4-CF 3 Ph- 
                 —CH 3   
                 —C 2 H 5   
                 oxalate 
                 126-128 
               
               
                 2207 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 —C 2 H 5   
                 oxalate 
                 111-113 
               
               
                 2208 
                 4-CF 3 Ph- 
                 —CH 3   
                 —C 2 H 5   
                 oxalate 
                 120-123 
               
               
                 2209 
                 4-CF 3 Ph- 
                 —OCH 3   
                 —CH 3   
                 hydrobromide 
                 205-208 
               
               
                 2210 
                 3,4-Cl 2 Ph- 
                 —OCH 3   
                 —C 2 H 5   
                 hydrobromide 
                 133-135 
               
               
                 2211 
                 4-CF 3 Ph- 
                 —F 
                 —CH 3   
                 hydrobromide 
                 203-205 
               
               
                 2212 
                 3,4-Cl 2 Ph- 
                 —F 
                 —CH 3   
                 hydrobromide 
                 185-188 
               
               
                 2213 
                 4-CF 3 Ph- 
                 —F 
                 —C 2 H 5   
                 oxalate 
                 121.0-122.5 
               
               
                 2214 
                 3,4-Cl 2 Ph- 
                 —F 
                 —C 2 H 5   
                 hydrobromide 
                 165.0-166.5 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 352 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 1029   
                 R 1030   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 2215 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.45 (9 H, s), 2.39-2.43 (4 H, m), 3.01 (3 H, s), 3.41-3.44 (4 H, m), 3.50 (2 H, s), 4.41 (2 H, s), 6.82 (1 H, d, J = 8.9 Hz), 7.01 (2 H, d, J = 8.4 Hz), 7.08-7.13 (2 H, m), 7.27-7.41 (4 H, m), 7.70 (1 H, d, J = 8.6 Hz). 
               
               
                   
               
               
                 2216 
                 —CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2.20 (3 H, s), 2.98 (3 H, s), 3.06 (1 H, dd, J = 14.0 Hz, 10.1 Hz), 3.52 (1 H, dd, J = 14.0 Hz, 3.8 Hz), 4.38 (2 H, s), 4.50 (1 H, dd, J = 10.1 Hz, 3.8 Hz), 6.77 (1 H, d, J = 8.9 Hz), 6.91 (1 H, d, J = 8.3 Hz), 7.03 (1 H, dd, J = 8.3 Hz, 2.1 Hz), 7.05-7.16 (3 H, m), 7.32 (1 H, d, J = 2.1 Hz), 7.39 (1 H, d, J = 8.3 Hz), 7.67 (1 H, d, J = 3.1 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 353 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 1031   
                 R 1032   
                 R 1033   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 2217 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 —H 
                 2.41 (4 H, brs), 3.02 (3 H, s), 3.19 (3 H, s), 3.36 (2 H, 
               
               
                   
                   
                   
                   
                 brs), 3.42 (2 H, s), 3.60 (2 H, brs), 4.41 (2 H, s), 
               
               
                   
                   
                   
                   
                 4.51 (2 H, s), 5.95 (2 H, s), 6.73-6.77 (2 H, m), 6.84- 
               
               
                   
                   
                   
                   
                 6.87 (2 H, m), 7.03 (2 H, d, J = 8.9 Hz), 7.07 (1 H, 
               
               
                   
                   
                   
                   
                 dd, J = 8.3 Hz, 2.0 Hz), 7.12 (1 H, dd, J = 8.9 Hz, 
               
               
                   
                   
                   
                   
                 3.1 Hz), 7.33 (1 H, d, J = 2.0 Hz), 7.40 (1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.3 Hz), 7.59 (2 H, d, J = 8.9 Hz), 7.69 (1 H, d, J = 
               
               
                   
                   
                   
                   
                 3.1 Hz). 
               
               
                 2218 
                 3,4-Cl 2 Ph- 
                 —C 2 H 5   
                 —H 
                 1.21 (3 H, t, J = 7.1 Hz), 2.41 (4 H, brs), 3.18 (3 H, 
               
               
                   
                   
                   
                   
                 s), 3.36 (2 H, brs), 3.42 (2 H, s), 3.46 (2 H, q, J = 7.1 
               
               
                   
                   
                   
                   
                 Hz), 3.60 (2 H, brs), 4.40 (2 H, s), 4.50 (2 H, s), 
               
               
                   
                   
                   
                   
                 5.94 (2 H, s), 6.73-6.77 (2 H, m), 6.81-6.84 (2 H, m), 
               
               
                   
                   
                   
                   
                 7.01-7.10 (4 H, m), 7.33 (1 H, d, J = 2.0 Hz), 
               
               
                   
                   
                   
                   
                 7.39 (1 H, d, J = 8.3 Hz), 7.54 (2 H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                   
                 7.64 (1 H, d, J = 3.0 Hz). 
               
               
                 2219 
                 4-CF 3 Ph- 
                 —CH 3   
                 —H 
                 2.41 (4 H, brs), 3.05 (3 H, s), 3.19 (3 H, s), 3.34- 
               
               
                   
                   
                   
                   
                 3.36 (2 H, m), 3.42 (2 H, s), 3.60 (2 H, brs), 4.50 (2 H, 
               
               
                   
                   
                   
                   
                 s), 4.54 (2 H, s), 5.95 (2 H, s), 6.73-6.74 (2 H, m), 
               
               
                   
                   
                   
                   
                 6.83 (1 H, brs), 6.85 (1 H, d, J = 8.9 Hz), 7.03 (2 H, 
               
               
                   
                   
                   
                   
                 d, J = 8.9 Hz), 7.13 (1 H, dd, J = 8.9 Hz, 3.3 Hz), 
               
               
                   
                   
                   
                   
                 7.34 (2 H, d, J = 7.9 Hz), 7.54 (2 H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                 7.59 (2 H, d, J = 8.1 Hz), 7.70 (1 H, d, J = 3.1 Hz). 
               
               
                 2220 
                 4-CF 3 Ph- 
                 —C 2 H 5   
                 —H 
                 1.22 (3 H, t, J = 7.1 Hz), 2.41 (4 H, brs), 3.19 (3 H, 
               
               
                   
                   
                   
                   
                 s), 3.35 (2 H, brs), 3.42 (2 H, s), 3.48 (2 H, q, J = 7.1 
               
               
                   
                   
                   
                   
                 Hz), 3.60 (2 H, brs), 4.50 (2 H, s), 4.52 (2 H, s), 
               
               
                   
                   
                   
                   
                 5.95 (2 H, s), 6.70-6.77 (2 H, m), 6.82 (1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.7 Hz), 6.84 (1 H, brs), 7.02 (2 H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                 7.07 (1 H, dd, J = 8.9 Hz, 3.1 Hz), 7.36 (2 H, d, J = 
               
               
                   
                   
                   
                   
                 7.9 Hz), 7.54 (2 H, d, J = 8.9 Hz), 7.58 (2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.1 Hz), 7.65 (1 H, d, J = 3.0 Hz). 
               
               
                 2221 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 —CH 3   
                 2.21 (3 H, s), 2.42 (4 H, brs), 3.00 (3 H, s), 3.21 (3 H, 
               
               
                   
                   
                   
                   
                 s), 3.34-3.38 (2 H, m), 3.42 (2 H, s), 3.59-3.62 (2 H, 
               
               
                   
                   
                   
                   
                 m), 4.39 (2 H, s), 4.51 (2 H, s), 5.95 (2 H, s), 6.73- 
               
               
                   
                   
                   
                   
                 6.77 (2 H, m), 6.80-6.83 (2 H, m), 6.91 (1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.6 Hz), 7.06 (1 H, dd, J = 8.2 Hz, 2.1 Hz), 
               
               
                   
                   
                   
                   
                 7.12 (1 H, dd, J = 8.9 Hz, 3.1 Hz), 7.32-7.44 (4 H, 
               
               
                   
                   
                   
                   
                 m), 7.65 (1 H, d, J = 3.1 Hz). 
               
               
                 2222 
                 4-CF 3 Ph- 
                 —CH 3   
                 —CH 3   
                 2.21 (3 H, s), 2.42 (4 H, brs), 3.02 (3 H, s), 3.20 (3 H, 
               
               
                   
                   
                   
                   
                 s), 3.34-3.38 (2 H, m), 3.42 (2 H, s), 3.58-3.62 (2 H, 
               
               
                   
                   
                   
                   
                 m), 4.51 (4 H, brs), 5.94 (2 H, s), 6.70-6.76 (2 H, m), 
               
               
                   
                   
                   
                   
                 6.79-6.83 (2 H, m), 6.90 (1 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                 7.12 (1 H, dd, J = 8.9 Hz, 3.3 Hz), 7.32-7.39 (3 H, 
               
               
                   
                   
                   
                   
                 m), 7.43 (1 H, d, J = 2.5 Hz), 7.58 (2 H, d, J = 8.1 
               
               
                   
                   
                   
                   
                 Hz), 7.66 (1 H, d, J = 3.0 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 354 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 1034   
                 R 1035   
                 R 1036   
                   1 H NMR (CDCl 3 ) δppm 
               
               
                   
               
               
                 2223 
                 3,4-Cl 2 Ph- 
                 —C 2 H 5   
                 —CH 3   
                 1.19(3 H, t, J = 7.1 Hz), 2.21(3 H, s), 2.41(4 H, brs), 
               
               
                   
                   
                   
                   
                 3.20(3H, s), 3.34-3.37(2 H, m), 3.42(2 H, s), 
               
               
                   
                   
                   
                   
                 3.43(2 H, q, J = 7.1 Hz), 3.58-3.62(2 H, m), 
               
               
                   
                   
                   
                   
                 4.38(2 H, s), 4.50(2 H, s), 5.95(2 H, s), 6.70- 
               
               
                   
                   
                   
                   
                 6.77(2 H, m), 6.79(1 H, d, J = 8.9 Hz), 6.83(1 H, d, 
               
               
                   
                   
                   
                   
                 J = 0.8 Hz), 6.91(1 H, d, J = 8.6 Hz), 7.04-7.09(2 H, 
               
               
                   
                   
                   
                   
                 m), 7.32-7.43(4 H, m), 7.60(1 H, d, J = 3.0 Hz). 
               
               
                 2224 
                 4-CF 3 Ph- 
                 —C 2 H 5   
                 —CH 3   
                 1.21(3 H, t, J = 7.1 Hz), 2.21(3 H, s), 2.41(4 H, brs), 
               
               
                   
                   
                   
                   
                 3.20(3 H, s), 3.34-3.37(2 H, m), 3.42(2 H, s), 
               
               
                   
                   
                   
                   
                 3.46(2 H, q, J = 7.1 Hz), 3.58-3.62(2 H, m), 
               
               
                   
                   
                   
                   
                 4.50(4 H, brs), 5.94(2 H, s), 6.70-6.74(2 H, m), 
               
               
                   
                   
                   
                   
                 6.78(1 H, d, J = 9.2 Hz), 6.83(1 H, brs), 6.90(1 H, d, 
               
               
                   
                   
                   
                   
                 J = 8.6 Hz), 7.04-7.08(1 H, m), 7.34-7.43(4 H, m), 
               
               
                   
                   
                   
                   
                 7.57(1 H, d, J = 8.1 Hz), 7.60(1 H, d, J = 3.0 Hz). 
               
               
                 2225 
                 4-CF 3 Ph- 
                 —CH 3   
                 —OCH 3   
                 2.42(4 H, brs), 3.01(3 H, s), 3.21(3 H, s), 3.37(2 H, 
               
               
                   
                   
                   
                   
                 brs), 3.42(2 H, s), 3.61(2 H, brs), 3.78(3 H, s), 
               
               
                   
                   
                   
                   
                 4.27(2 H, s), 4.53(2 H, s), 5.94(2 H, s), 6.72- 
               
               
                   
                   
                   
                   
                 6.76(2 H, m), 6.84(2 H, d, J = 8.4 Hz), 7.00(1 H, d, 
               
               
                   
                   
                   
                   
                 J = 8.4 Hz), 7.10-7.16(2 H, m), 7.24-7.26(1 H, m), 
               
               
                   
                   
                   
                   
                 7.33(2 H, d, J = 8.1 Hz), 7.57(2 H, d, J = 7.9 Hz), 
               
               
                   
                   
                   
                   
                 7.62(1 H, d, J = 3.0 Hz). 
               
               
                 2226 
                 4-CF 3 Ph- 
                 —C 2 H 5   
                 —OCH 3   
                 1.20(3 H, t, J = 6.9 Hz), 2.42(4 H, brs), 3.21(3 H, s), 
               
               
                   
                   
                   
                   
                 3.36(2 H, brs), 3.40-3.48(4 H, m), 3.61(2 H, brs), 
               
               
                   
                   
                   
                   
                 3.77(3 H, s), 4.48(2 H, s), 4.52(2 H, s), 5.94(2 H, s), 
               
               
                   
                   
                   
                   
                 6.73-6.76(2 H, m), 6.81-6.85(2 H, m), 6.99(1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.6 Hz), 7.07(1 H, dd, J = 9.1 Hz, 3.3 Hz), 
               
               
                   
                   
                   
                   
                 7.14(1 H, dd, J = 8.4 Hz, 2.3 Hz), 7.24(1 H, d, J = 
               
               
                   
                   
                   
                   
                 2.5 Hz), 7.34(2 H, d, J = 8.1 Hz), 7.54-7.57(3 H, m). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 355 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 1037   
                 R 1038   
                 R 1039   
                   1 H NMR (solvent) δppm 
               
               
                   
               
               
                 2227 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 —H 
                 (CDCl 3 ) 2.20(3 H, s), 2.48-2.54(4 H, m), 2.97(3 H, s), 
               
               
                   
                   
                   
                   
                 3.44(2 H, s), 3.70-3.73(2 H, m), 4.23-4.27(2 H, m), 
               
               
                   
                   
                   
                   
                 4.37(2 H, s), 5.95(2 H, s), 6.73-6.77(3 H, m), 6.85(1 H, 
               
               
                   
                   
                   
                   
                 brs), 6.95(1 H, d, J = 8.6 Hz), 7.06(1 H, dd, J = 8.2 
               
               
                   
                   
                   
                   
                 Hz, 2.0 Hz), 7.10(1 H, dd, J = 8.9 Hz, 3.1 Hz), 
               
               
                   
                   
                   
                   
                 7.32(1 H, d, J = 2.0 Hz), 7.37(1 H, dd, J = 8.6 Hz, 2.6 
               
               
                   
                   
                   
                   
                 Hz), 7.38(1 H, d, J = 8.2 Hz), 7.52(1 H, d, J = 2.5 
               
               
                   
                   
                   
                   
                 Hz), 7.66(1 H, d, J = 2.8 Hz), 9.12(1 H, brs). 
               
               
                 2228 
                 4-CF 3 Ph- 
                 —CH 3   
                 —H 
                 (CDCl 3 ) 2.20(3 H, s), 2.48-2.54(4 H, m), 3.00(3 H, s), 
               
               
                   
                   
                   
                   
                 3.44(2 H, s), 3.72(2 H, t, J = 5.0 Hz), 4.23-4.27(2 H, 
               
               
                   
                   
                   
                   
                 m), 4.49(2 H, s), 5.95(2 H, s), 6.73-6.77(3 H, m), 
               
               
                   
                   
                   
                   
                 6.85(1 H, brs), 6.95(1 H, d, J = 8.7 Hz), 7.10(1 H, dd, 
               
               
                   
                   
                   
                   
                 J = 8.9 Hz, 3.3 Hz), 7.32-7.39(3 H, m), 7.52(1 H, d, J = 
               
               
                   
                   
                   
                   
                 2.5 Hz), 7.57(2 H, d, J = 8.1 Hz), 7.67(1 H, d, J = 
               
               
                   
                   
                   
                   
                 3.3 Hz), 9.12(1 H, brs). 
               
               
                 2229 
                 3,4-Cl 2 Ph- 
                 —C 2 H 5   
                 —H 
                 (CDCl 3 ) 1.18(3 H, t, J = 7.1 Hz), 2.20(3 H, s), 2.48- 
               
               
                   
                   
                   
                   
                 2.53(4 H, m), 3.41(2 H, q, J = 7.1 Hz), 3.44(2 H, s), 
               
               
                   
                   
                   
                   
                 3.70-3.73(2 H, m), 4.23-4.27(2 H, m), 4.36(2 H, s), 
               
               
                   
                   
                   
                   
                 5.95(2 H, s), 6.72-6.77(3 H, m), 6.85(1 H, brs), 
               
               
                   
                   
                   
                   
                 6.95(1 H, d, J = 8.6 Hz), 7.02-7.09(2 H, m), 7.32- 
               
               
                   
                   
                   
                   
                 7.39(3 H, m), 7.51(1 H, d, J = 2.6 Hz), 7.60(1 H, d, J = 
               
               
                   
                   
                   
                   
                 3.1 Hz), 9.12(1 H, brs). 
               
               
                 2230 
                 4-CF 3 Ph- 
                 —C 2 H 5   
                 —H 
                 (CDCl 3 ) 1.19(3 H, t, J = 7.1 Hz), 2.20(3 H, s), 2.48- 
               
               
                   
                   
                   
                   
                 2.53(4 H, m), 3.43(2 H, q, J = 7.1 Hz), 3.44(2 H, s), 
               
               
                   
                   
                   
                   
                 3.70-3.73(2 H, m), 4.23-4.27(2 H, m), 4.48(2 H, s), 
               
               
                   
                   
                   
                   
                 5.95(2 H, s), 6.71-6.77(3 H, m), 6.85(1 H, brs), 
               
               
                   
                   
                   
                   
                 6.95(1 H, d, J = 8.7 Hz), 7.04(1 H, dd, J = 8.9 Hz, 3.1 
               
               
                   
                   
                   
                   
                 Hz), 7.32-7.38(3 H, m), 7.51(1 H, d, J = 2.5 Hz), 
               
               
                   
                   
                   
                   
                 7.56(2 H, d, J = 8.1 Hz), 7.61(1 H, d, J = 3.1 Hz), 
               
               
                   
                   
                   
                   
                 9.11(1 H, brs). 
               
               
                 2231 
                 3,4-Cl 2 Ph- 
                 —C 2 H 5   
                 —CH 3   
                 a mixture of the rotational isomers 
               
               
                   
                   
                   
                   
                 (DMSO-d 6 ) 1.09(3 H, t, J = 6.93 Hz), 2.29-2.42(7 H, 
               
               
                   
                   
                   
                   
                 m), 3.22-3.54(11 H, m), 4.48(2 H, s), 5.97-5.99(2 H, 
               
               
                   
                   
                   
                   
                 m), 6.64-6.94(5 H, m), 7.07-7.27(4 H, m), 7.46- 
               
               
                   
                   
                   
                   
                 7.59(3 H, m). 
               
               
                 2232 
                 4-CF 3 Ph- 
                 —C 2 H 5   
                 —CH 3   
                 a mixture of the rotational isomers 
               
               
                   
                   
                   
                   
                 (DMSO-d 6 ) 1.12(3 H, t, J = 6.93 Hz), 2.07-2.42(7 H, 
               
               
                   
                   
                   
                   
                 m), 3.22-3.55(11 H, m), 4.59(2 H, s), 5.97-5.99(2 H, 
               
               
                   
                   
                   
                   
                 m), 6.65-6.94(5 H, m), 7.07-7.18(1 H, m), 7.23- 
               
               
                   
                   
                   
                   
                 7.29(2 H, m), 7.44(2 H, d, J = 8.08 Hz), 7.53(1 H, d, J = 
               
               
                   
                   
                   
                   
                 3.13 Hz), 7.67(2 H, d, J = 8.41 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 356 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 1040   
                   1 H NMR (DMSO-d 6 ) δppm 
               
               
                   
               
               
                 2233 
                 3,4-Cl 2 Ph- 
                 a mixture of the rotational isomers 
               
               
                   
                   
                 2.09-2.12(3 H, m), 2.66-4.53(18 H, m), 6.05-6.08(2 H, m), 6.88- 
               
               
                   
                   
                 6.93(2 H, m), 6.96-7.11(3 H, m), 7.19-7.25(3 H, m), 7.32-7.36(1 H, m), 
               
               
                   
                   
                 7.48(1 H, d, J = 2.1 Hz), 7.55-7.60(2 H, m), 11.35(1 H, brs). 
               
               
                 2234 
                 4-CF 3 Ph- 
                 a mixture of the rotational isomers 
               
               
                   
                   
                 2.10-2.12(3 H, m), 2.66-4.64(18 H, m), 6.05-6.08(2 H, m), 6.87- 
               
               
                   
                   
                 6.92(2 H, m), 6.96-7.11(3 H, m), 7.18-7.25(2 H, m), 7.30-7.35(1 H, m), 
               
               
                   
                   
                 7.43(2 H, d, J = 8.1 Hz), 7.60-7.61(1 H, m), 7.68(2 H, d, J = 8.2 Hz), 
               
               
                   
                   
                 11.27(1 H, brs). 
               
               
                   
               
             
          
         
       
     
       Example 2235 
     Production of (4-{5-[benzyl-(3,4-dichlorobenzyl)-amino]pyridin-2-yloxy}(4-benzylpiperazin-1-yl)methanone 
       [1184]    (4-benzylpiperazin-1-yl){4-[5-(3,4-dichlorobenzylamino)pyridin-2-yloxy]phenyl}methanone (1.09 g, 2.0 mmol) was dissolved in DMF (30 mL). To this solution were added potassium carbonate (0.28 g, 2.0 mmol) and benzyl bromide (0.24 mL, 2.0 mmol), and the resulting solution was stirred at room temperature for 2 hours, then subsequently stirred for 1 hour at 70° C. To the resulting solution were further added potassium carbonate (0.03 g, 0.2 mmol) and benzyl bromide (0.02 mL, 0.2 mmol), and this solution was stirred for 3 hours at 70° C. To the resulting solution were again added potassium carbonate (0.03 g, 0.2 mmol), benzyl bromide (0.02 mL, 0.2 mmol) and sodium iodide (0.15 g, 1.0 mmol), and this solution was stirred for overnight at 70° C. The resulting reaction solution was concentrated under reduced pressure. The residue was diluted with chloroform, and this solution was washed with water, saturated sodium bicarbonate solution and brine. The organic layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was then purified by silica gel column chromatography (ethyl acetate), to thereby yield 0.64 g of the title compound. 
         [1185]    Appearance: Pale yellow oil 
         [1186]      1 H NMR (CDCl 3 ) δ 2.37 (4H, brs), 3.28-3.50 (6H, m), 4.71 (2H, s), 4.73 (2H, s), 6.90 (1H, d, J=8.9 Hz), 6.99 (2H, d, J=8.6 Hz), 7.22-7.37 (14H, m), 7.52 (1H, d, J=2.0 Hz), 7.58-7.61 (2H, m). 
         [1187]    The following compounds were produced in the same manner as in Example 2235. 
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 357 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 1041   
                 R 1042   
                 R 1043   
                   1 H NMR (CDCl 3 ) δppm 
               
               
                   
               
               
                 2236 
                 3,4-Cl 2 PhCON(CH 3 )— 
                 —OCH 3   
                 —C 2 H 5   
                 1.19(3 H, t, J = 7.1 Hz), 2.42(4 H, t, J = 4.8 
               
               
                   
                   
                   
                   
                 Hz), 3.30-3.55(4 H, m), 3.43(2 H, s), 
               
               
                   
                   
                   
                   
                 3.44(3 H, s), 3.58-3.70(2 H, m), 3.67(3 H, s), 
               
               
                   
                   
                   
                   
                 4.03(2 H, s), 5.95(2 H, s), 6.19(1 H, dd, J = 
               
               
                   
                   
                   
                   
                 8.8 Hz, 2.8 Hz), 6.30(1 H, d, J = 2.8 Hz), 
               
               
                   
                   
                   
                   
                 6.70-6.75(2 H, m), 6.79(1 H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                 6.85(1 H, s), 6.92(1 H, d, J = 8.8 Hz), 7.05 
               
               
                   
                   
                   
                   
                 (1 H, dd, J = 8.1 Hz, 2.0 Hz), 7.27(1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.1 Hz), 7.35(1 H, dd, J = 8.9 Hz, 2.6 
               
               
                   
                   
                   
                   
                 Hz), 7.41(1 H, d, J = 2.0 Hz), 7.80(1 H, d, J = 
               
               
                   
                   
                   
                   
                 2.6 Hz). 
               
               
                 2237 
                 4-CF 3 PhCON(CH 3 )— 
                 —CH 3   
                 —CH 3   
                 1.97(3 H, s), 2.43(4 H, t, J = 5.0 Hz), 
               
               
                   
                   
                   
                   
                 3.00(3 H, s), 3.44(2 H, s), 3.47(3 H, s), 3.42- 
               
               
                   
                   
                   
                   
                 3.57(2 H, m), 3.63(2 H, brs), 4.06(2 H, s), 
               
               
                   
                   
                   
                   
                 5.95(2 H, s), 6.44-6.55(2 H, m), 6.67- 
               
               
                   
                   
                   
                   
                 6.79(3 H, m), 6.82-6.90(2 H, m), 7.40- 
               
               
                   
                   
                   
                   
                 7.47(1 H, m), 7.37(2 H, d, J = 8.1 Hz), 7.48 
               
               
                   
                   
                   
                   
                 (2 H, d, J = 8.1 Hz), 7.81(1 H, brs). 
               
               
                 2238 
                 4-CF 3 PhCON(CH 3 )— 
                 —OCH 3   
                 —C 2 H 5   
                 1.18(3 H, t, J = 7.1 Hz), 2.41(4 H, t, J = 4.9 
               
               
                   
                   
                   
                   
                 Hz), 3.40(2 H, q, J = 7.1 Hz), 3.42(2 H, t, J = 
               
               
                   
                   
                   
                   
                 3.5 Hz), 3.47(3 H, s), 3.42-3.59(2 H, m), 
               
               
                   
                   
                   
                   
                 3.63(5 H, s), 4.02(2 H, s), 5.95(2 H, s), 
               
               
                   
                   
                   
                   
                 6.18(1 H, dd, J = 8.7 Hz, 2.8 Hz), 6.28(1 H, 
               
               
                   
                   
                   
                   
                 d, J = 2.8 Hz), 6.69-6.78(2 H, m), 6.77(1 H, 
               
               
                   
                   
                   
                   
                 d, J = 8.8 Hz), 6.85(1 H, s), 6.90(1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.7 Hz), 7.35(1 H, d, J = 8.8 Hz), 7.38(2 H, 
               
               
                   
                   
                   
                   
                 d, J = 8.4 Hz), 7.48(2 H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                 7.79(1 H, brs). 
               
               
                 2239 
                 3,4-Cl 2 PhN(CH 3 )CO— 
                 —OCH 3   
                 —C 2 H 5   
                 1.18(3 H, t, J = 7.1 Hz), 2.42(4 H, t, J = 5.0 
               
               
                   
                   
                   
                   
                 Hz), 3.42(2 H, s), 3.43(2 H, q, J = 7.1 Hz), 
               
               
                   
                   
                   
                   
                 3.45(3 H, s), 3.55(2 H, brs), 3.65(5 H, brs), 
               
               
                   
                   
                   
                   
                 4.02(2 H, s), 5.95(2 H, s), 6.19(1 H, dd, J = 
               
               
                   
                   
                   
                   
                 8.7 Hz, 2.8 Hz), 6.29(1 H, d, J = 2.8 Hz), 
               
               
                   
                   
                   
                   
                 6.71-6.74(3 H, m), 6.85(1 H, brs), 6.87(1 H, 
               
               
                   
                   
                   
                   
                 dd, J = 8.6 Hz, 2.5 Hz), 6.92(1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.7 Hz), 7.20(1 H, d, J = 2.5 Hz), 7.32(1 H, 
               
               
                   
                   
                   
                   
                 d, J = 8.4 Hz), 7.64(1 H, dd, J = 8.6 Hz, 
               
               
                   
                   
                   
                   
                 2.3 Hz), 8.05(1 H, d, J = 1.8 Hz). 
               
               
                 2240 
                 3,4-Cl 2 PhSO 2 N(CH 3 )— 
                 —F 
                 —CH 3   
                 2.44(2 H, brs), 3.03(3 H, s), 3.19(3 H, s), 
               
               
                   
                   
                   
                   
                 3.44(2 H, brs), 3.47(2 H, brs), 3.62(2 H, 
               
               
                   
                   
                   
                   
                 brs), 4.08(2 H, brs), 4.08(2 H, s), 5.95(2 H, 
               
               
                   
                   
                   
                   
                 s), 6.41(1 H, dd, J = 8.2 Hz, 3.1 Hz), 6.42- 
               
               
                   
                   
                   
                   
                 6.50(1 H, m), 6.70-6.79(2 H, m), 6.85(1 H, 
               
               
                   
                   
                   
                   
                 brs), 6.90(1 H, d, J = 8.7 Hz), 7.04(1 H, t, J = 
               
               
                   
                   
                   
                   
                 7.8 Hz), 7.34(1 H, dd, J = 8.4 Hz, 2.2 
               
               
                   
                   
                   
                   
                 Hz), 7.50(1 H, dd, J = 8.7 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                   
                 7.56(1 H, d, J = 8.4 Hz), 7.72(1 H, d, J = 
               
               
                   
                   
                   
                   
                 2.2 Hz), 7.77(1 H, d, J = 2.8 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 358 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 1044   
                 R 1045   
                 Xb 46   
                 Form 
                 mp (° C.) or  1 H NMR 
               
               
                   
               
               
                 2241 
                 4-CF 3 PhCON(CH 3 )— 
                 —CH 3   
                 —N(SO 2 CH 3 )— 
                 free 
                   1 H NMR (CDCl 3 ) δ 
               
               
                   
                   
                   
                   
                   
                 2.05(3 H, s), 2.42(4 H, brs), 
               
               
                   
                   
                   
                   
                   
                 3.20(3 H, s), 3.34-3.37(2 H, 
               
               
                   
                   
                   
                   
                   
                 m), 3.42(2 H, s), 3.48(3 H, 
               
               
                   
                   
                   
                   
                   
                 s), 3.59-3.61(2 H, m), 
               
               
                   
                   
                   
                   
                   
                 4.52(2 H, s), 5.95(2 H, s), 
               
               
                   
                   
                   
                   
                   
                 6.70-6.77(2 H, m), 6.84(1 H, 
               
               
                   
                   
                   
                   
                   
                 brs), 6.86(1 H, d, J = 8.7 
               
               
                   
                   
                   
                   
                   
                 Hz), 6.97(1 H, d, J = 8.1 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.37-7.51(7 H, m), 
               
               
                   
                   
                   
                   
                   
                 7.79(1 H, brs). 
               
               
                 2242 
                 3,4-Cl 3 PhCON(CH 3 )— 
                 —CH 3   
                 —N(SO 2 CH 3 )— 
                 free 
                   1 H NMR (CDCl 3 ) δ 
               
               
                   
                   
                   
                   
                   
                 2.09(3 H, s), 2.42(4 H, brs), 
               
               
                   
                   
                   
                   
                   
                 3.21(3 H, s), 3.37(2 H, brs), 
               
               
                   
                   
                   
                   
                   
                 3.43(2 H, s), 3.46(3 H, s), 
               
               
                   
                   
                   
                   
                   
                 3.61(2 H, brs), 4.52(2 H, s), 
               
               
                   
                   
                   
                   
                   
                 5.95(2 H, s), 6.70-6.80(2 H, 
               
               
                   
                   
                   
                   
                   
                 m), 6.84(1 H, brs), 6.89(1 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.7 Hz), 6.99(1 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.4 Hz), 7.09(1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 8.2 Hz, 1.8 Hz), 7.29(1 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.2 Hz), 7.38(1 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 2.0 Hz), 7.42-7.46(3 H, 
               
               
                   
                   
                   
                   
                   
                 m), 7.80(1 H, d, J = 2.5 
               
               
                   
                   
                   
                   
                   
                 Hz). 
               
               
                   
               
               
                 2243 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 —CH 2 — 
                 free 
                 mp 133.0-134.0 
               
               
                   
               
               
                 2244 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 —CH 2 — 
                 free 
                 mp 117.0-118.0 
               
               
                   
               
               
                 2245 
                 4-CF 3 PhN(CH 3 )SO 2 — 
                 —H 
                 —CH 2 — 
                 free 
                   1 H NMR (CDCl 3 ) δ2.33- 
               
               
                   
                   
                   
                   
                   
                 2.41(4 H, m), 2.63(2 H, t, J = 
               
               
                   
                   
                   
                   
                   
                 7.3 Hz), 2.99(2 H, t, J = 
               
               
                   
                   
                   
                   
                   
                 7.3 Hz), 3.22(3 H, s), 
               
               
                   
                   
                   
                   
                   
                 3.40(4 H, brs), 3.61- 
               
               
                   
                   
                   
                   
                   
                 3.64(2 H, m), 5.93(2 H, s), 
               
               
                   
                   
                   
                   
                   
                 6.69-6.76(2 H, m), 6.84(1 H, 
               
               
                   
                   
                   
                   
                   
                 s), 6.94(1 H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.06(2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.27-7.31(4 H, m), 7.59(2 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.4 Hz), 7.71(1 H, dd, 
               
               
                   
                   
                   
                   
                   
                 J = 8.7 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.37(1 H, d, J = 2.6 Hz). 
               
               
                 2246 
                 F 3 CCH═CHCON(CH 3 )— 
                 —CH 3   
                 —N(CH 3 )— 
                 hydro- 
                 mp 161.0-164.0 
               
               
                   
                   
                   
                   
                 chloride 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 359 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 1046   
                   1 H NMR (solvent) δppm 
               
               
                   
               
               
                 2247 
                 3,4-Cl 2 PhCON(CH 3 )— 
                 a mixture of the rotational isomers 
               
               
                   
                   
                 (DMSO-d 6 ) 1.93(3 H, brs), 2.08-2.42(4 H, m), 3.21- 
               
               
                   
                   
                 3.56(12 H, m), 5.97-5.99(2 H, m), 6.66-6.89(3 H, m), 6.90- 
               
               
                   
                   
                 7.07(2 H, m), 7.13-7.32(3 H, m), 7.48-7.54(2 H, m), 7.85- 
               
               
                   
                   
                 7.89(2 H, m). 
               
               
                 2248 
                 4-CF 3 PhCON(CH 3 )— 
                 a mixture of the rotational isomers 
               
               
                   
                   
                 (DMSO-d 6 ) 1.87(3 H, brs), 2.07-2.41(4 H, m), 3.20- 
               
               
                   
                   
                 3.55(12 H, m), 5.97-5.99(2 H, m), 6.66-6.89(3 H, m), 6.98- 
               
               
                   
                   
                 7.04(2 H, m), 7.12-7.21(1 H, m), 7.24-7.30(1 H, m), 7.47(2 H, 
               
               
                   
                   
                 brs), 7.61-7.64(2 H, m), 7.86-7.89(2 H, m). 
               
               
                 2249 
                 3,4-Cl 2 PhSO 2 N(CH 3 )— 
                 (CDCl 3 ) 2.17(3 H, s), 2.23-2.53(4 H, m), 3.21(3 H, brs), 3.32- 
               
               
                   
                   
                 3.82(9 H, m), 5.93-5.95(2 H, m), 6.65-6.78(3 H, m), 6.85- 
               
               
                   
                   
                 6.95(1 H, m0, 7.02-7.06(1 H, m), 7.07-7.18(2 H, m), 7.38- 
               
               
                   
                   
                 7.42(1 H, m), 7.53-7.58(2 H, m), 7.67-7.68(1 H, m), 7.78- 
               
               
                   
                   
                 7.80(1 H, m). 
               
               
                 2250 
                 4-CF 3 PhSO 2 N(CH 3 )— 
                 a mixture of the rotational isomers 
               
               
                   
                   
                 (DMSO-d 6 ) 2.07-2.43(7 H, m), 3.16-3.56(12 H, m), 6.67- 
               
               
                   
                   
                 6.70(2 H, m), 6.76-6.89(3 H, m), 7.05-7.36(4 H, m), 7.61- 
               
               
                   
                   
                 7.66(1 H, m), 7.77-7.80(2 H, m), 7.91-7.80(3 H, m). 
               
               
                 2251 
                 4-CF 3 PhSO 2 N(C 2 H 5 )— 
                 (CDCl 3 ) 1.13(3 H, t, J = 7.1 Hz), 2.18(3 H, s), 2.23-2.52(4 H, 
               
               
                   
                   
                 m), 3.32-3.66(11 H, m), 5.93-5.95(2 H, m), 6.66-6.95(4 H, 
               
               
                   
                   
                 m), 7.04-7.19(3 H, m), 7.46(1 H, dd, J = 8.7 Hz, 2.6 Hz), 
               
               
                   
                   
                 7.73-7.80(5 H, m). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 360 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 1047   
                 R 1048   
                 R 1049   
                   1 H NMR (CDCl 3 ) δppm 
               
               
                   
               
               
                 2252 
                 4-CF 3 Ph- 
                 —H 
                 benzyl 
                 1.34-1.46(2 H, m), 1.85-2.03(3 H, m), 2.29(2 H, d, 
               
               
                   
                   
                   
                   
                 J = 6.8 Hz), 2.43(4 H, brs), 2.73(2 H, t, J = 12.0 
               
               
                   
                   
                   
                   
                 Hz), 3.19(3 H, s), 3.47-3.65(8 H, m), 6.83(1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.7 Hz), 6.92-7.03(4 H, m), 7.26-7.33(5 H, m), 
               
               
                   
                   
                   
                   
                 7.48(1 H, dd, J = 8.9 Hz, 2.8 Hz), 7.70-7.78(5 H, 
               
               
                   
                   
                   
                   
                 m). 
               
               
                 2253 
                 3.4-Cl 2 Ph- 
                 —H 
                 piperonyl 
                 1.33-1.46(2 H, m), 1.85-2.04(3 H, m), 2.29(2 H, d, 
               
               
                   
                   
                   
                   
                 J = 6.8 Hz), 2.39-2.42(4 H, m), 2.74(2 H, t, J = 
               
               
                   
                   
                   
                   
                 12.2 Hz), 3.19(3 H, s), 3.43(2 H, s), 3.46-3.64(6 H, 
               
               
                   
                   
                   
                   
                 m), 5.94(2 H, s), 6.70-6.77(2 H, m), 6.83(2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.9 Hz), 6.92-7.03(4 H, m), 7.38(1 H, dd, J = 8.4 
               
               
                   
                   
                   
                   
                 Hz, 2.1 Hz), 7.49(1 H, dd, J = 9.9 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                   
                 7.56(1 H, d, J = 8.4 Hz), 7.70(1 H, d, J = 2.1 Hz), 
               
               
                   
                   
                   
                   
                 7.81(1 H, d, J = 2.3 Hz). 
               
               
                 2254 
                 4-CF 3 Ph- 
                 —H 
                 piperonyl 
                 1.34-1.46(4 H, m), 1.85-2.02(3 H, m), 2.28(2 H, d, 
               
               
                   
                   
                   
                   
                 J = 6.8 Hz), 2.39-2.42(4 H, m), 2.74(2 H, t, J = 
               
               
                   
                   
                   
                   
                 12.0 Hz), 3.20(3 H, s), 3.43(2 H, s), 3.46-3.64(6H, 
               
               
                   
                   
                   
                   
                 m), 5.94(2 H, s), 6.70-6.77(2 H, m), 6.81-7.03(6 H, 
               
               
                   
                   
                   
                   
                 m), 7.49(1 H, dd, J = 8.7 Hz, 2.8 Hz), 7.71- 
               
               
                   
                   
                   
                   
                 7.78(5 H, m). 
               
               
                 2255 
                 4-CF 3 Ph- 
                 —OCH 3   
                 benzyl 
                 1.31-1.42(2 H, m), 1.86-2.00(3 H, m), 2.29(2 H, d, 
               
               
                   
                   
                   
                   
                 J = 6.8 Hz), 2.42-2.45(4 H, m), 2.76(2 H, t, J = 
               
               
                   
                   
                   
                   
                 12.0 Hz), 3.19(3 H, s), 3.49-3.69(8 H, m), 3.75(3 H, 
               
               
                   
                   
                   
                   
                 s), 6.51(1 H, dd, J = 8.7 Hz, 2.5 Hz), 6.59(1 H, d, J = 
               
               
                   
                   
                   
                   
                 2.5 Hz), 6.83(1 H, d, J = 8.7 Hz), 6.98(1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.7 Hz), 7.26-7.33(5 H, m), 7.47(1 H, dd, J = 8.9 
               
               
                   
                   
                   
                   
                 Hz, 2.8 Hz), 7.69-7.75(5 H, m). 
               
               
                 2256 
                 3,4-Cl 2 Ph- 
                 —H 
                 benzyl 
                 1.39-1.42(2 H, m), 1.84-2.02(3 H, m), 2.28(2 H, d, 
               
               
                   
                   
                   
                   
                 J = 6.8 Hz), 2.41-2.45(4 H, m), 2.73(2 H, t, J = 
               
               
                   
                   
                   
                   
                 12.2 Hz), 3.19(3 H, s), 3.48-3.95(8 H, m), 6.83(1 H, 
               
               
                   
                   
                   
                   
                 d, J = 8.7 Hz), 6.92-7.03(4 H, m), 7.27-7.39(6 H, 
               
               
                   
                   
                   
                   
                 m), 7.48(1 H, dd, J = 8.7 Hz, 2.8 Hz), 7.55(1 H, d, 
               
               
                   
                   
                   
                   
                 J = 8.4 Hz), 7.70(1 H, d, J = 2.1 Hz), 7.81(1 H, d, 
               
               
                   
                   
                   
                   
                 J = 2.3 Hz). 
               
               
                 2257 
                 3,4-Cl 2 Ph- 
                 —OCH 3   
                 benzyl 
                 1.34-1.42(2 H, m), 1.82-2.00(3 H, m), 2.29(2 H, d, 
               
               
                   
                   
                   
                   
                 J = 6.8 Hz), 2.41-2.45(4 H, m), 2.76(2 H, t, J = 
               
               
                   
                   
                   
                   
                 12.2 Hz), 3.19(3 H, s), 3.49-3.65(8 H, m), 3.75(3 H, 
               
               
                   
                   
                   
                   
                 s), 6.51(1 H, dd, J = 8.7 Hz, 2.6 Hz), 6.58(1 H, d, J = 
               
               
                   
                   
                   
                   
                 2.6 Hz), 6.84(1 H, d, J = 8.7 Hz), 6.98(1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.6 Hz), 7.26-7.39(6 H, m), 7.46(1 H, dd, J = 8.7 
               
               
                   
                   
                   
                   
                 Hz, 2.6 Hz), 7.54(1 H, d, J = 8.4 Hz), 7.69(1 H, d, 
               
               
                   
                   
                   
                   
                 J = 2.0 Hz), 7.78(1 H, d, J = 2.5 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 361 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 1050   
                 R 1051   
                   1 H NMR (CDCl 3 ) δppm 
               
               
                   
               
               
                 2258 
                 4-CF 3 PhN(CH 3 )SO 2 — 
                 —H 
                 1.34-1.46(2 H, m), 1.85-2.00(3 H, m), 2.28(2 H, d, J = 
               
               
                   
                   
                   
                 6.8 Hz), 2.39-2.43(4 H, m), 2.75(2 H, t, J = 12.2 
               
               
                   
                   
                   
                 Hz), 3.21(3 H, s), 3.43(2 H, s), 3.46-3.64(6 H, m), 
               
               
                   
                   
                   
                 5.94(2 H, s), 6.70-6.77(2 H, m), 6.85-7.02(6 H, m), 
               
               
                   
                   
                   
                 7.26-7.31(2 H, m), 7.59(2 H, d, J = 8.6 Hz), 7.67(1 H, 
               
               
                   
                   
                   
                 dd, J = 8.7 Hz, 2.6 Hz), 8.39(1 H, d, J = 2.1 Hz). 
               
               
                 2259 
                 4-CF 3 PhSO 2 N(C 2 H 5 )— 
                 —OCH 3   
                 1.11(3 H, t, J = 7.1 Hz), 1.30-1.42(2 H, m), 1.85- 
               
               
                   
                   
                   
                 2.00(3 H, m), 2.29(2 H, d, J = 6.8 Hz), 2.39-2.44(4 H, 
               
               
                   
                   
                   
                 m), 2.76(2 H, t, J = 12.2 Hz), 3.40-3.70(10 H, m), 
               
               
                   
                   
                   
                 3.75(3 H, s), 5.94(2 H, s), 6.51(1 H, dd, J = 8.7 Hz, 
               
               
                   
                   
                   
                 2.6 Hz), 6.59(1 H, d, J = 2.6 Hz), 6.74-6.87(4 H, m), 
               
               
                   
                   
                   
                 6.99(1 H, d, J = 8.7 Hz), 7.37-7.48(2 H, m), 7.54(1 H, 
               
               
                   
                   
                   
                 d, J = 8.4 Hz), 7.73-7.75(2 H, m). 
               
               
                 2260 
                 4-CF 3 PhSO 2 N(C 2 H 5 )— 
                 —H 
                 1.11(3 H, t, J = 7.1 Hz), 1.35-1.47(2 H, m), 1.85- 
               
               
                   
                   
                   
                 2.00(3 H, m), 2.29(2 H, d, J = 6.8 Hz), 2.40-2.42(4 H, 
               
               
                   
                   
                   
                 m), 2.74(2 H, t, J = 12.0 Hz), 3.42-3.48(4 H, m), 
               
               
                   
                   
                   
                 3.57-3.64(6 H, m), 5.94(2 H, s), 6.74-6.77(2 H, m), 
               
               
                   
                   
                   
                 6.82-7.04(6 H, m), 7.41(1 H, dd, J = 8.7 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                 7.72-7.94(5 H, m). 
               
               
                 2261 
                 4-CF 3 PhSO 2 N(CH 3 )— 
                 —OCH 3   
                 1.39-1.47(2 H, m), 1.86-2.00(3 H, m), 2.29(2 H, d, J = 
               
               
                   
                   
                   
                 6.8 Hz), 2.41(4 H, brs), 2.76(2 H, t, J = 12.0 Hz), 
               
               
                   
                   
                   
                 3.19(3 H, s), 3.43(2 H, s), 3.48(2 H, brs), 3.60(4 H, 
               
               
                   
                   
                   
                 brs), 3.64(3 H, s), 5.93(2 H, s), 6.51(1 H, dd, J = 8.7 
               
               
                   
                   
                   
                 Hz, 2.5 Hz), 6.59(1 H, d, J = 2.5 Hz), 6.74-6.84(4 H, 
               
               
                   
                   
                   
                 m), 6.98(1 H, d, J = 8.6 Hz), 7.46(1 H, dd, J = 8.7 
               
               
                   
                   
                   
                 Hz, 2.6 Hz), 7.69-7.76(5 H, m). 
               
               
                 2262 
                 4-CF 3 PhN(CH 3 )SO 2 — 
                 —CH 3   
                 1.34-1.45(2 H, m), 1.85-2.01(3 H, m), 2.07(3 H, s), 
               
               
                   
                   
                   
                 2.29(2 H, d, J = 6.8 Hz), 2.41-2.43(4 H, m), 2.73(2 H, 
               
               
                   
                   
                   
                 t, J = 12.0 Hz), 3.22(3 H, s), 3.43(2 H, s), 3.46- 
               
               
                   
                   
                   
                 3.77(6 H, m), 5.94(2 H, s), 6.74-6.94(7 H, m), 
               
               
                   
                   
                   
                 7.29(2 H, d, J = 8.2 Hz), 7.58(2 H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                 7.68(1 H, dd, J = 8.7 Hz, 2.6 Hz), 8.38(1 H, d, J = 
               
               
                   
                   
                   
                 2.5 Hz). 
               
               
                 2263 
                 3,4-Cl 2 PhSO 2 N(CH 3 )— 
                 —CH 3   
                 1.38-1.41(2 H, m), 1.84-1.98(3 H, m), 2.11(3 H, s), 
               
               
                   
                   
                   
                 2.29(2 H, d, J = 6.8 Hz), 2.41(4 H, brs), 2.72(2 H, t, J = 
               
               
                   
                   
                   
                 12.0 Hz), 3.19(3 H, s), 3.43-3.64(8 H, m), 5.94(2 H, 
               
               
                   
                   
                   
                 s), 6.74-6.85(6 H, m), 6.93(1 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                 7.39(1 H, dd, J = 8.4 Hz, 2.1 Hz), 7.49(1 H, dd, J = 
               
               
                   
                   
                   
                 8.7 Hz, 2.8 Hz), 7.56(1 H, d, J = 8.4 Hz), 7.67(1 H, 
               
               
                   
                   
                   
                 d, J = 2.0 Hz), 7.78(1 H, d, J = 2.3 Hz). 
               
               
                 2264 
                 3,4-Cl 2 PhSO 2 N(CH 3 )— 
                 —OCH 3   
                 1.39-1.47(2 H, m), 1.85-2.02(3 H, m), 2.29(2 H, d, J = 
               
               
                   
                   
                   
                 6.8 Hz), 2.39-2.44(4 H, m), 2.76(2 H, t, J = 12.2 
               
               
                   
                   
                   
                 Hz), 3.19(3 H, s), 3.43(2 H, s), 3.49(2 H, brs), 3.59- 
               
               
                   
                   
                   
                 3.73(4 H, m), 3.75(3 H, s), 5.94(2 H, s), 6.51(1 H, dd, 
               
               
                   
                   
                   
                 J = 8.7 Hz, 2.6 Hz), 6.59(1 H, d, J = 2.6 Hz), 6.74- 
               
               
                   
                   
                   
                 6.85(4 H, m), 6.98(1 H, d, J = 8.6 Hz), 7.38(1 H, dd, 
               
               
                   
                   
                   
                 J = 8.2 Hz, 2.0 Hz), 7.46(1 H, dd, J = 8.7 Hz, 2.8 
               
               
                   
                   
                   
                 Hz), 7.55(1 H, d, J = 8.4 Hz), 7.69(1 H, d, J = 2.1 
               
               
                   
                   
                   
                 Hz), 7.78(1 H, d, J = 2.8 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 362 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 Xb 47   
                 R 1052   
                   1 H NMR (CDCl 3 ) δppm 
               
               
                   
               
               
                 2265 
                 —CO— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2.33(2 H, d, J = 5.1 Hz), 2.38(2 H, d, J = 5.1 Hz), 2.60(2 H, t, J = 5.1 Hz), 2.96(2 H, t, J = 8.0 Hz), 3.33-3.46(2 H, m), 3.40(2 H, s), 3.47(3 H, s), 3.62(2 H, t, J = 2.0 Hz), 5.94(2 H, s), 6.67- 6.79(2 H, m), 6.83(1 H, d, J = 8.7 Hz), 6.84(1 H, s), 6.99(2 H, d, J = 8.4 Hz), 7.22(2 H, d, J = 8.4 Hz), 7.34-7.45(1 H, m), 7.40(2 H, d, J = 8.2 Hz), 7.50(2 H, d, J = 8.2 Hz), 7.85(1 H, brs). 
               
               
                   
               
               
                 2266 
                 —CO— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 3.17(3 H, s), 3.21(3 H, s), 3.48(3 H, s), 6.70(1 H, d, J = 8.7 Hz), 6.72-6.84(6 H, m), 6.95(1 H, t, J = 7.4 Hz), 7.07(2 H, t, J = 7.8 Hz), 7.31-7.45(3 H, m), 7.46- 7.58(2 H, m), 7.79-7.92(1 H, m). 
               
               
                   
               
               
                 2267 
                 —SO 2 — 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.78-2.04(4 H, m), 2.11(3 H, s), 2.44 (4 H, brs), 2.53-2.76(3 H, m), 3.19(3 H, s), 3.53(4 H, brs), 3.67(4 H, brs), 6.76- 6.81(3 H, m), 6.93(1 H, d, J = 8.6 Hz), 7.26-7.33(5 H, m), 7.49(1 H, dd, J = 8.9 Hz, 2.8 Hz), 7.70-7.79(5 H, m). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 363 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 1053   
                 Form 
                   1 H NMR (DMSO-d 6 ) δppm 
               
               
                   
               
               
                 2268 
                 —CH 3   
                 free 
                 2.39(4 H, brs), 3.32-3.51(9 H, m), 7.08(1 H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                 7.09(2 H, d, J = 8.4 Hz), 7.25-7.31(6 H, m), 7.41(2 H, d, J = 
               
               
                   
                   
                   
                 8.6 Hz), 7.55-7.58(2 H, m), 7.87(1 H, dd, J = 8.7 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                 8.03(1 H, brs). 
               
               
                 2269 
                 benzyl 
                 hydro- 
                 3.12-3.43(8 H, m), 4.33(2 H, s), 5.09(2 H, s), 7.02(1 H, d, J = 
               
               
                   
                   
                 chloride 
                 8.7 Hz), 7.07(2 H, d, J = 7.8 Hz), 7.26-7.33(6 H, m), 7.45- 
               
               
                   
                   
                   
                 7.48(5 H, m), 7.55-7.58(3 H, m), 7.67(1 H, brs), 7.77(1 H, d, J = 
               
               
                   
                   
                   
                 8.7 Hz), 7.85(1 H, brs), 11.09(1 H, brs). 
               
               
                   
               
             
          
         
       
     
       Example 2270 
     Production of 1-(t-butoxycarbonyl)-4-{4-[4-(3,4-dichlorobenzoylamino)phenoxy]phenyl}-4-hydroxypiperidine 
       [1188]    To a solution of N-[4-(4-bromophenoxy)phenyl]-3,4-dichlorobenzamide (4.94 g, 11.3 mmol) in THF (100 mL) was stirred at −85° C., and added a solution of 2.46 M n-butyl lithium hexane (9.65 mL, 23.7 mmol) dropwise over 10 minutes. Upon stirring for 20 minutes at the same temperature, crystals were precipitated. To this reaction solution was added a solution of 1-(t-butoxycarbonyl)-4-piperidone (2.48 g, 12.4 mmol) in THF (20 mL). The temperature of the solution was raised over 3 hours to −40° C., and then aqueous saturated ammonium chloride was added to the solution. The resulting reaction solution was extracted with ethyl acetate, and dried over anhydrous magnesium sulfate. The solvent was then evaporated, and the residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=2:3 to 1:1), to yield 2.30 g of a white powder. These crystals were washed with ether, to thereby yield 1.80 g of the title compound. 
         [0000]    Appearance: White powder
 
Melting point: 208-209° C.
 
       Example 2271 
     Production of 1-(t-butoxycarbonyl)-4-(4-{4-[4-(3,4-dichlorobenzoylamino)phenoxy]phenyl}-1,2,5,6-tetrahydropyridine 
       [1189]    To a solution of 1-(t-butoxycarbonyl)-4-{4-[4-(3,4-dichlorobenzoylamino)phenoxy]phenyl}-4-hydroxypiperidine (1.56 g, 2.80 mmol) in toluene (32 mL) was added p-toluenesulfonic acid hydrate (53 mg, 0.28 mmol), and the resulting solution was refluxed for 18 hours. The resulting reaction solution was purified by silica gel column chromatography (dichloromethane methanol=20:1), to thereby yield 1.35 g of the title compound. 
         [1190]    Appearance: White powder 
         [1191]    Melting point: 173-174° C. 
       Example 2272 
     Production of 1-{4-[4-(3,4-dichlorobenzoylamino)-phenoxy]phenyl}-4-hydroxypiperidine 
       [1192]    To a solution of 1-{4-[4-(3,4-dichlorobenzoylamino)phenoxy]phenyl}-4-(methoxymethoxy)piperidine (5.50 g, 11.0 mmol) in ethanol (110 mL) was added 2 M hydrochloric acid (55 mL, 110 mmol), and the resulting solution was stirred for 8 hours at 60° C. To the resulting reaction solution was added potassium carbonate (16 g) at room temperature, and the solvent was evaporated under reduced pressure. Water (200 mL) was added to the residue. Precipitated crystals were collected by filtration, to thereby yield 5.0 g of the title compound. 
         [1193]    Appearance: Pale brown powder 
         [1194]    Melting point: 178-180° C. 
       Example 2273 
     Production of 1-(3-{4-[4-(3,4-dichlorobenzoylamino)-phenoxy]phenyl}propionyl)piperazine monohydrochloride 
       [1195]    To a solution of 1-(t-butoxycarbonyl)-4-(3-{4-[4-(3,4-dichlorobenzoylamino)phenoxy]phenyl}-propionyl)piperazine (2.40 g, 4.01 mmol) in dichloromethane (24 mL) was added trifluoroacetic acid (12 mL) under ice cooling, and the resulting solution was stirred for 3 hours at the same temperature. The solvent was evaporated. To the residue was added acetone (5 mL), and then added a saturated sodium bicarbonate solution to make the solution basic. The formed solids were collected by filtration and dried, whereby 2.00 g of a white powder free form was obtained. This free form (0.500 g) was dissolved in ethanol (10 mL) and 5 M hydrochloric acid (0.4 mL) by heating. The solvent was then evaporated, and the obtained solid was recrystallized from isopropanol, to thereby yield 0.388 g of the title compound. 
         [1196]    Appearance: White powder 
         [1197]    Melting point: 127-130° C. 
         [1198]    The following compounds were produced in the same manner as in Example 2273. 
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 364 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 1054   
                 R 1055   
                 Form 
                 mp (° C.) or  1 H NMR (solvent) δppm 
               
               
                   
               
               
                 2274 
                 —F 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 hydro- chloride 
                 mp 149-151 
               
               
                   
               
               
                 2275 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 mp 198-199 
               
               
                   
               
               
                 2276 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 mp 170-174 
               
               
                   
               
               
                 2277 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                   1 H NMR (CDCl 3 ) 2.43-2.46(2 H, m), 3.11(2 H, t, J = 5.5 Hz), 3.53(2 H, q, J = 3 Hz), 6.10(1 H, m), 6.97(2 H, d, J = 8.5 Hz), 7.04(2 H, d, J = 9.0 Hz), 7.36(2 H, d, J = 8.5 Hz), 7.56-7.59(3 H, m), 7.68-7.69(2 H, m), 7.97(1 H, d, J = 2.0 Hz). 
               
               
                   
               
               
                 2278 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                   1 H NMR (DMSO-d 6 ) 1.32-1.36(2 H, m), 1.85-1.91(2 H, m), 2.32(3 H, s), 2.45(1 H, m), 2.66-2.71(2 H, m), 3.54-3.56(2 H, m), 4.13(1 H, m), 6.89-6.97(6 H, m), 7.65- 7.71(3 H, m), 7.82(1 H, d, J = 8.5 Hz), 7.93(1 H, dd, J = 8.5 Hz, 2.0 Hz), 8.21(1 H, d, J = 2.0 Hz), 10.36(1 H, s). 
               
               
                   
               
               
                 2279 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                   1 H NMR (CDCl 3 ) 1.63(2 H, m), 1.83(2 H, brd, J = 14.0 Hz), 2.61(1 H, m), 2.75(2 H, dt, J = 2.5 Hz, 12.0 Hz), 3.20(2 H, brd, J = 12.0 Hz), 6.95(2 H, d, J = 8.5 Hz), 7.03(2 H, d, J = 9.0 Hz), 7.19(2 H, d, J = 8.5 Hz), 7.55(1 H, d, J = 8.0 Hz), 7.58(2 H, d, J = 8.5 Hz), 7.69(1 H, dd, J = 8.0 Hz, 2.0 Hz), 7.69(1 H, brs), 7.97(1 H, d, J = 2.0 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 365 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 1056   
                 Xb 48   
                 Xb 49   
                 Form 
                   1 H NMR (solvent) δppm 
               
               
                   
               
               
                 2280 
                 3,4-Cl 2 Ph- 
                 none 
                 —CO— 
                 trifluoro- 
                 (DMSO-d 6 ) 3.56(2 H, brs), 3.87(2 H, m), 
               
               
                   
                   
                   
                   
                 acetate 
                 3.92(2 H, brs), 7.14(1 H, d, J = 8.8 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.20(2 H, dd, J = 6.7 Hz, 2.2 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.35((2 H, dd, J = 6.7 Hz, 2.2 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.85(1 H, d, J = 8.4 Hz), 7.95(1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 8.4 Hz, 2.1 Hz), 8.22(1 H, dd, J = 8.8 
               
               
                   
                   
                   
                   
                   
                 Hz, 2.7 Hz), 8.23(1 H, d, J = 2.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.51(1 H, d, J = 2.7 Hz), 9.30(2 H, brs), 
               
               
                   
                   
                   
                   
                   
                 10.59(1 H, s). 
               
               
                 2281 
                 4-CF 3 Ph- 
                 none 
                 —CH 2 — 
                 free 
                 (CDCl 3 ) 3.07(4 H, t, J = 5.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 3.15(4 H, t, J = 5.0 Hz), 6.92(1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 9.0 Hz), 6.96(2 H, d, J = 9.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.06(2 H, d, J = 9.0 Hz), 7.77(1 H, brs), 
               
               
                   
                   
                   
                   
                   
                 7.78(2 H, d, J = 8.0 Hz), 7.99(2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.0 Hz), 8.19(1 H, brd, J = 9.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.25(1 H, d, J = 2.5 Hz). 
               
               
                 2282 
                 3,4-Cl 2 Ph- 
                 none 
                 —CH 2 — 
                 free 
                 (CDCl 3 ) 3.18(4 H, dd, J = 5.5 Hz, 2.5 
               
               
                   
                   
                   
                   
                   
                 Hz), 3.16(4 H, dd, J = 5.5 Hz, 2.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.90(1 H, d, J = 9.0 Hz), 6.95(2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 9.0 Hz), 7.05(2 H, d, J = 9.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.58(1 H, d, J = 8.5 Hz), 7.71(1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 8.5 Hz, 2.0 Hz), 7.88(1 H, brs), 
               
               
                   
                   
                   
                   
                   
                 7.98(1 H, d, J = 2.0 Hz), 8.16(1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 9.0 Hz, 2.5 Hz), 8.24(1 H, d, J = 2.5 
               
               
                   
                   
                   
                   
                   
                 Hz). 
               
               
                 2283 
                 3,4-Cl 2 Ph- 
                 —CH 2 — 
                 —CH 2 — 
                 free 
                 (DMSO-d 6 ) 2.45-2.47(4 H, m), 2.88- 
               
               
                   
                   
                   
                   
                   
                 2.92(4 H, m), 3.49(2 H, s), 7.05- 
               
               
                   
                   
                   
                   
                   
                 7.09(3 H, m), 7.33(2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.84(1 H, d, J = 8.6 Hz), 7.95-7.99(1 H, 
               
               
                   
                   
                   
                   
                   
                 m), 8.18-8.25(2 H, m), 8.51(1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 2.6 Hz), 10.62(1 H, s). 
               
               
                 2284 
                 3,4-Cl 2 Ph- 
                 —CO— 
                 —CH 2 — 
                 free 
                 (DMSO-d 6 ) 2.69(4 H, brs), 3.40(4 H, 
               
               
                   
                   
                   
                   
                   
                 brs), 7.12-7.17(3 H, s), 7.41-7.44(2 H, 
               
               
                   
                   
                   
                   
                   
                 m), 7.84(1 H, d, J = 8.4 Hz), 7.96(1 H, 
               
               
                   
                   
                   
                   
                   
                 dd, J = 8.4 Hz, 2.2 Hz), 8.21-8.26(2 H, 
               
               
                   
                   
                   
                   
                   
                 m), 8.52(1 H, d, J = 2.7 Hz), 10.62(1 H, 
               
               
                   
                   
                   
                   
                   
                 brs). 
               
               
                 2285 
                 4-CF 3 Ph- 
                 —CH 2 — 
                 —CH 2 — 
                 free 
                 (DMSO-d 6 ) 2.44-2.46(4 H, m), 2.89- 
               
               
                   
                   
                   
                   
                   
                 2.92(4 H, m), 3.49(2 H, s), 4.79(1 H, 
               
               
                   
                   
                   
                   
                   
                 brs), 7.06-7.09(3 H, m), 7.33(2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.6 Hz), 7.94(2 H, d, J = 8.1 Hz), 8.16- 
               
               
                   
                   
                   
                   
                   
                 8.25(3 H, m), 8.52(1 H, d, J = 2.7 Hz), 
               
               
                   
                   
                   
                   
                   
                 10.65(1 H, s). 
               
               
                 2286 
                 3,4-(CH 3 ) 2 Ph- 
                 —CO— 
                 —CH 2 — 
                 free 
                 (DMSO-d 6 ) 2.29(3 H, s), 2.30(3 H, s), 
               
               
                   
                   
                   
                   
                   
                 2.73(4 H, brs), 3.44(4 H, brs), 7.09- 
               
               
                   
                   
                   
                   
                   
                 7.16(3 H, m), 7.29(1 H, d, J = 7.9 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.40-7.44(2 H, m), 7.69-7.72(1 H, m), 
               
               
                   
                   
                   
                   
                   
                 7.75(1 H, brs), 8.22-8.26(1 H, m), 
               
               
                   
                   
                   
                   
                   
                 8.53(1 H, d, J = 2.8 Hz), 10.31(1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 366 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 1057   
                 Xb 50   
                 M 
                   1 H NMR (solvent) δppm 
               
               
                   
               
               
                 2287 
                 3,4-Cl 2 PhCH 2 N(CH 3 )— 
                 none 
                 1 
                 (DMSO-d 6 ) 2.51-2.54(4 H, m), 3.00(3 H, s), 
               
               
                   
                   
                   
                   
                 3.06-3.08(4 H, m), 3.50(2 H, s), 4.55(2 H, s), 
               
               
                   
                   
                   
                   
                 6.88(1 H, d, J = 8.9 Hz), 6.94(2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.4 Hz), 7.19-7.32(4 H, m), 7.49(1 H, d, J = 
               
               
                   
                   
                   
                   
                 1.5 Hz), 7.58(1 H, d, J = 8.2 Hz), 7.64(1 H, 
               
               
                   
                   
                   
                   
                 d, J = 3.1 Hz), 8.73(1 H, brs). 
               
               
                 2288 
                 4-CF 3 PhCONH— 
                 none 
                 3 
                 (CDCl 3 ) 1.77-1.96(6 H, m), 2.35-2.44(6 H, 
               
               
                   
                   
                   
                   
                 m), 2.61-2.66(2 H, m), 6.92(1 H, d, J = 8.6 
               
               
                   
                   
                   
                   
                 Hz), 7.01-7.05(2 H, m), 7.17-7.23(2 H, m), 
               
               
                   
                   
                   
                   
                 7.74(2 H, d, J = 8.4 Hz), 8.00(2 H, d, J = 8.4 
               
               
                   
                   
                   
                   
                 Hz), 8.21(1 H, dd, J = 8.6 Hz, 2.6 Hz), 8.27- 
               
               
                   
                   
                   
                   
                 8.28(2 H, m). 
               
               
                 2289 
                 3,4-Cl 2 PhCONH— 
                 —CO— 
                 2 
                 (DMSO-d 6 ) 2.59-2.69(6 H, m), 2.79- 
               
               
                   
                   
                   
                   
                 2.85(2 H, m), 3.37-3.43(4 H, m), 4.31(1 H, 
               
               
                   
                   
                   
                   
                 brs), 7.00-7.06(3 H, m), 7.27(2 H, d, J = 8.6 
               
               
                   
                   
                   
                   
                 Hz), 7.84(1 H, d, J = 8.4 Hz), 7.95(1 H, dd, 
               
               
                   
                   
                   
                   
                 J = 8.4 Hz, 2.1 Hz), 8.16-8.22(2 H, m), 
               
               
                   
                   
                   
                   
                 8.46(1 H, d, J = 2.3 Hz), 10.54(1 H, s). 
               
               
                 2290 
                 4-CF 3 PhCONH— 
                 —COCO— 
                 1 
                 (CDCl 3 ) 1.69(1 H, brs), 2.51(2 H, t, J = 5.1 
               
               
                   
                   
                   
                   
                 Hz), 2.77(2 H, t, J = 5.1 Hz), 3.15(2 H, t, J = 
               
               
                   
                   
                   
                   
                 5.1 Hz), 3.53(2 H, t, 5.1 Hz), 4.05(2 H, s), 
               
               
                   
                   
                   
                   
                 6.98(1 H, d, J = 8.7 Hz), 7.11(2 H, d, J = 8.5 
               
               
                   
                   
                   
                   
                 Hz), 7.29(2 H, d, J = 8.5 Hz), 7.76(2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.2 Hz), 7.99(2 H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                 8.01(1 H, brs), 8.21(1 H, dd, J = 8.7 Hz, 2.7 
               
               
                   
                   
                   
                   
                 Hz), 8.25(1 H, d, J = 2.7 Hz). 
               
               
                   
               
             
          
         
       
     
       Example 2291 
     [3-(4-{5-[3-(3,4-Dichlorophenyl)ureido]pyridin-2-yloxy}-3-methylphenyl)-2-oxotetrahydropyrimidin-1-yl]acetic acid 
       [1199]      1 H NMR (DMSO-d 6 ) δ 1.87-2.15 (5H, m), 3.25-3.47 (2H, m), 3.58-3.75 (2H, m), 3.95 (2H, s), 6.82-7.00 (2H, m), 7.01-7.12 (1H, m), 7.17 (1H, d, J=2.4 Hz), 7.29-7.32 (1H, m), 7.50 (1H, d, J=8.8 Hz), 7.85 (1H, d, J=2.4 Hz), 7.89-8.02 (1H, m), 8.11 (1H, d, J=2.7 Hz), 8.95 (1H, s), 9.17 (1H, s), 12.50 (1H, s). 
         [1200]    The following compounds were produced in the same manner as in Reference Example 922. 
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 367 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 1058   
                 R 1059   
                   1 H NMR (DMSO-d 6 ) δppm 
               
               
                   
               
               
                 2292 
                 3,4-Cl 2 Ph- 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.40-1.65(2 H, m), 1.95-2.18(2 H, m), 2.40- 2.65(3 H, m), 3.00(2 H, brs), 3.25(1 H, brs), 3.85(1 H, brs), 4.40(1 H, brs), 7.15(1 H, d, J = 9.0 Hz), 7.19(2 H, d, J = 8.7 Hz), 7.43(2 H, d, J = 8.7 Hz), 7.84(1 H, d, J = 8.4 Hz), 7.99(1 H, dd, J = 8.4 Hz, 2.0 Hz), 8.22-8.30(2 H, m), 8.56(1 H, d, J = 2.0 Hz), 10.71(1 H, s). 
               
               
                   
               
               
                 2293 
                 3,4-Cl 2 Ph- 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.70-2.05(4 H, m), 2.60-2.80(1 H, m), 2.80- 3.05(2 H, m), 3.44(2 H, d, J = 7.1 Hz), 7.03(1 H, d, J = 8.7 Hz), 7.07(2 H, d, J = 8.9 Hz), 7.65(2 H, d, J = 8.9 Hz), 7.84(1 H, d, J = 8.4 Hz), 7.98(1 H, dd, J = 8.4 Hz, 2.0 Hz), 8.20(1 H, dd, J = 8.7 Hz, 2.7 Hz), 8.26(1 H, d, J = 2.0 Hz), 8.50(1 H, d, J = 2.7 Hz), 10.22(1 H, s), 10.65(1 H, s). 
               
               
                   
               
               
                 2294 
                 4-CF 3 Ph- 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.75-1.90(2 H, m), 1.95-2.30(2 H, m), 2.84(3 H, s), 2.70-3.15(2 H, m), 3.20-3.42(2 H, m), 4.55(1 H, brs), 6.51(1 H, brs), 7.16(1 H, d, J = 8.8 Hz), 7.17(2 H, d, J = 8.4 Hz), 7.47(2 H, d, J = 8.4 Hz), 7.94(2 H, d, J = 8.1 Hz), 8.22(2 H, d, J = 8.1 Hz), 8.31(1 H, dd, J = 8.8 Hz, 2.6 Hz), 8.60(1 H, d ,J = 2.6 Hz), 10.84(1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 368 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 1060   
                 R 1061   
                 Xb 51   
                 M 
                 Form 
                   1 H NMR (solvent) δppm 
               
               
                   
               
               
                 2295 
                 —H 
                 —H 
                 none 
                 0 
                 dihydro- 
                 (DMSO-d 6 ) 3.16(4 H, brs), 3.75(4 H, 
               
               
                   
                   
                   
                   
                   
                 chloride 
                 brs), 7.16(1 H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.19(2 H, d, J = 8.7 Hz), 7.53(2 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.7 Hz), 7.93(2 H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 8.21(2 H, d, J = 8.1 Hz), 8.30(1 H, dd, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.9 Hz, 2.5 Hz), 8.60(1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 2.5 Hz), 10.81(1 H, s). 
               
               
                 2296 
                 —H 
                 —H 
                 none 
                 2 
                 dihydro- 
                 (DMSO-d 6 ) 2.68(1 H, d, J = 6.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 chloride 
                 2.71(1 H, d, J = 8.4 Hz), 2.82(1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.4 Hz), 2.84(1 H, d, J = 6.5 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 3.04(4 H, brs), 3.70(4 H, t, J = 5.0 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.03(2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.05(1 H, d, J = 8.9 Hz), 7.29(2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.6 Hz), 7.41(1 H, brs), 7.92(2 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.5 Hz), 8.21(2 H, d, J = 8.5 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 8.25(1 H, dd, J = 8.9 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 8.54(1 H, d, J = 2.8 Hz), 10.80(1 H, s). 
               
               
                 2297 
                 —CH 3   
                 —H 
                 —N(CH 3 )— 
                 1 
                 free 
                 (CDCl 3 ) 2.11(3 H, s), 2.74-2.96(4 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 3.01(3 H, s), 3.39-3.70(4 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 4.08(2 H, s), 6.54(1 H, dd, J = 8.6 Hz, 
               
               
                   
                   
                   
                   
                   
                   
                 3.0 Hz), 6.57(1 H, d, J = 3.0 Hz), 6.81 
               
               
                   
                   
                   
                   
                   
                   
                 (1 H, d, J = 8.9 Hz), 6.91(1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.6 Hz), 7.75(2 H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.93-8.02(3 H, m), 8.13(1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.9 Hz, 2.7 Hz), 8.24(1 H, d, J = 2.7 
               
               
                   
                   
                   
                   
                   
                   
                 Hz). 
               
               
                 2298 
                 —H 
                 —CH 2 CONHNH 2   
                 none 
                 0 
                 trihydro- 
                 (DMSO-d 6 ) 3.42(4 H, brs), 3.75(4 H, 
               
               
                   
                   
                   
                   
                   
                 chloride 
                 brs), 4.21(2 H, s), 7.17(1 H, d, J = 8.8 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.21(2 H, d, J = 8.6 Hz), 7.53 
               
               
                   
                   
                   
                   
                   
                   
                 (2 H, d, J = 8.6 Hz), 7.94(2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.1 Hz), 8.22(2 H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 8.31(1 H, dd, J = 8.8 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 8.62(1 H, d, J = 2.6 Hz), 10.87(1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 s). 
               
               
                   
               
             
          
         
       
     
       Example 2299 
     Production of 1-(3-{4-[4-(3,4-dichlorobenzoylamino)-phenoxy]phenyl}propionyl)-4-piperonylpiperazine monohydrochloride 
       [1201]    To a suspension consisting of 1-(3-{4-[4-(3,4-dichlorobenzoylamino)phenoxy]phenyl}propionyl)-piperazine (0.500 g, 1.00 mmol) and diisopropyl-ethylamine (0.262 mL, 1.50&lt;mmol) in acetonitrile (12 mL) was added piperonyl chloride (0.188 g, 1.10 mmol), and the resulting solution was heated to reflux for 1.5 hours. Water was added to this reaction solution, and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatography (dichloromethane:methanol=30:1), to thereby yield 0.486 g of a free form. This free form was dissolved in ethanol (10 mL) and 5 M hydrochloric acid (0.3 mL) by heating. The solvent was then evaporated, and the obtained solid was recrystallized from 90% ethanol (17.5 mL), to thereby yield 0.322 g of the title compound. 
         [1202]    Appearance: White powder 
         [1203]    Melting point: 221-224° C. 
         [1204]    A crude titled product (9.95 g, 14.9 mmol) obtained using the same procedures was recrystallized from 80% ethanol (350 mL), to thereby yield 9.37 g of the title compound. 
         [1205]    Appearance: White powder 
         [1206]    Melting point: 232-234° C. 
         [1207]    The following compounds were produced in the same manner as in Example 2299. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 369 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                 mp (° C.) or  1 H NMR 
               
               
                 No. 
                 R 1062   
                 Xb 52   
                 Xb 53   
                 R 1063   
                 Form 
                 (CDCl 3 ) δppm 
               
               
                   
               
               
                 2300 
                 —H 
                 —(CH 2 ) 2 — 
                 —CO— 
                 —(CH 2 ) 2 Ph 
                 hydro- 
                 mp 205-207 
               
               
                   
                   
                   
                   
                   
                 chloride 
               
               
                 2301 
                 —H 
                 —(CH 2 ) 2 — 
                 —CO— 
                 —(CH 2 ) 2 OH 
                 hydro- 
                 mp 101-105 
               
               
                   
                   
                   
                   
                   
                 chloride 
               
               
                 2302 
                 —H 
                 —(CH 2 ) 2 — 
                 —CO— 
                 —(CH 2 ) 2 Ph 
                 ½ 
                 mp 156-159 
               
               
                   
                   
                   
                   
                   
                 fumarate 
               
               
                 2303 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 4-CH 3 PhCH 2 — 
                 free 
                 mp 105-107 
               
               
                 2304 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 4-CH 3 OPhCH 2 — 
                 free 
                 mp 137-139 
               
               
                 2305 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 2-CF 3 PhCH 2 — 
                 free 
                 mp 130-132 
               
               
                 2306 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 2-naphthyl- 
                 hydro- 
                 mp 172-175 
               
               
                   
                   
                   
                   
                 methyl 
                 chloride 
               
               
                 2307 
                 —H 
                 —(CH 2 ) 2 — 
                 —CO— 
                 —CH 2 COOC 2 H 5   
                 free 
                   1 H NMR 1.25 (3H, t, J = 7.1 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 2.39-2.53 (4H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 2.58 (2H, t, J = 7.8 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 2.90 (2H, t, J = 7.8 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 3.19 (2H, s), 3.36-3.48 (2H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 3.58-3.69 (2H, m), 4.16 (2H, q, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 7.1 Hz), 6.89 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.6 Hz), 6.96 (2H, d, J = 8.9 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.12 (2H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.47-7.59 (3H, m), 7.69 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 dd, J = 8.3 Hz, 2.1 Hz), 7.96 
               
               
                   
                   
                   
                   
                   
                   
                 (1H, d, J = 2.1 Hz), 8.14 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs). 
               
               
                 2308 
                 —H 
                 none 
                 —CO— 
                 —(CH 2 ) 2 Ph 
                 hydro- 
                 mp 210-218 
               
               
                   
                   
                   
                   
                   
                 chloride 
               
               
                 2309 
                 —H 
                 none 
                 none 
                 —(CH 2 ) 2 Ph 
                 free 
                 mp 214-215 
               
               
                 2310 
                 —H 
                 none 
                 none 
                 benzyl 
                 free 
                 mp 189-190 
               
               
                 2311 
                 —H 
                 none 
                 none 
                 —(CH 2 ) 3 Cl 
                 free 
                   1 H NMR 2.00 (2H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 2.56 (2H, t, J = 7.0 Hz), 2.62- 
               
               
                   
                   
                   
                   
                   
                   
                 2.64 (4H, m), 3.16-3.18 (4H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 3.64 (2H, t, J = 7.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 6.92 (2H, d, J = 7.0 Hz), 6.95- 
               
               
                   
                   
                   
                   
                   
                   
                 6.98 (4H, m), 7.52 (2H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 9.0 Hz), 7.57 (1H, d, J = 8.0 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.69 (1H, dd, J = 8.0 Hz, 
               
               
                   
                   
                   
                   
                   
                   
                 2.0 Hz), 7.70 (1H, s), 7.96 (1H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 2.0 Hz). 
               
               
                 2312 
                 —H 
                 none 
                 none 
                 —CH 2 COOC 2 H 5   
                 free 
                   1 H NMR 1.30 (3H, t, J = 7.0 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 2.76 (4H, t, J = 5.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 3.21 (4H, t, J = 5.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 3.28 (2H, s), 4.21 (2H, q, J = 
               
               
                   
                   
                   
                   
                   
                   
                 7.0 Hz), 6.91-6.98 (6H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.52 (2H, d, J = 9.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.57 (1H, d, J = 8.5 Hz), 7.69 
               
               
                   
                   
                   
                   
                   
                   
                 (1H, dd, J = 8.5 Hz, 2.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.72 (1H, brs), 7.96 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 2.0 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 370 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 1064   
                 mp (° C.) or  1 H NMR (CDCl 3 ) δppm 
               
               
                   
               
               
                 2313 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 mp 189-195 
               
               
                   
               
               
                 2314 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 2.60 (2H, brs), 2.85 (2H, m), 3.31 (2H, m), 3.39 (2H, s), 3.76 (3H, s), 6.00 (1H, brs), 6.95 (2H, d, J = 8.5 Hz), 7.03 (2H, d, J = 8.5 Hz), 7.34 (2H, d, J = 8.5 Hz), 7.57 (2H, d, J = 8.5 Hz), 7.57 (1H, brs), 7.70 (1H, d, J = 7.0 Hz), 7.75 (1H, brs), 7.97 (1H, s). 
               
               
                   
               
               
                 2315 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.28 (3H, t, J = 7.0 Hz), 1.60-1.70 (2H, m), 1.93-1.96 (2H, m), 2.46 (3H, s), 2.60-2.72 (3H, m), 3.37 (2H, s), 3.64-3.66 (2H, m), 4.20 (2H, q, J = 7.0 Hz), 6.93-6.98 (6H, m), 7.52 (2H, m), 7.57 (1H, d, J = 8.5 Hz), 7.68-7.70 (2H, m), 7.96 (1H, d, J = 2.0 Hz). 
               
               
                   
               
               
                 2316 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 1.29 (3H, t, J = 7.0 Hz), 1.81-1.88 (4H, m), 2.30 (2H, brt, J = 11.0 Hz), 2.49 (1H, m), 3.06 (2H, brd, J = 11.0 Hz), 4.21 (2H, q, J = 7.0 Hz), 6.94 (2H, d, J = 8.5 Hz), 7.01 (2H, d, J = 9.0 Hz), 7.18 (2H, d, J = 8.5 Hz), 7.55-7.68 (3H, m), 7.69 (1H, d, J = 2.0 Hz), 7.75 (1H, brs), 7.97 (1H, d, J = 2.0 Hz). 
               
               
                   
               
               
                 2317 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 2.04 (2H, m), 2.56 (2H, brs), 2.62 (2H, t, J = 7.0 Hz), 2.72 (2H, t, J = 5.5 Hz), 3.17 (2H, brs), 3.64 (2H, t, J = 6.5 Hz), 6.02 (1H, brs), 6.96 (2H, d, J = 9.0 Hz), 7.04 (2H, d, J = 9.0 Hz), 7.36 (2H, d, J = 9.0 Hz), 7.58 (3H, m), 7.70 (1H, dd, J = 8.5 Hz, 2.0 Hz), 7.77 (1H, brs), 7.98 (1H, d, J = 2.0 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 371 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 1065   
                 R 1066   
                   1 H NMR (solvent) δppm 
               
               
                   
               
               
                 2318 
                 4-CF 3 Ph- 
                 —(CH 2 ) 2 Ph 
                 (DMSO-d 6 ) 2.31-2.60 (6H, m), 2.67-2.81 (2H, 
               
               
                   
                   
                   
                 m), 3.51 (4H, brs), 7.16 (1H, d, J = 8.8 Hz), 
               
               
                   
                   
                   
                 7.17 (2H, d, J = 8.5 Hz), 7.10-7.33 (5H, m), 
               
               
                   
                   
                   
                 7.44 (2H, d, J = 8.5 Hz), 7.94 (2H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                 8.17 (2H, d, J = 8.2 Hz), 8.26 (1H, dd, J = 8.8 
               
               
                   
                   
                   
                 Hz, 2.6 Hz), 8.55 (1H, d, J = 2.6 Hz), 10.67 (1H, 
               
               
                   
                   
                   
                 s). 
               
               
                 2319 
                 3,4-Cl 2 Ph- 
                 4-CNPhCH 2 — 
                 (CDCl 3 ) 2.46 (4H, brs), 3.59 (2H, s), 3.75 (4H, 
               
               
                   
                   
                   
                 brs), 6.97 (1H, d, J = 8.9 Hz), 7.11-7.14 (2H, m), 
               
               
                   
                   
                   
                 7.40-7.43 (2H, m), 7.46 (2H, d, J = 7.8 Hz), 
               
               
                   
                   
                   
                 7.56-7.65 (3H, m), 7.72-7.76 (1H, m), 8.02 (1H, 
               
               
                   
                   
                   
                 d, J = 2.2 Hz), 8.16 (1H, dd, J = 8.9 Hz, 2.7 Hz), 
               
               
                   
                   
                   
                 8.27 (1H, brs), 8.30 (1H, d, J = 2.7 Hz). 
               
               
                 2320 
                 3,4-Cl 2 Ph- 
                 —CH 2 COPh 
                 (CDCl 3 ) 2.65 (4H, brs), 3.60-3.82 (4H, m), 
               
               
                   
                   
                   
                 3.89 (2H, s), 6.99 (1H, d, J = 8.7 Hz), 7.15 (2H, 
               
               
                   
                   
                   
                 d, J = 8.6 Hz), 7.43-7.50 (4H, m), 7.56-7.60 (2H, 
               
               
                   
                   
                   
                 m), 7.72-7.76 (1H, m), 7.97-8.02 (3H, m), 8.13- 
               
               
                   
                   
                   
                 8.21 (2H, m), 8.30 (1H, d, J = 2.5 Hz). 
               
               
                 2321 
                 3,4-Cl 2 Ph- 
                 3,4-(CH 3 ) 2 PhCH 2 — 
                 (CDCl 3 ) 2.25 (3H, s), 2.26 (3H, s), 2.44 (4H, brs), 
               
               
                   
                   
                   
                 3.47 (2H, s), 3.73 (4H, brs), 6.89 (1H, d, J = 8.9 
               
               
                   
                   
                   
                 Hz), 7.01-7.10 (5H m) 7.32-7.36 (2H, m), 
               
               
                   
                   
                   
                 7.51 (1H, d, J = 8.4 Hz), 7.74-7.78 (1H, m), 
               
               
                   
                   
                   
                 8.05 (1H, d, J = 8.1 Hz), 8.09 (1H, dd, J = 8.8 
               
               
                   
                   
                   
                 Hz, 2.7 Hz), 8.30 (1H, d, J = 2.7 Hz), 9.06 (1H, 
               
               
                   
                   
                   
                 brs). 
               
               
                 2322 
                 3,4-Cl 2 Ph- 
                 4-C(CH 3 ) 3 COPhCH 2 — 
                 (CDCl 3 ) 1.36 (9H, s), 2.48 (4H, brs), 3.58 (2H, s), 
               
               
                   
                   
                   
                 3.70 (4H, brs), 6.96 (1H, d, J = 8.7 Hz), 7.11- 
               
               
                   
                   
                   
                 7.14 (2H, m), 7.39-7.43 (4H, m), 7.57 (1H, d, J = 
               
               
                   
                   
                   
                 8.4 Hz), 7.69 (2H, d, J = 8.3 Hz), 7.73-7.77 (1H, 
               
               
                   
                   
                   
                 m), 8.03 (1H, d, J = 2.0 Hz), 8.15 (1H, dd, J = 
               
               
                   
                   
                   
                 8.9 Hz, 2.7 Hz), 8.30 (1H, d, J = 2.7 Hz), 
               
               
                   
                   
                   
                 8.37 (1H, brs). 
               
               
                 2323 
                 3,4-Cl 2 Ph- 
                 4-PhCH 2 OPhCH 2 — 
                 (CDCl 3 ) 2.45 (4H, brs), 3.49 (2H, s), 3.73 (4H, 
               
               
                   
                   
                   
                 brs), 5.06 (2H, s), 6.92-6.98 (3H, m), 7.11- 
               
               
                   
                   
                   
                 7.15 (2H, m), 7.23 (2H, d, J = 8.6 Hz), 7.32- 
               
               
                   
                   
                   
                 7.46 (7H, m), 7.57 (1H, d, J = 8.1 Hz), 7.75 (1H, 
               
               
                   
                   
                   
                 dd, J = 8.4 Hz, 2.2 Hz), 8.03 (1H, d, J = 2.2 Hz), 
               
               
                   
                   
                   
                 8.16 (1H, dd, J = 8.9 Hz, 2.7 Hz), 8.26 (1H, brs), 
               
               
                   
                   
                   
                 8.29 (1H, d, J = 2.7 Hz). 
               
               
                 2324 
                 3,4-Cl 2 Ph- 
                 4-C(CH 3 ) 3 PhCH 2 — 
                 (CDCl 3 ) 1.32 (9H, s), 2.48 (4H, brs), 3.53 (2H, s), 
               
               
                   
                   
                   
                 3.70 (4H, brs), 6.98 (1H, d, J = 8.4 Hz), 7.13 (2H, 
               
               
                   
                   
                   
                 d, J = 8.6 Hz), 7.21-7.27 (2H, m), 7.36 (2H, d, J = 
               
               
                   
                   
                   
                 8.4 Hz), 7.43 (2H, d, J = 8.6 Hz), 7.59 (1H, d, J = 
               
               
                   
                   
                   
                 8.1 Hz), 7.72-7.76 (1H, m), 8.02 (1H, d, J = 2.2 
               
               
                   
                   
                   
                 Hz), 8.13 (1H brs), 8.16-8.20 (1H, m), 8.30 (1H, 
               
               
                   
                   
                   
                 d, J = 2.2 Hz). 
               
               
                 2325 
                 3,4-Cl 2 Ph- 
                 3-CH 3 PhCH 2 — 
                 (CDCl 3 ) 2.36 (3H, s), 2.47 (4H, brs), 3.52 (2H, s), 
               
               
                   
                   
                   
                 3.74 (4H, brs), 6.97 (1H, d, J = 8.7 Hz), 7.08- 
               
               
                   
                   
                   
                 7.26 (6H, m), 7.41-7.44 (2H, m), 7.58 (1H, d, J = 
               
               
                   
                   
                   
                 8.4 Hz), 7.76 (1H, dd, J = 8.4 Hz, 2.1 Hz), 
               
               
                   
                   
                   
                 8.04 (1H, d, J = 2.1 Hz), 8.14-8.19 (1H, m), 
               
               
                   
                   
                   
                 8.26 (1H, brs), 8.30 (1H, d, J = 2.2 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 372 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 1067   
                 R 1068   
                   1 H NMR (CDCl 3 ) δppm 
               
               
                   
               
               
                 2326 
                 3,4-Cl 2 Ph- 
                 4-CH(CH 3 ) 2 PhCH 2 — 
                 1.25 (6H, d, J = 7.3 Hz), 2.46 (4H, brs), 2.85- 
               
               
                   
                   
                   
                 2.96 (1H, m), 3.52 (2H, s), 3.75 (4H, brs), 
               
               
                   
                   
                   
                 6.95 (1H, d, J = 8.9 Hz), 7.10-7.13 (2H, m), 7.17- 
               
               
                   
                   
                   
                 7.26 (4H, m), 7.38-7.42 (2H, m), 7.57 (1H, d, J = 
               
               
                   
                   
                   
                 8.1 Hz), 7.75 (1H, dd, J = 8.4 Hz, 2.2 Hz), 
               
               
                   
                   
                   
                 8.04 (1H, d, J = 2.2 Hz), 8.14 (1H, dd, J = 8.9 Hz, 
               
               
                   
                   
                   
                 2.7 Hz), 8.30 (1H, d, J = 2.7 Hz), 8.41 (1H, brs). 
               
               
                 2327 
                 3,4-Cl 2 Ph- 
                 4-CH 3 PhCH 2 — 
                 2.34 (3H, s), 2.45 (4H, brs), 3.51 (2H, s), 3.73 (4H, 
               
               
                   
                   
                   
                 brs), 6.93 (1H, d, J = 8.7 Hz), 7.07-7.22 (6H, m), 
               
               
                   
                   
                   
                 7.35-7.38 (2H, m), 7.54 (1H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                 7.77 (1H, dd, J = 8.4 Hz, 2.2 Hz), 8.05 (1H, d, J = 
               
               
                   
                   
                   
                 2.2 Hz), 8.12 (1H, dd, J = 8.9 Hz, 2.7 Hz), 
               
               
                   
                   
                   
                 8.30 (1H, d, J = 2.7 Hz), 8.82 (1H, s). 
               
               
                 2328 
                 3,4-Cl 2 Ph- 
                 3,4-F 2 PhCH 2 — 
                 2.45 (4H, brs), 3.49-3.73 (6H, m), 6.96 (1H, d, J = 
               
               
                   
                   
                   
                 8.7 Hz), 7.01-7.23 (5H, m), 7.39-7.42 (2H, m), 
               
               
                   
                   
                   
                 7.56 (1H, d, J = 8.4 Hz), 7.76 (1H, dd, J = 8.4 Hz, 
               
               
                   
                   
                   
                 2.1 Hz), 8.03 (1H, d, J = 2.1 Hz), 8.17 (1H, dd, J = 
               
               
                   
                   
                   
                 8.7 Hz, 2.7 Hz), 8.30 (1H, d, J = 2.7 Hz), 
               
               
                   
                   
                   
                 8.50 (1H, s). 
               
               
                 2329 
                 3,4-Cl 2 Ph- 
                 4-CH 3 OPhCH 2 — 
                 2.43 (4H, brs), 3.48 (2H, s), 3.73 (4H, brs), 
               
               
                   
                   
                   
                 3.81 (3H, s), 6.85-6.93 (3H, m), 7.06-7.10 (2H, m), 
               
               
                   
                   
                   
                 7.21-7.24 (2H, m) 7.34-7.37 (2H, m), 7.53 (1H, d, 
               
               
                   
                   
                   
                 J = 8.4 Hz), 7.77 (1H, dd, J = 8.4 Hz, 2.1 Hz), 
               
               
                   
                   
                   
                 8.05 (1H, d, J = 2.1 Hz), 8.10 (1H, dd, J = 8.9 Hz, 
               
               
                   
                   
                   
                 2.7 Hz), 8.30 (1H, d, J = 2.7 Hz), 8.90 (1H, s). 
               
               
                 2330 
                 4-CF 3 Ph- 
                 4-CF 3 PhCH 2 — 
                 2.48 (4H, brs), 3.60 (2H, s), 3.70 (4H, brs), 
               
               
                   
                   
                   
                 7.00 (1H, d, J = 8.9 Hz), 7.12-7.17 (2H, m), 7.41- 
               
               
                   
                   
                   
                 7.48 (4H, m), 7.60 (2H, d, J = 7.9 Hz), 7.77 (2H, 
               
               
                   
                   
                   
                 d, J = 8.1 Hz), 8.02 (2H, d, J = 8.1 Hz), 8.14 (1H, 
               
               
                   
                   
                   
                 brs), 8.19-8.24 (1H, m), 8.32 (1H, d, J = 2.3 Hz). 
               
               
                 2331 
                 4-CF 3 Ph- 
                 3,4-(CH 3 ) 2 PhCH 2 — 
                 2.25 (3H, s), 2.26 (3H, s), 2.45 (4H, brs), 3.47 (2H, 
               
               
                   
                   
                   
                 s), 3.40-3.90 (4H, m), 6.98 (1H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                 6.97-7.10 (3H, m), 7.13 (2H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                 7.42 (2H, d, J = 8.7 Hz), 7.76 (2H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                 8.02 (2H, d, J = 8.1 Hz), 8.18 (1H, brs), 8.20 (1H, 
               
               
                   
                   
                   
                 dd, J = 8.7 Hz, 2.5 Hz), 8.31 (1H, d, J = 2.5 Hz). 
               
               
                 2332 
                 4-CF 3 Ph- 
                 3-CH 3 PhCH 2 — 
                 2.35 (3H, s), 2.46 (4H, brs), 3.35-3.90 (4H, m), 
               
               
                   
                   
                   
                 3.50 (2H, s), 6.98 (1H, d, J = 8.9 Hz), 7.12 (2H, d, 
               
               
                   
                   
                   
                 J = 8.6 Hz), 7.05-7.30 (4H, m), 7.41 (2H, d, J = 
               
               
                   
                   
                   
                 8.6 Hz), 7.76 (2H, d, J = 8.1 Hz), 8.02 (2H, d, J = 
               
               
                   
                   
                   
                 8.1 Hz), 8.19 (1H, dd, J = 8.9 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                 8.28 (1H, brs), 8.31 (1H, d, J = 2.6 Hz). 
               
               
                 2333 
                 4-CF 3 Ph- 
                 4-CH 3 PhCH 2 — 
                 2.34 (3H, s), 2.44 (4H, brs), 3.50 (2H, s), 3.35- 
               
               
                   
                   
                   
                 3.85 (4H, m), 6.97 (1H, d, J = 8.9 Hz), 7.12 (2H, 
               
               
                   
                   
                   
                 d, J = 8.8 Hz), 7.12 (2H, d, J = 8.1 Hz), 7.20 (2H, 
               
               
                   
                   
                   
                 d, J = 8.1 Hz), 7.40 (2H, d, J = 8.8 Hz), 7.75 (2H, 
               
               
                   
                   
                   
                 d, J = 8.1 Hz), 8.02 (2H, d, J = 8.1 Hz), 8.18 (1H, 
               
               
                   
                   
                   
                 dd, J = 8.9 Hz, 2.5 Hz), 8.32 (1H, d, J = 2.5 Hz), 
               
               
                   
                   
                   
                 8.38 (1H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 373 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 1069   
                 R 1070   
                   1 H NMR (CDCl 3 ) δppm 
               
               
                   
               
               
                 2334 
                 3,4-Cl 2 Ph- 
                 3-CH 3 OPhCH 2 — 
                 2.47 (4H, brs), 3.46-3.82 (6H, m), 3.86 (3H, s), 
               
               
                   
                   
                   
                 6.80-6.84 (1H, m), 6.88-6.92 (2H, m) 6.95 (1H, d, 
               
               
                   
                   
                   
                 J = 8.8 Hz), 7.10-7.13 (2H, m), 7.23 (1H, d, J = 8.1 
               
               
                   
                   
                   
                 Hz), 7.38-7.41 (2H, m), 7.56 (1H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                 7.73-7.77 (1H, m), 8.04 (1H, d, J = 2.1 Hz), 8.12- 
               
               
                   
                   
                   
                 8.16 (1H, m), 8.29 (1H, d, J = 2.7 Hz), 8.44 (1H, 
               
               
                   
                   
                   
                 brs). 
               
               
                 2335 
                 3,4-Cl 2 Ph- 
                 2-quinolylmethyl 
                 2.58 (4H, brs), 3.58-3.76 (4H, m), 3.88 (2H, s), 
               
               
                   
                   
                   
                 6.94 (1H, d, J = 8.8 Hz), 7.11 (2H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                 7.40 (2H, d, J = 8.6 Hz), 7.51-7.57 (2H, m), 
               
               
                   
                   
                   
                 7.62 (1H, d, J = 8.4 Hz), 7.68-7.84 (3H, m), 
               
               
                   
                   
                   
                 8.04 (1H, d, J = 2.1 Hz), 8.07 (1H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                 8.12-8.17 (2H, m), 8.29 (1H, d, J = 2.5 Hz), 
               
               
                   
                   
                   
                 8.65 (1H, brs). 
               
               
                 2336 
                 3,4-Cl 2 Ph- 
                 4-CF 3 PhCH 2 — 
                 2.47 (4H, brs), 3.44-3.85 (6H, m), 6.98 (1H, d, J = 
               
               
                   
                   
                   
                 8.9 Hz), 7.11-7.16 (2H, m), 7.39-7.48 (4H, m), 
               
               
                   
                   
                   
                 7.56-7.61 (3H, m), 7.75 (1H, dd, J = 8.4 Hz, 2.1 
               
               
                   
                   
                   
                 Hz), 8.02 (1H, d, J = 2.1 Hz), 8.14-8.18 (1H, m), 
               
               
                   
                   
                   
                 8.24 (1H, brs), 8.30 (1H, d, J = 2.6 Hz). 
               
               
                 2337 
                 3,4-Cl 2 Ph- 
                 4-CF 3 OPhCH 2 — 
                 2.46 (4H, brs), 3.46-3.84 (6H, m), 6.96 (1H, d, J = 
               
               
                   
                   
                   
                 8.9 Hz), 7.10-7.20 (4H, m), 7.34-7.41 (4H, m), 
               
               
                   
                   
                   
                 7.56 (1H, d, J = 8.4 Hz), 7.76 (1H, dd, J = 8.4 Hz, 
               
               
                   
                   
                   
                 2.1 Hz), 8.03 (1H, d, J = 2.1 Hz), 8.11-8.16 (1H, 
               
               
                   
                   
                   
                 m), 8.30 (1H, d, J = 2.5 Hz), 8.49 (1H, brs). 
               
               
                 2338 
                 3,4-Cl 2 Ph- 
                 PhO(CH 2 ) 2 — 
                 2.60 (4H, brs), 2.85 (2H, t, J = 5.4 Hz), 3.53- 
               
               
                   
                   
                   
                 3.75 (4H, m), 4.12 (2H, t, J = 5.4 Hz), 6.88- 
               
               
                   
                   
                   
                 6.99 (4H, m), 7.06-7.13 (2H, m), 7.25-7.37 (4H, m), 
               
               
                   
                   
                   
                 7.51 (1H, d, J = 8.4 Hz), 7.77 (1H, dd, J = 8.4 Hz, 
               
               
                   
                   
                   
                 2.1 Hz), 8.05 (1H, d, J = 2.1 Hz), 8.07-8.12 (1H, 
               
               
                   
                   
                   
                 m), 8.32 (1H, d, J = 2.6 Hz), 9.10 (1H, brs). 
               
               
                 2339 
                 4-CF 3 Ph- 
                 4-CNPhCH 2 — 
                 2.45 (4H, brs), 3.58 (2H, s), 3.63 (4H, brs), 
               
               
                   
                   
                   
                 6.98 (1H, d, J = 8.8 Hz), 7.13 (2H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                 7.41 (2H, d, J = 8.7 Hz), 7.46 (2H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                 7.62 (2H, d, J = 8.1 Hz), 7.75 (2H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                 8.01 (2H, d, J = 8.1 Hz), 8.20 (1H, dd, J = 8.8 Hz, 
               
               
                   
                   
                   
                 2.6 Hz), 8.28 (1H, brs), 8.33 (1H, d, J = 2.6 Hz). 
               
               
                 2340 
                 4-CF 3 Ph- 
                 3,4-F 2 PhCH 2 — 
                 2.44 (4H, brs), 3.48 (2H, s), 3.64 (4H, brs), 
               
               
                   
                   
                   
                 6.98 (1H, d, J = 8.9 Hz), 6.97-7.25 (3H, m), 
               
               
                   
                   
                   
                 7.12 (2H, d, J = 8.7 Hz), 7.41 (2H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                 7.75 (2H, d, J = 8.0 Hz), 8.01 (2H, d, J = 8.0 Hz), 
               
               
                   
                   
                   
                 8.19 (1H, dd, J = 8.9 Hz, 2.3 Hz), 8.30 (1H, brs), 
               
               
                   
                   
                   
                 8.32 (1H, d, J = 2.3 Hz). 
               
               
                 2341 
                 4-CF 3 Ph- 
                 4-CH 3 OPhCH 2 — 
                 2.43 (4H, brs), 3.48 (2H, s), 3.60 (4H, brs), 
               
               
                   
                   
                   
                 3.80 (3H, s), 6.86 (2H, d, J = 8.7 Hz), 6.96 (1H, d, 
               
               
                   
                   
                   
                 J = 8.7 Hz), 7.11 (2H, d, J = 8.7 Hz), 7.22 (2H, d, 
               
               
                   
                   
                   
                 J = 8.7 Hz), 7.38 (2H, d, J = 8.7 Hz), 7.74 (2H, d, 
               
               
                   
                   
                   
                 J = 8.1 Hz), 8.02 (2H, d, J = 8.1 Hz), 8.17 (1H, dd, 
               
               
                   
                   
                   
                 J = 8.7 Hz, 2.4 Hz), 8.32 (1H, d, J = 2.4 Hz), 
               
               
                   
                   
                   
                 8.52 (1H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 374 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                 mp (° C.) or 
               
               
                 No. 
                 R 1071   
                 R 1072   
                   1 H NMR (CDCl 3 ) δppm 
               
               
                   
               
               
                 2342 
                 3,4-(CH 3 ) 2 Ph- 
                 4-CNPhCH 2 — 
                   1 H NMR 2.33 (6H, s), 2.45 (4H, brs), 3.58 (2H, 
               
               
                   
                   
                   
                 s), 3.64 (4H, brs), 6.97 (1H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                 7.11-7.16 (2H, m), 7.24 (1H, d, J = 7.6 Hz), 
               
               
                   
                   
                   
                 7.41-7.47 (4H, m), 7.58-7.67 (4H, m), 7.94 
               
               
                   
                   
                   
                 (1H, brs), 8.24 (1H, dd, J = 8.7 Hz, 2.7 Hz), 
               
               
                   
                   
                   
                 8.31 (1H, d, J = 2.7 Hz). 
               
               
                 2343 
                 3,4-(CH 3 ) 2 Ph- 
                 3,4-F 2 PhCH 2 — 
                   1 H NMR 2.34 (6H, s), 2.45 (4H, brs), 3.48 (2H, 
               
               
                   
                   
                   
                 s), 3.65 (4H, brs), 6.98 (1H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                 7.03-7.23 (6H, m), 7.41-7.46 (2H, m), 7.59- 
               
               
                   
                   
                   
                 7.62 (1H, m), 7.67 (1H, d, J = 1.8 Hz), 7.95 
               
               
                   
                   
                   
                 (1H, brs), 8.26 (1H, dd, J = 8.9 Hz, 2.7 Hz), 
               
               
                   
                   
                   
                 8.31 (1H, d, J = 2.7 Hz). 
               
               
                 2344 
                 4-CF 3 Ph- 
                 3-CH 3 OPhCH 2 — 
                 mp 118-120 
               
               
                 2345 
                 4-CF 3 Ph- 
                 2-quinolylmethyl 
                   1 H NMR 2.56 (4H, brs), 3.43-3.81 (4H, m), 
               
               
                   
                   
                   
                 3.87 (2H, s), 6.94 (1H, d, J = 8.9 Hz), 7.08- 
               
               
                   
                   
                   
                 7.13 (2H, m), 7.35-7.40 (2H, m), 7.51-7.57 (1H, 
               
               
                   
                   
                   
                 m), 7.61 (1H, d, J = 8.4 Hz), 7.68-7.74 (3H, 
               
               
                   
                   
                   
                 m), 7.81-7.84 (1H, m), 8.01-8.20 (5H, m), 
               
               
                   
                   
                   
                 8.33 (1H, d, J = 2.7 Hz), 8.94 (1H, s). 
               
               
                 2346 
                 4-CF 3 Ph- 
                 PhO(CH 2 ) 2 — 
                 mp 161-162 
               
               
                   
               
               
                 2347 
                 4-CF 3 Ph- 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR 2.48 (4H, brs), 3.55 (2H, brs), 3.66 (2H, s), 3.75 (2H, brs), 6.97 (1H, d, J = 8.7 Hz), 7.12 (2H, d, J = 8.4 Hz), 7.32- 7.43 (1H, m), 7.41 (2H, d, J = 8.4 Hz), 7.55 (1H, d, J = 8.4 Hz), 7.70-7.80 (1H, m), 7.75 (2H, d, J = 8.1 Hz), 8.02 (2H, d, J = 8.1 Hz), 8.10 (1H, s), 8.20 (1H, dd, J = 8.7 Hz, 2.6 Hz), 8.32 (1H, d, J = 2.6 Hz), 8.41 (1H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 375 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 1073   
                 R 1074   
                   1 H NMR (CDCl 3 ) δppm 
               
               
                   
               
               
                 2348 
                 3,4-Cl 2 Ph- 
                 2,6-F 2 PhCH 2 — 
                 2.42 (4H, brs), 2.54-2.60 (2H, m), 2.83-2.88 (2H, 
               
               
                   
                   
                   
                 m), 3.38-3.42 (2H, m), 3.55-3.58 (2H, m), 
               
               
                   
                   
                   
                 3.69 (2H, s), 6.85-6.98 (5H, m), 7.12 (2H, d, J = 
               
               
                   
                   
                   
                 8.6 Hz), 7.19-7.31 (1H, m), 7.48 (1H, d, J = 8.4 
               
               
                   
                   
                   
                 Hz), 7.74 (1H, dd, J = 8.4 Hz, 2.1 Hz), 7.99 (1H, 
               
               
                   
                   
                   
                 d, J = 2.1 Hz), 8.14-8.18 (1H, m), 8.30 (1H, d, J = 
               
               
                   
                   
                   
                 2.8 Hz), 9.19 (1H, brs). 
               
               
                 2349 
                 3,4-Cl 2 Ph- 
                 4-CF 3 PhCH 2 — 
                 2.33-2.41 (4H, m), 2.59-2.65 (2H, m), 2.92- 
               
               
                   
                   
                   
                 2.97 (2H, m), 3.40-3.44 (2H, m), 3.55 (2H, s), 
               
               
                   
                   
                   
                 3.61-3.64 (2H, m), 6.93 (1H, d, J = 8.8 Hz), 
               
               
                   
                   
                   
                 7.02-7.06 (2H, m), 7.20 (2H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                 7.44 (2H, d, J = 8.4 Hz), 7.54-7.60 (3H, m), 
               
               
                   
                   
                   
                 7.74 (1H, dd, J = 8.4 Hz, 2.2 Hz), 8.01 (1H, d, J = 
               
               
                   
                   
                   
                 2.2 Hz), 8.17-8.21 (1H, m), 8.28 (1H, d, J = 
               
               
                   
                   
                   
                 2.6 Hz), 8.44 (1H, brs). 
               
               
                   
               
               
                 2350 
                 4-CF 3 Ph- 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2.28 (2H, t, J = 4.9 Hz), 2.43 (2H, t, J = 4.9 Hz), 2.61 (2H, t, J = 7.5 Hz), 2.96 (2H, t, J = 7.5 Hz), 3.30 (2H, t, J = 4.9 Hz), 3.59 (2H, s), 3.63 (2H, t, J = 4.9 Hz), 6.96 (1H, d, J = 8.3 Hz), 7.04 (2H, d, J = 8.5 Hz), 7.21 (2H, d, J = 8.5 Hz), 7.36 (1H, dd, J = 8.5 Hz, 1.5 Hz), 7.53 (1H, d, J = 8.4 Hz), 7.73 (1H, brs), 7.75 (2H, d, J = 8.3 Hz), 8.01 (1H, s), 8.02 (2H, d, J = 8.3 Hz), 8.25 (1H, s), 8.27 (1H, dd, J = 8.3 Hz, 2.6 Hz), 8.58 (1H, s). 
               
               
                   
               
               
                 2351 
                 3,4-Cl 2 Ph- 
                 3,4-F 2 PhCH 2 — 
                 2.31-2.40 (4H, m), 2.60-2.65 (2H, m), 2.93- 
               
               
                   
                   
                   
                 2.99 (2H, m), 3.39-3.45 (4H, m), 3.61-3.65 (2H, 
               
               
                   
                   
                   
                 m), 6.95 (1H, d, J = 8.8 Hz), 7.03-7.24 (7H, m), 
               
               
                   
                   
                   
                 7.57 (1H, d, J = 8.3 Hz), 7.73 (1H, dd, J = 8.4 
               
               
                   
                   
                   
                 Hz, 2.1 Hz), 8.00 (1H, d, J = 2.1 Hz), 8.10 (1H, 
               
               
                   
                   
                   
                 brs), 8.16-8.20 (1H, m), 8.26 (1H, d, J = 2.3 
               
               
                   
                   
                   
                 Hz). 
               
               
                 2352 
                 3,4-Cl 2 Ph- 
                 3,5-F 2 PhCH 2 — 
                 2.32-2.38 (4H, m), 2.58-2.64 (2H, m), 2.89- 
               
               
                   
                   
                   
                 2.94 (2H, m), 3.40-3.46 (4H, m), 3.59-3.62 (2H, 
               
               
                   
                   
                   
                 m), 6.66-6.74 (1H, m), 6.85-7.03 (5H, m), 
               
               
                   
                   
                   
                 7.17 (2H, d, J = 8.6 Hz), 7.52 (1H, d, J = 8.2 
               
               
                   
                   
                   
                 Hz), 7.71-7.75 (1H, m), 7.99 (1H, d, J = 2.0 Hz), 
               
               
                   
                   
                   
                 8.16-8.20 (1H, m), 8.28 (1H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                 8.77 (1H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 376 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 1075   
                 Xb 54   
                 R 1076   
                   1 H NMR (CDCl 3 ) δppm 
               
               
                   
               
               
                 2353 
                 3,4-Cl 2 Ph- 
                 —CO— 
                 —CH 3   
                 3.03 (2H, t, J = 5.2 Hz), 3.39 (2H, s), 3.51 (2H, s), 
               
               
                   
                   
                   
                   
                 3.76 (2H, t, J = 5.2 Hz), 3.77 (3H, s), 6.98 (1H, d, J = 
               
               
                   
                   
                   
                   
                 8.9 Hz), 7.15 (2H, dd, J = 8.8 Hz, 2.1 Hz), 
               
               
                   
                   
                   
                   
                 7.30 (2H, dd, J = 8.8 Hz, 2.1 Hz), 7.59 (1H, d, J = 
               
               
                   
                   
                   
                   
                 8.4 Hz), 7.72 (1H, dd, J = 8.4 Hz, 2.1 Hz), 
               
               
                   
                   
                   
                   
                 7.99 (1H, d, J = 2.1 Hz), 8.15 (1H, dd, J = 8.9 Hz, 
               
               
                   
                   
                   
                   
                 2.7 Hz), 8.29 (1H, d, J = 2.7 Hz). 
               
               
                 2354 
                 3,4-Cl 2 Ph- 
                 —CH 2 — 
                 —CH 3   
                 2.75 (4H, t, J = 5.0 Hz), 3.23 (4H, t, J = 5.0 Hz), 
               
               
                   
                   
                   
                   
                 3.30 (2H, s), 3.75 (3H, s), 6.90 (1H, d, J = 9.0 Hz), 
               
               
                   
                   
                   
                   
                 6.95 (2H, d, J = 9.0 Hz), 7.04 (2H, d, J = 9.0 Hz), 
               
               
                   
                   
                   
                   
                 7.58 (1H, d, J = 8.5 Hz), 7.70 (1H, dd, J = 8.5 Hz, 
               
               
                   
                   
                   
                   
                 2.0 Hz), 7.76 (1H, brs), 7.98 (1H, d, J = 2.0 Hz), 
               
               
                   
                   
                   
                   
                 8.15 (1H, dd, J = 9.0 Hz, 3.0 Hz), 8.23 (1H, d, J = 
               
               
                   
                   
                   
                   
                 3.0 Hz). 
               
               
                 2355 
                 3,4-Cl 2 Ph- 
                 —CH 2 — 
                 —C 2 H 5   
                 1.31 (3H, t, J = 7.0 Hz), 2.75 (4H, t, J = 5.0 Hz), 
               
               
                   
                   
                   
                   
                 3.23 (4H, t, J = 5.0 Hz), 3.28 (2H, s), 4.21 (2H, q, J = 
               
               
                   
                   
                   
                   
                 7.0 Hz), 6.90 (1H, d, J = 9.0 Hz), 6.95 (2H, d, J = 
               
               
                   
                   
                   
                   
                 9.0 Hz), 7.04 (2H, d, J = 9.0 Hz), 7.57 (1H, d, J = 
               
               
                   
                   
                   
                   
                 8.5 Hz), 7.71 (1H, dd, J = 8.5 Hz, 2.0 Hz), 
               
               
                   
                   
                   
                   
                 7.88 (1H, brs), 7.98 (1H, d, J = 2.0 Hz), 8.15 (1H, 
               
               
                   
                   
                   
                   
                 dd, J = 9.0 Hz, 2.5 Hz), 8.24 (1H, d, J = 2.5 Hz). 
               
               
                 2356 
                 4-CF 3 Ph- 
                 —CH 2 — 
                 —CH 3   
                 2.75 (4H, t, J = 5.0 Hz), 3.24 (4H, t, J = 5.0 Hz), 
               
               
                   
                   
                   
                   
                 3.30 (2H, s), 3.75 (3H, s), 6.92 (1H, d, J = 9.0 Hz), 
               
               
                   
                   
                   
                   
                 6.96 (2H, d, J = 9.0 Hz), 7.06 (2H, d, J = 9.0 Hz), 
               
               
                   
                   
                   
                   
                 7.74 (1H, brs), 7.78 (2H, d, J = 8.0 Hz), 7.99 (2H, d, 
               
               
                   
                   
                   
                   
                 J = 8.0 Hz), 8.19 (1H, dd, J = 9.0 Hz, 2.5 Hz), 8.25 
               
               
                   
                   
                   
                   
                 (1H, d, J = 2.5 Hz). 
               
               
                   
               
             
          
         
       
     
       Example 2357 
     Production of 3,4-dichloro-N-[6-(4-{4-[(3,4-difluorobenzyl)methylamino]piperidine-1-carbonyl}phenoxy)pyridin-3-yl]benzamide 
       [1208]    3,4-dichloro-N-{6-[4-(4-methylamino-piperidine-1-carbonyl)phenoxy]pyridin-3-yl}benzamide dihydrochloride (114 mg, 0.2 mmol) was dissolved in DMF (3 mL). To the resulting solution were added 4-bromomethyl-1,2-difluorobenzene (31 μl, 0.24 mmol) and potassium carbonate (111 mg, 0.8 mmol), and this solution was stirred for 4 hours at room temperature. The resulting reaction solution was concentrated under reduced pressure. The residue was diluted with ethyl acetate and washed with water and brine. The organic layer was dried over anhydrous magnesium sulfate, and evaporated. This residue was purified by silica gel column chromatography (chloroform:methanol=50:1), to thereby yield 60 mg of the title compound. 
         [1209]    Appearance: White powder 
         [1210]      1 H NMR (CDCl 3 ) δ 1.64 (4H, brs), 1.84 (2H, brs), 2.20 (3H, s), 2.65-2.90 (3H, m), 3.54 (2H, s), 6.95-7.08 (4H, m), 7.13 (2H, d, J=9.3 Hz), 7.41 (2H, d, J=9.2 Hz), 7.57 (1H, d, J=8.4 Hz), 7.75 (1H, dd, J=8.4 Hz, 2.0 Hz), 8.03 (1H, d, J=2.0 Hz), 8.15 (1H, dd, J=8.9 Hz, 2.8 Hz), 8.30 (1H, brs), 8.31 (1H, d, J=2.2 Hz). 
         [1211]    The following compounds were produced in the same manner as in Example 2357. 
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 377 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 1077   
                   1 H NMR (CDCl 3 ) δppm 
               
               
                   
               
               
                 2358 
                 2,4-F 2 Ph- 
                 1.66 (4H, brs), 1.91 (2H, brs), 2.25 (3H, s), 2.73-3.08 (3H, m), 
               
               
                   
                   
                 3.63 (2H, s), 6.75-6.89 (3H, m), 6.97 (1H, d, J = 8.7 Hz), 7.13 (2H, 
               
               
                   
                   
                 d, J = 9.2 Hz), 7.42 (2H, d, J = 9.2 Hz), 7.57 (1H, d, J = 8.3 Hz), 
               
               
                   
                   
                 7.76 (1H, dd, J = 8.3 Hz, 2.1 Hz), 8.04 (1H, d, J = 2.1 Hz), 
               
               
                   
                   
                 8.16 (1H, dd, J = 8.9 Hz, 2.8 Hz), 8.31 (1H, d, J = 2.3 Hz), 8.37 
               
               
                   
                   
                 (1H, brs). 
               
               
                 2359 
                 2,5-F 2 Ph- 
                 1.72 (4H, brs), 1.88 (2H, brs), 2.25 (3H, s), 2.67-2.96 (3H, m), 
               
               
                   
                   
                 3.62 (2H, s), 6.85-7.02 (3H, m), 7.09-7.23 (3H, m), 7.39 (2H, d, J = 
               
               
                   
                   
                 8.9 Hz), 7.55 (1H, d, J = 8.3 Hz), 7.77 (1H, dd, J = 8.4 Hz, 2.1 
               
               
                   
                   
                 Hz), 8.05 (1H, d, J = 2.1 Hz), 8.12 (1H, dd, J = 8.9 Hz, 2.8 Hz), 
               
               
                   
                   
                 8.31 (1H, d, J = 2.6 Hz), 8.66 (1H, brs). 
               
               
                 2360 
                 4-CH(CH 3 ) 2 Ph- 
                 1.25 (6H, d, J = 6.9 Hz), 1.57-2.21 (7H, m), 2.66-3.07 (4H, m), 
               
               
                   
                   
                 3.56 (2H, s), 3.90 (1H, brs), 4.66 (1H, brs), 6.90 (1H, d, J = 8.9 
               
               
                   
                   
                 Hz), 7.04-7.10 (2H, m), 7.16-7.25 (4H, m), 7.31-7.36 (2H, m), 
               
               
                   
                   
                 7.50 (1H, d, J = 8.4 Hz), 7.77 (1H, dd, J = 8.4 Hz, 2.1 Hz), 8.06- 
               
               
                   
                   
                 8.10 (2H, m), 8.33 (1H, d, J = 2.5 Hz), 9.37 (1H, s). 
               
               
                 2361 
                 4-C(CH 3 ) 3 Ph- 
                 1.32 (9H, s), 1.58 (2H, brs), 1.89 (2H, brs), 2.22 (3H, s), 2.62- 
               
               
                   
                   
                 3.10 (3H, m), 3.57 (2H, s), 3.92 (1H, brs), 4.69 (1H, brs), 
               
               
                   
                   
                 6.92 (1H, d, J = 8.6 Hz), 7.06-7.11 (2H, m), 7.22-7.25 (2H, m), 
               
               
                   
                   
                 7.32-7.37 (4H, m), 7.53 (1H, d, J = 8.6 Hz), 7.78 (1H, dd, J = 8.4 
               
               
                   
                   
                 Hz, 2.2 Hz), 8.07 (1H, d, J = 2.2 Hz), 8.11 (1H, d, J = 2.7 Hz), 
               
               
                   
                   
                 8.32 (1H, d, J = 2.7 Hz), 9.07 (1H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 378 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 1078   
                   1 H NMR (CDCl 3 ) δppm 
               
               
                   
               
               
                 2362 
                 4-CNPh- 
                 1.54 (1H, brs), 1.86 (3H, brs), 2.20 (3H, s), 2.64-3.04 (3H, m), 3.64 (2H, 
               
               
                   
                   
                 s), 3.91 (1H, brs), 4.69 (1H, brs), 6.91 (1H, d, J = 8.9 Hz), 7.05-7.10 (2H, 
               
               
                   
                   
                 m), 7.32-7.37 (2H, m), 7.45 (2H, d, J = 8.4 Hz), 7.50 (1H, d, J = 8.4 Hz), 
               
               
                   
                   
                 7.59-7.62 (2H, m), 7.75-7.79 (1H, m), 8.05 (1H, d, J = 2.0 Hz), 8.10 (1H, 
               
               
                   
                   
                 dd, J = 8.9 Hz, 2.7 Hz), 8.35 (1H, d, J = 2.7 Hz), 9.31 (1H, brs). 
               
               
                 2363 
                 Ph- 
                 1.55 (2H, brs), 1.87 (2H, brs), 2.22 (3H, s), 2.61-2.80 (2H, m), 2.90 (1H, 
               
               
                   
                   
                 brs), 3.60 (2H, s), 3.93 (1H, brs), 4.72 (1H, brs), 6.98 (1H, d, J = 8.9 Hz), 
               
               
                   
                   
                 7.14 (2H, d, J = 8.7 Hz), 7.18-7.37 (5H, m), 7.43 (2H, d, J = 8.7 Hz), 
               
               
                   
                   
                 7.58 (1H, d, J = 8.4 Hz), 7.75 (1H, dd, J = 8.4 Hz, 2.0 Hz), 8.02 (1H, d, J = 
               
               
                   
                   
                 2.0 Hz), 8.16 (1H, dd, J = 8.9 Hz, 2.4 Hz), 8.19 (1H, brs), 8.30 (1H, d, 
               
               
                   
                   
                 J = 2.4 Hz). 
               
               
                 2364 
                 2-ClPh- 
                 1.50 (2H, brs), 1.90 (2H, brs), 2.26 (3H, s), 2.68-2.85 (2H, m), 2.98 (1H, 
               
               
                   
                   
                 brs), 3.70 (2H, s), 3.95 (1H, brs), 4.75 (1H brs), 6.98 (1H, d, J = 8.7 Hz), 
               
               
                   
                   
                 7.14 (2H, d, J = 8.5 Hz), 7.15-7.30 (2H, m), 7.34 (1H, dd, J = 7.2 Hz, 2.0 
               
               
                   
                   
                 Hz), 7.43 (2H, d, J = 8.5 Hz), 7.47 (1H, dd, J = 7.2 Hz, 2.0 Hz), 
               
               
                   
                   
                 7.58 (1H, d, J = 8.4 Hz), 7.75 (1H, dd, J = 8.4 Hz, 2.0 Hz), 8.04 (1H, d, J = 
               
               
                   
                   
                 2.0 Hz), 8.16 (1H, dd, J = 8.7 Hz, 2.8 Hz), 8.31 (1H, d, J = 2.8 Hz), 
               
               
                   
                   
                 8.32 (1H, brs). 
               
               
                 2365 
                 3-ClPh- 
                 1.50 (2H, brs), 1.87 (2H, brs), 2.21 (3H, s), 2.55-3.20 (3H, m), 3.57 (2H, 
               
               
                   
                   
                 s), 3.95 (1H, brs), 4.70 (1H, brs), 6.99 (1H, d, J = 8.8 Hz), 7.14 (2H, d, J = 
               
               
                   
                   
                 8.7 Hz), 7.15-7.28 (3H, m), 7.33 (1H, brs), 7.44 (2H, d, J = 8.7 Hz), 
               
               
                   
                   
                 7.59 (1H, d, J = 8.4 Hz), 7.74 (1H, dd, J = 8.4 Hz, 2.0 Hz), 8 02 (1H, d, J = 
               
               
                   
                   
                 2.0 Hz), 8.09 (1H, brs), 8.17 (1H, dd, J = 8.8 Hz, 2.8 Hz), 8.30 (1H, d, 
               
               
                   
                   
                 J = 2.8 Hz). 
               
               
                 2366 
                 3,4-Cl 2 Ph- 
                 1.50 (2H, brs), 1.85 (2H, brs), 2.20 (3H, s), 2.60-3.15 (3H, m), 3.54 (2H, 
               
               
                   
                   
                 s), 3.95 (1H, brs), 4.70 (1H, brs), 6.97 (1H, d, J = 8.9 Hz), 7.13 (2H, d, J = 
               
               
                   
                   
                 8.6 Hz), 7.10-7.19 (1H, m), 7.36 (1H, s), 7.41 (2H, d, J = 8.6 Hz), 7.35- 
               
               
                   
                   
                 7.47 (1H, m), 7.57 (1H, d, J = 8.4 Hz), 7.75 (1H, dd, J = 8.4 Hz, 2.1 Hz), 
               
               
                   
                   
                 8.03 (1H, d, J = 2.1 Hz), 8.14 (1H, dd, J = 8.9 Hz, 2.5 Hz), 8.30 (1H, d, J = 
               
               
                   
                   
                 2.5 Hz), 8.40 (1H, s). 
               
               
                 2367 
                 2,3-Cl 2 Ph- 
                 1.60 (2H, brs), 1.90 (2H, brs), 2.26 (3H, s), 2.65-3.20 (3H, m), 3.72 (2H, 
               
               
                   
                   
                 s), 3.90 (1H, brs), 4.72 (1H, brs), 6.97 (1H, d, J = 8.8 Hz), 7.13 (2H, d, J = 
               
               
                   
                   
                 8.6 Hz), 7.20 (1H, d, J = 8.0 Hz), 7.36 (1H, dd, J = 8.0 Hz, 1.5 Hz), 
               
               
                   
                   
                 7.42 (2H, d, J = 8.6 Hz), 7.37-7.46 (1H, m), 7.57 (1H, d, J = 8.2 Hz), 
               
               
                   
                   
                 7.75 (1H, dd, J = 8.4 Hz, 2.0 Hz), 8.04 (1H, d, J = 2.0 Hz), 8.14 (1H, dd, 
               
               
                   
                   
                 J = 8.8 Hz, 2.7 Hz), 8.30 (1H, d, J = 2.7 Hz), 8.38 (1H, brs). 
               
               
                 2368 
                 2-FPh- 
                 1.55 (2H, brs), 1.85 (2H, brs), 2.25 (3H, s), 2.50-3.20 (3H, m), 3.65 (2H, 
               
               
                   
                   
                 s), 3.95 (1H, brs), 4.70 (1H, brs), 6.97 (1H, d, J = 8.8 Hz), 6.95-7.17 (2H, 
               
               
                   
                   
                 m), 7.13 (2H, d, J = 8.7 Hz), 7.18-7.29 (1H, m), 7.32-7.45 (1H, m), 
               
               
                   
                   
                 7.42 (2H, d, J = 8.7 Hz), 7.57 (1H, d, J = 8 2 Hz), 7.75 (1H, dd, J = 8.2 
               
               
                   
                   
                 Hz, 2.1 Hz), 8.04 (1H, d, J = 2.1 Hz), 8.14 (1H, dd, J = 8.8 Hz, 2.5 Hz), 
               
               
                   
                   
                 8.30 (1H, d, J = 2.5 Hz), 8.34 (1H, brs). 
               
               
                 2369 
                 2-CH 3 Ph- 
                 1.67 (4H, brs), 1.89 (2H, brs), 2.19 (3H, s), 2.36 (3H, s), 2.67-2.96 (3H, 
               
               
                   
                   
                 m), 3.57 (2H, s), 6.96 (1H, d, J = 8.7 Hz), 7.07-7.26 (6H, m), 7.41 (2H, d, 
               
               
                   
                   
                 J = 8.1 Hz), 7.57 (1H, d, J = 8.4 Hz), 7.77 (1H, dd, J = 8.4 Hz, 2.0 Hz), 
               
               
                   
                   
                 8.05 (1H, d, J = 2.0 Hz), 8.14 (1H, dd, J = 8.9 Hz, 2.6 Hz), 8.31 (1H, d, J = 
               
               
                   
                   
                 2.6 Hz), 8.51 (1H brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 379 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 1079   
                 Form 
                   1 H NMR (solvent) δppm 
               
               
                   
               
               
                 2370 
                 3,5-(CH 3 O) 2 Ph- 
                 hydro- 
                 (DMSO-d 6 ) 1.67-1.93 (2H, m), 2.08-2.30 (2H, m), 
               
               
                   
                   
                 chloride 
                 2.61 (3H, d, J = 4.8 Hz), 2.95 (1H, brs), 3.31-3.75 (4H, 
               
               
                   
                   
                   
                 m), 3.77 (6H, s), 4.02-4.18 (1H, m), 4.31-4.45 (1H, m), 
               
               
                   
                   
                   
                 6.57 (1H, t, J = 2.0 Hz), 6.83 (2H, d, J = 2.0 Hz), 
               
               
                   
                   
                   
                 7.16 (1H, d, J = 8.7 Hz), 7.20 (2H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                 7.49 (2H, d, J = 8.6 Hz), 7.85 (1H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                 7.97 (1H, dd, J = 8.4 Hz, 2.1 Hz), 8.24 (1H, d, J = 2.1 
               
               
                   
                   
                   
                 Hz), 8.24 (1H, dd, J = 8.7 Hz, 2.6 Hz), 8.55 (1H, d, J = 
               
               
                   
                   
                   
                 2.6 Hz), 10.64 (1H, brs). 
               
               
                 2371 
                 3-CH 3 OPh- 
                 free 
                 (CDCl 3 ) 1.60 (2H, brs), 1.87 (2H, brs), 2.23 (3H, s), 2.52- 
               
               
                   
                   
                   
                 3.20 (3H, m), 3.58 (2H, s), 3.81 (3H, s), 3.95 (1H, brs), 
               
               
                   
                   
                   
                 4.70 (1H, brs), 6.75-6.90 (3H, m), 6.97 (1H, d, J = 8.9 
               
               
                   
                   
                   
                 Hz), 7.13 (2H, d, J = 8.6 Hz), 7.21 (1H, d, J = 8.0 Hz), 
               
               
                   
                   
                   
                 7.41 (2H, d, J = 8.6 Hz), 7.57 (1H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                 7.75 (1H, dd, J = 8.4 Hz, 2.0 Hz), 8.04 (1H, d, J = 2.0 
               
               
                   
                   
                   
                 Hz), 8.14 (1H, dd, J = 8.9 Hz, 2.6 Hz), 8.30 (1H, d, J = 
               
               
                   
                   
                   
                 2.6 Hz), 8.36 (1H, brs). 
               
               
                 2372 
                 3-CH 3 Ph- 
                 free 
                 (CDCl 3 ) 1.61 (4H, brs), 1.88 (2H, brs), 2.22 (3H, s), 
               
               
                   
                   
                   
                 2.35 (3H, s), 2.68-3.01 (3H, m), 3.56 (2H, s), 6.98 (1H, d, 
               
               
                   
                   
                   
                 J = 8.9 Hz), 7.06-7.29 (6H, m), 7.42 (2H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                 7.58 (1H, d, J = 8.2 Hz), 7.76 (1H, dd, J = 8.3 Hz, 2.0 
               
               
                   
                   
                   
                 Hz), 8.04 (1H, d, J = 2.0 Hz), 8.16 (1H, dd, J = 8.9 Hz, 
               
               
                   
                   
                   
                 2.6 Hz), 8.31 (1H, d, J = 2.3 Hz), 8.38 (1H, brs). 
               
               
                 2373 
                 3,5-F 2 Ph- 
                 free 
                 (CDCl 3 ) 1.42-1.96 (4H, m), 2.21 (3H, s), 2.65-3.10 (3H, 
               
               
                   
                   
                   
                 m), 3.56 (2H, s), 3.90 (1H, brs), 4.68 (1H, brs), 6.64- 
               
               
                   
                   
                   
                 6.70 (1H, m), 6.85-6.92 (3H, m), 7.04-7.09 (2H, m), 7.31- 
               
               
                   
                   
                   
                 7.36 (2H, m), 7.50 (1H, d, J = 8.4 Hz), 7.74-7.79 (1H, 
               
               
                   
                   
                   
                 m), 8.05-8.10 (2H, m), 8.33 (1H, d, J = 2.5 Hz), 9.30 
               
               
                   
                   
                   
                 (1H, brs). 
               
               
                 2374 
                 3,4-(CH 3 ) 2 Ph- 
                 free 
                 (CDCl 3 ) 1.59 (4H, brs), 1.90-1.98 (2H, m), 2.22 (3H, s), 
               
               
                   
                   
                   
                 2.25 (3H, s), 2.26 (3H, s), 2.67-2.97 (3H, m), 3.59 (2H, s), 
               
               
                   
                   
                   
                 6.99 (1H, d, J = 8.7 Hz), 7.05-7.10 (3H, m), 7.15 (2H, d, 
               
               
                   
                   
                   
                 J = 9.4 Hz), 7.44 (2H, d, J = 9.4 Hz), 7.59 (1H, d, J = 
               
               
                   
                   
                   
                 8.3 Hz), 7.74 (1H, dd, J = 8.3 Hz, 2.2 Hz), 8.02 (1H, d, J = 
               
               
                   
                   
                   
                 2.0 Hz), 8.03 (1H, brs), 8.18 (1H, dd, J = 8.7 Hz, 2.8 
               
               
                   
                   
                   
                 Hz), 8.31 (1H, d, J = 2.8 Hz). 
               
               
                 2375 
                 3-FPh- 
                 free 
                 (CDCl 3 ) 1.59-1.85 (6H, m), 2.22 (3H, s), 2.67-2.99 (3H, 
               
               
                   
                   
                   
                 m), 3.59 (2H, s), 6.94-6.97 (2H, m), 7.05-7.13 (5H, m), 
               
               
                   
                   
                   
                 7.39 (2H, d, J = 8.4 Hz), 7.56 (1H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                 7.77 (1H, dd, J = 8.4 Hz, 2.0 Hz), 8.05 (1H, d, J = 2.0 
               
               
                   
                   
                   
                 Hz), 8.13 (1H, dd, J = 8.7 Hz, 2.6 Hz), 8.31 (1H, d, J = 
               
               
                   
                   
                   
                 2.5 Hz), 8.63 (1H, brs). 
               
               
                 2376 
                 2,6-F 2 Ph- 
                 free 
                 (CDCl 3 ) 1.65 (4H, brs), 1.81-1.91 (2H, m), 2.28 (3H, s), 
               
               
                   
                   
                   
                 2.69-3.03 (3H, m), 3.69 (2H, s), 6.83-6.92 (3H, m), 
               
               
                   
                   
                   
                 6.99 (1H, d, J = 8.9 Hz), 7.15 (2H, d, J = 9.2 Hz), 
               
               
                   
                   
                   
                 7.44 (2H, d, J = 9.2 Hz), 7.59 (1H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                 7.75 (1H, dd, J = 8.4 Hz, 2.2 Hz), 8.03 (1H, d, J = 2.2 
               
               
                   
                   
                   
                 Hz), 8.17 (1H, brs), 8.18 (1H, dd, J = 8.7 Hz, 2.8 Hz), 
               
               
                   
                   
                   
                 8.31 (1H, d, J = 2.6 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 380 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 1080   
                 mp (° C.) or MS 
               
               
                   
               
               
                 2377 
                 4-CF 3 OPh- 
                 mp 180-181 
               
               
                 2378 
                 2-NO 2 Ph- 
                 MS 634 (M +  + H) 
               
               
                 2379 
                 3-NO 2 Ph- 
                 MS 634 (M +  + H) 
               
               
                 2380 
                 4-NO 2 Ph- 
                 MS 634 (M +  + H) 
               
               
                 2381 
                 2-CF 3 Ph- 
                 MS 657 (M +  + H) 
               
               
                 2382 
                 3-CF 3 Ph- 
                 MS 657 (M +  + H) 
               
               
                 2383 
                 4-CF 3 Ph- 
                 MS 657 (M +  + H) 
               
               
                 2384 
                 2-CF 3 OPh- 
                 MS 673 (M +  + H) 
               
               
                   
               
               
                 2385 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 647 (M +  + H) 
               
               
                   
               
               
                 2386 
                 4-biphenylyl 
                 MS 665 (M +  + H) 
               
               
                   
               
               
                 2387 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 647 (M +  + H) 
               
               
                   
               
               
                 2388 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 699 (M +  + H) 
               
               
                   
               
               
                 2389 
                 2-pyridyl 
                 MS 590 (M +  + H) 
               
               
                 2390 
                 2-quinolyl 
                 MS 640 (M +  + H) 
               
               
                   
               
               
                 2391 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 671 (M +  + H) 
               
               
                   
               
               
                 2392 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 609 (M +  + H) 
               
               
                   
               
               
                 2393 
                 2,4-Cl 2 Ph- 
                 MS 657 (M +  + H) 
               
               
                 2394 
                 2,5-Cl 2 Ph- 
                 MS 657 (M +  + H) 
               
               
                 2395 
                 2,6-Cl 2 Ph- 
                 MS 657 (M +  + H) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 381 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 1081   
                 Xb 55   
                 Xb 56   
                 R 1082   
                 mp (° C.) or MS 
               
               
                   
               
               
                 2396 
                 —H 
                 none 
                 none 
                 Ph- 
                 mp 155-158 
               
               
                 2397 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 Ph- 
                 MS 634 (M +  + H) 
               
               
                 2398 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 2-ClPh- 
                 MS 668 (M +  + 1) 
               
               
                 2399 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 3-ClPh- 
                 MS 668 (M +  + H) 
               
               
                 2400 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 4-ClPh- 
                 MS 668 (M +  + H) 
               
               
                 2401 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 2,3-Cl 2 Ph- 
                 MS 702 (M +  + 1) 
               
               
                 2402 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 2,4-Cl 2 Ph- 
                 MS 701 (M + ) 
               
               
                 2403 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 2,5-Cl 2 Ph- 
                 MS 702 (M +  + 1) 
               
               
                 2404 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 2,6-Cl 2 Ph- 
                 MS 702 (M +  + H) 
               
               
                 2405 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 3,4-Cl 2 Ph- 
                 MS 703 (M + ) 
               
               
                 2406 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 3-pyridyl 
                 MS 634 (M + ) 
               
               
                 2407 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 2-quinolyl 
                 MS 685 (M +  + H) 
               
               
                   
               
               
                 2408 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 716 (M +  + H) 
               
               
                   
               
               
                 2409 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 654 (M +  + H) 
               
               
                   
               
               
                 2410 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 MS 730 (M +  + H) 
               
               
                   
               
               
                 2411 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 3-CH 3 OPh- 
                 MS 662 (M +  − 1) 
               
               
                 2412 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 3,5-(CH 3 O) 2 Ph- 
                 MS 693 (M + ) 
               
               
                 2413 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 2-CH 3 Ph- 
                 MS 648 (M +  + H) 
               
               
                 2414 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 3-CH 3 Ph- 
                 MS 648 (M +  + H) 
               
               
                 2415 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 4-CH 3 Ph- 
                 MS 648 (M +  + H) 
               
               
                 2416 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 3,4-(CH 3 ) 2 Ph- 
                 MS 662 (M +  + 1) 
               
               
                 2417 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 2-FPh- 
                 MS 652 (M +  + H) 
               
               
                 2418 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 3-FPh- 
                 MS 652 (M +  + H) 
               
               
                 2419 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 4-FPh- 
                 MS 652 (M +  + 1) 
               
               
                 2420 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 2,4-F 2 Ph- 
                 MS 670 (M +  + H) 
               
               
                 2421 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 2,5-F 2 Ph- 
                 MS 670 (M +  + H) 
               
               
                 2422 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 2,6-F 2 Ph- 
                 MS 671 (M +  + 2) 
               
               
                 2423 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 3,4-F 2 Ph- 
                 MS 670 (M +  + H) 
               
               
                 2424 
                 —F 
                 —(CH 2 ) 2 — 
                 —CO— 
                 3,5-F 2 Ph- 
                 MS 670 (M +  + H) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 382 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 1083   
                 MS 
               
               
                   
               
               
                 2425 
                 2-NO 2 Ph- 
                 679 (M +  + H) 
               
               
                 2426 
                 3-NO 2 Ph- 
                 678 (M + ) 
               
               
                 2427 
                 4-NO 2 Ph- 
                 679 (M +  + H) 
               
               
                 2428 
                 2-CF 3 Ph- 
                 701 (M +  ) 
               
               
                 2429 
                 3-CF 3 Ph- 
                 702 (M +  + H) 
               
               
                 2430 
                 4-CF 3 Ph- 
                 701 (M + ) 
               
               
                 2431 
                 4-CNPh- 
                 659 (M +  + H) 
               
               
                 2432 
                 2-CF 3 OPh- 
                 718 (M +  + H) 
               
               
                 2433 
                 3-CF 3 OPh- 
                 718 (M +  + H) 
               
               
                 2434 
                 4-CF 3 OPh- 
                 718 (M +  + H) 
               
               
                   
               
               
                 2435 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 692 (M +  + H) 
               
               
                   
               
               
                 2436 
                 4-biphenylyl 
                 710 (M +  + H) 
               
               
                   
               
               
                 2437 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 692 (M +  + H) 
               
               
                   
               
               
                 2438 
                 4-C 2 H 5 Ph- 
                 662 (M +  + H) 
               
               
                 2439 
                 4-CH(CH 3 ) 2 Ph- 
                 676 (M +  + H) 
               
               
                 2440 
                 4-C(CH 3 ) 3 Ph- 
                 690 (M +  + H) 
               
               
                   
               
               
                 2441 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 744 (M +  + H) 
               
               
                   
               
               
                 2442 
                 2-naphthyl 
                 684 (M +  + H) 
               
               
                 2443 
                 2-pyridyl 
                 635 (M +  + H) 
               
               
                   
               
             
          
         
       
     
       Example 2444 
     Production of 1-(4-piperonylpiperazin-1-yl)-2-{4-[5-(4-trifluoromethylphenoxymethyl)pyridin-2-yloxy]-phenylamino}ethanone 
       [1212]    4-[5-(4-trifluoromethylphenoxymethyl)pyridin-2-yloxy]phenylamine (4.50 g, 12.5 mmol) was dissolved in DMF (150 mL). To the resulting solution were added potassium carbonate (2.60 g, 18.8 mmol) and sodium iodide (1.87 g, 12.5 mmol), and then to this solution was added 2-chloro-1-(4-piperonylpiperazin-1-yl)ethanone (4.21 g, 12.5 mmol). The resulting solution was stirred for 11 hours under a nitrogen atmosphere at 80° C. The resulting reaction solution was concentrated under reduced pressure. To the residue was added ethyl acetate and washed with a saturated sodium bicarbonate solution and brine. The organic layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatography (dichloromethane:methanol=80:1), to thereby yield 5.2 g of the title compound. 
         [1213]    Appearance: White powder 
         [1214]      1 H NMR (CDCl 3 ) δ 2.44-2.46 (4H, m), 3.43-3.47 (4H, m), 3.69 (2H, t, J=5.0 Hz), 3.86 (2H, s), 4.91 (1H, brs), 5.02 (2H, s), 5.94 (2H, s), 6.64 (2H, d, J=8.9 Hz), 6.74-6.75 (2H, m), 6.85-6.89 (2H, m), 6.96-7.03 (4H, m), 7.55 (2H, d, J=8.4 Hz), 7.72 (1H, dd, J=8.4 Hz, 2.5 Hz), 8.22 (1H, d, J=2.0 Hz). 
       Example 2445 
     Production of N-{6-[4-(4-thiazole-2-ylmethylpiperazine-1-carbonyl)phenoxy]pyridin-3-yl}-4-trifluoromethyl-benzamide 
       [1215]    To a suspension of N-{6-[4-(piperazine-1-carbonyl)phenoxy]pyridin-3-yl}-4-trifluoromethyl-benzamide dihydrochloride (400 mg, 0.74 mmol) in 1,2-dichloroethane (20 mL) were added 2-formylthiazole (125 mg, 1.10 mmol) and triethylamine (0.21 mL, 1.50 mmol). After the resulting solution was stirred at room temperature for 30 minutes, sodium triacetyloxy borohydride (312 mg, 1.47 mmol) was added under ice cooling. The reaction mixture was stirred at the same temperature for 30 minutes and at room temperature for 1 hour. Acetic acid (0.085 mL, 1.48 mmol) was added to the reaction mixture, and stirred at room temperature for 17 hours. The reaction mixture was poured into ice water, and extracted with chloroform. The chloroform layer was washed with a saturated sodium bicarbonate solution and brine, and dried over anhydrous magnesium sulfate. A significant part of the solvent was evaporated. The white precipitate was then filtered off and washed with ethyl acetate, to thereby yield 293 mg of the title compound. 
         [1216]    Appearance: White powder 
         [1217]      1 H NMR (DMSO-d 6 ) δ 2.55 (4H, brs), 3.55 (4H, brs), 3.90 (2H, s), 7.15 (1H, d, J=8.7 Hz), 7.16 (2H, d, J=8.6 Hz), 7.45 (2H, d, J=8.6 Hz), 7.68 (1H, d, J=3.2 Hz), 7.73 (1H, d, J=3.2 Hz), 7.94 (2H, d, J=8.1 Hz), 8.17 (2H, d, J=8.1 Hz), 8.26 (1H, dd, J=8.7 Hz, 2.3 Hz), 8.55 (1H, d, J=2.3 Hz), 10.68 (1H, s). 
         [1218]    The following compounds were produced in the same manner as in Example 2445. 
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 383 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 1084   
                 R 1085   
                   1 H NMR (solvent) δppm 
               
               
                   
               
               
                 2446 
                 3,4-Cl 2 Ph- 
                 3,4-(CH 3 ) 2 Ph- 
                 (CDCl 3 ) 2.27 (3H, s), 2.29 (3H, s), 2.42 (4H, brs), 
               
               
                   
                   
                   
                 3.49 (2H, s), 3.70 (4H, brs), 6.90 (1H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                 7.05-7.10 (5H, m), 7.34-7.36. (2H, m), 7.50 (1H, d, J = 
               
               
                   
                   
                   
                 8.4 Hz), 7.75-7.79 (1H, m), 8.00-8.14 (2H, m), 8.33 (1H, 
               
               
                   
                   
                   
                 d, J = 2.7 Hz), 9.30 (1H, brs). 
               
               
                 2447 
                 4-CF 3 Ph- 
                 2-FPh- 
                 (CDCl 3 ) 2.50 (4H, brs), 3.55 (2H, brs), 3.70 (2H, brs), 
               
               
                   
                   
                   
                 3.62 (2H, s), 6.98 (1H, d, J = 8.8 Hz), 6.95-7.17 (2H, m), 
               
               
                   
                   
                   
                 7.12 (2H, d, J = 8.7 Hz), 7.20-7.41 (2H, m), 7.40 (2H, d, 
               
               
                   
                   
                   
                 J = 8.7 Hz), 7.76 (2H, d, J = 8.2 Hz), 8.02 (2H, d, J = 
               
               
                   
                   
                   
                 8.2 Hz), 8.19 (1H, dd, J = 8.8 Hz, 2.8 Hz), 8.31 (1H, s), 
               
               
                   
                   
                   
                 8.32 (1H, d, J = 2.8 Hz). 
               
               
                 2448 
                 4-CF 3 Ph- 
                 3-pyridyl 
                 (CDCl 3 ) 2.46 (4H, brs), 3.55 (2H, s), 3.58-3.73 (4H, m), 
               
               
                   
                   
                   
                 6.97 (1H, d, J = 8.7 Hz), 7.10-7.15 (2H, m), 7.25- 
               
               
                   
                   
                   
                 7.30 (1H, m), 7.38-7.43 (2H, m), 7.65-7.69 (1H, m), 
               
               
                   
                   
                   
                 7.74 (2H, d, J = 8.1 Hz), 8.03 (2H, d, J = 8.1 Hz), 8.19- 
               
               
                   
                   
                   
                 8.23 (1H, m), 8.32 (1H, d, J = 2.3 Hz), 8.51-8.53 (1H, 
               
               
                   
                   
                   
                 m), 8.54 (1H, d, J = 1.5 Hz), 8.62 (1H, brs). 
               
               
                 2449 
                 4-CF 3 Ph- 
                 cyclohexyl 
                 (DMSO-d 6 ) 0.60-1.90 (11H, m), 2.10 (2H, d, J = 7.2 
               
               
                   
                   
                   
                 Hz), 2.34 (4H, brs), 3.50 (4H, brs), 7.15 (1H, d, J = 8.8 
               
               
                   
                   
                   
                 Hz), 7.16 (2H, d, J = 8.7 Hz), 7.43 (2H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                 7.94 (2H, d, J = 8.1 Hz), 8.17 (2H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                 8.26 (1H, dd, J = 8.8 Hz, 2.7 Hz), 8.55 (1H, d, J = 2.7 
               
               
                   
                   
                   
                 Hz), 10.66 (1H, s). 
               
               
                 2450 
                 4-CF 3 Ph- 
                 3-furyl 
                 (CDCl 3 ) 2.46 (4H, brs), 3.42 (2H, s), 3.40-3.90 (4H, m), 
               
               
                   
                   
                   
                 6.39 (1H, brs), 6.98 (1H, d, J = 8.9 Hz), 7.13 (2H, d, J = 
               
               
                   
                   
                   
                 8.7 Hz), 7.34 (1H, brs), 7.33-7.42 (1H, m), 7.41 (2H, d, J = 
               
               
                   
                   
                   
                 8.7 Hz), 7.76 (2H, d, J = 8.1 Hz), 8.02 (2H, d, J = 8.1 
               
               
                   
                   
                   
                 Hz), 8.20 (1H, dd, J = 8.9 Hz, 2.5 Hz), 8.29 (1H, s), 
               
               
                   
                   
                   
                 8.32 (1H, d, J = 2.5 Hz). 
               
               
                 2451 
                 4-CF 3 Ph- 
                 4-pyridyl 
                 (CDCl 3 ) 2.45 (4H, brs), 3.41-3.81 (6H, m), 6.95 (1H, d, J = 
               
               
                   
                   
                   
                 8.9 Hz), 7.08-7.13 (2H, m), 7.28 (2H, d, J = 5.9 Hz), 
               
               
                   
                   
                   
                 7.35-7.40 (2H, m), 7.70 (2H, d, J = 8.4 Hz), 8.02 (2H, d, 
               
               
                   
                   
                   
                 J = 8.4 Hz), 8.21 (1H, dd, J = 8.9 Hz, 2.7 Hz), 8.33 (1H, 
               
               
                   
                   
                   
                 d, J = 2.7 Hz), 8.53-8.55 (2H, m), 9.02 (1H, s). 
               
               
                 2452 
                 4-CF 3 Ph- 
                 2-furyl 
                 (CDCl 3 ) 2.50 (4H, brs), 3.59 (2H, s), 3.73 (4H, brs), 
               
               
                   
                   
                   
                 6.23 (1H, d, J = 3.0 Hz), 6.33 (1H, dd, J = 3.0 Hz, 2.0 
               
               
                   
                   
                   
                 Hz), 6.99 (1H, d, J = 8.9 Hz), 7.13 (2H, d, J = 8.8 Hz), 
               
               
                   
                   
                   
                 7.41 (2H, d, J = 8.8 Hz), 7.35-7.48 (1H, m), 7.76 (2H, d, 
               
               
                   
                   
                   
                 J = 8.1 Hz), 8.02 (2H, d, J = 8.1 Hz), 8.20 (1H, dd, J = 
               
               
                   
                   
                   
                 8.9 Hz, 2.5 Hz), 8.24 (1H, brs), 8.32 (1H, d, J = 2.5 Hz) 
               
               
                 2453 
                 4-CF 3 Ph- 
                 4-NO 2 Ph- 
                 (CDCl 3 ) 2.48 (4H, brs), 3.63 (2H, s), 3.73 (4H, brs), 
               
               
                   
                   
                   
                 7.00 (1H, d, J = 8.8 Hz), 7.14 (2H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                 7.43 (2H, d, J = 8.7 Hz), 7.53 (2H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                 7.76 (2H, d, J = 8.0 Hz), 8.01 (2H, d, J = 8.0 Hz), 
               
               
                   
                   
                   
                 8.15 (1H, brs), 8.20 (2H, d, J = 8.4 Hz), 8.21 (1H, dd, J = 
               
               
                   
                   
                   
                 8.8 Hz, 2.5 Hz), 8.32 (1H, d, J = 2.5 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 384 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 1086   
                 R 1087   
                 mp (° C.) or  1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 2454 
                 4-CF 3 Ph- 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (CDCl 3 ) 2.43(4 H, brs), 3.46(2 H, s), 3.55(4 H, brs), 3.65 (3 H, s), 5.95-6.08(2 H, m), 6.61(1 H, t, J = 2.2 Hz), 6.98(1 H, d, J = 8.9 Hz), 7.13(2 H, d, J = 8.8 Hz), 7.41(2 H, d, J = 8.8 Hz), 7.76(2 H, d, J = 8.1 Hz), 8.02(2 H, d, J = 8.1 Hz), 8.20(1 H, dd, J = 8.9 Hz, 2.5 Hz), 8.25(1 H, brs), 8.31(1 H, d, J = 2.5 Hz). 
               
               
                   
               
               
                 2455 
                 4-CF 3 Ph- 
                 2-pyridyl 
                 mp 175-176 
               
               
                 2456 
                 4-CF 3 Ph- 
                 4-OHPh- 
                   1 H NMR (DMSO-d 6 ) 2.36(4 H, brs), 3.32(2 H, s), 
               
               
                   
                   
                   
                 3.49(4 H, brs), 6.70(2 H, d, J = 8.4 Hz), 7.09(2 H, d, J = 
               
               
                   
                   
                   
                 8.4 Hz), 7.15(1 H, d, J = 8.9 Hz), 7.16(2 H, d, J = 8.6 
               
               
                   
                   
                   
                 Hz), 7.43(2 H, d, J = 8.6 Hz), 7.94(2 H, d, J = 8.0 Hz), 
               
               
                   
                   
                   
                 8.17(2 H, d, J = 8.0 Hz), 8.26(1 H, dd, J = 8.9 Hz, 2.5 
               
               
                   
                   
                   
                 Hz), 8.54(1 H, d, J = 2.5 Hz), 9.27(1 H, s), 10.66(1 H, s). 
               
               
                 2457 
                 4-CF 3 Ph- 
                 2-OHPh- 
                   1 H NMR (CDCl 3 ) 2.59(4 H, brs), 3.68(4 H, brs), 
               
               
                   
                   
                   
                 3.75(2 H, s), 6.72-6.88(2 H, m), 6.92-7.10(1 H, m), 
               
               
                   
                   
                   
                 7.01(1 H, d, J = 8.8 Hz), 7.15(2 H, d, J = 8.8 Hz), 
               
               
                   
                   
                   
                 7.10-7.25(1 H, m), 7.44(2 H, d, J = 8.8 Hz), 7.76(2 H, d, J = 
               
               
                   
                   
                   
                 8.1 Hz), 8.01(2 H, d, J = 8.1 Hz), 8.12(1 H, brs), 
               
               
                   
                   
                   
                 8.22(1 H, dd, J = 8.8 Hz, 2.3 Hz), 8.31(1 H, d, J = 2.3 
               
               
                   
                   
                   
                 Hz). 
               
               
                 2458 
                 4-CF 3 Ph- 
                 4-AcNHPh- 
                   1 H NMR (DMSO-d 6 ) 2.02(3 H, s), 2.38(4 H, brs), 
               
               
                   
                   
                   
                 3.45(2 H, s), 3.45 (4 H, brs), 7.15(1 H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                 7.16(2 H, d, J = 8.6 Hz), 7.22(2 H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                 7.44(2 H, d, J = 8.6 Hz), 7.52(2 H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                 7.94(2 H, d, J = 8.1 Hz), 8.17(2 H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                 8.26(1 H, dd, J = 8.9 Hz, 2.6 Hz), 8.54(1 H, d, J = 2.6 
               
               
                   
                   
                   
                 Hz), 9.90(1 H, s), 10.66(1 H, s). 
               
               
                 2459 
                 4-CF 3 Ph- 
                 2,3-(CH 3 ) 2 Ph- 
                   1 H NMR (CDCl 3 ) 2.25(3 H, s), 2.28(3 H, s), 2.42(4 H, 
               
               
                   
                   
                   
                 brs), 3.47(2 H, s), 3.67(4 H, brs), 6.95(1 H, d, J = 8.7 
               
               
                   
                   
                   
                 Hz), 6.95-7.12(3 H, m), 7.10 (2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                 7.38(2 H, d, J = 8.6 Hz), 7.73(2 H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                 8.00(2 H, d, J = 8.1 Hz), 8.17(1 H, dd, J = 8.7 Hz, 2.7 
               
               
                   
                   
                   
                 Hz), 8.30 (1 H, d, J = 2.7 Hz), 8.43(1 H, s). 
               
               
                 2460 
                 4-CF 3 Ph- 
                 3-thienyl 
                   1 H NMR (CDCl 3 ) 2.45(4 H, brs), 3.55(2 H, brs), 
               
               
                   
                   
                   
                 3.56(2 H, s), 3.72 (2 H, brs), 6.97(1 H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                 7.05(1 H, dd, J = 5.0 Hz, 1.1 Hz), 7.08-7.17(1 H, m), 
               
               
                   
                   
                   
                 7.12(2 H, d, J = 8.7 Hz), 7.29(1 H, dd, J = 5.0 Hz, 3.0 
               
               
                   
                   
                   
                 Hz), 7.39(2 H, d, J = 8.7 Hz), 7.75(2 H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                 8.02(2 H, d, J = 8.1 Hz), 8.19(1 H, dd, J = 8.9 Hz, 2.8 
               
               
                   
                   
                   
                 Hz), 8.32(1 H, d, J = 2.8 Hz), 8.41(1 H, brs). 
               
               
                 2461 
                 3,4-Cl 2 Ph- 
                 3-pyridyl 
                   1 H NMR (CDCl 3 ) 2.46(4 H, brs), 3.46(2 H, s), 
               
               
                   
                   
                   
                 3.55-3.80(4 H, m), 6.96(1 H, d, J = 8.9 Hz), 7.12(2 H, d, J = 
               
               
                   
                   
                   
                 8.4 Hz), 7.26-7.30(1 H, m), 7.40(2 H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                 7.56(1 H, d, J = 8.4 Hz), 7.65-7.78(2 H, m), 8.04(1 H, d, 
               
               
                   
                   
                   
                 J = 2.2 Hz), 8.16(1 H, dd, J = 8.9 Hz, 2.7 Hz), 8.29(1 H, 
               
               
                   
                   
                   
                 d, J = 2.2 Hz), 8.51-8.56(2 H, m), 8.61(1 H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 385 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 1088   
                 R 1089   
                 Form 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 2462 
                 4-CF 3 Ph- 
                 cyclopropyl 
                 free 
                 (CDCl 3 ) 0.11(2 H, dd, J = 10.5 Hz, 4.5 
               
               
                   
                   
                   
                   
                 Hz), 0.54(2 H, dd, J = 12.5 Hz, 6.5 Hz), 
               
               
                   
                   
                   
                   
                 0.77-0.93(1 H, m), 2.29(2 H, d, J = 6.5 Hz), 
               
               
                   
                   
                   
                   
                 2.52(4 H, brs), 3.55(2 H, brs), 3.75(2 H, 
               
               
                   
                   
                   
                   
                 brs), 6.98(1 H, d, J = 8.9 Hz), 7.14(2 H, d, 
               
               
                   
                   
                   
                   
                 J = 8.7 Hz), 7.42(2 H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                 7.76(2 H, d, J = 8.1 Hz), 8.03(2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.1 Hz), 8.20 (1 H, dd, J = 8.9 Hz, 2.5 Hz), 
               
               
                   
                   
                   
                   
                 8.33(1 H, d, J = 2.5 Hz), 8.36 (1 H, brs). 
               
               
                 2463 
                 4-CF 3 Ph- 
                 3-OHPh- 
                 hydro- 
                 (DMSO-d 6 ) 2.90-3.70(6 H, m), 
               
               
                   
                   
                   
                 chloride 
                 3.90-4.20(2 H, m), 4.24 (2 H, d, J = 3.9 Hz), 
               
               
                   
                   
                   
                   
                 6.86(1 H, dd, J = 8.1 Hz, 1.7 Hz), 6.97 
               
               
                   
                   
                   
                   
                 (1 H, brs), 7.01(1 H, d, 4 7.7 Hz), 
               
               
                   
                   
                   
                   
                 7.16(1 H, d, J = 8.9 Hz), 7.20(2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.6 Hz), 7.25(1 H, t, J = 7.7 Hz), 7.52 (2 H, 
               
               
                   
                   
                   
                   
                 d, J = 8.6 Hz), 7.94(2 H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                 8.20(2 H, d, J = 8.1 Hz), 8.29(1 H, dd, J = 
               
               
                   
                   
                   
                   
                 8.9 Hz, 2.5 Hz), 8.58(1 H, d, J = 2.5 Hz), 
               
               
                   
                   
                   
                   
                 10.77(1 H, s). 
               
               
                 2464 
                 4-CF 3 Ph- 
                 —C(CH 3 ) 3   
                 free 
                 (CDCl 3 ) 0.88(9 H, s), 2.09(2 H, s), 2.52(4 H, 
               
               
                   
                   
                   
                   
                 brs), 3.49(2 H, brs), 3.68(2 H,brs), 
               
               
                   
                   
                   
                   
                 6.97(1 H, d, J = 8.8 Hz), 7.12(2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.5 Hz), 7.39(2 H, d, J = 8.5 Hz), 7.75(2 H, 
               
               
                   
                   
                   
                   
                 d, J = 8.1 Hz), 8.03(2 H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                 8.19(1 H, dd, J = 8.8 Hz, 2.5 Hz), 8.33(1 H, 
               
               
                   
                   
                   
                   
                 d, J = 2.5 Hz), 8.47(1 H, s). 
               
               
                   
               
               
                 2465 
                 4-CF 3 Ph- 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 (CDCl 3 ) 2.42(3 H, s), 2.59(4 H, brs), 3.48-3.76(4 H, m), 3.91(2 H, s), 4.56(2 H, s), 7.00(1 H, d, J = 8.9 Hz), 7.13(2 H, d, J = 8.7 Hz), 7.39(2 H, d, J = 8.6 Hz), 7.71(2 H, d, J = 8.3 Hz), 7.79(1 H, s), 8.00(2 H, d, J = 8.1 Hz), 8.22-8.29(2 H, m), 8.81(1 H, brs). 
               
               
                   
               
               
                 2466 
                 4-CF 3 Ph- 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 (CDCl 3 ) 2.55(3 H, s), 2.35-2.70(4 H, m), 3.66(2 H, s), 3.40-3.95(4 H, m), 6.98(1 H, d, J = 8.7 Hz), 7.05(1 H, d, J = 7.6 Hz), 7.12(2 H, d, J = 8.5 Hz), 7.22(1 H, d, J = 7.6 Hz), 7.42(2 H, d, J = 8.5 Hz), 7.56(1 H, t, J = 7.6 Hz), 7.75 (2 H, d, J = 8.2 Hz), 8.02(2 H, d, J = 8.2 Hz), 8.21(1 H, dd, J = 8.7 Hz, 2.8 Hz), 8.31(1 H, d, J = 2.8 Hz), 8.38(1 H, s). 
               
               
                   
               
               
                 2467 
                 3,4-Cl 2 Ph- 
                 4-AcNHPh- 
                 free 
                 (DMSO-d 6 ) 2.02(3 H, s), 2.38(4 H, brs), 
               
               
                   
                   
                   
                   
                 3.44(2 H, s), 3.55 (4 H, brs), 7.14(1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.8 Hz), 7.16(2 H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                 7.21(2 H, d, J = 8.4 Hz), 7.43(2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.7 Hz), 7.52 (2 H, d, J = 8.4 Hz), 7.84(1 H, 
               
               
                   
                   
                   
                   
                 d, J = 8.4 Hz), 7.95(1 H, dd, J = 8.4 Hz, 
               
               
                   
                   
                   
                   
                 2.0 Hz), 8.22(1 H, d, J = 2.0 Hz), 8.23(1 H, 
               
               
                   
                   
                   
                   
                 dd, J = 8.8 Hz, 2.6 Hz), 8.51(1 H, d, J = 
               
               
                   
                   
                   
                   
                 2.6 Hz), 9.90(1 H, s), 10.59(1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 386 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   
               
               
                 No. 
                 Xb 57   
                 R 1090   
                 R 1091   
                 Xb 58   
                 Form 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 2468 
                 —NH— 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —CH 2 — 
                 trihydro- cloride 
                 (DMSO-d 6 ) 2.60-3.20(7 H, m), 3.22-3.60(3 H, m), 3.71(3 H, s), 4.10(1 H, d, J = 13.2 Hz), 4.30 (2 H, d, J = 4.8 Hz), 4.48(1 H, d, J = 13.2 Hz), 6.05(1 H, t, J = 2.5 Hz), 6.32(1 H, dd, J = 3.6 Hz, 1.9 Hz), 6.87(1 H, t, J = 2.5 Hz), 7.04(2 H, d, J = 8.4 Hz), 7.06 (1 H, d, J = 8.8 Hz), 7.29(2 H, d, J = 8.4 Hz), 7.93(2 H, d, J = 8.5 Hz), 8.19(2 H, d, J = 8.5 Hz), 8.22 (1 H, dd, J = 8.8 Hz, 2.6 Hz), 8.51(1 H, d, J = 2.6 Hz), 10.70(1 H, s). 
               
               
                   
               
               
                 2469 
                 —NH— 
                 —H 
                 3-furylmethyl 
                 —CH 2 — 
                 free 
                 (CDCl 3 ) 2.25-2.45(4 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 2.60(2 H, t, J = 7.7 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 2.93(2 H, t, J = 7.7 Hz), 3.37 
               
               
                   
                   
                   
                   
                   
                   
                 (2 H, s), 3.40(2 H, t, J 5.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 3.60 (2 H, t, J = 5.0 Hz), 6.37 
               
               
                   
                   
                   
                   
                   
                   
                 (1 H, d, J = 1.5 Hz), 6.93(1 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.8 Hz), 7.02(2 H, d, J = 8.6 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.19(2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.33(1 H, s), 7.39(1 H, t, J = 1.5 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.73(2 H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 8.01(2 H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 8.21(1 H, dd, J = 8.8 Hz, 2.6 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 8.28(1 H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 8.46(1 H, s). 
               
               
                 2470 
                 —NH— 
                 —H 
                 furfuryl 
                 —CH 2 — 
                 free 
                 (CDCl 3 ) 2.31-2.52(4 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 2.60(2 H, t, J = 7.2 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 2.93(2 H, t, J = 7.2 Hz), 3.43 
               
               
                   
                   
                   
                   
                   
                   
                 (2 H, t, J = 5.0 Hz), 3.55(2 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 3.63 (2 H, t, J = 5.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 6.21(1 H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 6.32(1 H, d, J = 3.0 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 6.94(1 H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.02(2 H, d, J = 8.5 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.19(2 H, d, J = 8.5 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.38(1 H, d, J = 2.8 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.74(2 H, d, J = 8.0 Hz), 8.00 
               
               
                   
                   
                   
                   
                   
                   
                 (2 H, d, J = 8.0 Hz), 8.21(1 H, dd, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 8.9 Hz, 2.5 Hz), 8.28(1 H, d, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 2.5 Hz), 8.35(1 H, s). 
               
               
                 2471 
                 none 
                 —CH 3   
                 piperonyl 
                 —N(CH 3 )— 
                 free 
                 (CDCl 3 ) 2.12(3 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 2.42-2.45(4 H, m), 3.03(3 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 3.44(2 H, s), 3.47-3.52(2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 3.62-3.65(2 H, m), 4.09(2 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 5.95 (2 H, s), 6.54-6.59(2 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 6.71-6.77 (2 H, m), 6.85(1 H, s), 
               
               
                   
                   
                   
                   
                   
                   
                 6.92-6.96(2 H, m), 7.75(2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.4 Hz), 7.87(2 H, d, J = 8.1 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 8.17(1 H, dd, J = 8.6 Hz, 
               
               
                   
                   
                   
                   
                   
                   
                 2.5 Hz), 8.58(1 H d J = 2.1 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 387 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 1092   
                 Xb 59   
                 Xb 60   
                 R 1093   
                   1 H NMR (DMSO-d 6 ) δ ppm 
               
               
                   
               
               
                 2472 
                 3,4-Cl 2 Ph- 
                 —NH— 
                 none 
                 benzyl 
                 1.55-1.82(4 H, m) 1.96(2 H, t, J = 
               
               
                   
                   
                   
                   
                   
                 10.5 Hz), 2.21-2.40(1 H, m), 
               
               
                   
                   
                   
                   
                   
                 2.87(2 H, d, J = 10.5 Hz), 3.47(2 H, 
               
               
                   
                   
                   
                   
                   
                 s), 7.02(1 H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.05(2 H, d, J = 9.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.18-7.42(5 H, m), 7.62(2 H, d, J = 9.1 
               
               
                   
                   
                   
                   
                   
                 Hz, 7.84(1 H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.94(1 H, dd, J = 8.4 Hz, 2.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.17(1 H, dd, J = 8.9 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.22(1 H, d, J = 2.0 Hz), 8.46(1 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 2.6 Hz), 9.89(1 H, s), 
               
               
                   
                   
                   
                   
                   
                 10.53(1 H, s). 
               
               
                 2473 
                 3,4-Cl 2 Ph- 
                 —NH— 
                 none 
                 3-furylmethyl 
                 1.55-1.85(4 H, m), 1.85-2.07(2 H, 
               
               
                   
                   
                   
                   
                   
                 m), 2.18-2.40(1 H, m), 
               
               
                   
                   
                   
                   
                   
                 2.80-3.00(2 H, m), 3.32(2 H, s), 6.44(1 H, 
               
               
                   
                   
                   
                   
                   
                 s), 7.02(1 H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.05(2 H, d, J = 8.9 Hz), 7.57(1 H, 
               
               
                   
                   
                   
                   
                   
                 s) 7.57-7.66(1 H, m), 7.62(2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.9 Hz), 7.84(1 H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.94(1 H, dd, J = 8.4 Hz, 2.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.17(1 H, dd, J = 8.9 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.22(1 H, d, J = 2.0 Hz), 8.45(1 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 2.6 Hz), 9.89(1 H, s), 
               
               
                   
                   
                   
                   
                   
                 10.54(1 H, s). 
               
               
                 2474 
                 4-CF 3 Ph- 
                 none 
                 —N(CH 3 )— 
                 benzyl 
                 1.50-2.30(6 H, m), 2.84(5 H, brs), 
               
               
                   
                   
                   
                   
                   
                 3.44(2 H, brs), 4.27(1 H, brs), 
               
               
                   
                   
                   
                   
                   
                 7.16(3 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.18-7.39(5 H, m), 7.41(2 H, d, J = 8.5 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.95(2 H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.17(2 H, d, J = 8.1 Hz), 8.27(1 H, 
               
               
                   
                   
                   
                   
                   
                 dd, J = 8.9 Hz, 2.5 Hz), 8.56 (1 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 2.5 Hz), 10.68(1 H, s). 
               
               
                 2475 
                 4-CF 3 Ph- 
                 none 
                 —N(CH 3 )— 
                 3-furylmethyl 
                 1.50-2.20(6 H, m), 2.83(3 H, s), 
               
               
                   
                   
                   
                   
                   
                 2.72-3.02(2 H, m), 3.30(2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 3.5 Hz), 4.28(1 H, brs), 6.41(1 H, s), 
               
               
                   
                   
                   
                   
                   
                 7.15(1 H, d, J = 8.8 Hz), 7.16(2 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.4 Hz), 7.41(2 H, d, J = 8.4 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.53 (1 H, s), 7.60(1 H, s), 
               
               
                   
                   
                   
                   
                   
                 7.95(2 H, d, J = 8.1 Hz), 8.17(2 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.1 Hz), 8.27(1 H, dd, J = 8.8 
               
               
                   
                   
                   
                   
                   
                 Hz, 2.5 Hz), 8.55(1 H, d, J = 2.5 
               
               
                   
                   
                   
                   
                   
                 Hz), 10.68 (1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 388 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 1094   
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 2476 
                 cyclohexyl 
                 1.00-1.40(5 H, m), 1.52-1.70(1 H, m), 1.70-1.92(4 H, m), 2.21-2.40(1 H, 
               
               
                   
                   
                 m), 2.57 (4 H, brs), 3.52(2 H, brs),3.73(2 H, brs), 6.98(1 H, d, J = 8.9 
               
               
                   
                   
                 Hz), 7.13(2 H, d, J = 8.8 Hz), 7.41(2 H, d, J = 8.8 Hz), 7.76(2 H, d, J = 
               
               
                   
                   
                 8.2 Hz), 8.03(2 H, d, J = 8.2 Hz), 8.19 (1 H, dd, J = 8.9 Hz, 2.5 Hz), 
               
               
                   
                   
                 8.33(1 H, d, J = 2.5 Hz), 8.36(1 H, brs). 
               
               
                   
               
               
                 2477 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1.40-1.85(4 H, m), 2.38-2.60(1 H, m), 2.57(4 H, brs), 3.38(2 H, t, J = 11.0 Hz), 3.72 (4 H, brs), 4.03(2 H, dd, J = 11.0 Hz, 3.5 Hz), 7.00(1 H, d, J = 8.7 Hz), 7.15(2 H, d, J = 8.7 Hz), 7.43(2 H, d, J = 8.7 Hz), 7.77(2 H, d, J = 8.5 Hz), 8.02(2 H, d, J = 8.5 Hz), 8.16(1 H, brs), 8.21(1 H, dd, J = 8.7 Hz, 2.5 Hz), 8.32(1 H, d, J = 2.5 Hz). 
               
               
                   
               
               
                 2478 
                 cyclopropyl 
                 0.33-0.58(4 H, m), 1.45-1.72(1 H, m), 2.62(4 H, brs), 3.49(2 H, brs), 
               
               
                   
                   
                 3.68(2 H, brs), 7.00(1 H, d, J = 8.9 Hz), 7.15(2 H, d, J = 8.4 Hz), 
               
               
                   
                   
                 7.43(2 H, d, J = 8.4 Hz), 7.77(2 H, d, J = 8.4 Hz), 8.02(2 H, d, J = 8.4 
               
               
                   
                   
                 Hz), 8.21(1 H, s), 8.21(1 H, dd, J = 8.9 Hz, 2.6 Hz), 8.33(1 H, d, J = 2.6 
               
               
                   
                   
                 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
           
               
                 TABLE 389 
               
               
                   
               
               
                 Example 
                   
                   
               
               
                 No. 
                 Chemical structure 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
             
             
               
                 2479 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (DMSO-d 6 ) 2.77-3.10(2 H, m), 3.17-3.63(4 H, m), 3.71-3.89(1 H, m), 4.18(2 H, s), 4.24(2 H, s), 4.27-4.44(1 H, m), 6.07(2 H, s), 6.92-7.06(2 H, m), 7.09(3 H, d, J = 8.6 Hz), 7.22(1 H, s), 7.28(2 H, d, J = 8.6 Hz), 7.92(2 H, d, J = 8.0 Hz), 8.18(2 H, d, J = 8.0 Hz), 8.24(1 H, dd, J = 8.8 Hz, 2.5 Hz), 8.53(1 H, d, J = 2.5 Hz), 10.69(1 H, s). 
               
               
                   
               
               
                 2480 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 2.25-2.52(4 H, m), 2.77-2.95 (2 H, m), 3.12-3.29(1 H, m), 3.29-3.46 (1 H, m), 3.41(2 H, s), 3.43-3.59(1 H, m), 3.65-3.84(2 H, m), 5.30(1 H, brs), 5.92 (2 H, s), 6.73(2 H, s), 6.84(1 H, s), 6.95 (1 H, d, J = 9.0 Hz), 7.05(2 H, d, J = 8.4 Hz), 7.23(2 H, d, J = 8.4 Hz), 7.75(2 H, d, J = 8.1 Hz), 7.98(2 H, d, J = 8.1 Hz), 8.03(1 H, brs), 8.20(1 H, dd, J = 9.0 Hz, 2.5 Hz), 8.22(1 H, s). 
               
               
                   
               
               
                 2481 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 1.32-1.44(2 H, m), 1.83-2.02 (3 H, m), 2.30(2 H, d, J = 6.8 Hz), 2.42-2.47(4 H, m), 2.69(2 H, t, J = 12.0 Hz), 3.48-3.66(8 H, m), 6.86-6.99(6 H, m), 7.25-7.32(7 H, m), 7.50(2 H, d, J = 8.6 Hz), 7.98(1 H, dd, J = 8.7 Hz, 2.6 Hz), 8.59(1 H, d, J = 2.0 Hz). 
               
               
                   
               
             
          
         
       
     
       Example 2482 
     Production of N-(6-{4-[4-((1S,2S)-2-hydroxy-cyclohexyl)piperazine-1-carbonyl]phenoxy}pyridin-3-yl)-4-trifluoromethylbenzamide 
       [1219]    To a solution of N-{6-[4-(piperazine-1-carbonyl)phenoxy]-pyridin-3-yl}-4-trifluoromethyl-benzamide (430 mg, 0.91 mmol) in methanol was added 1,2-epoxycyclohexane (180 mg, 1.83 mmol), and the resulting solution was stirred for 1 day under reflux. The resulting reaction solution was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol=35:1), and then ethyl acetate was added. The precipitated white powder was filtered off and washed with ethyl acetate, to thereby yield 284 mg of the title compound. 
         [1220]    Appearance: White powder 
         [1221]      1 H NMR (CDCl 3 ) δ 1.03-1.38 (4H, m), 1.42-1.88 (3H, m), 2.06-2.35 (2H, m), 2.31 (2H, brs), 2.74 (2H, brs), 3.30-4.00 (6H, m), 7.00 (1H, d, J=8.9 Hz), 7.15 (2H, d, J=8.7 Hz), 7.43 (2H, d, J=8.7 Hz), 7.77 (2H, d, J=8.1 Hz), 8.02 (2H, d, J=8.1 Hz), 8.21 (1H, brs), 8.22 (1H, dd, J=8.9 Hz, 2.7 Hz), 8.33 (1H, d, J=2.7 Hz). 
       Example 2483 
     Production of 3,4-dichloro-N-[6-({4-[3-oxo-3-(4-piperonylpiperazin-1-yl)propyl]phenyl}methylamino)-pyridin-3-yl]benzamide dioxalate 
       [1222]    To a solution of 3,4-dichloro-N-(6-{4-[3-oxo-3-(4-piperonylpiperazin-1-yl)propyl]phenylamino}pyridin-3-yl)benzamide (250 mg, 0.395 mmol) in methanol (3 mL) were added acetic acid (0.500 mL) and 37% aqueous formaldehyde (0.640 mL, 7.89 mmol), and the resulting solution was stirred for 30 minutes at 50° C. To the reaction solution was added sodium cyanoborohydride (0.160 g, 2.55 mmol) at room temperature, and stirred for 8 hours at 50° C. Water was added to the reaction solution and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatography (dichloromethane:methanol=10:1), to yield a free form. This free form was dissolved in isopropanol (5 mL) and oxalic acid dihydrate (7.0 mg, 0.555 mmol) by heating. The solvent was evaporated, and the resulting solid was recrystallized from isopropanol, to thereby yield 0.193 g of the title compound. 
         [1223]    Appearance: Pale yellow powder 
         [1224]    Melting point: 127-129° C. 
         [1225]    The following compound was produced in the same manner as in Example 2483. 
       Example 2484 
     2-(Ethyl{4-[5-(4-trifluoromethylphenoxymethyl)pyridin-2-yloxy]phenyl}amino)-1-(4-piperonylpiperazin-1-yl)ethanone 
       [1226]      1 H NMR (CDCl 3 ) δ 1.18 (3H, t, j 7.1 Hz), 2.41-2.44 (4H, m), 3.39-3.47 (4H, m), 3.51 (2H, brs), 3.64 (2H, brs), 4.03 (2H, s), 5.03 (2H, s), 5.94 (2H, s), 6.68 (2H, d, J=19.1 Hz), 6.73-6.74 (2H, m), 6.85-6.88 (2H, m), 6.99 (2H, d, J=9.1 Hz), 7.01 (2H, d, J=8.4 Hz), 7.55 (2H, d, J=8.7 Hz), 7.71 (1H, dd, J=8.6° Hz, 2.5 Hz), 8.22 (1H, d, J=2.3 Hz). 
       Example 2485 
     Production of 3,4-dichloro-N-[6-(4-thiomorpholine-4-ylmethylphenoxy)pyridin-3-yl]benzamide monohydrochloride 
       [1227]    3,4-dichloro-N-[6-(4-chloromethylphenoxy)-pyridin-3-yl]benzamide (0.61 g, 1.5 mmol) was dissolved in DMF (5 mL). To the resulting solution were added triethylamine (0.84 mL, 6.0 mmol) and thiomorpholine (0.15 mL, 1.5 mmol), and this solution was stirred overnight at 40° C. The resulting reaction solution was concentrated under reduced pressure. To the residue was added ethyl acetate and washed with a saturated sodium bicarbonate solution and brine. The organic layer was dried over anhydrous magnesium sulfate and evaporated. This residue was purified by silica gel column chromatography (chloroform:methanol=80:1). The obtained solid (0.56 g, 1.18 mmol) was dissolved in ethyl acetate (50 mL), and a solution of 4 N hydrogen chloride in ethyl acetate (0.295 mL, 1.18 mmol) was added, and this solution was stirred for 1 hour at room temperature. The precipitated crystals were collected by suction filtration, and recrystallized from methanol, to thereby yield 0.38 g of the title compound. 
         [1228]    Appearance: White powder 
         [1229]      1 H NMR (DMSO-d 6 ) δ 2.80-2.83 (2H, m), 3.09-3.17 (4H, m), 3.61 (2H, m), 4.35 (2H, s), 7.14 (1H, d, J=8.9 Hz), 7.21 (2H, d, J=8.3 Hz), 7.60 (2H, d, J=8.3 Hz), 7.85 (1H, d, J=8.6 Hz), 7.96 (1H, dd, J=8.3 Hz, 2.0 Hz), 8.23 (1H, dd, J=8.9 Hz, 2.6 Hz), 8.24 (1H, d, J=2.0 Hz), 8.53 (1H, d, J=2.6 Hz), 10.45 (1H, brs), 10.62 (1H, brs). 
         [1230]    The following compounds were produced in the same manner as in Example 2485. 
       Example 2486 
     3,4-Dichloro-N-(4-{4-[1-(3-imidazole-1-ylpropyl)-1,2,3,6-tetrahydropyridine-4-yl]phenoxy}phenyl)-benzamide 
       [1231]    Melting point: 169-171° C. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 390 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 1095   
                 Xb 61   
                 R 1096   
                 Form 
                 mp (° C.) 
               
               
                   
               
               
                 2487 
                 —F 
                 —CH 2 — 
                 benzyl 
                 dihydro- 
                 178-179 
               
               
                   
                   
                   
                   
                 chloride 
               
               
                 2488 
                 —F 
                 —CH 2 — 
                 piperonyl 
                 dihydro- 
                 192-195 
               
               
                   
                   
                   
                   
                 chloride 
               
               
                 2489 
                 —F 
                 —(CH 2 ) 2 — 
                 benzyl 
                 dihydro- 
                 208-210 
               
               
                   
                   
                   
                   
                 chloride 
               
               
                 2490 
                 —F 
                 —(CH 2 ) 2 — 
                 piperonyl 
                 dihydro- 
                 202-205 
               
               
                   
                   
                   
                   
                 chloride 
               
               
                 2491 
                 —F 
                 —(CH 2 ) 3 — 
                 benzyl 
                 dihydro- 
                 260-262 
               
               
                   
                   
                   
                   
                 chloride 
               
               
                 2492 
                 —F 
                 —(CH 2 ) 3 — 
                 piperonyl 
                 dihydro- 
                 258-260 
               
               
                   
                   
                   
                   
                 chloride 
               
               
                 2493 
                 —F 
                 —(CH 2 ) 4 — 
                 benzyl 
                 dihydro- 
                 245-248 
               
               
                   
                   
                   
                   
                 chloride 
               
               
                 2494 
                 —F 
                 —(CH 2 ) 4 — 
                 piperonyl 
                 dihydro- 
                 256-258 
               
               
                   
                   
                   
                   
                 chloride 
               
               
                   
               
               
                 2495 
                 —H 
                 none 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 172-173 
               
               
                   
               
               
                 2496 
                 —H 
                 none 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 131-134 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 391 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                   
                 Example 
                   
                   
                   
               
               
                   
                 No. 
                 M 
                 Form 
                 mp (° C.) 
               
               
                   
                   
               
               
                   
                 2497 
                 1 
                 hydrochloride 
                 165-168 
               
               
                   
                 2498 
                 2 
                 free 
                 143-144 
               
               
                   
                 2499 
                 3 
                 oxalate 
                 173-175 
               
               
                   
                 2500 
                 4 
                 hydrochloride 
                 226-228 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 392 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 M 
                 mp (° C.) 
               
               
                   
               
               
                 2501 
                 1 
                 183-185 
               
               
                 2502 
                 4 
                 141-143 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 393 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 1097   
                 R 1098   
                 M 
                 Form 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 2503 
                 3,4-Cl 2 Ph- 
                 piperidino 
                 1 
                 free 
                 (CDCl 3 ) 1.42-1.58(6 H, m), 2.36-2.38(4 H, 
               
               
                   
                   
                   
                   
                   
                 m), 3.44(2 H, s), 6.86(1 H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.99(2 H, dd, J 6.6 Hz, 2.0 Hz), 7.26 
               
               
                   
                   
                   
                   
                   
                 7.31(2 H, m), 7;47(1 H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.67(1 H, dd, J = 8.3 Hz, 2.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.94(1 H, d, J = 2.3 Hz), 8.10(1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 8.9 Hz, 2.6 Hz), 8.21(1 H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.69(1 H, brs). 
               
               
                 2504 
                 3,4-Cl 2 Ph- 
                 piperidino 
                 3 
                 dihydro- 
                 (DMSO-d 6 ) 1.67-1.77(6 H, m), 1.99-2.10 
               
               
                   
                   
                   
                   
                 chloride 
                 (2 H, m), 2.61-3.05 (6 H, m), 3.40-3.43(2 H, 
               
               
                   
                   
                   
                   
                   
                 m), 6.01(1 H, brs), 7.04-7.08(3 H, m), 
               
               
                   
                   
                   
                   
                   
                 7.28(9 H d, J = 8.6 Hz), 7.84(1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.4 Hz), 7.96-8.00 (1 H, m), 8.198.23(1 H, 
               
               
                   
                   
                   
                   
                   
                 m), 8.26(1 H, d, J = 1.9 Hz), 8.51 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 2.7 Hz), 10.24(1 H, brs), 10.67(1 H, s). 
               
               
                 2505 
                 3,4-Cl 2 Ph- 
                 piperidino 
                 4 
                 free 
                 (CDCl 3 ) 1.40-1.50(2 H, m), 1.50-1.75(8 H, 
               
               
                   
                   
                   
                   
                   
                 m), 2.25-2.50 (6 H, m), 2.63(2 H, t, J = 7.0 
               
               
                   
                   
                   
                   
                   
                 Hz), 6.93(1 H, d, J = 9.0 Hz), 7.03(2 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.5 Hz), 7.19(2 H, d, J = 8.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.58(1 H, d, J = 8.5 Hz), 7.71(1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 8.5 Hz, 2.0 Hz) 7 82(1 H, s), 7.98(1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 2.0 Hz), 8.16(1 H, dd, J = 9.0 Hz, 3.0 
               
               
                   
                   
                   
                   
                   
                 Hz), 8.25(1 H, d, J = 3.0 Hz). 
               
               
                 2506 
                 3,4-Cl 2 Ph- 
                 piperidino 
                 5 
                 free 
                 (CDCl 3 ) 1.20-1.80(12 H, m), 2.31(2 H, t, J = 
               
               
                   
                   
                   
                   
                   
                 7.8 Hz), 2.40 (4 H, brs), 2.61(2 H, t, J = 
               
               
                   
                   
                   
                   
                   
                 7.8 Hz), 6.94(1 H, d, J = 8.8 Hz), 7.04(2 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.4 Hz), 7.20(2 H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.58(1 H, d, J = 8.2 Hz), 7.72(1 H, s), 
               
               
                   
                   
                   
                   
                   
                 7.71(1 H, dd, J = 8.2 Hz, 2.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.98(1 H, d, J = 2.3 Hz), 8.16(1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 8.8 Hz, 2.8 Hz), 8.24(1 H, d, J = 2.8 Hz). 
               
               
                 2507 
                 4-CF 3 Ph- 
                 morpholino 
                 1 
                 free 
                 (DMSO-d 6 ) 2.37(4 H, t, J = 4.6 Hz), 3.46 
               
               
                   
                   
                   
                   
                   
                 (2 H, s), 3.59(4 H, t, J = 4.6 Hz), 7.07(3 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.6 Hz), 7.33(2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.93(2 H, d, J = 8.6 Hz), 8.15-8.24(3 H, m), 
               
               
                   
                   
                   
                   
                   
                 8.51(1 H, d, J = 2.6 Hz), 10.63(1 H, s). 
               
               
                 2508 
                 3,4-Cl 2 Ph- 
                 morpholino 
                 1 
                 free 
                 (CDCl 3 ) 2.56(4 H, t, J = 4.6 Hz), 3.60(2 H, 
               
               
                   
                   
                   
                   
                   
                 s), 3.82(4 H, t, J = 4 6 Hz), 7.05(1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.6 Hz), 7.18(2 H, dd, J = 6.6 Hz, 2.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.45(2 H, d, J = 8.6 Hz), 7.67(1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.6 Hz), 7.80(1 H, dd, J = 8.3 Hz, 2.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.99(1 H, brs), 8.07(1 H, d, J = 2.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.25-8.29(1 H, m), 8.35(1 H, d, J = 2.6 Hz). 
               
               
                 2509 
                 3,4-Cl 2 Ph- 
                 morpholino 
                 2 
                 free 
                 (CDCl 3 ) 2.54-2.85(8 H, m), 3.74-3.78(4 H, 
               
               
                   
                   
                   
                   
                   
                 m), 6.95(1 H, d, J = 8.9 Hz) 7 04-7.07(2 H, 
               
               
                   
                   
                   
                   
                   
                 m), 7.22-7.26(2 H, m), 7.58-1 H, d, J = 8.6 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.68-7.72(1 H, m), 7.79(1 H, brs), 
               
               
                   
                   
                   
                   
                   
                 7.98(1 H, d, J = 2.0 Hz), 8.17(1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 8.9 Hz, 2.6 Hz), 8.24(1 H, d, J = 2.6 Hz). 
               
               
                 2510 
                 3,4-Cl 2 Ph- 
                 morpholino 
                 3 
                 free 
                 (CDCl 3 ) 1.78-1.83(2 H, m), 2.34-2.45(6 H, 
               
               
                   
                   
                   
                   
                   
                 m), 2.60-2.66 (2 H, m), 3.70-3.73(4 H, m), 
               
               
                   
                   
                   
                   
                   
                 6.88(1 H, d, J = 8.6 Hz), 7.00 (2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.6 Hz), 7.18(2 H, d, J = 8.6 Hz), 7.51(1 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.6 Hz), 7.667.70(1 H, m), 7.94(1 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 2.2 Hz), 8.108.14(1 H, m), 8.22(1 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 2.7 Hz), 8.40(1 H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 394 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 1099   
                 M 
                 Form 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 2511 
                 morpholino 
                 4 
                 dihydro- 
                 (DMSO-d 6 ) 1.55-1.90(4 H, m), 2.63(2 H, t, J = 7.2 Hz), 
               
               
                   
                   
                   
                 chloride 
                 2.90-3.20(4 H, m), 3.30-3.50(2 H, m), 3.79(2 H, t, J = 11.2 
               
               
                   
                   
                   
                   
                 Hz), 3.93(2 H, s), 7.04(2 H, d, J = 8.2 Hz), 7.05(1 H, d, J = 
               
               
                   
                   
                   
                   
                 9 0 Hz), 7.26(2 H, d, J = 8.2 Hz), 7.84(1 H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                 7198(1 H, dd, J = 8.2 Hz, 2.0 Hz), 8.20(1 H dd J = 9.0 
               
               
                   
                   
                   
                   
                 Hz, 2.7 Hz), 8.25(1 H, d, J = 2.0 Hz), 8.50(1 H, d, J = 2.7 
               
               
                   
                   
                   
                   
                 Hz), 10.65(1 H, s). 
               
               
                 2512 
                 morpholino 
                 5 
                 free 
                 (CDCl 3 ) 1.30-1.45(2 H, m), 1.45-1.75(4 H, m), 2.33(2 H, t, 
               
               
                   
                   
                   
                   
                 J = 7.2 Hz), 2.44(4 H, t, J = 4.6 Hz), 2.62(2 H, t, J = 7.7 
               
               
                   
                   
                   
                   
                 Hz), 3.72(4 H, t, J = 4.6 Hz), 6.94(1 H, d, 4 9.0 Hz), 
               
               
                   
                   
                   
                   
                 7.04(2 H, d, J = 8.5 Hz), 7.20(2 H, d, J = 8.5 Hz) 
               
               
                   
                   
                   
                   
                 7.58(1 H, d, J = 8.2 Hz), 7.65-7.75(2 H, m), 7.98(1 H, d, J = 
               
               
                   
                   
                   
                   
                 2.0 Hz), 8.16 (1 H, dd, J = 9.0 Hz, 2.6 Hz), 8.24(1 H, d, 
               
               
                   
                   
                   
                   
                 J = 2.6 Hz). 
               
               
                   
               
               
                 2513 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 3 
                 free 
                 (CDCl 3 ) 1.97-2.03(2 H, m), 2.67(2 H, t, 4 7.6 Hz), 3.68-3.73(2 H, m), 3.88(2 H, s), 6.95(1 H, d, J = 8.9 Hz), 7.05(2 H, d, J = 8.6 Hz), 7.21(2 H, d, J = 8.6 Hz) 7.56(1 H, d, J = 8.3 Hz), 7.69-7.74(2 H, m), 7.98(1 H, d, J = 2.3 Hz), 8.14-8.18(1 H, m), 8.23(1 H, d, J = 3.0 Hz). 
               
               
                   
               
               
                 2514 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1 
                 free 
                 (DMSO-d 6 ) 5.20(2 H, s), 6.91(1 H, s), 7.07(1 H, d, J = 8.6 Hz), 7.10(2 H, d, J = 8.6 Hz), 7.22(1 H, s), 7.31(2 H, d, J = 8.6 Hz), 7.77(1 H, s), 7.84 (1 H, d, J = 8.6 Hz), 7.94(1 H, dd, J = 8.6 Hz, 2.0 Hz), 8.19(1 H, dd, J = 8.6 Hz, 2.3 Hz), 8.22(1 H, d, J = 2.0 Hz), 8.46(1 H, d, J = 2.3 Hz), 10.57 (1 H, s). 
               
               
                   
               
               
                 2515 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1 
                 hydro- chloride 
                 (DMSO-d 6 ) 5.48(2 H, s), 7.09(1 H, d, J = 8.5 Hz), 7.12(2 H, d, J = 8.6 Hz), 7.38(2 H, d, J = 8.6 Hz), 7.83(1 H, d, J = 8.5 Hz), 7.98(1 H, dd J = 8.5 Hz, 2.0 Hz), 8.23(1 H, dd, J = 8.5 Hz, 2.3 Hz), 8.26(1 H, s), 8.26(1 H, d, J = 2.0 Hz), 8.51(1 H, d, J = 2.3 Hz), 9.05(1 H, s), 10.70(1 H, s). 
               
               
                   
               
               
                 2516 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1 
                 free 
                 (DMSO-d 6 ) 5.63(2 H, d, J = 8.6 Hz), 7.09(1 H, d, J = 8.6 Hz), 7.11(2 H, d, J = 8.6 Hz), 7.36(2 H, d, J = 8.6 Hz), 7.76(1 H, d, J = 1.0 Hz), 7.84(1 H, d, J = 8.3 Hz), 7.94(1 H, dd, J = 8.3 Hz, 2.0 Hz), 8.20(1 H, dd, J = 8.6 Hz, 2.6 Hz) 8.23(2 H, s), 8.46(1 H, d, J = 2.6 Hz), 10.55(1 H, s). 
               
               
                   
               
               
                 2517 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1 
                 hydro- chloride 
                 (DMSO-d 6 ) 5.66(2 H, s), 7.09(1 H, d, J = 8.6 Hz, 7.10(2 H, d, J = 8.6 Hz), 7.32(2 H, d, J = 8.6 Hz), 7.83(2 H, s), 7.83(1 H, d, J = 8.5 Hz), 7.96 (1 H, dd, J = 8.5 Hz, 2.0 Hz), 8.21(1 H, dd, J = 8.5 Hz, 2.3 Hz), 8.23(1 H, d, J = 2.0 Hz), 8.47(1 H, d, J = 2.3 Hz), 10.61(1 H, s). 
               
               
                   
               
               
                 2518 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1 
                 hydro- chloride 
                 (DMSO-d 6 ) 5.34(2 H, s), 6.28(1 H, t, J = 2.0 Hz), 7.06(1 H, d, J = 9.0 Hz), 7.07(2 H, d, J = 8.6 Hz), 7.26(2 H, d, J = 8.6 Hz), 7.47(1 H, d, J = 2.0 Hz), 7.83(1 H, d, J = 8.6 Hz), 7.85(1 H, d, J = 2.0 Hz), 7.96(1 H, dd, J = 8.6 Hz, 2.0 Hz), 8.20(1 H, dd, J = 9.0 Hz, 2.6 Hz), 8.23(1 H, d, J = 2.0 Hz), 8.47(1 H, d, J = 2.6 Hz), 10.61(1 H, s). 
               
               
                   
               
               
                 2519 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2 
                 free 
                 (CDCl 3 ) 3.04(2 H, t, J = 7.0 Hz), 4.17(2 H, t, J = 7.0 Hz), 6.87(1 H, t, J = 1.3 Hz), 6.94(1 H, d, J = 8.7 Hz), 7.02(1 H, brs), 7.05(4 H, s), 7.30(1 H, brs), 7.56(1 H, d, J = 8.3 Hz), 7.75(1 H, dd, J = 8.3 Hz, 2.1 Hz), 8.03(1 H, d, J = 2.1 Hz), 8.17(1 H, dd, J = 8.7 Hz, 2.3 Hz), 8.23(1 H, d, J = 2.3 Hz), 8.6 1(1 H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 395 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 1100   
                 R 1101   
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 2520 
                 4-ClPh- 
                 piperonyl 
                 (CDCl 3 ) 2.48(8 H, brs), 3.42(2 H, s),3.50(2 H, s), 5.93(2 H, 
               
               
                   
                   
                   
                 s), 6.74 (2 H, s), 6.85(1 H, s), 6.94(1 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                 7.07(2 H, d, J = 8.6 Hz), 7.33(2 H, d, J = 8.6 Hz), 7.49(2 H, 
               
               
                   
                   
                   
                 d, J = 8.6 Hz), 7.73(1 H, brs), 7.82(2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                 8.18-8.24(2 H, m). 
               
               
                 2521 
                 4-CNPh- 
                 piperonyl 
                 (CDCl 3 ) 2.48(8 H, brs), 3.42(2 H, s), 3.51(2 H, s), 5.93(2 H, 
               
               
                   
                   
                   
                 s), 6.73-6.74(2 H, m), 6.85(1 H, s), 6.96(1 H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                 7.07(2 H, d, J = 8.6 Hz), 7.34(2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                 7.79-7.82(3 H, m), 7.99(2 H, d, J = 8.2 Hz), 8.19(1 H, dd, J = 
               
               
                   
                   
                   
                 8.9 Hz, 2.6 Hz), 8.26(1 H, d, J = 2.6 Hz). 
               
               
                 2522 
                 3,4-Cl 2 Ph- 
                 benzyl 
                 (CDCl 3 ) 2.51(8 H, brs), 3.52(2 H, s), 3.53(2 H, s), 6.95(1 H, 
               
               
                   
                   
                   
                 d, J = 8.9 Hz), 7.07(2 H, d, J = 8.2 Hz), 7.26-7.36(7 H, m), 
               
               
                   
                   
                   
                 7.59(1 H, d, J = 8.6 Hz), 7.69-7.73(2 H, ml), 7.99(1 H, d, J = 
               
               
                   
                   
                   
                 2.0 Hz), 8.18(1 H, dd, J = 8.9 Hz, 2.6 Hz), 8.25(1 H, d, J = 
               
               
                   
                   
                   
                 2.6 Hz). 
               
               
                 2523 
                 3,4-Cl 2 Ph- 
                 —COOC(CH 3 ) 3   
                 (CDCl 3 ) 1.46(9 H, s), 2.40(4 H, t, J = 5.0 Hz), 3.43(4 H, t, J = 
               
               
                   
                   
                   
                 5.0 Hz), 3.50(2 H, s), 6.95(1 H, d, J = 8.9 Hz), 7.08(2 H, 
               
               
                   
                   
                   
                 d, J = 8.6 Hz), 7.34 (2 H, d, J = 8.6 Hz), 7.57(1 H, d, J = 
               
               
                   
                   
                   
                 8.3 Hz), 7.70-7.74(1 H, m), 8.00 (1 H, d, J = 2.0 Hz), 
               
               
                   
                   
                   
                 8.07(1 H, brs), 8.17-8.21(1 H, m), 8.27(1 H, d, J = 2.6 Hz). 
               
               
                 2524 
                 3,4-Cl 2 Ph- 
                 —C 2 H 5   
                 (CDCl 3 ) 1.08(3 H, t, J = 7.3 Hz), 2.38-2.49(10 H, m), 
               
               
                   
                   
                   
                 3.48(2 H, s), 6.88(1 H, d, J = 8.9 Hz), 7.01(2 H, d, J = 8.3 
               
               
                   
                   
                   
                 Hz), 7.30(2 H, d, J = 8.6 Hz), 7.49(1 H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                 7.66-7.70(1 H, m), 7.95(1 H, d, J = 2.0 Hz), 8.13(1 H, dd, J = 
               
               
                   
                   
                   
                 8.9 Hz, 2.6 Hz), 8.23(1 H, d, J = 2.6 Hz), 8.58 (1 H, brs). 
               
               
                 2525 
                 3,4-Cl 2 Ph- 
                 -Ph 
                 (CDCl 3 ) 2.64(4 H, t, J = 5.0 Hz), 3.22(4 H, t, J = 5.0 Hz), 
               
               
                   
                   
                   
                 3.57(2 H, s), 6.83-6.88(1 H, m), 6.92-6.99(3 H, m), 
               
               
                   
                   
                   
                 7.10(2 H, d, J = 8.6 Hz), 7.23-7.29(2 H, m), 7.39(2 H, d, J = 
               
               
                   
                   
                   
                 8.6 Hz), 7.59(1 H, d, J = 8.6 Hz), 7.71(1 H, dd, J = 8.3 
               
               
                   
                   
                   
                 Hz, 2.0 Hz), 7.76(1 H, s), 7.99(1 H, d, J = 2.0 Hz), 
               
               
                   
                   
                   
                 8.19(1 H, dd, J = 8.6 Hz, 2.6 Hz), 8.26(1 H, d, J = 2.6 Hz). 
               
               
                 2526 
                 4-CF 3 Ph- 
                 —COOC(CH 3 ) 3   
                 (DMSO-d 6 ) 1.40(9 H, s), 2.32-2.36(4 H, m), 3.30-3.35(4 H, 
               
               
                   
                   
                   
                 m), 3.49 (2 H, s), 7.06-7.09(3 H, m), 7.32-7.36(2 H, m), 
               
               
                   
                   
                   
                 7.94(2 H, d, J = 8.4 Hz), 8.18(2 H, d, J = 8.1 Hz), 8.24(1 H, 
               
               
                   
                   
                   
                 dd, J = 8.9 Hz, 2.7 Hz), 8.52 (1 H, d, J = 2.7 Hz), 
               
               
                   
                   
                   
                 10.64(1 H, s). 
               
               
                 2527 
                 3,4-Cl 2 Ph 
                 —CH 3   
                 (CDCl 3 ) 2.27(3 H, s), 2.45(8 H, brs), 3.47(2 H, s), 6.87(1 H, 
               
               
                   
                   
                   
                 d, J = 8.9 Hz), 6.99-7.03(2 H, m), 7.27-7.31(2 H, m), 
               
               
                   
                   
                   
                 7.48(1 H, dd, J = 8.3 Hz, 2.6 Hz), 7.68(1 H, dd, J = 8.6 
               
               
                   
                   
                   
                 Hz, 2.0 Hz), 7.94(1 H, d, J = 2.0 Hz), 8.12(1 H, dd, J = 8.9 
               
               
                   
                   
                   
                 Hz, 2.6 Hz), 8.23(1 H, d, J = 2.6 Hz), 8.76(1 H, brs). 
               
               
                 2528 
                 3,4-Cl 2 Ph- 
                 piperonyl 
                 (CDCl 3 ) 2.47(8 H, brs), 3.42(2 H, s), 3.49(2 H, s), 5.93(2 H, 
               
               
                   
                   
                   
                 s), 6.73 (2 H, d, J = 0.7 Hz), 6.84(1 H, s), 6.91(1 H, d, J = 
               
               
                   
                   
                   
                 8.9 Hz), 7.04(2 H, d, J = 8.6 Hz), 7.31(2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                 7.53(1 H, d, J = 8.2 Hz), 7.70 (1 H, dd, J = 8.3 Hz, 2.0 
               
               
                   
                   
                   
                 Hz), 7.97(1 H, d, J = 2.3 Hz), 8.138.18(1 H, m), 8.24(2 H, 
               
               
                   
                   
                   
                 d, J = 2.6 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 396 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 1102   
                 Xb 62   
                 R 1103   
                 Form 
                   1 H NMR (solvent) δ ppm 
               
               
                   
               
               
                 2529 
                 3,4-Cl 2 Ph- 
                 —(CH 2 ) 2 — 
                 piperonyl 
                 free 
                 (CDCl 3 ) 1.97-2.01(2 H, m), 
               
               
                   
                   
                   
                   
                   
                 2.85-2.90(8 H, m), 3.68(2 H, s), 
               
               
                   
                   
                   
                   
                   
                 3.75(2 H, s), 5;95(2 H, s), 
               
               
                   
                   
                   
                   
                   
                 6.74-6.84(2 H, m), 6.94-6.97(2 H, m), 
               
               
                   
                   
                   
                   
                   
                 7.08(2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.41(2 H, d, J = 8.6 Hz),. 
               
               
                   
                   
                   
                   
                   
                 7.57(1 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.75(1 H, dd, J = 8.6 Hz, 2.3 
               
               
                   
                   
                   
                   
                   
                 Hz), 8.01-8.02(2 H, m), 8.20(1 H, 
               
               
                   
                   
                   
                   
                   
                 dd, J = 8.9 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.31(1 H, d, J = 2.6 Hz). 
               
               
                 2530 
                 3,4-Cl 2 Ph- 
                 —(CH 2 ) 2 — 
                 benzyl 
                 trihydro- 
                 (DMSO-d 6 ) 2.25(2 H, brs), 3.38 
               
               
                   
                   
                   
                   
                 chloride 
                 (4 H, brs), 3.78(4 H, brs), 4.38 
               
               
                   
                   
                   
                   
                   
                 (4 H, s), 7.127.22(3 H, m), 
               
               
                   
                   
                   
                   
                   
                 7.46-7.48(3 H, m), 7.62-7.67 (4 H, m), 
               
               
                   
                   
                   
                   
                   
                 7.84(1 H, d, J = 8.6 Hz), 7.98 
               
               
                   
                   
                   
                   
                   
                 (1 H, dd, J = 8.6 Hz, 2.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.22-8.27(2 H, m), 8.55 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 2.6 Hz), 10.68(1 H, s). 
               
               
                 2531 
                 3,4-Cl 2 Ph- 
                 —CO— 
                 benzyl 
                 free 
                 (CDCl 3 ) 2.66(2 H, t, J 5.9 Hz), 
               
               
                   
                   
                   
                   
                   
                 3.22-3.25(4 H, m), 3.55(2 H, s), 
               
               
                   
                   
                   
                   
                   
                 4.60(2 H, s), 6.95(1 H, d, J = 8.9 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.08(2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.23-7.35(7 H, m), 7.56(1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.3 Hz, 7.72(1 H, dd, J = 2.0 
               
               
                   
                   
                   
                   
                   
                 Hz, 8.6 Hz), 8.00(1 H, d, J = 2.0 
               
               
                   
                   
                   
                   
                   
                 Hz), 8.10(1 H, s), 8.18(1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 2.6 Hz, 8.6 Hz), 8.28 (1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 2.6 Hz). 
               
               
                   
               
               
                 2532 
                 4-CF 3 Ph- 
                 —CH 2 — 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 (CDCl 3 ) 2.6 1(4 H, brs), 3.38(4 H, brs), 3.55(2 H, s), 6.85-6.94(3 H, m), 7.06-7.14 (4 H, m), 7.36(2 H, d, J = 8.3 Hz), 7.64(2 H, d, J = 8.3 Hz), 7.70-7.75(4 H, m), 7.99 (2 H, t, J = 8.3 Hz), 8.24(1 H, dd, J = 8.7 Hz, 2.5 Hz), 8.40(1 H, d, J = 2.6 Hz), 9.19 (1 H, s). 
               
               
                   
               
               
                 2533 
                 4-CF 3 Ph- 
                 —CH 2 — 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 (CDCl 3 ) 2.58-2.62(4 H, m), 3.14-3.17(4 H, m), 3.54(2 H, s), 3.86(2 H, s), 6.83-7.14 (11 H, m), 7.36(2 H, d, J = 8.4 Hz), 7.71 (2 H, d, J = 8.3 Hz), 7.96(2 H, d, J = 8.1 Hz), 8.15-8.26(3 H, m). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 397 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 1104   
                 R 1105   
                 M 
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 2534 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 2 
                 2.30(3 H, s), 2.50-2.81(12 H, m), 6.86(1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.6 Hz), 6.98 (2 H, d, J = 8.6 Hz), 7.18(2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.3 Hz), 7.47(1 H, d, J = 8.3 Hz), 7.67(1 H, dd, J = 
               
               
                   
                   
                   
                   
                 8.3 Hz, 2.0 Hz), 7.94(1 H, d, J = 2.0 Hz), 8.11(1 H, 
               
               
                   
                   
                   
                   
                 dd, J = 8.9 Hz, 2.6 Hz), 8.21(1 H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                   
                 8.66 (1 H, brs). 
               
               
                 2535 
                 3,4-Cl 2 Ph- 
                 piperonyl 
                 2 
                 2.51-2.83(12 H, m), 3.43(2 H, s), 5.93(2 H, s), 6.74 
               
               
                   
                   
                   
                   
                 (2 H, d, J = 1.0 Hz), 6.86-7.03(4 H, m), 7.20(2 H, d, 
               
               
                   
                   
                   
                   
                 J = 8.3 Hz), 7.53(1 H, d, J = 8.6 Hz), 7.68-7.72 
               
               
                   
                   
                   
                   
                 (1 H, m), 7.97(1 H, d, J = 2.0 Hz), 8.15(1 H, dd, 
               
               
                   
                   
                   
                   
                 J = 8.9 Hz, 2.6 Hz), 8.23(2 H, d, J = 2.6 Hz). 
               
               
                 2536 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 3 
                 1.78-1.84(2 H, m), 2.29(3 H, s), 2.36-2.48(10 H, m), 
               
               
                   
                   
                   
                   
                 2.59-2.65 (2 H, m), 6.89(1 H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                 7.00(2 H, d, J = 8.4 Hz), 7.18 (2 H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                 7.52(1 H, d, J = 8.6 Hz), 7.67-7.71(1 H,m), 
               
               
                   
                   
                   
                   
                 7.96(1 H, d, J = 2.2 Hz), 8.11-8.15(1 H, m), 
               
               
                   
                   
                   
                   
                 8.23(1 H, d, J = 2.7 Hz), 8.31(1 H, brs). 
               
               
                 2537 
                 3,4-Cl 2 Ph- 
                 piperonyl 
                 3 
                 1.78-1.84(2 H, m), 2.36-2.47(10 H, m), 2.60-2.65 
               
               
                   
                   
                   
                   
                 (2 H, m), 3.41 (2 H, s), 5.93(2 H, s), 6.73(2 H, d, J = 
               
               
                   
                   
                   
                   
                 0.8 Hz), 6.85(1 H, s), 6.91 (1 H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                 7.02(2 H, d, J = 8.4 Hz), 7.19(2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                 7.55(1 H, d, J = 8.1 Hz), 7.68-7.71(1 H, m), 
               
               
                   
                   
                   
                   
                 7.96-7.97(2 H, m), 8.14-8.17(1 H, m), 8.23(1 H, d, J = 
               
               
                   
                   
                   
                   
                 2.7 Hz). 
               
               
                 2538 
                 4-CF 3 Ph- 
                 —COOC(CH 3 ) 3 — 
                 3 
                 1.46(9 H,.s), 1.78-1.89(2 H, m), 2.36-2.42(6 H, m), 
               
               
                   
                   
                   
                   
                 2.62-2.68 (2 H, m), 3.42-3.45(4 H, m), 6.94(1 H, d, 
               
               
                   
                   
                   
                   
                 J = 8.9 Hz), 7.01-7.06 (2 H, m), 7.18-7.23(2 H, m), 
               
               
                   
                   
                   
                   
                 7.76(2 H, d, J = 8.2 Hz), 7.99-8.03 (3 H, m), 
               
               
                   
                   
                   
                   
                 8.22(1 H, dd, J = 8.9 Hz, 2.6 Hz), 8.28(1 H, d, J = 
               
               
                   
                   
                   
                   
                 2.6 Hz). 
               
               
                 2539 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 4 
                 1.50-1.80(4 H, m), 2.32(3 H, s), 2.38(2 H, t, J = 7.3 
               
               
                   
                   
                   
                   
                 Hz), 2.30-2.70(8 H, m), 2.64(2 H, t, J = 7.3 Hz), 
               
               
                   
                   
                   
                   
                 6.94(1 H, d, J = 8.8 Hz), 7.03(2 H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                 7.19(2 H, d, J = 8.2 Hz), 7.58(1 H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                 7.72(1 H, dd, J = 8.2 Hz, 2.0 Hz), 7.84(1 H, s), 
               
               
                   
                   
                   
                   
                 8.00(1 H, d, J = 2.0 Hz), 8.18(1 H, dd, J = 8.8 Hz, 
               
               
                   
                   
                   
                   
                 2.6 Hz), 8.26 (1 H, d, J = 2.6 Hz). 
               
               
                 2540 
                 3,4-Cl 2 Ph- 
                 benzyl 
                 4 
                 1.45-1.75(4 H, m), 2.36(2 H, t, J = 7.5 Hz), 
               
               
                   
                   
                   
                   
                 2.30-2.65(8 H, m), 2.62(2 H, t, J = 7.7 Hz), 3.51(2 H, s), 
               
               
                   
                   
                   
                   
                 6.92(1 H, d, J = 8.6 Hz), 7.03(2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                 7.19(2 H, d, J = 8.6 Hz), 7.15-7.40(5 H, m), 
               
               
                   
                   
                   
                   
                 7.57(1 H, d, J = 8.2 Hz), 7.71(1 H, dd, J = 8.2 Hz, 
               
               
                   
                   
                   
                   
                 2.0 Hz), 7.85(1 H, s), 7.98(1 H, d, 4 2.0 Hz), 
               
               
                   
                   
                   
                   
                 8.16(1 H, dd, J = 8.6 Hz, 2.5 Hz), 8.24(1 H, d, J = 
               
               
                   
                   
                   
                   
                 2.5 Hz). 
               
               
                 2541 
                 3,4-Cl 2 Ph- 
                 benzyl 
                 5 
                 1.25-1.45(2 H, m), 1.45-1.75(4 H, m), 2.34(2 H, t, J = 
               
               
                   
                   
                   
                   
                 7.7 Hz), 2.30-2.70(8 H, m), 2.61(2 H, t, J = 7.7 
               
               
                   
                   
                   
                   
                 Hz), 3.51(2 H, s), 6.93(1 H, d, J = 8.7 Hz), 
               
               
                   
                   
                   
                   
                 7.03(2 H, d, J = 8.6 Hz), 7.19(2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                 7.20-7.40(5 H, m), 7.58(1 H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                   
                 7.70(1 H, dd, J = 8.3 Hz, 2.0 Hz), 7.71(1 H, d, J = 
               
               
                   
                   
                   
                   
                 2.0 Hz), 7.98(1 H, d, J = 2.0 Hz), 8.16(1 H, dd, J = 
               
               
                   
                   
                   
                   
                 8.7 Hz, 2.6 Hz), 8.24(1 H, d, J = 2.6 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 398 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 1106   
                 R 1107   
                 Form 
                   1 H NMR (DMSO-d 6 ) δ ppm 
               
               
                   
               
               
                 2542 
                 3,4-Cl 2 Ph- 
                 —H 
                 hydro- 
                 1.12(3 H, d, J = 6.3 Hz), 2.75-3.03(2 H, 
               
               
                   
                   
                   
                 chloride 
                 m), 3.24-3.39(2 H, m), 378-3.98(3 H, m), 
               
               
                   
                   
                   
                   
                 4.31(2 H, brs) 7.13(1 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                 7.20 (2 H, d, J = 8.3 Hz), 7.63(2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.3 Hz), 7.84(1 H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                 7.98(1 H, dd, J = 8.2 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                   
                 8.24(1 H, dd, J = 8.9 Hz, 2.6 Hz), 
               
               
                   
                   
                   
                   
                 8.25(1 H, d, J = 2.0 Hz), 8.55(1 H, d, J =  
               
               
                   
                   
                   
                   
                 2.6 Hz), 10.67(1 H, brs), 11.10(1 H, brs). 
               
               
                 2543 
                 3,4-Cl 2 Ph- 
                 —O(CH 2 ) 3 CH 3   
                 hydro- 
                 0.87(3 H, t, J = 7.3 Hz), 1.22-1.36(2 H, 
               
               
                   
                   
                   
                 chloride 
                 m), 1.41-1.51(2 H, m), 2.90-3.07(2 H, m), 
               
               
                   
                   
                   
                   
                 3.23-3.50(611, m), 3.80-3.88(1 H, m), 
               
               
                   
                   
                   
                   
                 3.99-4.02(2 H, m), 4.35(2 H, brs), 
               
               
                   
                   
                   
                   
                 7.13(1 H, d, J = 8.9 Hz), 7.21 (2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.6 Hz), 7.63(2 H, d, J = 8.3 Hz), 
               
               
                   
                   
                   
                   
                 7.84(1 H, d, J = 8.6 Hz), 7.97(1 H, dd, J = 
               
               
                   
                   
                   
                   
                 8.3 Hz, 2.0 Hz), 8.24(1 H, dd, J = 8.9 Hz, 
               
               
                   
                   
                   
                   
                 2.6 Hz), 8.25(1 H, d, J = 2.0 Hz), 
               
               
                   
                   
                   
                   
                 8.54(1 H, d, J = 2.6 Hz), 10.66(1 H, brs), 
               
               
                   
                   
                   
                   
                 11.17(1 H, brs). 
               
               
                 2544 
                 3,4-Cl 2 Ph- 
                 piperidino 
                 dihydro- 
                 1.38-1.77(6 H, m), 2.92-3.10(5 H, m), 
               
               
                   
                   
                   
                 chloride 
                 3.22-3.33(4 H, m), 3.47-3.51(1 H, m), 
               
               
                   
                   
                   
                   
                 3.97-4.06(2 H, m), 4.27-4.55(3 H, m), 7.13 
               
               
                   
                   
                   
                   
                 (1 H, d, J = 8.9 Hz), 7.21(2 H, d, J = 8.6 
               
               
                   
                   
                   
                   
                 Hz), 7.67(2 H, d, J = 8.6 Hz), 7.84(1 H, d, 
               
               
                   
                   
                   
                   
                 J = 8.6 Hz), 7.99(1 H, dd, J = 8.2 Hz, 2.0 
               
               
                   
                   
                   
                   
                 Hz), 8.26(1 H, dd, J = 8.6 Hz, 3.0 Hz), 
               
               
                   
                   
                   
                   
                 8.28(1 H, d, J = 2.3 Hz), 8.57(1 H, d, J = 
               
               
                   
                   
                   
                   
                 2.6 Hz), 10.27(1 H, brs), 10.74(1 H, brs), 
               
               
                   
                   
                   
                   
                 11.91 (1 H, brs). 
               
               
                 2545 
                 4-CF 3 Ph- 
                 —H 
                 hydro- 
                 1.12(3 H, d, J = 6.1 Hz), 2.68-2.80(1 H, 
               
               
                   
                   
                   
                 chloride 
                 m), 2.983.06(1 H, m), 3.24-3.28(2 H, m), 
               
               
                   
                   
                   
                   
                 3.80-3.90(3 H, m), 4.31(2 H, brs), 
               
               
                   
                   
                   
                   
                 7.14(1 H, d, J = 8.7 Hz), 7.21(2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.4 Hz), 7.64(2 H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                 7.93(2 H, d, J = 8.4 Hz), 8.19(2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.2 Hz), 8.27(1 H, dd, J = 8.9 Hz, 2.6 
               
               
                   
                   
                   
                   
                 Hz), 8.57(1 H, d, J = 2.6 Hz), 10.75(1 H, 
               
               
                   
                   
                   
                   
                 brs), 11.19(1 H, brs). 
               
               
                 2546 
                 4-CF 3 Ph- 
                 —OCH 
                 hydro- 
                 2.92-3.12(2 H, m), 3.26(3 H, s), 3.34-3.47 
               
               
                   
                   
                   
                 chloride 
                 (4 H, m), 3.80-4.02 (3 H, m), 4.34(2 H, 
               
               
                   
                   
                   
                   
                 brs), 7.14(1 H, d, J = 8.9 Hz), 7.21(2 H, d, 
               
               
                   
                   
                   
                   
                 J = 8.6 Hz), 7.63(2 H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                 7.94(2 H, d, J = 8.4 Hz), 8.18 (2 H, d, J = 
               
               
                   
                   
                   
                   
                 8.1 Hz), 8.27(1 H, dd, J 8.7 Hz, 2.6 
               
               
                   
                   
                   
                   
                 Hz), 8.57(1 H, d, J = 2.6 Hz), 10.73(1 H, 
               
               
                   
                   
                   
                   
                 brs), 11.13(1 H, brs). 
               
               
                 2547 
                 3,4-Cl 2 Ph- 
                 —OCH 3   
                 hydro- 
                 2.92-3.11(2 H, m), 3.26(3 H, s), 3.31-3.52 
               
               
                   
                   
                   
                 chloride 
                 (4 H, m), 3.79-3.87 (1 H, m), 3.95-4.04 
               
               
                   
                   
                   
                   
                 (2 H, m), 4.34(2 H, brs), 7.14(1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.9 Hz), 7.21(2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                 7.62(2 H, d, J = 8.6 Hz), 7.84(1 H, d, J = 
               
               
                   
                   
                   
                   
                 8.4 Hz), 7.97(1 H, dd, J = 8.4 Hz, 2.2 
               
               
                   
                   
                   
                   
                 Hz), 8.24-8.26(2 H, m), 8.54(1 H, d, J = 
               
               
                   
                   
                   
                   
                 2.6 Hz), 10.66(1 H, brs), 11.02(1 H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 399 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 1108   
                 M 
                 Form 
                   1 H NMR (solvent) δppm 
               
               
                   
               
               
                 2548 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 5 
                 free 
                 (CDCl 3 ) 1.30-1.45 (2H, m), 1.45-1.75 (4H, m), 2.30 (3H, s), 2.25-2.40 (2H, m), 2.49 (8H, brs), 2.62 (2H, t, J = 7.5 Hz), 6.94 (1H, d, J = 8.9 Hz), 7.04 (2H, d, J = 8.6 Hz), 7.20 (2H, d, J = 8.6 Hz), 7.59 (1H, d, J = 8.2 Hz), 7.65-7.75 (2H, m), 7.98 (1H, d, J = 2.0 Hz), 8.17 (1H, dd, J = 8.9 Hz, 3.0 Hz), 8.24 (1H, d, J = 3.0 Hz). 
               
               
                   
               
               
                 2549 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1 
                 hydro- chloride 
                 (DMSO-d 6 ) 1.13 (6H, d, J = 6.6 Hz), 2.66-2.76 (2H, m), 3.25-3.34 (2H, m), 3.91-3.99 (2H, m), 4.30 (2H, s), 7.14 (1H, d, J = 8.6 Hz), 7.21 (2H, d, J = 8.6 Hz), 7.62 (2H, d, J = 8.3 Hz), 7.85 (1H, d, J = 8.6 Hz), 7.97 (1H, dd, J = 8.6 Hz, 2.0 Hz), 8.24 (.1H, dd, J = 8.6 Hz, 3.0 Hz), 8.25 (1H, d, J = 2.3 Hz), 8.55 (1H, d, J = 2.6 Hz), 10.65 (1H, brs), 10.96 (1H, brs). 
               
               
                   
               
               
                 2550 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1 
                 hydro- chloride 
                 (DMSO-d 6 ) 1.11 (3H, d, J = 6.3 Hz), 1.40 (3H, d, J = 6.9 Hz), 2.67-2.75 (1H, m), 3.10 (2H, m), 3.25- 3.33 (1H, m), 4.02-4.32 (4H, m), 7.14 (1H, d, J = 8.9 Hz), 7.21 (2H, d, J = 8.3 Hz), 7.65 (2H, d, J = 8.6 Hz), 7.85 (1H, d, J = 8.2 Hz), 7.97 (1H, dd, J = 8.6 Hz, 2.0 Hz), 8.21-8.26 (2H, m), 8.54 (1H, d, J = 2.3 Hz), 10.46 (1H, brs), 10.64 (1H, brs). 
               
               
                   
               
             
          
         
       
     
       Example 2551 
     Production of 1-(3-{4-[4-(3,4-dichlorobenzoylamino)-phenoxy]phenyl}propionyl)-4-[2-(morpholino)acetyl]-piperazine 
       [1232]    To a solution of 1-chloroacetyl-4-(3-{4-[4-(3,4-dichlorobenzoylamino)phenoxy]phenyl}propionyl)-piperazine (0.515 g, 0.896 mmol) and diisopropylethylamine (0.234 mL, 1.34 mmol) in acetonitrile (11 mL) was added morpholine (0.117 mL, 1.34 mmol), and the resulting solution was refluxed for 1 hour. This reaction solution was concentrated under reduced pressure. To the residue was added a saturated sodium bicarbonate solution, and extracted with chloroform. The chloroform layer was dried over anhydrous magnesium sulfate, and evaporated. The obtained solid was recrystallized from water-containing acetone, to thereby yield 0.441 g of the title compound. 
         [1233]    Appearance: White powder 
         [1234]    Melting point: 187-190° C. 
         [1235]    The following compounds were produced in the same manner as in Example 2551. 
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 400 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 1109   
                 Form 
                 mp (° C.) or  1 H NMR 
               
               
                   
               
               
                 2552 
                 —COCH 2 N(C 2 H 5 ) 2   
                 3/2 oxalate 
                 mp 107-118 
               
               
                 2553 
                 —COCH 2 NHCH 2 Ph 
                 hydrochloride 
                 mp 199-202 
               
               
                 2554 
                 —COCH 2 N(C 2 H 5 )CH 2 Ph 
                 fumarate 
                   1 H NMR (DMSO-d 6 ) δ 0.99 (3H, t, J = 
               
               
                   
                   
                   
                 7.1 Hz), 2.56-2.70 (2H, m), 2.73 
               
               
                   
                   
                   
                 2.86 (2H, m), 3.09-3.50 (12H, m), 
               
               
                   
                   
                   
                 3.59 (2H, s), 6.61 (2H, s), 6.91 (2H, d, J = 
               
               
                   
                   
                   
                 8.0 Hz), 6.98 (2H, d, J = 9.0 Hz), 
               
               
                   
                   
                   
                 7.14-7.37 (7H, m), 7.74 (2H, d, J = 9.0 
               
               
                   
                   
                   
                 Hz), 7.81 (1H, d, J = 8.4 Hz), 7.92 (1H, 
               
               
                   
                   
                   
                 dd, J = 8.4 Hz, 2.1 Hz), 8.20 (1H, d, J = 
               
               
                   
                   
                   
                 2.1 Hz), 10.39 (1H, s), 13.09 (2H, 
               
               
                   
                   
                   
                 brs). 
               
               
                   
               
               
                 2555 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 dihydrochloride 
                 mp 173-176 
               
               
                   
               
               
                 2556 
                 —COCH 2 N(C 2 H 5 )Ph 
                 free 
                 mp 140-143 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 401 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 1110   
                 mp (° C.) 
               
               
                   
               
               
                 2557 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 206-210 
               
               
                   
               
               
                 2558 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 154-156 
               
               
                   
               
               
                 2559 
                 morpholino 
                 177-178 
               
               
                   
               
               
                 2560 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 204-206 
               
               
                   
               
               
                 2561 
                 —N(CH 3 )CH 2 Ph 
                 182-184 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 402 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 1111   
                 mp (° C.) 
               
               
                   
               
               
                 2562 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 151-152 
               
               
                   
               
               
                 2563 
                 morpholino 
                 177-178 
               
               
                   
               
               
                 2564 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 146-147 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 403 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 1112   
                 mp (° C.) 
               
               
                   
               
               
                 2565 
                 morpholino 
                 195-197 
               
               
                   
               
               
                 2566 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 146-148 
               
               
                   
               
               
                 2567 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 173-176 
               
               
                   
               
               
                 2568 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 150-153 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 404 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 1113   
                 Form 
                 mp (° C.) 
               
               
                   
               
               
                 2569 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 dihydrochloride 
                 152-155 
               
               
                   
               
               
                 2570 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 dihydrochloride 
                 181-185 
               
               
                   
               
               
                 2571 
                 morpholino 
                 hydrochloride 
                 146-150 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 405 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 1114   
                 mp (° C.) 
               
               
                   
               
               
                 2572 
                 morpholino 
                 157-160 
               
               
                   
               
               
                 2573 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 241-243 
               
               
                   
               
               
                 2574 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 193-196 
               
               
                   
               
               
                 2575 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 180-182 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 406 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 1115   
                 Xb 63   
                 R 1116   
                 mp (° C.) or  1 H NMR 
               
               
                   
               
               
                 2576 
                 3,4-Cl 2 Ph— 
                 none 
                 morpholino 
                   1 H NMR (DMSO-d 6 ) δ 2.50- 
               
               
                   
                   
                   
                   
                 2.53 (4H, m), 3.55-3.61 (4H, 
               
               
                   
                   
                   
                   
                 m), 3.82 (2H, s), 7.20 (1H, d, J = 
               
               
                   
                   
                   
                   
                 8.7 Hz), 7.21 (2H, d, J = 8.1 
               
               
                   
                   
                   
                   
                 Hz), 7.85 (1H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                 7.96 (1H, dd, J = 8.4 Hz, 1.2 
               
               
                   
                   
                   
                   
                 Hz), 8.06 (2H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                 8.23 (1H, d, J = 1.5 Hz), 8.27 (1H, dd, J = 8.9 Hz, 2.8 Hz), 8.55 (1H, d, J = 2.8 Hz), 10.61 (1H, brs). 
               
               
                   
               
               
                 2577 
                 4-CF 3 Ph— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 mp 179-181 
               
               
                   
               
               
                 2578 
                 4-CF 3 Ph— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 mp 172-174 
               
               
                   
               
               
                 2579 
                 4-CF 3 Ph— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 morpholino 
                 mp 144-146 
               
               
                   
               
               
                 2580 
                 4-CF 3 Ph— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —N(CH 3 )CH 2 Ph 
                 mp 188-190 
               
               
                   
               
               
                 2581 
                 4-CF 3 Ph— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 mp 192-193 
               
               
                   
               
             
          
         
       
     
         [1236]    The following compound was produced in the same manner as in Reference Example 860. 
       Example 2582 
     1-{4-[5-(3,4-Dichlorobenzoylamino)pyridin-2-yloxy]benzyl}piperazine-4-carboxylic acid ethyl ester 
       [1237]    Appearance: Pale yellow oil 
         [1238]      1 H NMR (CDCl 3 ) δ 1.25 (3H, t, J=7.0 Hz), 1.76 (2H, m), 1.77 (2H, m), 2.03 (2H, t, J=11.5 Hz), 2.28 (1H, m), 2.87 (2H, brd, J=11.5 Hz), 3.48 (2H, s), 4.13 (2H, q, J=7.0 Hz), 6.94 (1H, d, J=9.0 Hz), 7.06 (2H, d, J=8.5 Hz), 7.33 (2H, d, J=9.0 Hz), 7.57 (1H, d, J=8.5 Hz), 7.70 (1H, dd, J=8.5 Hz, 2.0 Hz), 7.88 (1H, brs), 7.97 (1H, d, J=2.0 Hz), 8.17 (1H, dd, J=9.0 Hz, 3.0 Hz), 8.24 (1H, d, J=3.0 Hz). 
       Example 2583 
     Production of 3,4-dichloro-N-{6-[4-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl)phenoxy]pyridin-3-yl}benzamide 
       [1239]    To uracil (200 mg, 1.8 mmol) was added hexamethyldisilazane (5 mL), and the resulting solution was stirred for 5.5 hours at 150° C. Insoluble matter was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was dissolved in a solution of acetonitrile (10 mL)-THF (5 mL), and to this solution were added 3,4-dichloro-N-[6-(4-chloromethylphenoxy)pyridin-3-yl]benzamide (500 mg, 1.2 mmol) and tin tetrachloride (3 drops). The resulting solution was refluxed for 2.5 hours. To this reaction solution was added methanol (1 mL), and the resulting solution was stirred for 30 minutes at room temperature. The resulting reaction solution was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (methanol:chloroform=1:99→3:97), to thereby yield 20 mg of the title compound. 
         [1240]    Appearance: White powder 
         [1241]      1 H NMR (DMSO-d 6 ) δ 4.88 (2H, s), 5.61 (1H, dd, J=7.9 Hz, 2.3 Hz), 7.07-7.13 (3H, m), 7.35 (2H, d, J=8.6 Hz), 7.79-7.85 (2H, m), 7.95 (1H, dd, J=8.6 Hz, 2.0 Hz), 8.18 (1H, d, J=2.6 Hz), 8.22 (1H, d, J=2.0 Hz), 8.47 (1H, d, J=2.6 Hz), 10.55 (1H, s), 11.33 (1H, s).; 
         [1242]    MS: m/z 482 (M + ). 
       Example 2584 
     Production of N-{6-[4-(4-benzyl-2-oxopiperazin-1-ylmethyl)phenoxy]pyridin-3-yl}-3,4-dichlorobenzamide dihydrochloride 
       [1243]    To a solution of 4-benzylpiperazin-2-one (0.56 g, 2.95 mmol) in DMF (10 mL) was added 60% sodium hydride (0.12 g, 2.95 mmol), and this solution was stirred at room temperature for 30 minutes. 2-(4-chloromethylphenoxy)-5-nitropyridine (0.78 g, 2.95 mmol) was added to the reaction mixture, and the mixture was stirred for 1 hour at room temperature. To this mixture was added brine (50 mL), and extracted with ethyl acetate (50 mL). The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. The remaining oil was dissolved in ethyl acetate (5 mL), and to the resulting solution was added iron powder (0.33 g, 5.89 mmol). This solution was stirred for 2 hours at room temperature. The resulting reaction solution was concentrated under reduced pressure, and a saturated sodium bicarbonate solution (50 mL) was added to the residue. The obtained mixture was extracted with ethyl acetate (50 mL). The ethyl acetate layer was washed with brine, dried over anhydrous sodium sulfate, and evaporated. The remaining oil was dissolved in THF (10 mL). To the resulting solution were added triethylamine (0.21 mL, 1.47 mmol) and 3,4-dichlorobenzoyl chloride (0.31 mL, 1.47 mmol), and this solution was stirred at room temperature for 2 hours. A saturated sodium bicarbonate solution (50 mL) was added to the solution, and extracted with ethyl acetate (50 mL). The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol=40:1). The obtained oil was dissolved in ethyl acetate (5 mL), and to the resulting solution was added a solution of 4 N hydrogen chloride in ethyl acetate (1.5 mL, 6 mmol). The formed white powder was collected by suction filtration, to thereby yield 0.045 g of the title compound. 
         [1244]    Appearance: White powder 
         [1245]      1 H NMR (DMSO-d 6 ) δ 3.54 (4H, m), 3.86 (2H, brs), 4.42 (2H, s), 4.59 (2H, brs), 7.06-7.12 (3H, m), 7.34 (2H, d, J=8.6 Hz), 7.48-7.51 (3H, m), 7.57-7.60 (2H, m), 7.84 (1H, d, J=8.6 Hz), 7.97 (1H, dd, J=2.0 Hz, 8.3 Hz), 8.18-8.24 (2H, m), 8.49 (1H, d, J=2.6 Hz), 10.61 (1H, s). 
         [1246]    The following compound was produced in the same manner as in Reference Example 656. 
       Example 2585 
     2-({4-[5-(3,4-Dichlorophenylamino)pyridin-2-yloxy]-2-trifluoromethylphenyl}ethylamino)-1-(4-piperonylpiperazin-1-yl)ethanone 
       [1247]      1 H NMR (CDCl 3 ) δ 1.02 (3H, t, J=7.1 Hz), 2.30-2.45 (4H, m), 3.22 (2H, q, J=7.1 Hz), 3.40 (2H, s), 3.45-3.65 (4H, m), 3.85 (2H, s), 5.57 (1H, brs), 5.94 (2H, s), 6.65-6.80 (3H, m), 6.85 (1H, s), 6.95 (1H, d, J=8.7 Hz), 7.00 (1H, d, J=2.7 Hz), 7.29-7.31 (2H, m), 7.39 (1H, d, J=2.7 Hz), 7.53 (1H, dd, J=8.7 Hz, 2.9 Hz), 7.64 (1H, d, J=8.8 Hz), 7.99 (1H, d, J=2.7 Hz). 
         [1248]    The following compounds were produced in the same manner as in Reference Example 658. 
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 407 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example No. 
                 R 1117   
                 R 1118   
                 M 
                 mp (° C.) or  1 H NMR (DMSO-d 6 ) δ ppm 
               
               
                   
               
               
                 2586 
                 4-CF 3 Ph- 
                 —H 
                 2 
                   1 H NMR 2.14-2.30 (2H, m), 2.62-3.12 (7H, m), 3.20-3.58 (3H, 
               
               
                   
                   
                   
                   
                 m), 3.77 (2H, t, J = 5.9 Hz), 3.81-4.15 (3H, m), 4.16-4.32 (2H, 
               
               
                   
                   
                   
                   
                 m), 4.49-4.57 (1H, m), 6.08 (2H, s), 6.96-7.09 (5H, m), 7.21 (1H, 
               
               
                   
                   
                   
                   
                 s), 7.29 (2H, d, J = 8.5 Hz), 7.58 (2H, d, J = 8.5 Hz), 7.70 (2H, d, 
               
               
                   
                   
                   
                   
                 J = 8.8 Hz), 7.86 (1H, dd, J = 2.8 Hz, 8.8 Hz), 8.13 (1H, d, 
               
               
                   
                   
                   
                   
                 J = 2.8 Hz), 10.78-11.01 (1H, m). 
               
               
                 2587 
                 3,4-Cl 2 Ph- 
                 —H 
                 2 
                 mp 182.0-183.0 
               
               
                 2588 
                 3-CF 3 Ph- 
                 —H 
                 1 
                 mp 200.0-203.0 
               
               
                 2589 
                 4-CF 3 Ph- 
                 —OCH 3   
                 1 
                 mp 153.0-154.0 
               
               
                 2590 
                 3,4-Cl 2 Ph- 
                 —OCH 3   
                 1 
                 mp 169.0-171.0 
               
               
                 2591 
                 4-CF 3 Ph- 
                 —OCH 3   
                 2 
                 mp 134.0-136.0 
               
               
                 2592 
                 3,4-Cl 2 Ph- 
                 —OCH 3   
                 2 
                 mp 130.0-132.0 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 408 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example No. 
                 R 1119   
                 M 
                 mp (° C.) or  1 H NMR (DMSO-d 6 ) δ ppm 
               
               
                   
               
               
                 2593 
                 4-CF 3 Ph- 
                 1 
                   1 H NMR 1.90-2.06 (2H, m), 2.07 (3H, s), 3.18-3.32 (2H, m), 
               
               
                   
                   
                   
                 3.55-3.70 (2H, m), 3.73 (3H, s), 3.74 (3H, s), 3.91-4.12 (4H, 
               
               
                   
                   
                   
                 m), 4.43 (2H, s), 4.49-4.93 (1H, m), 6.81 (1H, dd, J = 1.8 Hz, 
               
               
                   
                   
                   
                 8.1 Hz), 6.88 (1H, d, J = 1.8 Hz), 6.92 (1H, d, J = 8.1 Hz), 6.97 
               
               
                   
                   
                   
                 (1H, d, J = 8.5 Hz), 7.06 (1H, d, J = 9.0 Hz), 7.12 (1H, dd, J = 
               
               
                   
                   
                   
                 2.4 Hz, 8.5 Hz), 7.21 (1H, d, J = 2.4 Hz), 7.71 (2H, d, J = 8.9 
               
               
                   
                   
                   
                 Hz), 7.83 (2H, d, J = 8.9 Hz), 8.19 (1H, dd, J = 2.9 Hz, 9.0 Hz), 
               
               
                   
                   
                   
                 8.27 (1H, d, J = 2.9 Hz). 
               
               
                 2594 
                 3,4-Cl 2 Ph- 
                 1 
                 mp 146.0-148.0 
               
               
                 2595 
                 3,4-Cl 2 Ph- 
                 2 
                   1 H NMR 1.91-2.11 (5H, m), 2.12-2.24 (2H, m), 3.19-3.32 (2H, 
               
               
                   
                   
                   
                 m), 3.58-3.83 (10H, m), 3.85-4.22 (3H, m), 4.42 (2H, s), 6.81 
               
               
                   
                   
                   
                 (1H, dd, J = 1.8 Hz, 8.1 Hz), 6.87 (1H, d, J = 1.8 Hz), 6.91 (1H, 
               
               
                   
                   
                   
                 d, J = 8.1 Hz), 6.94-7.02 (2H, m), 7.12 (1H, dd, J = 2.5 Hz, 8.6 
               
               
                   
                   
                   
                 Hz), 7.21 (1H, d, J = 2.5 Hz), 7.35 (1H, dd, J = 2.5 Hz, 8.8 Hz), 
               
               
                   
                   
                   
                 7.57 (1H, d, J = 8.8 Hz), 7.66 (1H, d, J = 2.5 Hz), 7.82 (1H, dd, 
               
               
                   
                   
                   
                 J = 2.5 Hz, 8.8 Hz), 8.07 (1H, d, J = 2.5 Hz). 
               
               
                   
               
             
          
         
       
     
       Example 2596 
     Production of 3-(4-{5-[4-(3,4-dichlorophenyl)piperazin-1-yl]pyridin-2-yloxy}phenyl)-1-(4-pipeonylpiperazin-1-yl)propane-1-one 
       [1249]    To a solution of 3-[4-(5-bromopyridin-2-yloxy)phenyl]-1-(4-piperonylpiperazin-1-yl)propane-1-one (359 mg, 0.69 mmol) and 1-(3,4-dichlorophenyl)-piperazine (206 mg, 0.89 mmol) in toluene (16 mL) were added with Pd 2 (dba) 3  (25 mg, 0.027 mmol), Xantphos (32 mg, 0.055 mmol) and sodium t-butoxide (99 mg, 1.03 mmol), and the resulting solution was refluxed under an argon atmosphere for 3 hours. The solution was left to cool, water was added to this reaction mixture. The resulting solution was extracted with dichloromethane, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane methanol=30:1), to thereby yield 236 mg of the title compound. 
         [1250]    Appearance: Pale yellow powder 
         [1251]      1 H NMR (CDCl 3 ) δ 2.31-2.40 (4H, m), 2.58-2.64 (2H, m), 2.92-2.98 (2H, m), 3.23-3.38 (8H, m), 3.41 (4H, brs), 3.63 (2H, t, J=4.9 Hz), 5.94 (2H, s), 6.72-6.73 (2H, m), 6.78 (1H, dd, J=8.9 Hz, 2.8 Hz), 6.84-6.90 (2H, m), 6.99-7.06 (3H, m), 7.19-7.24 (3H, m), 7.32 (1H, dd, J=9.4 Hz, 3.1 Hz), 7.88 (1H, d, J=3.0 Hz). Tris(dibenzylideneacetone)dipalladium is abbreviated to Pd 2 (dba) 3 . Hereinafter, the same. 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene is abbreviated to Xantphos. Hereinafter the same. 
         [1252]    The following compounds were produced in the same manner as in Example 2596. 
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 409 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 R 1120   
                 R 1121    
                 Xb 64   
                   1 H NMR (CDCl 3 ) δppm 
               
               
                   
               
               
                 2597 
                 4-CF 3 PhCH 2 — 
                 —H 
                 —CH 2 — 
                 2.31-2.38 (4H, m), 2.60-2.64 (6H, m), 2.95 (2H, t, J = 
               
               
                   
                   
                   
                   
                 7.3 Hz), 3.11-3.15 (4H, m), 3.40 (4H, brs), 
               
               
                   
                   
                   
                   
                 3.61 (4H, brs), 5.93 (2H, s), 6.73 (2H, s), 6.83 (2H, 
               
               
                   
                   
                   
                   
                 d, J = 9.1 Hz), 6.99 (2H, d, J = 8.4 Hz), 7.19 (2H, 
               
               
                   
                   
                   
                   
                 d, J = 8.4 Hz), 7.29 (1H, dd, J = 8.9 Hz, 3.1 Hz), 
               
               
                   
                   
                   
                   
                 7.47 (2H, d, J = 8.2 Hz), 7.58 (2H, d, J = 8.1 Hz), 
               
               
                   
                   
                   
                   
                 7.83 (1H, d, J = 3.0 Hz). 
               
               
                 2598 
                 3,4-Cl 2 Ph— 
                 —CH 3   
                 —N(CH 3 )— 
                 2.13 (3H, s), 2.40-2.44 (4H, m), 3.00 (3H, s), 3.18- 
               
               
                   
                   
                   
                   
                 3.38 (8H, m), 3.43 (2H, s), 3.49 (2H, brs), 3.63 (2H, 
               
               
                   
                   
                   
                   
                 brs), 4.06 (2H, s), 5.94 (2H, s), 6.52-6.57 (2H, m), 
               
               
                   
                   
                   
                   
                 6.69-6.91 (6H, m), 7.00 (1H, d, J = 3.0 Hz), 7.26- 
               
               
                   
                   
                   
                   
                 7.32 (2H, m), 7.86 (1H, d, J = 2.8 Hz). 
               
               
                 2599 
                 4-CF 3 Ph— 
                 —CH 3   
                 —N(CH 3 )— 
                 2.13 (3H, s), 2.41-2.44 (4H, m), 3.00 (3H, s), 3.20- 
               
               
                   
                   
                   
                   
                 3.24 (4H, m), 3.34-3.43 (6H, m), 3.49 (2H, brs), 
               
               
                   
                   
                   
                   
                 3.63 (2H, brs), 4.06 (2H, s), 5.94 (2H, s), 6.52- 
               
               
                   
                   
                   
                   
                 6.58 (2H, m), 6.70-6.77 (3H, m), 6.85-6.98 (4H, m), 
               
               
                   
                   
                   
                   
                 7.31 (1H, dd, J = 9.1 Hz, 3.1 Hz), 7.50 (2H, d, J = 
               
               
                   
                   
                   
                   
                 8.6 Hz), 7.87 (1H, d, J = 2.6 Hz). 
               
               
                 2600 
                 4-CF 3 Ph— 
                 —H 
                 —CH 2 — 
                 2.31-2.40 (4H, m), 2.61 (2H, t, J = 7.3 Hz), 
               
               
                   
                   
                   
                   
                 2.96 (2H, t, J = 7.3 Hz), 3.23-3.27 (4H, m), 3.38- 
               
               
                   
                   
                   
                   
                 3.45 (8H, m), 3.63 (2H, t, J = 4.8 Hz), 5.94 (2H, s), 
               
               
                   
                   
                   
                   
                 6.70-6.76 (2H, m), 6.84-7.06 (6H, m), 7.19- 
               
               
                   
                   
                   
                   
                 7.26 (2H, m), 7.36 (1H, dd, J = 8.9 Hz, 3.1 Hz), 
               
               
                   
                   
                   
                   
                 7.51 (2H, d, J = 8.9 Hz), 7.89 (1H, d, J = 3.0 Hz). 
               
               
                   
               
             
          
         
       
     
         [1253]    The following compounds were produced in the same manner as in Reference Example 659. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 410 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 1122   
                 Xb 65   
                 Xb 66   
                 R 1123   
                   1 H NMR (CDCl 3 ) δppm 
               
               
                   
               
               
                 2601 
                 4-CF 3 Ph— 
                 —N(CH 3 )— 
                 —CH 2 — 
                 piperonyl 
                 2.41-2.44 (4H, m), 3.03 (3H, s), 3.43 (2H, 
               
               
                   
                   
                   
                   
                   
                 s), 3.47-3.50 (2H, m), 3.61-3.65 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 4.09 (2H, s), 5.93 (2H, s), 6.68-6.77 (4H, 
               
               
                   
                   
                   
                   
                   
                 m), 6.83-6.86 (2H, m) 6.99 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 16.5 Hz), 7.00-7.06 (2H, m), 7.10 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 16.5 Hz), 7.54-7.61 (4H, m), 7.84 (1H, 
               
               
                   
                   
                   
                   
                   
                 dd, J = 8.6 Hz, 2.5 Hz), 8.26 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 2.5 Hz). 
               
               
                 2602 
                 3,4-Cl 2 Ph— 
                 —N(CH 3 )— 
                 —CH 2 — 
                 piperonyl 
                 2.42-2.45 (4H, m), 3.04 (3H, s), 3.44 (2H, 
               
               
                   
                   
                   
                   
                   
                 s), 3.48-3.52 (2H, m), 3.62-3.66 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 4.09 (2H, s), 5.95 (2H, s), 6.68-6.86 (6H, 
               
               
                   
                   
                   
                   
                   
                 m), 6.94 (1H, d, J = 17.3 Hz), 6.99 
               
               
                   
                   
                   
                   
                   
                 7.04 (3H, m), 7.31 (1H, dd, J = 8.4 Hz, 2.0 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.42 (1H, d, J = 8.4 Hz), 7.57 (1H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 2.0 Hz), 7.82 (1H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.24 (1H, brs). 
               
               
                 2603 
                 4-CF 3 Ph— 
                 —CH 2 — 
                 —CH 2 — 
                 piperonyl 
                 2.32-2.41 (4H, m), 2.60-2.66 (2H, m), 
               
               
                   
                   
                   
                   
                   
                 2.96-3.01 (2H, m), 3.39-3.43 (4H, m), 
               
               
                   
                   
                   
                   
                   
                 3.62-3.66 (2H, m), 5.95 (2H, s), 6.70- 
               
               
                   
                   
                   
                   
                   
                 6.77 (2H, m), 6.84-6.85 (1H, m), 6.93 (1H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.6 Hz), 7.00-7.09 (3H, m), 
               
               
                   
                   
                   
                   
                   
                 7.12 (1H, d, J = 16.5 Hz), 7.23-7.27 (2H, 
               
               
                   
                   
                   
                   
                   
                 m), 7.56-7.64 (4H, m), 7.90 (1H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 8.7 Hz, 2.6 Hz), 8.27 (1H, d, J = 2.6 Hz). 
               
               
                 2604 
                 4-CF 3 Ph— 
                 none 
                 none 
                 benzyl 
                 2.47 (4H, brs), 3.55-3.77 (6H, m), 
               
               
                   
                   
                   
                   
                   
                 6.97 (1H, d, J = 8.6 Hz), 7.05 (1H, d, J = 
               
               
                   
                   
                   
                   
                   
                 16.3 Hz), 7.10-7.27 (3H, m), 7.28- 
               
               
                   
                   
                   
                   
                   
                 7.34 (5H, m), 7.45-7.50 (2H, m), 7.57- 
               
               
                   
                   
                   
                   
                   
                 7.64 (4H, m), 7.93 (1H, dd, J = 8.6 Hz, 2.4 
               
               
                   
                   
                   
                   
                   
                 Hz), 8.29 (1H, d, J = 2.4 Hz). 
               
               
                 2605 
                 3,4-Cl 2 Ph— 
                 none 
                 none 
                 benzyl 
                 2.52 (4H, brs), 3.49-3.90 (6H, m), 6.89 
               
               
                   
                   
                   
                   
                   
                 6.98 (2H, m), 7.03 (1H, d, J = 16.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.15-7.20 (2H, m), 7.30-7.50 (9H, m), 
               
               
                   
                   
                   
                   
                   
                 7.58 (1H, d, J = 2.1 Hz), 7.90 (1H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 8.7 Hz, 2.5 Hz), 8.26 (1H, d, J = 2.5 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 411 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 1124   
                 Form 
                   1 H NMR (solvent) δppm 
               
               
                   
               
               
                 2606 
                 piperonyl 
                 hydrobromide 
                 (DMSO-d 6 ) 1.89-2.06 (2H, m), 2.06 (3H, s), 
               
               
                   
                   
                   
                 3.18-3.35 (2H, m), 3.57-3.71 (2H, m), 4.40 (2H, 
               
               
                   
                   
                   
                 s), 4.42-4.80 (1H, m, 5.99 (2H, s), 6.77 (1H, dd, 
               
               
                   
                   
                   
                 J = 1.6 Hz, 7.9 Hz), 6.84 (1H, d, J = 1.6 Hz), 
               
               
                   
                   
                   
                 6.87 (1H, d, J = 7.9 Hz), 7.01 (1H, d, J = 8.6 
               
               
                   
                   
                   
                 Hz), 7.07 (1H, d, J = 8.6 Hz), 7.13 (1H, dd, J = 
               
               
                   
                   
                   
                 2.5 Hz, 8.6 Hz), 7.23 (1H, d, J = 2.5 Hz), 
               
               
                   
                   
                   
                 7.32 (1H, d, J = 16.5 Hz), 7.42 (1H, d, J = 16.5 
               
               
                   
                   
                   
                 Hz), 7.72 (2H, d, J = 8.5 Hz), 7.79 (2H, d, J = 
               
               
                   
                   
                   
                 8.5 Hz), 8.19 (1H, dd, J = 2.4 Hz, 8.6 Hz), 
               
               
                   
                   
                   
                 8.30 (1H, d, J = 2.4 Hz). 
               
               
                 2607 
                 3,4- 
                 free 
                 (CDCl 3 ) 1.99-2.14 (2H, m), 2.18 (3H, s), 3.22- 
               
               
                   
                 (CH 3 O) 2 PhCH 2 — 
                   
                 3.38 (2H, m), 3.63-3.79 (2H, m), 3.89 (3H, s), 
               
               
                   
                   
                   
                 3.90 (3H, s), 4.57 (2H, s), 6.76-6.95 (4H, m), 
               
               
                   
                   
                   
                 6.97-7.20 (4H, m), 7.51-7.67 (4H, m), 7.88 (1H, 
               
               
                   
                   
                   
                 dd, J = 2.5 Hz, 8.6 Hz), 8.27 (1H, d, J = 2.5 
               
               
                   
                   
                   
                 Hz). 
               
               
                   
               
             
          
         
       
     
       Example 2608 
     Production of 1-(3,4-dimethoxybenzyl)-3-{3-methyl-4-[5-(4-trifluoromethylphenylethynyl)pyridin-2-yloxy]phenyl}tetrahydropyrimidin-2-one 
       [1254]    To a solution of 1-[4-(5-bromopyridin-2-yloxy)-3-methylphenyl]-3-(3,4-dimethoxybenzyl)tetrahydropyrimidin-2-one (0.3 g, 0.59 mmol) in N-methylpyrrolidone (10 mL) were added bis(triphenylphosphine)palladium dichloride (20 mg, 0.03 mmol), copper iodide (11 mg, 0.059 mmol), 4-ethynyl-α,α,α-trifluorotoluene (0.14 mL, 0.88 mmol) and triethylamine (0.14 mL, 10 mmol) under a nitrogen atmosphere. The resulting solution was stirred for 3 hours at 110 to 120° C. After being left to cool, water was added to the reaction solution. The resulting solution was extracted with ethyl acetate. The ethyl acetate layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was then evaporated, and the residue was purified by silica gel chromatography (n-hexane:ethyl acetate=4:1→1:1), to thereby yield 0.28 g of the title compound. 
         [1255]    Appearance: Pale brown amorphous powder 
         [1256]      1 H NMR (CDCl 3 ) δ 1.97-2.15 (2H, m), 2.16 (3H, s), 3.31 (2H, t, J=6.0 Hz), 3.72 (2H, t, J=6.0 Hz), 3.88 (3H, s), 3.89 (3H, s), 4.57 (2H, s), 6.72-6.95 (5H, m), 7.04 (1H, d, J=8.6 Hz), 7.17 (1H, dd, J=2.6 Hz, 8.6 Hz), 7.55-7.68 (4H, m), 7.78 (1H, dd, J=2.3 Hz, 8.6 Hz), 8.36 (1H, d, J=2.3 Hz). 
       Example 2609 
     Production of 3-(3-methyl-4-{5-[2-oxo-2-(4-trifluoromethylphenyl)ethyl]pyridin-2-yloxy}phenyl)-1-piperonyltetrahydropyrimidin-2-one hydrobromide 
       [1257]    To a solution of 3-[4-(5-bromopyridin-2-yloxy)-3-methylphenyl]-1-piperonyltetrahydropyrimidin-2-one (0.11 g, 0.22 mmol) in toluene (10 mL) were added Pd 2 (dba) 3  (10 mg, 0.01 mmol) and Xantphos (15 mg, 0.03 mmol) under a nitrogen atmosphere. The resulting solution was stirred for 5 minutes, and then 4′-(trifluoromethyl)acetophenone (63 mg, 0.33 mmol) and potassium bis(trimethylsilyl)amide (66 mg, 0.33 mmol) were added to the reaction % solution. The resulting solution was stirred at 70 to 80° C. for 30 minutes, and left to cool. Water was added to the reaction solution, and extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=2:1→1:1), to yield 50 mg of a free form. To this free form was added an equivalent amount of hydrobromic acid, to thereby yield 50 mg of the title compound. 
         [1258]    Appearance: Colorless amorphous powder 
         [1259]      1 H NMR (DMSO-d 6 ) δ 1.85-2.10 (2H, m), 2.06 (3H, s), 3.14-3.47 (2H, m), 3.50-3.76 (2H, m), 4.40 (2H, s), 4.49 (2H, s), 4.70-5.40 (1H, m), 5.98 (2H, s), 6.70-6.80 (1H, m), 6.81-6.90 (2H, m), 6.90-7.04 (2H, m), 7.12 (1H, d, J=2.2 Hz, 8.6 Hz), 7.18-7.26 (1H, m), 7.72 (1H, dd, J=2.2 Hz, 8.5 Hz), 7.93 (2H, d, J=8.2 Hz), 7.95-8.02 (1H, m), 8.24 (2H, d, J=8.2 Hz). 
         [1260]    The following compounds were produced in the same manner as in Example 2609. 
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 412 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 1125   
                 R 1126   
                   1 H NMR (CDCl 3 ) δppm 
               
               
                   
               
               
                 2610 
                 3,4-Cl 2 Ph— 
                 piperonyl 
                 1.82-2.10 (2H, m), 2.07 (3H, s), 3.12-3.32 (2H, m), 
               
               
                   
                   
                   
                 3.53-3.72 (2H, m), 4.40 (2H, s), 4.45 (2H, s), 4.80- 
               
               
                   
                   
                   
                 5.40 (1H, m), 5.99 (2H, s), 6.71-6.80 (1H, m), 6.81- 
               
               
                   
                   
                   
                 6.90 (2H, m), 6.98 (2H, dd, J = 2.4 Hz, 8.5 Hz), 
               
               
                   
                   
                   
                 7.12 (1H, dd, J = 2.4 Hz, 8.5 Hz), 7.21 (1H, d, J = 2.4 
               
               
                   
                   
                   
                 Hz), 7.70 (1H, dd, J = 2.2Hz, 8.4 Hz), 7.84 (1H, d, J = 
               
               
                   
                   
                   
                 8.4 Hz), 7.96 (1H, d, J = 2.2 Hz), 8.00 (1H, dd, J = 
               
               
                   
                   
                   
                 2.0 Hz, 8.4 Hz), 8.25 (1H, d, J = 2.0 Hz). 
               
               
                 2611 
                 4-CF 3 Ph— 
                 3,4-(CH 3 O) 2 Ph— 
                 1.87-2.11 (5H, m), 3.15-3.32 (2H, m), 3.43-3.71 (3H, 
               
               
                   
                   
                   
                 m), 3.74 (3H, s), 3.75 (3H, s), 4.44 (2H, s), 4.51 (2H, s), 
               
               
                   
                   
                   
                 6.78-6.86 (1H, m), 6.87-6.91 (1H, m), 6.93 (1H, d, J = 
               
               
                   
                   
                   
                 8.5 Hz), 6.99 (1H, d, J = 8.5 Hz), 7.00 (1H, d, J = 8.5 
               
               
                   
                   
                   
                 Hz), 7.14 (1H, dd, J = 2.4 Hz, 8.5 Hz), 7.19-7.25 (1H, 
               
               
                   
                   
                   
                 m), 7.73 (1H, dd J = 2.4 Hz, 8.5 Hz), 7.94 (1H, d, J = 
               
               
                   
                   
                   
                 8.3 Hz), 7.97-8.01 (1H, m), 8.25 (1H, d, J = 8.3 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 413 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                 mp (° C.) or 
               
               
                 No. 
                 R 1127   
                   1 H NMR (solvent) δppm 
               
               
                   
               
               
                 2612 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (CDCl 3 ) 2.44 (4H, brs), 3.44 (2H, s), 3.54 (2H, brs), 3.73 (2H, brs), 4.29 (2H, s), 5.94 (2H, s), 6.74 (2H, s), 6.85 (1H, s), 6.94 (1H, d, J = 8.4 Hz), 7.16 (2H, d, J = 8.6 Hz), 7.45 (2H, d, J = 8.6 Hz), 7.63 (1H, dd, J = 8.4 Hz, 2.5 Hz), 7.76 (2H, d, J = 8.1 Hz), 8.07 (1H, d, J = 2.5 Hz), 8.11 (2H, d, J = 8.1 Hz). 
               
               
                   
               
               
                 2613 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   1 H NMR (DMSO-d 6 ) 2.31 (3H, s), 2.76- 3.45 (9H, m), 3.69-4.57 (8H, m), 6.07 (2H, s), 6.81-7.22 (6H, m), 7.74 (1H, dd, J = 2.2 Hz, 8.4 Hz), 7.89-8.00 (2H, m), 8.24 (1H, d, J = 8.4 Hz), 9.49-9.79 (1H, m). 
               
               
                   
               
               
                 2614 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 mp 164.0-166.0 
               
               
                   
               
             
          
         
       
     
         [1261]    The following compounds were produced in the same manner as in Reference Example 111. 
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 414 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                   
                 Example 
                   
                   
               
               
                   
                 No. 
                 Xb 67   
                   1 H NMR (solvent) δppm 
               
               
                   
                   
               
               
                   
                 2615 
                 —N(CH 3 )— 
                 2.42-2.45 (4H, m), 3.05 (3H, s), 3.44 (2H, s), 3.47-3.51 (2H, m), 3.62- 
               
               
                   
                   
                   
                 3.65 (2H, m), 4.11 (2H, s), 5.95 (2H, s), 6.69-6.77 (4H, m), 6.85 (1H, 
               
               
                   
                   
                   
                 s), 6.97 (1H, d, J = 8.7 Hz), 7.01-7.07 (2H, m), 7.75 (2H, d, J = 8.4 
               
               
                   
                   
                   
                 Hz), 7.87 (2H, d, J = 8.1 Hz), 8.17 (1H, dd, J = 8.7 Hz, 2.3 Hz), 
               
               
                   
                   
                   
                 8.58 (1H, d, J = 2.3 Hz). 
               
               
                   
                 2616 
                 —CH 2 — 
                 2.32-2.41 (4H, m), 2.61-2.67 (2H, m), 2.97-3.03 (2H, m), 3.41- 
               
               
                   
                   
                   
                 3.43 (4H, m), 3.62-3.66 (2H, m), 5.95 (2H, s), 6.70-6.77 (2H, m), 
               
               
                   
                   
                   
                 6.84 (1H, s), 7.03-7.13 (3H, m), 7.28-7.32 (2H, m), 7.76 (2H, d, J = 8.1 
               
               
                   
                   
                   
                 Hz), 7.88 (2H, d, J = 8.1 Hz), 8.22 (1H, dd, J = 8.6 Hz, 2.4 Hz), 
               
               
                   
                   
                   
                 8.58 (1H, d, J = 2.4 Hz). 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 415 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 1128   
                 R 1129   
                   1 H NMR (CDCl 3 ) δppm 
               
               
                   
               
               
                 2617 
                 —H 
                 —CH 2 COOC 2 H 5   
                 1.27 (3H, t, J = 7.1 Hz), 1.34-1.48 (2H, m), 1.81-1.99 (3H, 
               
               
                   
                   
                   
                 m), 2.29 (2H, d, J = 6.9 Hz), 2.73 (2H, t, J = 12.2 Hz), 
               
               
                   
                   
                   
                 3.63 (2H, d, J = 12.2 Hz), 4.15 (2H, q, J = 7.3 Hz), 6.91- 
               
               
                   
                   
                   
                 7.01 (4H, m), 7.18-7.26 (3H, m), 7.54 (2H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                 8.26 (1H, d, J = 2.3 Hz), 8.43 (1H, d, J = 2.3 Hz). 
               
               
                 2618 
                 —CH 3   
                 —CH 2 COOC 2 H 5   
                 1.28 (3H, t, J = 7.1 Hz), 1.30-1.39 (2H, m), 1.80-1.96 (3H, 
               
               
                   
                   
                   
                 m), 2.07 (3H, s), 2.29 (2H, d, J = 6.9 Hz), 2.70 (2H, t, J = 
               
               
                   
                   
                   
                 12.0 Hz), 3.61 (2H, d, J = 12.4 Hz), 4.17 (2H, q, J = 7.3 
               
               
                   
                   
                   
                 Hz), 6.74-6.78 (2H, m), 6.92 (1H, d, J = 8.6 Hz), 7.20- 
               
               
                   
                   
                   
                 7.26 (3H, m), 7.52 (2H, d, J = 8.4 Hz), 8.28 (1H, d, J = 2.3 
               
               
                   
                   
                   
                 Hz), 8.41 (1H, d, J = 2.3 Hz). 
               
               
                 2619 
                 —H 
                 —COOC 2 H 5   
                 1.27 (3H, t, J = 7.1 Hz), 1.92-2.00 (2H, m), 2.01-2.05 (2H, 
               
               
                   
                   
                   
                 m), 2.38-2.47 (1H, m), 2.74-2.84 (2H, m), 3.59-3.63 (2H, 
               
               
                   
                   
                   
                 m), 4.15 (2H, q, J = 7.1 Hz), 6.93-7.02 (4H, m), 7.17 
               
               
                   
                   
                   
                 7.26 (3H, m), 7.54 (2H, d, J = 8.4 Hz), 8.26 (1H, d, J = 2.3 
               
               
                   
                   
                   
                 Hz), 8.43 (1H, d, J = 2.3 Hz). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 416 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 1130   
                 R 1131   
                 mp (° C.) or  1 H NMR (DMSO-d 6 ) δppm 
               
               
                   
               
               
                 2620 
                 4-CF 3 Ph- 
                 piperonyl 
                 mp 129.0-130.5 
               
               
                 2621 
                 4-CF 3 Ph- 
                 3,4-(CH 3 O) 2 PhCH 2 — 
                 mp 130.0-132.0 
               
               
                 2622 
                 3,4-Cl 2 Ph- 
                 3,4-(CH 3 O) 2 PhCH 2 — 
                   1 H NMR 1.85-2.14(5 H, m), 3.13-3.33( 2 H, 
               
               
                   
                   
                   
                 m), 3.58-3.71(2 H, m), 3.73(3 H, s), 3.74(3 H, 
               
               
                   
                   
                   
                 s), 4.12-4.78(3 H, m), 6.73-6.94(3 H, m), 
               
               
                   
                   
                   
                 7.04(1 H, d, J = 8.6 Hz), 7.11-7.20(2 H, m), 
               
               
                   
                   
                   
                 7.25(1 H, d, J = 2.4 Hz), 7.61(1 H, d, J = 8.8 
               
               
                   
                   
                   
                 Hz), 7.71(1 H, dd, J = 2.4 Hz, 8.8 Hz), 
               
               
                   
                   
                   
                 8.11(1 H, d, J = 2.4 Hz), 8.34(1 H, dd J = 2.4 
               
               
                   
                   
                   
                 Hz, 8.8 Hz), 8.66(1 H, d, J = 2.4 Hz), 
               
               
                   
                   
                   
                 10.53(1 H, s). 
               
               
                   
               
             
          
         
       
     
       Example 2623 
     Production of 2-[4-(3-{4-[4-(3,4-dichlorobenzoylamino)-phenoxy]phenyl}propionyl)piperazin-1-yl]acetic acid hydrochloride 
       [1262]    To a solution of ethyl 2-[4-(3-{4-[4-(3,4-dichlorobenzoylamino)phenoxy]phenyl}propionyl)piperazin-1-yl]acetate (0.493° g, 0.843 mmol) in THF (5 mL) and ethanol (5 mL) were added 5 M aqueous sodium hydroxide (0.253 mL, 1.27 mmol) and water (1 mL), and the resulting solution was refluxed for 1 hour. This reaction solution was concentrated under reduced pressure, and the residue was dissolved in 50% aqueous ethanol. To the resulting solution was added 5 M hydrochloric acid (0.253 mL, 1.27 mmol), and the obtained solid was collected by filtration. To this solid was dissolved in ethanol (10 mL) and 5 M hydrochloric acid (0.3 mL) by heating. The solvent was then evaporated, and the obtained solid was recrystallized from ethanol-diethyl ether, to thereby yield 0.381 g of the title compound. 
         [1263]    Appearance: White powder 
         [1264]    Melting point: 215-218° C. 
         [1265]    The following compounds were produced in the same manner as in Example 2623. 
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 417 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 1132   
                   1 H NMR (solvent) δppm 
               
               
                   
               
               
                 2624 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (DMSO-d 6 ) 2.71-2.73(4 H, m), 3.12-3.14(4 H, m), 3.21(2 H, s), 6.91-6.98(6 H, m), 7.71(2 H, dd, J = 7.0 Hz, 2.0 Hz), 7.82(1 H, d, J = 8.0 Hz), 7.93(1 H, dd, J = 8.0 Hz, 2.0 Hz), 8.21(1 H, d, J = 2.0 Hz), 10.38(1 H, s). 
               
               
                   
               
               
                 2625 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 2.68(2 H, m), 3.05(2 H, m), 3.35(2 H, s), 3.49(2 H, m), 6.00(1 H, m), 6.98(2 H, d, J = 8.5 Hz), 7.05(2 H, d, J = 8.5 Hz), 7.35(2 H, d, J = 8.5 Hz), 7.58(2 H, d, J = 8.5 Hz), 7.58(1 H, brs), 7.77(2 H, m), 7.97(1 H, s). 
               
               
                   
               
               
                 2626 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (DMSO-d 6 ) 1.60-1.70(2 H, m), 1.85-1.90(2 H, m), 2.50(1 H, m), 2.65-2.73(2 H, m), 3.55(2 H, brd, J = 12.5 Hz), 6.90-6.98(6 H, m), 7.71(2 H, d, J = 9.0 Hz), 7.81(1 H, d, J = 8.5 Hz), 7.93(1 H, dd, J = 8.5 Hz, 2.0 Hz), 8.21(1 H, d, J = 2.0 Hz), 10.37(1 H, s), 12.20(1 H, brs). 
               
               
                   
               
               
                 2627 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (DMSO-d 6 ) 1.51-1.58(2 H, m), 1.90-1.95(2 H, m), 2.78-2.82(2 H, m), 3.43(2 H, m), 3.52(1 H, m), 3.92(2 H, s), 6.89-6.98(6 H, m), 7.70(2 H, d, J = 9.0 Hz), 7.82(1 H, d, J = 8.5 Hz), 7.93(1 H, dd, J = 8.5 Hz, 2.0 Hz), 8.21(1 H, d, J = 2.0 Hz), 10.40(1 H, s). 
               
               
                   
               
               
                 2628 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (DMSO-d 6 ) 1.59-1.66(2 H, m), 1.94-1.97(2 H, m), 2.54(3 H, s), 3.62(2 H, t, J = 11.0 Hz), 2.98(1 H, m), 3.29(2 H, s), 3.67- 3.70(2 H, m), 6.90-6.99(6 H, m), 7.71(2 H, ,d J = 9.0 Hz), 7.82(1 H, d, J = 8.5 Hz), 7.93(1 H, dd, J = 8.5 Hz, 2.0 Hz), 8.21(1 H, d, J = 2.0 Hz), 10.39(1 H, s). 
               
               
                   
               
               
                 2629 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (CDCl 3 ) 1.80-1.83(4 H, m), 2.61-2.65(3 H, m), 3.24(2 H, s), 3.25(2 H, brd, J = 11.0 Hz), 6.94(2 H, d, J = 8.5 Hz), 7.03(2 H, d, J = 9.0 Hz), 7.25(2 H, d, J = 8.5 Hz), 7.76(2 H, d, J = 9.0 Hz), 7.83(1 H, d, J = 8.5 Hz), 7.94(1 H, dd, J = 8.5 Hz, 2.0 Hz), 8.21(1 H, d, J = 2.0 Hz), 10.41(1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 418 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 1133   
                 Xb 68   
                 Xb 69   
                 M 
                   1 H NMR (DMSO-d 6 ) δppm 
               
               
                   
               
               
                 2630 
                 4-CF 3 Ph- 
                 —N(CH 3 )— 
                 none 
                 1 
                 1.20-1.45(2 H, m), 1.70-1.95(3 H, m), 
               
               
                   
                   
                   
                   
                   
                 2.20(2 H, d, J = 6.6 Hz), 2.67(2 H, t, J = 12.4 
               
               
                   
                   
                   
                   
                   
                 Hz), 3.32(3 H, s), 3.67(2 H, d, J = 12.4 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.42(1 H, d, J = 9.1 Hz), 6.99(2 H, d, J = 8.9 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.11(2 H, d, J = 8.9 Hz), 7.73(1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 9.1 Hz, 2.3 Hz), 7.90(2 H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.15(2 H, d, J = 8.2 Hz), 8.46(1 H, d, J = 2.3 
               
               
                   
                   
                   
                   
                   
                 Hz), 10.33(1 H, s). 
               
               
                 2631 
                 3.4-Cl 2 Ph- 
                 —O— 
                 —CH 2 — 
                 0 
                 1.57(2 H, brs), 1.81(2 H, brs), 2.00(2 H, brs), 
               
               
                   
                   
                   
                   
                   
                 2.23(1 H, brs), 2.77(2 H, brs), 3.44(2 H, brs), 
               
               
                   
                   
                   
                   
                   
                 7.05(1 H, d, J = 9.0 Hz), 7.07(2 H, d, J = 8.5 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.35(2 H, d, J = 8.5 Hz), 7.84(1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.5 Hz), 7.95(1 H, d, J = 8.5 Hz), 8.20(1 H, 
               
               
                   
                   
                   
                   
                   
                 dd, J = 9.0 Hz, 3.0 Hz), 8.22(1 H, d, J = 2.0 
               
               
                   
                   
                   
                   
                   
                 Hz), 8.49(1 H, d, J = 3.0 Hz), 10.56(1 H, s), 
               
               
                   
                   
                   
                   
                   
                 12.15(1 H, brs). 
               
               
                 2632 
                 3,4-Cl 2 Ph- 
                 —O— 
                 —CO— 
                 0 
                 1.52(2 H, m), 1.86(2 H, brs), 2.52(1 H, m), 
               
               
                   
                   
                   
                   
                   
                 3.10(2 H, brs), 3.65(1 H, brs), 4.31(1 H, brs), 
               
               
                   
                   
                   
                   
                   
                 7.15(1 H, d, J = 9.0 Hz), 7.16(2 H, d, J = 8.5 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.43(2 H, d, J = 8.5 Hz), 7.84(2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.5 Hz), 7.95(1 H, dd, J = 8.5 Hz, 2.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.23(1 H, d, J = 2.0 Hz), 8.24(1 H, dd, J = 9.0 
               
               
                   
                   
                   
                   
                   
                 Hz, 3.0 Hz), 8.52(1 H, d, J = 3.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 10.60(1 H, s). 
               
               
                 2633 
                 4-CF 3 Ph- 
                 —O— 
                 —CO— 
                 0 
                 1.52(2 H, m), 1.86(2 H, brs), 2.54(1 H, m), 
               
               
                   
                   
                   
                   
                   
                 3.05(2 H, brs), 3.63(1 H, brs), 4.31(1 H, brs), 
               
               
                   
                   
                   
                   
                   
                 7.15(1 H, d, J = 9.0 Hz), 7.16(2 H, d, J = 8.5 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.44(2 H, d, J = 8.5 Hz), 7.94(2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.5 Hz), 8.17(2 H, d, J = 8.5 Hz), 8.27(1 H, 
               
               
                   
                   
                   
                   
                   
                 dd, J = 9.0 Hz, 2.5 Hz), 8.55(1 H, d, J = 2.5 
               
               
                   
                   
                   
                   
                   
                 Hz), 10.67(1 H, s). 
               
               
                 2634 
                 3,4-Cl 2 Ph- 
                 —O— 
                 none 
                 0 
                 1.63-1.71(2 H, m), 1.92(2 H, brd, J = 10.0 
               
               
                   
                   
                   
                   
                   
                 Hz), 2.74(2 H, t, J = 11.5 Hz), 3.58(2 H, brd, 
               
               
                   
                   
                   
                   
                   
                 J = 12.5 Hz), 6.96( 1 H, d J = 9.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.98(4 H, s), 7.83(1 H, d,J = 8.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.94(1 H, dd, J = 8.5 Hz, 2.0 Hz), 8.14(1 H, 
               
               
                   
                   
                   
                   
                   
                 dd, J = 9.0 Hz, 2.5 Hz), 8.21(1 H, d, J = 2.0 
               
               
                   
                   
                   
                   
                   
                 Hz), 8.44(1 H, d, J = 2.5 Hz), 10.50(1 H, s), 
               
               
                   
                   
                   
                   
                   
                 12.20(1 H, brs). 
               
               
                 2635 
                 3,4-Cl 2 Ph- 
                 —O— 
                 none 
                 1 
                 1.31-1.34(2 H, m), 1.77(2 H, brd, J = 11.5 
               
               
                   
                   
                   
                   
                   
                 Hz), 2.20(2 H, t, J = 6.5 Hz), 2.64(2 H, brt, J = 
               
               
                   
                   
                   
                   
                   
                 10.5 Hz), 3.61(2 H, brd, J = 12.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.96(1 H, d, J = 9.0 Hz), 6.96(4 H, s), 7.83 
               
               
                   
                   
                   
                   
                   
                 (1 H, d, J = 8.5 Hz), 7.94(1 H, dd, J = 8.5 Hz, 
               
               
                   
                   
                   
                   
                   
                 2.0 Hz), 8.14(1 H, dd, J = 9.0 Hz, 2.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.21(1 H, d, J = 2.0 Hz), 8.44(1 H, d, J = 2.5 
               
               
                   
                   
                   
                   
                   
                 Hz), 10.50(1 H, s), 12.06(1 H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 419 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 1134   
                 Xb 70   
                 Xb 71   
                 Xb 72   
                   1 H NMR (DMSO-d 6 ) δppm 
               
               
                   
               
               
                 2636 
                 4-CF 3 Ph- 
                 —O— 
                 —CO— 
                 —CH 2 — 
                 3.30(4 H, brs), 3.77(4 H, brs), 3.99(2 H, 
               
               
                   
                   
                   
                   
                   
                 s), 7.17(1 H, d, J = 8.8 Hz), 7.21(2 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.6 Hz), 7.51(2 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.94(2 H, d, J = 8.0 Hz), 8.20(2 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 8.0 Hz), 8.29(1 H, dd, J = 8.8 Hz, 2.6 
               
               
                   
                   
                   
                   
                   
                 Hz), 8.59(1 H, d, J = 2.6 Hz), 10.79(1 H, 
               
               
                   
                   
                   
                   
                   
                 s). 
               
               
                 2637 
                 3,4-Cl 2 Ph- 
                 —O— 
                 none 
                 —CH 2 — 
                 2.71(4 H, t, J = 5.0 Hz), 3.13(2 H, s), 
               
               
                   
                   
                   
                   
                   
                 3.14(4 H, t, J = 5.0 Hz), 6.96-7.00(5 H, 
               
               
                   
                   
                   
                   
                   
                 m), 7.82(1 H, d, J = 8.5 Hz), 7.96(1 H, 
               
               
                   
                   
                   
                   
                   
                 dd, J = 8.5 Hz, 2.0 Hz), 8.16(1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 9.0 Hz, 2.5 Hz), 8.24(1 H, d, J = 2.0 
               
               
                   
                   
                   
                   
                   
                 Hz), 8.37(1 H, s) ,8.46(1 H, d, J = 2.5 
               
               
                   
                   
                   
                   
                   
                 Hz), 10.62(1 H, brs). 
               
               
                 2638 
                 4-CF 3 Ph- 
                 —N(CH 3 )— 
                 none 
                 —CH 2 — 
                 2.64(4 H, brs), 2.95(2 H, s), 3.15(4 H, 
               
               
                   
                   
                   
                   
                   
                 brs), 3.33(3 H, s), 6.42(1 H, d, J = 9.1 
               
               
                   
                   
                   
                   
                   
                 Hz), 6.99(2 H, d, J = 8.9 Hz), 7.13(2 H, 
               
               
                   
                   
                   
                   
                   
                 d, J = 8.9 Hz), 7.75(1 H, dd, J = 9.1 Hz, 
               
               
                   
                   
                   
                   
                   
                 2.5 Hz), 7.89(2 H, d, J = 8.2 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.17(2 H, d, J = 8.2 Hz), 8.49(1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 2.5 Hz), 10.46(1 H, s). 
               
               
                 2639 
                 4-CF 3 Ph- 
                 —O— 
                 none 
                 —CH 2 — 
                 2.72(4 H, t, J = 5.0 Hz), 3.15(4 H, t, J = 
               
               
                   
                   
                   
                   
                   
                 5.0 Hz), 3.20(2 H, s), 6.96-7.01(5 H, 
               
               
                   
                   
                   
                   
                   
                 m), 7.93(2 H, d, J = 8.5 Hz), 8.16(2 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.5 Hz), 8.18(1 H, dd, J = 8.0 Hz, 2.5 
               
               
                   
                   
                   
                   
                   
                 Hz), 8.46(1 H, d, J = 2.5 Hz), 10.60(1 H, 
               
               
                   
                   
                   
                   
                   
                 s). 
               
               
                 2640 
                 3,4-Cl 2 Ph- 
                 —O— 
                 none 
                 —CO— 
                 3.13(2 H, brs), 3.17(2 H, s), 3.48(2 H, 
               
               
                   
                   
                   
                   
                   
                 brs), 3.71(2 H, brs), 7.12(1 H, d, J = 8.9 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.15(2 H, dd, J = 6.8 Hz, 2.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.36(2 H, dd, J = 6.8 Hz, 2.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.84(1 H, d, J = 8.4 Hz), 7.95(1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 8.4 Hz, 2.1 Hz), 8.22(1 H, dd, J = 8.9 
               
               
                   
                   
                   
                   
                   
                 Hz, 2.7 Hz), 8.23(1 H, d, J = 2.1 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.49(1 H, d, J = 2.7 Hz), 10.58(1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 420 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                   1 H NMR (solvent) 
               
               
                 No. 
                 R 1135   
                 Xb 73   
                 Xb 74   
                 Xb 75   
                 R 1136   
                 δppm 
               
               
                   
               
               
                 2641 
                 4-CF 3 PhCO— 
                 none 
                 none 
                 none 
                 benzyl 
                 (CD 3 OD) 3.47(8 H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs), 4.43(2 H, s), 6.96 
               
               
                   
                   
                   
                   
                   
                   
                 (1 H, d, J = 8.9 Hz), 
               
               
                   
                   
                   
                   
                   
                   
                 7.14(1 H, d, J = 8.9 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.30(1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.9 Hz, 3.0 Hz), 7.51- 
               
               
                   
                   
                   
                   
                   
                   
                 7.59(6 H, m), 7.82(2 H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 8.3 Hz), 8.12- 
               
               
                   
                   
                   
                   
                   
                   
                 8.18(3 H, m), 8.36(1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 d, J = 2.5 Hz). 
               
               
                 2642 
                 3,4-Cl 2 PhSO 2 — 
                 —N(C 2 H 5 )— 
                 —CH 2 — 
                 —CO— 
                 piperonyl 
                 (DMSO-d 6 ) 1.11(3 H, t, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 7.0 Hz), 2.20-2.45 
               
               
                   
                   
                   
                   
                   
                   
                 (4 H, m), 3.30-3.55(8 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 4.22(2 H, s), 5.99 
               
               
                   
                   
                   
                   
                   
                   
                 (2 H, s), 6.70-7.00(7 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 7.40-7.50(1 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.55-7.60(1 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.66(1 H, d, J = 2.7 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.84(1 H,d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 8.4 Hz), 7.88(1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 2.1 Hz), 01.27(1 H, 
               
               
                   
                   
                   
                   
                   
                   
                 brs), 12.51(1 H, brs). 
               
               
                 2643 
                 3,4-Cl 2 PhNHCO— 
                 —N(C 2 H 5 )— 
                 —CH 2 — 
                 —CO— 
                 piperonyl 
                 (DMSO-d 6 ) 1.13(3 H, t, 
               
               
                   
                   
                   
                   
                   
                   
                 J = 7.0 Hz), 2.20-2.50 
               
               
                   
                   
                   
                   
                   
                   
                 (4 H, m), 3.30-3.60(8 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 4.21(2 H, s), 5.99 
               
               
                   
                   
                   
                   
                   
                   
                 (2 H, s), 6.60-7.05(7 H, 
               
               
                   
                   
                   
                   
                   
                   
                 m), 7.30-7.40(1 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.47(1 H, d, J = 8.8 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 7.65-7.85(1 H, m), 
               
               
                   
                   
                   
                   
                   
                   
                 7.90(1 H, d, J = 2.3 
               
               
                   
                   
                   
                   
                   
                   
                 Hz), 8.06(1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                   
                 2.6 Hz), 9.80(2 H, brs), 
               
               
                   
                   
                   
                   
                   
                   
                 12.40(1 H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 421 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 1137   
                 R 1138   
                 R 1139   
                 R 1140   
                   1 H NMR (solvent) δppm 
               
               
                   
               
               
                 2644 
                 3,4-Cl 2 Ph- 
                 —H 
                 —H 
                 —COOH 
                 (CDCl 3 ) 1.80(1 H, m), 1.86-1.94(3 H, 
               
               
                   
                   
                   
                   
                   
                 m), 2.82(1 H, m), 3.14(2 H, m), 3.32 
               
               
                   
                   
                   
                   
                   
                 (2 H, m), 6.94(1 H, d, J = 9.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.06(4 H, s), 7.57(1 H, d, J = 8.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.72(1 H, d, J = 8.5 Hz), 7.93(1 H, 
               
               
                   
                   
                   
                   
                   
                 brs), 7.99(1 H, s), 8.18(1 H, brd, J = 
               
               
                   
                   
                   
                   
                   
                 9.0 Hz), 8.26(1 H, d, J = 2.5 Hz). 
               
               
                 2645 
                 4-CF 3 Ph- 
                 —H 
                 —CH 2 COOH 
                 —H 
                 (CDCl 3 ) 1.44-1.50(2 H, m), 1.90(2 H, 
               
               
                   
                   
                   
                   
                   
                 brd, J = 13.5 Hz), 1.94(1 H, m), 2.36 
               
               
                   
                   
                   
                   
                   
                 (2 H, d, J = 7.0 Hz), 2.75(2 H, dt, J = 
               
               
                   
                   
                   
                   
                   
                 2.5 Hz, 12.0 Hz), 3.63(2 H, brd, J = 
               
               
                   
                   
                   
                   
                   
                 12.0 Hz), 6.92(1 H, d, J = 9.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.97(2 H, d, J = 9.0 Hz), 7.04(2 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 9.0 Hz), 7.72(1 H, s), 7.78(2 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 8.0 Hz), 7.99(2 H, d, J = 8.0 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.19(1 H, dd, J = 9.0 Hz, 2.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.25(1 H, d, J = 2.5 Hz). 
               
               
                 2646 
                 3-CF 3 Ph- 
                 —H 
                 —CH 2 COOH 
                 —H 
                 (CDCl 3 ) 1.46-1.49(2 H, m), 1.89(2 H, 
               
               
                   
                   
                   
                   
                   
                 brd,J &#39;2 15.0 Hz), 1.95(1 H, m), 
               
               
                   
                   
                   
                   
                   
                 2.3692 H, d, J = 7.0 Hz), 2.74(2 H, dt, 
               
               
                   
                   
                   
                   
                   
                 J = 2.0 Hz, 12.0 Hz), 3.63(2 H, brd, 
               
               
                   
                   
                   
                   
                   
                 J = 12.0 Hz), 6.92(1 H, d, J = 9.0 
               
               
                   
                   
                   
                   
                   
                 Hz), 6.97(2 H, d, J = 9.0 Hz), 7.05 
               
               
                   
                   
                   
                   
                   
                 (2 H, d, J = 9.0 Hz), 7.66(1 H, t, J = 
               
               
                   
                   
                   
                   
                   
                 7.5 Hz), 7.73(2 H, brs), 7.84(1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 7.5 Hz), 8.07(1 H, d, J = 7.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.14(1 H, brs), 8.17(1 H, dd, J = 9.0 
               
               
                   
                   
                   
                   
                   
                 Hz, 2.5 Hz), 8.27(1 H, d, J = 2.5 Hz). 
               
               
                 2647 
                 4-CF 3 Ph- 
                 —OCH 3   
                 —CH 2 COOH 
                 —H 
                 (DMSO-d 6 ) 1.31-1.36(2 H, m), 1.77- 
               
               
                   
                   
                   
                   
                   
                 1.81(3 H, m), 2.21(2 H, d, J = 7.4 
               
               
                   
                   
                   
                   
                   
                 Hz), 2.68-2.75(2 H, m), 3.64(2 H, 
               
               
                   
                   
                   
                   
                   
                 brs), 3.68(3 H, s), 6.52(1 H, brs), 
               
               
                   
                   
                   
                   
                   
                 6.68(1 H, brs), 6.89-6.96(2 H, m), 
               
               
                   
                   
                   
                   
                   
                 7.92(2 H, d, J = 8.4 Hz), 8.09- 
               
               
                   
                   
                   
                   
                   
                 8.17(3 H, m), 8.38(1 H, d, J = 2.5 
               
               
                   
                   
                   
                   
                   
                 Hz), 10.54(1 H, s), 12.10(1 H, brs). 
               
               
                 2648 
                 4-CF 3 Ph- 
                 —H 
                 —COOH 
                 —H 
                 (CDCl 3  + CD 3 OD) 1.82-1.96(2 H, m), 
               
               
                   
                   
                   
                   
                   
                 2.04-2.09(2 H, m), 2.38-2.48(1 H, 
               
               
                   
                   
                   
                   
                   
                 m), 2.74-2.84(2 H, m), 3.52-3.61(2 H, 
               
               
                   
                   
                   
                   
                   
                 m), 6.86(1 H, dd, J = 8.9 Hz, 0.5 
               
               
                   
                   
                   
                   
                   
                 Hz), 6.96-7.05(4 H, m), 7.69- 
               
               
                   
                   
                   
                   
                   
                 7.76(2 H, m), 8.06(2 H, d, J = 8.1 
               
               
                   
                   
                   
                   
                   
                 Hz), 8.16(1 H, d, J = 8.1 Hz), 8.23- 
               
               
                   
                   
                   
                   
                   
                 8.33(2 H, m). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 422 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 1141   
                 R 1142   
                   1 H NMR (DMSO-d 6 ) δppm 
               
               
                   
               
               
                 2649 
                 4-CF 3 Ph- 
                 —CH 3   
                 1.41(2 H, brs), 1.84-1.96(3 H, m), 1.97(3 H, s), 2.22(2 H, d, J = 
               
               
                   
                   
                   
                 6.6 Hz), 2.55-2.75(2 H, m), 3.58(2 H, d, J = 11.9 Hz), 6.72- 
               
               
                   
                   
                   
                 7.11(4 H, m), 7.52(1 H, dd, J = 8.9 Hz, 2.8 Hz), 7.74(1 H, d, J = 
               
               
                   
                   
                   
                 2.6 Hz), 7.89-7.99(4 H, m), 10.49(1 H, s), 12.14(1 H, brs). 
               
               
                 2650 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 1.38(2 H, brs), 1.82-1.96(3 H, m), 1.97(3 H, s), 2.22(2 H, d, J = 
               
               
                   
                   
                   
                 6.4 Hz), 2.55-2.75(2 H, m), 3.59(2 H, d, J = 11.9 Hz), 6.88- 
               
               
                   
                   
                   
                 6.91(4 H, m), 7.51(1 H, dd, J = 8.7 Hz, 2.5 Hz), 7.63(1 H, dd, J = 
               
               
                   
                   
                   
                 8.4 Hz, 2.1 Hz), 7.74(1 H, d, J = 2.8 Hz), 7.83-7.87(2 H, m), 
               
               
                   
                   
                   
                 10.38(1 H, s), 12.12(1 H, brs). 
               
               
                 2651 
                 3.4-Cl 2 Ph- 
                 —H 
                 1.30-1.37(2 H, m), 1.75-1.91(3 H, m), 2.20(2 H, d, J = 6.9 Hz), 
               
               
                   
                   
                   
                 2.51-2.62(2 H, m), 3.60(2 H, d, J = 12.0 Hz), 6.87-6.94(5 H, 
               
               
                   
                   
                   
                 m), 7.50(1 H, dd, J = 8.7 Hz, 2.8 Hz), 7.62(1 H, dd, J = 8.6 
               
               
                   
                   
                   
                 Hz, 2.3 Hz), 7.77(1 H, d, J = 2.8 Hz), 7.84-7.89(2 H, m), 
               
               
                   
                   
                   
                 10.39(1 H, s), 12.09(1 H, brs). 
               
               
                 2652 
                 4-CF 3 Ph- 
                 —H 
                 1.29-1.33(2 H, m), 1.74-1.91(3 H, m), 2.19(2 H, d, J = 6.8 Hz), 
               
               
                   
                   
                   
                 2.63-2.75(2 H, m), 3.59(2 H, d, J = 12.2 Hz), 6.86-6.93(5 H, 
               
               
                   
                   
                   
                 m), 7.50(1 H, dd, J = 8.9 Hz, 2.8 Hz), 7.77(1 H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                 7.89-7.99(4 H, m), 10.47(1 H, s), 12.09(1 H, brs). 
               
               
                 2653 
                 4-CF 3 Ph- 
                 —OCH 3   
                 1.41(2 H, brs), 1.81-1.85(3 H, m), 2.25(2 H, d, J = 6.4 Hz), 
               
               
                   
                   
                   
                 2.55-2.79(2 H, m), 3.64(3 H, s), 3.68(2 H, brs), 6.73-6.95(4 H, 
               
               
                   
                   
                   
                 m), 7.51(1 H, dd, J = 8.7 Hz, 2.5 Hz), 7.73(1 H, d, J = 2.6 Hz), 
               
               
                   
                   
                   
                 7.92-8.02(4 H, m), 10.45(1 H, s), 12.14(1 H, brs). 
               
               
                 2654 
                 3,4-Cl 2 Ph- 
                 —OCH 3   
                 1.42(2 H, brs), 1.79-1.91(3 H, m), 2.23(2 H, d, J = 6.6 Hz), 
               
               
                   
                   
                   
                 2.76-2.83(2 H, m), 3.63(5 H, brs), 6.63-6.98(4 H, m), 7.48(1 H, 
               
               
                   
                   
                   
                 dd, J = 8.7 Hz, 2.6 Hz), 7.63(1 H, dd, J = 8.4 Hz, 2.0 Hz), 
               
               
                   
                   
                   
                 7.71(1 H, d, J = 2.8 Hz), 7.85-7.88(2 H, m), 10.36(1 H, s), 
               
               
                   
                   
                   
                 12.33(1 H, brs). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 423 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 1143   
                 R 1144   
                   1 H NMR (DMSO-d 6 ) δppm 
               
               
                   
               
               
                 2655 
                 4-CF 3 Ph- 
                 —CH 3   
                 1.81-1.99(4 H, m), 2.00(3 H, s), 2.41-2.44(1 H, m), 2.75(2 H, 
               
               
                   
                   
                   
                 brs), 3.58(2 H, d, J = 12.2 Hz), 6.91-7.20(4 H, m), 7.53(1 H, 
               
               
                   
                   
                   
                 dd, J = 8.9 Hz, 2.6 Hz), 7.75(1 H, d, J = 2.6 Hz), 7.90- 
               
               
                   
                   
                   
                 7.99(4 H, m), 10.52(1 H, s), 12.41(1 H, brs). 
               
               
                 2656 
                 3,4-Cl 2 Ph- 
                 —CH 3   
                 1.63-1.71(2 H, m), 1.91-1.94(2 H, m), 1.95(3 H, s), 2.41- 
               
               
                   
                   
                   
                 2.48(1 H, m), 2.75-2.80(2 H, m), 3.58(2 H, d, J = 12.9 Hz), 
               
               
                   
                   
                   
                 6.85-6.89(3 H, m), 7.50(1 H, dd, J = 8.7 Hz, 2.6 Hz), 7.68- 
               
               
                   
                   
                   
                 7.79(2 H, m), 7.81-7.98(4 H, m), 10.43(1 H, s), 12.35(1 H, 
               
               
                   
                   
                   
                 brs). 
               
               
                 2657 
                 3,4-Cl 2 Ph- 
                 —H 
                 1.74(2 H, brs), 1.93-1.98(2 H, m), 2.49-2.51(2 H, m), 
               
               
                   
                   
                   
                 2.88(1 H, brs), 3.55-3.60(2 H, m), 6.90-7.01(5 H, m), 7.50- 
               
               
                   
                   
                   
                 7.89(5 H, m), 10.41(1 H, s), 12.13(1 H, brs). 
               
               
                 2658 
                 4-CF 3 Ph- 
                 —H 
                 1.66-1.71(2 H, m), 1.88-1.92(2 H, m), 2.34-2.42(1 H, m), 
               
               
                   
                   
                   
                 2.68-2.76(2 H, m), 3.56(2 H, d, J = 12.4 Hz), 6.85-6.92(5 H, 
               
               
                   
                   
                   
                 m), 7.48(1 H, d, J = 2.8 Hz), 7.51(1 H, d, J = 2.8 Hz), 7.77- 
               
               
                   
                   
                   
                 7.99(4 H, m), 10.47(1 H, s), 12.21(1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 424 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 1145   
                 R 1146   
                   1 H NMR (DMSO-d 6 ) δppm 
               
               
                   
               
               
                 2659 
                 —H 
                 —CH 2 COOH 
                 1.26-1.32(2 H, m), 1.74-1.91(3 H, m), 2.20(2 H, d, J = 6.6 
               
               
                   
                   
                   
                 Hz), 2.66(2 H, t, J = 11.0 H), 3.63(2 H, d, J = 12.5 Hz), 
               
               
                   
                   
                   
                 6.93-7.03(4 H, m), 7.13-7.35(2 H, m), 7.65(2 H, d, J = 8.6 
               
               
                   
                   
                   
                 Hz), 8.42(1 H, d, J = 2.3 Hz), 8.47(1 H, d, J = 2.3 Hz), 
               
               
                   
                   
                   
                 11.00(1 H, s), 12.07(1 H, brs). 
               
               
                 2660 
                 —CH 3   
                 —CH 2 COOH 
                 1.30-1.41(2 H, m), 1.80-2.00(3 H, m), 1.99(3 H, s), 2.20(2 H, 
               
               
                   
                   
                   
                 d, J = 6.6 Hz), 2.68-2.76(2 H, m), 3.62(2 H, d, J = 12.2 Hz), 
               
               
                   
                   
                   
                 6.88-6.96(3 H, m), 7.33(2 H, d, J = 8.2 Hz), 7.65(2 H, d, J = 
               
               
                   
                   
                   
                 8.6 Hz), 8.44(2 H, s), 11.00(1 H, s), 12.10(1 H, brs). 
               
               
                 2661 
                 —H 
                 —COOH 
                 1.63-1.70(2 H, m), 1.88-1.92(2 H, m), 2.41-2.45(1 H, m), 
               
               
                   
                   
                   
                 2.71-2.79(2 H, m), 3.61(2 H, d, J = 12.5 Hz), 6.93-7.00(4 H, 
               
               
                   
                   
                   
                 m), 7.31(2 H, d, J = 8.6 Hz), 7.63(2 H, d, J = 8.7 Hz), 8.40- 
               
               
                   
                   
                   
                 8.47(2 H, m), 10.63(1 H, s), 12.21(1 H, s). 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 425 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
               
               
                 No. 
                 R 1147   
                   1 H NMR (DMSO-d 6 ) δppm 
               
               
                   
               
               
                 2662 
                 4-CF 3 PhCO— 
                 2.08(3 H, s), 2.09-2.32(2 H, m), 3.65-3.93(4 H, m), 7.01(1 H, d, J = 
               
               
                   
                   
                 8.6 Hz), 7.06(1 H, d, J = 8.9 Hz), 7.19(1 H, dd, J = 2.6 Hz, 8.6 Hz), 
               
               
                   
                   
                 7.29(1 H, d, J = 2.6 Hz), 7.42-7.51(2 H, m), 7.81-7.98(4 H, m), 
               
               
                   
                   
                 8.10-8.18(2 H, m), 8.21(1 H, dd, J = 2.6 Hz, 8.9 Hz), 8.43(1 H, d, J = 
               
               
                   
                   
                 2.6 Hz), 10.60(1 H, s), 12.60-12.91(1 H, m). 
               
               
                 2663 
                 3,4-Cl 2 PhSO 2 — 
                 1.99(3 H, s), 2.07-2.31(2 H, m), 3.60-3.91(4 H, m), 6.97(1 H, d, J = 
               
               
                   
                   
                 8.5 Hz), 6.98(1 H, d, J = 8.8 Hz), 7.16(1 H, dd, J = 2.4 Hz, 8.5 Hz), 
               
               
                   
                   
                 7.25(1 H, d, J = 2.2 Hz), 7.40-7.51(2 H, m), 7.54(1 H, dd, J = 2.8 
               
               
                   
                   
                 Hz, 8.8 Hz), 7.62(1 H, dd, J = 2.2 Hz, 8.5 Hz), 7.75(1 H, d, J = 2.8 
               
               
                   
                   
                 Hz), 7.79-7.93(4 H, m). 
               
               
                   
               
             
          
         
       
     
       Example 2664 
     Production of (4-{5-[(4-trifluoromethylphenylamino)-methyl]-pyridin-2-yloxy}phenyl)(4-piperonylpiperazin-1-yl)methanone 
       [1266]    Methanesulfonic acid 6-[4-(4-piperonylpiperazine-1-carbonyl)phenoxy]pyridin-3-yl ester (0.433 g, 0.824 mmol) and 4-trifluoromethyl phenylamine (0.310 mL, 2.47 mmol) were mixed together, and the resulting mixture was stirred for 2 hours at 100° C. The formed yellow mass was stirred together with a saturated sodium bicarbonate solution, ethyl acetate and THF (20 ml of each). The organic layer was collected, washed with brine, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane:methanol=50:1), to thereby yield 0.236 g of the title compound. 
         [1267]    Appearance: Pale yellow amorphous powder 
         [1268]      1 H NMR (CDCl 3 ) δ 2.44 (4H, brs), 3.45 (2H, s), 3.57 (2H, brs), 3.75 (2H, brs), 4.30-4.35 (1H, m), 4.36 (2H, s), 5.95 (2H, s), 6.63 (2H, d, J=8.7 Hz), 6.74-6.77 (2H, m), 6.85 (1H, s), 6.93 (1H, d, J=8.4 Hz), 7.15 (2H, d, J=8.4 Hz), 7.39-7.47 (4H, m), 7.71 (1H, dd, J=2.5 Hz, 8.4 Hz), 8.18 (1H, d, J=2.3 Hz). 
         [1269]    The following compounds were produced in the same manner as in Example 2664. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 426 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
               
               
                 No. 
                 R 1148   
                 Xb 76   
                 Xb 77   
                 Form 
                   1 NMR (solvent) δppm 
               
               
                   
               
               
                 2665 
                 3,4-Cl 2 Ph- 
                 —N(CH 3 )— 
                 —CH 2 — 
                 free 
                 (CDCl 3 ) 2.42-2.44(4 H, m), 3.03(3 H, s), 
               
               
                   
                   
                   
                   
                   
                 3.43(2 H, brs), 3.49-3.50(2 H, m), 
               
               
                   
                   
                   
                   
                   
                 3.63(2 H, brs), 4.08(2 H, s), 4.94(2 H, s), 
               
               
                   
                   
                   
                   
                   
                 5.94(2 H, s), 6.70(2 H, d, J = 9.2 Hz), 
               
               
                   
                   
                   
                   
                   
                 6.74(2 H, brs), 6.80(1 H, dd, J = 8.9 Hz, 
               
               
                   
                   
                   
                   
                   
                 2.8 Hz), 6.83-6.86(2 H, m), 7.01(2 H, d, 
               
               
                   
                   
                   
                   
                   
                 J = 9.1 Hz), 7.05(1 H, d, J = 2.8 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.32(1 H, d, J = 8.9 Hz), 7.86(1 H, dd, J = 
               
               
                   
                   
                   
                   
                   
                 8.6 Hz, 2.5 Hz), 8.19(1 H, d, J = 1.8 
               
               
                   
                   
                   
                   
                   
                 Hz). 
               
               
                 2666 
                 4-CF 3 Ph- 
                 —N(CH 3 )— 
                 —CH 2 — 
                 free 
                 (CDCl 3 ) 2.41-2.44(4 H, m), 3.03(3 H, s), 
               
               
                   
                   
                   
                   
                   
                 3.43(2 H, brs), 3.49(2 H, brs), 3.63(2 H, 
               
               
                   
                   
                   
                   
                   
                 brs), .408(2 H, s), 5.02(2 H, s), 5.95(2 H, 
               
               
                   
                   
                   
                   
                   
                 s), 6.69-6.74(4 H, m), 6.85-6.88(2 H, m), 
               
               
                   
                   
                   
                   
                   
                 7.00-7.03(4 H, m), 7.56(2 H, d, J = 8.6 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.72(1 H, dd, J = 8.6 Hz, 2.5 Hz), 
               
               
                   
                   
                   
                   
                   
                 8.22(1 H, d, J = 2.3 Hz). 
               
               
                 2667 
                 4-CF 3 Ph- 
                 none 
                 none 
                 hydro- 
                 (DMSO-d 6 ) 3.10-3.42( 8 H, m), 4.24(2 H, 
               
               
                   
                   
                   
                   
                 chloride 
                 brs), 5.20(2 H, s), 6.07(2 H, s), 6.97- 
               
               
                   
                   
                   
                   
                   
                 7.04(2 H, m), 7.15(1 H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                   
                 7.21-7.24(5 H, m), 7.52(2 H, d, J = 8.6 
               
               
                   
                   
                   
                   
                   
                 Hz), 7.68(2 H, d, J = 8.7 Hz), 8.01(1 H, 
               
               
                   
                   
                   
                   
                   
                 dd, J = 2.5 Hz, 8.4 Hz), 8.29(1 H, d, J = 
               
               
                   
                   
                   
                   
                   
                 2.3 Hz), 11.00(1 H, brs). 
               
               
                   
               
             
          
         
       
     
       Example 2668 
     Production of 2-(methyl-{4-[5-(5-trifluoromethyl-pyridin-2-yloxymethyl)pyridin-2-yloxy]phenyl}amino)-1-(4-piperonylpiperazin-1-yl)ethanone 
       [1270]    2-{[4-(5-hydroxymethylpyridin-2-yloxy)phenyl]methylamino}-1-(4-piperonylpiperazin-1-yl)ethanone (0.98 g, 2.0 mmol) was dissolved in DMF (30 mL). To the resulting solution was added 60% sodium hydride (60%, 88 mg, 2.2 mmol) under ice cooling, and this solution was stirred for 30 minutes at 0° C. To the reaction solution was added 2-chloro-5-(trifluoromethyl)pyridine (0.36 g, 2.0 mol), and this solution was stirred under a nitrogen atmosphere for 3 hours at 60° C. The resulting reaction solution was concentrated under reduced pressure. To the residue was added ethyl acetate, and this solution was washed with water and brine. The organic layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatography (n-hexane ethyl acetate=1:5), to thereby yield 0.68 g of the title compound. 
         [1271]    Appearance: White powder 
         [1272]      1 H NMR (CDCl 3 ) δ 2.41-2.44 (4H, m), 3.02 (3H, s), 3.43 (2H, s), 3.48 (2H, brs), 3.63 (2H, brs), 4.08 (2H, s), 5.37 (2H, s), 5.94 (2H, s), 6.68-6.77 (4H, m), 6.81-6.84 (3H, m), 7.00 (2H, d, J=9.1 Hz), 7.72-7.79 (2H, m), 8.27 (1H, d, J=2.3 Hz), 8.44 (1H, brs). 
         [1273]    The following compounds were produced in the same manner as in Example 2668. 
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 427 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example No. 
                 R 1149   
                 mp (° C.) 
               
               
                   
               
               
                 2669 
                 4-CF 3 Ph- 
                 165.0-166.0 
               
               
                 2670 
                 3-CF 3 Ph- 
                 163.0-165.0 
               
               
                 2671 
                 3,4-Cl 2 Ph- 
                 160.0-161.5 
               
               
                   
               
             
          
         
       
     
       Example 2672 
     3,4-dichloro-N-{6-[4-(3,5-dioxoisoxazolidine-4-ylidenemethyl)phenoxy]pyridin-3-yl}benzamide 
       [1274]    To a solution of hydroxylamine hydrochloride (500 mg, 1.0 mmol) in water (0.2 mL) were added sodium carbonate (1.05 g, 9.91 mmol) and a solution of 2-{4-[5-(3,4-dichlorobenzoylamino)pyridin-2-yloxy]benzylidene}malonic acid dimethyl ester (500 mg, 1.0 mmol) in THF (5 mL). To the resulting solution was subsequently added methanol (5 mL) and stirred for 8 hours at 60° C. The reaction solution was concentrated under reduced pressure. Water was added to the residue, and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatography (dichloromethane:methanol=30:1). To the resulting white precipitate was added ethyl acetate, filtered, and the filtrate was washed with diethyl ether, to thereby yield 105 mg of the title compound. 
         [1275]    Appearance: White powder 
         [1276]      1 H NMR (DMSO-d 6 ) δ 7.12 (1H, d, J=8.9 Hz), 7.14 (2H, d, J=8.8 Hz), 7.63 (2H, d, J=8.8 Hz), 7.84 (1H, d, J=58.4 Hz), 7.95 (1H, dd, J=8.4 Hz, 2.0 Hz), 8.15 (1H, s), 8.22 (1H, dd, J=8.9 Hz, 2.6 Hz), 8.22 (1H, d, J=2.0 Hz), 8.51 (1H, d, J=2.6 Hz), 10.57 (1H, s), 11.16 (1H, s). 
       Example 2673 
     Production of 3,4-dichloro-N-{6-[4-(5-methyl-[1,2,4]oxadiazol-3-ylmethyl)phenoxy]pyridin-3-yl}benzamide monohydrochloride 
       [1277]    To 3,4-dichloro-N-{6-[4-(N-acetoxycarbamimidoylmethyl)phenoxy]pyridin-3-yl}benzamide (340 mg, 0.788 mmol) was added acetic acid (4 mL), and the resulting solution was stirred under reflux for 10 minutes. This reaction solution was concentrated under reduced pressure. To the residue was added a saturated sodium bicarbonate solution, and the resulting solution was extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatography (chloroform:methanol=40:1), and the obtained reside was dissolved in ethyl acetate (5 mL). To this solution was added a solution of 4 N hydrogen chloride in ethyl acetate until the compound no longer precipitated out. The obtained white powder was filtered, and washed with diethyl ether, to thereby yield 154 mg of the title compound. 
         [1278]    Appearance: White powder 
         [1279]      1 H NMR (DMSO-d 6 ) δ 2.55 (3H, s), 4.05 (2H, s), 7.07 (1H, d, J=8.7 Hz), 7.07 (2H, d, J=8.6 Hz), 7.33 (2H, d, J=8.6 Hz), 7.83 (1H, d, J=8.4 Hz), 7.96 (1H, dd, J=8.4 Hz, 2.0 Hz), 8.21 (1H, dd, J=8.7 Hz, 2.6 Hz), 8.24 (1H, d, J=2.0 Hz), 8.48 (1H, d, J=2.6 Hz), 10.62 (1H, s). 
       Example 2674 
     Production of 1-(3-{4-[5-(3,4-dichlorobenzoylamino)-2-pyridylmethyl]phenyl}propionyl)-4-piperonylpiperazine monohydrochloride 
       [1280]    To a solution of ethyl 3-(4-{5-[bis(3,4-dichlorobenzoyl)amino]-2-pyridylmethyl}phenyl)propionate (177 mg, 0.281 mmol) in THF (5 mL) and ethanol (5 mL) were added 5 M aqueous sodium hydroxide (0.0929 mL, 0.463 mmol) and water (1 mL), and the resulting solution was refluxed for 1 hour. To this reaction solution was added 5 M hydrochloric acid (0.12 mL), and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was dissolved in DMF (3 mL), and to the resulting solution were then added 1-piperonylpiperazine (102 mg, 0.463 mmol), triethylamine (0.137 mL, 0.983 mmol) and diethyl cyanophosphonate (0.0703 mL, 463 mmol), and stirred for 1.5 hours at room temperature. Water was added to the resulting reaction solution, and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatography (dichloromethane:methanol=70:1→40:1→20:1), to thereby yield 44.1 mg of a free form. This free form was dissolved in ethanol (5 mL) and 5 M hydrochloric acid (0.03 mL) by heating. The solvent was then evaporated, and the obtained solid was recrystallized from water-containing isopropanol, to thereby yield 19.6 mg of the title compound. 
         [1281]    Appearance: Pale yellow powder 
         [1282]    Melting point: 181-183° C. 
       Example 2675 
     Production of N-(6-{4-[4-(5-oxo-4,5-dihydro-[1,3,4]oxadiazole-2-ylmethyl)piperazine-1-carbonyl]-phenoxy}pyridin-3-yl)-4-trifluoromethylbenzamide monooxalate 
       [1283]    To a suspension of N-{6-[4-(4-hydrazinocarbonylmethylpiperazine-1-carbonyl)phenoxy]pyridin-3-yl}-4-trifluoromethylbenzamide trihydrochloride (300 mg, 0.46 mmol) in THF (7 mL) was added triethylamine (0.29 mL, 2.08 mmol), and the resulting solution was stirred for 10 minutes at room temperature. To the solution was added N,N′-carbonyldiimidazole (97 mg, 0.60 mmol) under ice cooling, and the resulting solution was stirred for 1 hour at room temperature. The reaction solution was concentrated under reduced pressure. To the residue was added a saturated sodium bicarbonate solution, and extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was then purified by silica gel column chromatography (chloroform methanol=15:1). The obtained residue was dissolved in ethanol, and to the resulting solution was added oxalic acid. Ethanol was evaporated under reduced pressure, after which the solidified white substance was filtered, and washed with diethyl ether, to thereby yield 140 mg of the title compound. 
         [1284]    Appearance: White powder 
         [1285]      1 H NMR (DMSO-d 6 ) δ 2.31-2.69 (4H, m), 3.53 (2H, s), 3.53 (4H, brs), 7.16 (1H, d, J=8.9 Hz), 7.17 (2H, d, J=8.5 Hz), 7.45 (2H, d, J=8.5 Hz), 7.94 (2H, d, J=8.1 Hz), 8.17 (2H, d, J=8.1 Hz), 8.26 (1H, dd, J=8.9 Hz, 2.7 Hz), 8.55 (1H, d, J=2.7 Hz), 10.67 (1H, s), 12.27 (1H, s). 
       Example 2676 
     Production of 4-(4-{4-[4-(3,4-dichlorobenzoylamino)-2-fluorophenoxy]phenyl}-4-hydroxybutyryl)morpholine 
       [1286]    To a suspension of 4-(4-{4-[4-(3,4-dichlorobenzoylamino)-2-fluorophenoxy]phenyl}-4-oxobutyryl)morpholine (1.00 g, 1.83 mmol) in THF (20 mL) and methanol (5 mL) was added sodium borohydride (0.0694 g, 1.83 mmol), and the resulting solution was stirred for 1 hour at room temperature. To this reaction solution were added water and saturated aqueous ammonium chloride, and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by silica gel column chromatography (dichloromethane:methanol=30:1). The obtained solid was recrystallized from water-containing isopropanol, to thereby yield 0.850 g of the title compound. 
         [1287]    Appearance: White powder 
         [1288]    Melting point: 108-111° C. 
         [1289]    The following compounds were produced in the same manner as in Example 2676. 
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 428 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 1150   
                 Form 
                 mp (° C.) 
               
               
                   
               
               
                 2677 
                 morpholino 
                 free 
                 142-145 
               
               
                   
               
               
                 2678 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                 150-152 
               
               
                   
               
               
                 2679 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 hydro- chloride 
                 197-199 
               
               
                   
               
               
                 2680 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 hydro- chloride 
                 222-225 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 429 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
               
               
                 No. 
                 Xb 78   
                 R 1151   
                 Form 
                 mp (° C.) or  1 H NMR 
               
               
                   
               
               
                 2681 
                 —O— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 free 
                   1 H NMR (DMSO-d 6 ) δ 2.38- 2.54(6 H, m), 3.58(4 H, t, J = 4.5 Hz), 4.73-4.77(1 H, m), 5.06(1 H, d, J = 3.8 Hz), 7.04-7.07(3 H, m), 7.38(2 H, d, J = 8.4 Hz), 7.84(1 H, d, J = 8.4 Hz), 7.95(1 H, dd, J = 8.4 Hz, 1.2 Hz), 8.22(1 H, d, J = 2.0 Hz), 8.19(1 H, dd, J = 8.9 Hz, 2.8 Hz), 8.48(1 H, d, J = 2.6 Hz), 10.55(1 H, brs). 
               
               
                   
               
               
                 2682 
                 —CH(OH)— 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 oxalate 
                 mp 102-108 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 430 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
               
               
                 No. 
                 R 1152   
                 Xb 79   
                   1 H NMR (CDCl 3 ) δppm 
               
               
                   
               
               
                 2683 
                 —OCH 3   
                 —CH 2 — 
                 2.30-2.39(4 H, m), 2.57-2.62(2 H, m), 2.90-2.95(2 H, m), 3.36- 
               
               
                   
                   
                   
                 3.43(4 H, m), 3.58-3.61(2 H, m), 3.70(3 H, s), 5.83(1 H, s), 
               
               
                   
                   
                   
                 5.93(2 H, s), 6.69-6.88(6 H, m), 6.99(1 H, d, J = 8.1 Hz), 7.47- 
               
               
                   
                   
                   
                 7.62(5 H, m), 8.07(1 H, d, J = 2.3 Hz). 
               
               
                 2684 
                 —H 
                 N(CH 3 )— 
                 2.38-2.43(4 H, m), 2.99(3 H, s), 3.42-3.60(6 H, m), 4.05(2 H, s), 
               
               
                   
                   
                   
                 5.77(1 H, s), 5.94(2 H, s), 6.64-6.84(6 H, m), 6.93-6.99(2 H, m), 
               
               
                   
                   
                   
                 7.47(2 H, d, J = 8.1 Hz), 7.53-7.59(3 H, m) ,8.10(1 H, d, J = 2.1 
               
               
                   
                   
                   
                 Hz). 
               
               
                   
               
             
          
         
       
     
       Example 2685 
     Production of {6-[4-(4-piperonylpiperazin-1-ylmethyl)phenoxy]pyridin-3-ylmethyl}-(4-trifluoromethylphenyl)amine 
       [1290]    To a suspension of lithium aluminum hydride (0.106 g, 2.80 mmol) in THF (10 mL) was added dropwise a solution of 6-[4-(4-piperonylpiperazine-1-carbonyl)-phenoxy]-N-(4-trifluoromethylphenyl)nicotinamide (0.423 g, 0.700 mmol) in THF (10 mL) under ice cooled stirring. Once the entire amount was added dropwise, the solution temperature was slowly raised, and stirred under reflux, for 2 hours. After cooling, ice water (50 mL) was added to the solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatography (dichloromethane methanol 40:1), to thereby yield 0.125 g of the title compound. 
         [1291]    Appearance: Pale Yellow oil 
         [1292]    MS 576 (M + ) 
         [1293]    The following compounds were produced in the same manner as in Example 2685. 
       Example 2686 
     N-[6-(2-fluoro-4-{methyl[2-(4-piperonylpiperazin-1-yl)ethyl]amino}phenoxy)pyridin-3-yl]-3,4-dichlorobenzenesulfonamide 
       [1294]      1 H NMR (CDCl 3 ) δ 2.50-2.55 (10H, m), 2.92 (3H, s), 3.41-3.45 (4H, m), 5.93 (2H, s), 6.39-6.49 (2H, m), 6.73-6.74 (2H, m), 6.84-6.89 (2H, m), 6.99 (1H, t, J=9.1 Hz), 7.42-7.70 (4H, m), 7.81 (1H, brs). 
       Example 2687 
     Production of 3-(3-methyl-4-{5-[2-(4-trifluoromethyl-phenyl)ethyl]pyridin-2-yloxy}phenyl)-1-piperonyl-tetrahydropyrimidin-2-one hydrobromide 
       [1295]    To a solution of 3-(3-methyl-4-{5-[(E)-2-(4-trifluoromethylphenyl)vinyl]pyridin-2-yloxy}phenyl)-1-piperonyltetrahydropyrimidin-2-one (0.16 g, 0.27 mmol) in ethyl acetate (15 mL) was added 5% platinum-carbon (0.05 g) under a nitrogen atmosphere, and the resulting solution was then stirred under a hydrogen atmosphere for 4.5 hours at room temperature. The resulting reaction solution was filtered through Celite, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate:=n-hexane 1:4-1:2), and to the resulting product was added hydrobromide, to thereby yield 50 mg of the title compound. 
         [1296]    Appearance: Colorless amorphous powder 
         [1297]      1 H NMR (DMSO-d 6 ) δ 1.85-2.09 (5H, m), 2.77-3.02 (4H, m), 3.15-3.33 (2H, m), 3.55-3.70 (2H, m), 3.75-4.15 (1H, m), 4.40 (2H, s), 5.99 (2H, s), 6.76 (1H, dd, J=1.5 Hz, 7.8 Hz), 6.80-6.98 (4H, m), 7.10 (1H, dd, J=2.6 Hz, 8.5 Hz), 7.19 (1H, d, J=2.6 Hz), 7.44 (2H, d, J=8.1 Hz), 7.62 (2H, d, J=8.1 Hz), 7.71 (1H, dd, J=2.4 Hz, 8.4 Hz), 7.91 (1H, d, J=2.4 Hz). 
         [1298]    The following compounds were produced in the same manner as in Reference Example 673. 
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 431 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example No. 
                 R 1153    
                 R 1154   
                 M 
                   1 H NMR (CDCl 3 ) δ ppm 
               
               
                   
               
               
                 2688 
                 —H 
                 piperonyl 
                 1 
                 1.31-1.45 (2H, m), 1.84-2.02 (3H, m), 2.30 (2H, d, J = 6.8 Hz), 
               
               
                   
                   
                   
                   
                 2.41-2.43 (4H, m), 2.72 (2H, t, J = 12.2 Hz), 3.43 (2H, s), 3.44- 
               
               
                   
                   
                   
                   
                 3.65 (6H, m), 5.95 (2H, s), 6.71-6.77 (2H, m), 6.85-7.00 (6H, m), 
               
               
                   
                   
                   
                   
                 7.21-7.26 (3H, m), 7.51 (2H, d, J = 8.6 Hz), 7.98 (1H, dd, J = 8.7 
               
               
                   
                   
                   
                   
                 Hz, 2.6 Hz), 8.60 (1H, d, J = 2.6 Hz). 
               
               
                 2689 
                 —H 
                 —H 
                 1 
                 1.38-1.46 (2H, m), 1.84-2.00 (3H, m), 2.31 (2H, d, J = 6.8 Hz), 
               
               
                   
                   
                   
                   
                 2.71 (2H, t, J = 12.2 Hz), 2.86-2.89 (4H, m), 3.48-3.63 (7H, m), 
               
               
                   
                   
                   
                   
                 6.86-6.99 (5H, m), 7.23-7.29 (3H, m), 7.49 (2H, d, J = 8.4 Hz), 
               
               
                   
                   
                   
                   
                 7.97 (1H, dd, J = 8.9 Hz, 2.6 Hz), 8.60 (1H, d, J = 2.1 Hz). 
               
               
                 2690 
                 —CH 3   
                 piperonyl 
                 1 
                 1.36-1.40 (2H, m), 1.82-2.02 (3H, m), 2.03 (3H, s), 2.30 (2H, d, J = 
               
               
                   
                   
                   
                   
                 6.8 Hz), 2.41-2.43 (4H, m), 2.68 (2H, t, J = 12.0 Hz), 3.43 (2H, s), 
               
               
                   
                   
                   
                   
                 3.49-3.65 (6H, m), 5.94 (2H, s), 6.74-6.89 (8H, m), 7.24 (2H, d, J = 
               
               
                   
                   
                   
                   
                 8.2 Hz), 7.49 (2H, d, J = 8.6 Hz), 7.99 (1H, dd, J = 8.7 Hz, 2.5 Hz), 
               
               
                   
                   
                   
                   
                 8.58 (1H, d, J = 2.1 Hz). 
               
               
                 2691 
                 —H 
                 piperonyl 
                 0 
                 1.78-2.03 (4H, m), 2.46 (4H, brs), 2.55-2.77 (3H, m), 3.46 (2H, s), 
               
               
                   
                   
                   
                   
                 3.55 (2H, brs), 3.67 (4H, brs), 5.95 (2H, s), 6.75-6.78 (2H, m), 
               
               
                   
                   
                   
                   
                 6.85-7.01 (6H, m), 7.21-7.26 (3H, m), 7.52 (2H, d, J = 8.6 Hz), 
               
               
                   
                   
                   
                   
                 7.98 (1H, dd, J = 8.7 Hz, 2.6 Hz), 8.60 (1H, d, J = 2.5 Hz). 
               
               
                   
               
             
          
         
       
     
       Example 2692 
     Production of 1-[3-(4-{1-[5-(3,4-dichlorobenzoylamino)-2-pyridyl]-1-hydroxyimino}methylphenyl)propionyl]-4-piperonylpiperazine 
       [1299]    To a solution of 1-(3-{4-[5-(3,4-dichloro-benzoylamino)pyridine-2-carbonyl]phenyl}propionyl)-4-piperonylpiperazine (0.330 g, 0.511 mmol) in pyridine (7 mL) was added hydroxylamine hydrochloride (53.3 mg, 0.767 mmol), and the resulting solution was refluxed for 0.5 hours. The reaction solution was concentrated under reduced pressure, and to the residue was added brine. This solution was extracted with dichloromethane. The dichloromethane layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatography (dichloromethane:methanol=15:1), whereby 0.225 g of the title compound was obtained as a mixture of the syn form and the anti form (1:1) of the oxime. 
         [1300]    Appearance: Colorless amorphous powder 
         [1301]      1 H NMR (CDCl 3 ) δ 2.21-2.39 (4H, m), 2.49-2.60 (2H, m), 2.78-2.90 (2H, m), 3.29-3.44 (4H, m), 3.55 (2H, s), 5.90 (2H, s), 6.62-6.73 (2H, m), 6.80 (1H, s), 7.07 (1H, d, J=7.7 Hz), 7.12 (1H, d, J=7.7 Hz), 7.15-7.30 (2.5H, m), 7.39 (0.5H, d, J=8.4 Hz), 7.42 (0.5H, d, J=8.4 Hz), 7.45-7.51 (0.5H, m), 7.62-7.74 (1H, m), 7.94 (0.5H, d, J=2.0 Hz), 7.99 (0.5H, d, J=2.0 Hz), 8.09-8.28 (1H, m), 8.62 (0.5H, s), 8.85 (0.5H, s), 9.40 (0.5H, brs), 9.62 (0.5H, brs), 10.21 (0.5H, brs), 13.85 (0.5H, brs). 
       Example 2693 
     Production of 4-(2-oxo-3-{4-[5-(4-trifluoromethyl-benzoylamino)pyridin-2-yloxy]phenyl}propionyl)-piperazine-1-carboxylic acid t-butyl ester 
       [1302]    To a solution of 4-(2-hydroxy-3-{4-[5-(4-trifluoromethylbenzoylamino)pyridin-2-yloxy]phenyl}propionyl)piperazine-1-carboxylic acid t-butyl ester (0.58 g, 0.94 mmol) in dichloromethane (4 mL) was added a Dess-Martin reagent (0.8 g, 1.89 mmol), and the resulting solution was then stirred under a nitrogen gas flow for 4 hours at room temperature. The reaction solution was concentrated under reduced pressure. To the residue was added 1 N aqueous sodium hydroxide (50 mL), and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel chromatography (dichloromethane:methanol=50:1), to thereby yield 0.31 g of the title compound. 
         [1303]    Appearance: Yellow powder 
         [1304]      1 H NMR (CDCl 3 ) δ 1.41 (9H, s), 2.99-3.22 (4H, m), 3.25-3.41 (2H, m), 3.42-3.60 (2H, m), 4.04 (2H, s), 6.97 (1H, d, J=8.9 Hz), 7.10 (2H, d, J=8.4 Hz), 7.27 (2H, d, J=8.4 Hz), 7.73 (2H, d, J=8.0 Hz), 7.99 (2H, d, J=8.0 Hz), 8.13 (1H, d, J=2.8 Hz), 8.30 (1H, dd, J=8.9 Hz, 2.8 Hz), 8.45 (1H, brs). 
       Example 2694 
     Production of 3,4-dichloro-N-{3-fluoro-4-[4-(1-hydroxy-2-morpholine-4-ylethyl)phenoxy]phenyl}benzamide 
       [1305]    3,4-Dichloro-N-{3-fluoro-4-[4-(1-hydroxy-2-morpholine-4-ylethyl)phenoxy]phenyl}benzamide (37.4 g) was recrystallized from ethanol (700 mL) to yield 34.34 g of the title compound. 
         [1306]    Appearance: White powder 
         [1307]    Melting point: 175-176° C. 
       Example 2695 
     Production of N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]ethylamino}-2-fluorophenoxy)pyridin-3-yl]-3,4-dichlorobenzenesulfonamide 
       [1308]    N-[6-(4-{2-(4-Piperonylpiperazin-1-yl)-2-oxoethyl]ethylamino}-2-fluorophenoxy)pyridin-3-yl]-3,4-dichlorobenzenesulfonamide (8.15 g) was recrystallized from ethanol (60 mL) to yield 7.78 g of the title compound. 
         [1309]    Appearance: White powder 
         [1310]    Melting point: 163-166° C. 
       Example 2696 
     Production of N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-methylphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide 
       [1311]    N-[6-(4-{[2-(4-Piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-methylphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide (5.1 g, 7.7 mmol) was recrystallized from acetone (15 mL) to yield 3.7 g of the title compound. 
         [1312]    Appearance: White powder 
         [1313]    Melting point: 128-131° C. 
       Example 2697 
     Production of N-{6-[4-(4-benzylpiperazine-1-carbonyl)phenoxy]pyridin-3-yl}-4-trifluoromethyl-benzamide 
       [1314]    N-{[6-[4-(4-Benzylpiperazine-1-carbonyl)-phenoxy]pyridin-3-yl}-4-trifluoromethylbenzamide (78.86 g) was recrystallized from ethanol (530 mL) to yield 96.66 g of the title compound. 
         [1315]    Appearance: White needles 
         [1316]    Melting point: 177.6-179.2° C. 
       Example 2698 
     Production of N-(6-{4-[4-(2-oxo-1,2,3,4-tetrahydro-quinoline-6-ylmethyl)piperazine-1-carbonyl]phenoxy}-pyridin-3-yl)-4-trifluoromethylbenzamide 
       [1317]    To a solution of 4-[5-(4-trifluoromethylbenzoylamino)pyridin-2-yloxy]benzoic acid (4.30 g, 10.7 mmol) in DMF (150 mL) were added 1-(2-oxo-1,2,3,4-tetrahydroquinoline-6-ylmethyl)-piperazine (2.6 g, 10.7 mmol), 1-hydroxybenzotriazole monohydrate (1.64 g, 10.7 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.46 g, 12.8 mmol) under ice cooling, and the resulting solution was stirred for 1 hour under ice cooling and for 17 hours at room temperature. This reaction solution was concentrated under reduced pressure. To the residue was added a saturated sodium bicarbonate solution, and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was recrystallized from ethyl acetate, to thereby yield 5.24 g of the title compound. 
         [1318]    Appearance: White powder 
         [1319]    Melting point: 250.5-252.5° C. 
       Example 2699 
     Production of N-(6-{4-[4-(4-benzylpiperidine-1-carbonyl)piperazine-1-carbonyl]phenoxy}pyridin-3-yl)-3,4-dichlorobenzamide 
       [1320]    To a solution of 1-{4-[5-(3,4-dichlorobenzoylamino)pyridin-2-yloxy]benzoyl}piperidine-4-carboxylic acid (4.5 g, 8.8 mmol) in DMF (88 mL) were added 1-benzylpiperazine (1.83 mL, 10.5 mmol), 1-hydroxybenzotriazole monohydrate (1.61 g, 10.5 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.02 g, 10.5 mmol) under ice cooling, and the resulting solution was stirred overnight at room temperature. To this reaction solution was added a saturated sodium bicarbonate solution, and the resulting solution was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was recrystallized from isopropyl alcohol (700 mL), to thereby yield 3.2 g of the title compound. 
         [1321]    Appearance: White powder 
         [1322]    Melting point: 223-225° C. 
       Example 2700 
     Production of N-[6-(4-{[2-(4-benzylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-methylphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide 
       [1323]    To a suspension of 1-(4-benzylpiperazin-1-yl)-2-{methyl[3-methyl-4-(5-nitropyridin-2-yloxy)phenyl]amino}ethanone (2.85 g, 6.0 mmol) in ethyl acetate (30 mL) was added 5% platinum-carbon (0.30 g) under a nitrogen atmosphere, and the resulting solution was stirred for 3 hours at 40° C. under a hydrogen atmosphere. The platinum-carbon was separated off with Celite, and the filtrate was concentrated. The residue was dissolved in THF (30 mL), and to this solution was added triethylamine (1.26 mL, 9.1 mmol) under ice cooling. To the resulting solution was then added dropwise 4-(trifluoromethyl)benzoyl chloride (1.16 mL, 7.8 mmol). This reaction solution was stirred overnight, then a saturated sodium bicarbonate solution was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water, and then dried over anhydrous sodium sulfate. The solvent was evaporated, and the residue was purified by silica gel column chromatography (dichloromethane:methanol=20:1). The resulting product was then recrystallized from a mixed solvent consisting of diisopropyl ether-acetone, to thereby yield 1.37 g of the title compound. 
         [1324]    Appearance: White powder 
         [1325]    Melting point: 112-113° C. 
       Example 2701 
     Production of (4-benzylpiperazin-1-yl)(4-{5-[methyl(4-trifluoromethylbenzyl)amino]pyridin-2-yloxy}phenyl)-methanone 
       [1326]    To a solution of (4-benzylpiperazin-1-yl){4-[5-(4-trifluoromethylbenzylamino)pyridin-2-yloxy]phenyl}methanone (5.40 g, 9.88 mmol) in methanol (150 mL) were added 37% aqueous formaldehyde (2.8 mL), sodium cyanoborohydride (1.86 g, 29.6 mmol) and acetic acid (1.7 mL) under ice cooling, and the resulting solution was stirred at room temperature for 2 hours. The solvent was evaporated under reduced pressure. Water was added to the residue, and this solution was neutralized with a saturated sodium bicarbonate solution, and extracted with chloroform. The organic layer was washed with water, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel column chromatography (chloroform:methanol=60:1). To the resulting product was then added a solution of 4 M hydrogen chloride in ethyl acetate until the resulting solution had a pH of 1. The precipitates were collected by filtration and recrystallized from ethanol (80 mL), to thereby yield 2.5 g of the title compound. 
         [1327]    Appearance: White powder 
         [1328]    Melting point: 180-183.5° C. 
       Example 2702 
     Production of 4-piperonylpiperazine-1-carboxyl 4-[5-(3,4-dichlorobenzoylamino)pyridin-2-yloxy]benzylamide hydrochloride 
       [1329]    To a solution of 4-piperonylpiperazine-1-carboxyl 4-(5-aminopyridin 2-yloxy)benzylamide (2.48 g, 5.4 mmol) in THF (50 mL) were added triethylamine (0.9 mL, 6.5 mmol) and 3,4-dichlorobenzoyl chloride (1.13 g, 5.4 mmol) under ice cooling, and the resulting solution was stirred under ice cooling for 10 minutes. Water was added to the residue, and extracted with ethyl acetate. The ethyl acetate layer was washed with water and brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatography (dichloromethane:methanol=25:1) to yield 2.97 g of a white powder. This white powder was dissolved in ethanol (45 mL), and to the resulting solution was added a solution of 4 M hydrogen chloride in ethyl acetate until the solution had a pH of 1. The precipitates were collected by filtration and recrystallized from 83% ethanol (36 mL), to thereby yield 2.72 g of the title compound. 
         [1330]    Appearance: White powder 
         [1331]    Melting point: 243.5-246.5° C. 
       Example 2703 
     Production of N-[6-(4-{4-[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}-2-methylphenoxy)pyridin-3-yl]-4-trifluoromethylbenzenesulfonamide 
       [1332]    N-[6-(4-{4-[2-(4-Piperonylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}-2-methylphenoxy)pyridin-3-yl]-4-trifluoromethylbenzenesulfonamide (1.35 g) was recrystallized from ethanol (20 mL) to yield 1.23 g of the title compound. 
         [1333]    Appearance: White powder 
         [1334]    Melting point: 156-158° C. 
       Example 2704 
     Production of N-(6-{4-[4-(4-piperonylpiperazine-1-carbonyl)piperidin-1-yl]phenoxy}pyridin-3-yl)-3,4-dichlorobenzenesulfonamide 
       [1335]    N-(6-{4-[4-(4-Piperonylpiperidine-1-carbonyl)piperidin-1-yl]phenoxy}pyridin-3-yl)-3,4-dichlorobenzenesulfonamide (1.95 g) was recrystallized from ethanol (35 mL) to yield 1.70 g of the title compound. 
         [1336]    Appearance: White powder 
         [1337]    Melting point: 130-133° C. 
       Example 2705 
     Production of N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-methylphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide 
       [1338]    N-[6-(4-{[2-(4-Piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-methylphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide (0.86 g, 1.30 mmol) was recrystallized from a mixed solvent of acetone (3 mL) diethyl ether (4 mL) and n-hexane (1 mL) to yield 0.72 g of the title compound. 
         [1339]    Appearance: Pale yellow powder 
         [1340]    Melting point: 154-155° C. 
       Example 2706 
     Production of N-(6-{4-[4-(4-benzylpiperazine-1-carbonyl)piperidin-1-yl]phenoxy}pyridin-3-yl)-4-trifluoromethylbenzensulfonamide 
       [1341]    N-(6-{4-[4-(4-Benzylpiperidin-1-carbonyl)piperidin-1-yl]phenoxy}pyridin-3-yl)-4-trifluoromethylbenzensulfonamide (1.55 g) was recrystallized from ethanol (60 mL) to yield 1.41 g of the title compound. 
         [1342]    Appearance: White powder 
         [1343]    Melting point: 199-201° C. 
       Example 2707 
     Production of N-[6-(4-{4-[2-(4-benzylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}-2-methylphenoxy)pyridin-3-yl]-3,4-dichlorobenzenesulfonamide 
       [1344]    To a solution of (1-{4-[5-(3,4-dichlorobenzenesulfonylamino)pyridin-2-yloxy]-3-methylphenyl}piperidine-4-yl)acetic acid (1.70 g, 3.1 mmol) and 1-benzylpiperazine (0.71 g, 4.0 mmol) in DMF (40 mL) were added triethylamine (1.08 mL, 7.8 mmol) and diethyl cyanophosphonate (0.76 g, 4.3 mmol) under ice cooling, and the resulting solution was stirred for 1 hour under ice cooling. To this reaction solution was added a saturated sodium bicarbonate solution, and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine, dried over anhydrous sodium sulfate, and evaporated. The residue was purified by silica gel column chromatography (dichloromethane:methanol=40:1), after which the resulting product was recrystallized from ethanol, to thereby yield 1.61 g of the title compound. 
         [1345]    Appearance: White needles 
         [1346]    Melting point: 151-155° C. 
       Example 2708 
     Production of N-[6-(4-{[2-(4-benzothiazole-6-ylmethylpiperazin-1-yl)-2-oxoethyl]methylamino}-phenoxy)pyridin-3-yl]-3,4-dichlorobenzamide dihydrochloride 
       [1347]    To a solution of ({4-[5-(3,4-dichlorobenzoyl-amino)pyridin-2-yloxy]phenyl}methylamino)acetic acid (1.02 g, 2.3 mmol) and 1-(benzothiazole-6-ylmethyl)-piperazine (0.58 g, 2.5 mmol) in DMF (15 mL) were added triethylamine (0.95 mL, 6.9 mmol) and diethyl cyanophosphonate (0.447 mL, 2.7 mmol) under ice cooling, and the resulting solution was stirred for 30 minutes under ice cooling and for 45 minutes at room temperature. Water was added to the solution, and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine, dried over anhydrous sodium sulfate, and evaporated. The residue was purified by silica gel column chromatography (dichloromethane:methanol=30:1) to obtain 1.28 g of a white powder. This white powder was dissolved in ethanol (15 mL), and to the resulting solution was added a solution of 4 M hydrogen chloride in ethyl acetate until the resulting solution had a pH of 1. The precipitates were collected by filtration and recrystallized from 85% ethanol (30 mL), to thereby yield 1.06 g of the title compound. 
         [1348]    Appearance: White powder 
         [1349]    Melting point: 202-223° C. 
       Example 2709 
     Production of 3,4-dichloro-N-{6-[4-({2-[4-(2,3-dihydrobenzo[1,4]dioxin-6-ylmethyl)piperazin-1-yl]-2-oxoethyl}methylamino)phenoxy]pyridin-3-yl}benzamide maleate 
       [1350]    To a solution of ({4-[5-(3,4-dichlorobenzoyl-amino)pyridin-2-yloxy]phenyl}methylamino)acetic acid (2.50 g, 5.6 mmol) in DMF (55 mL) were added 1-(2,3-dihydrobenzo[1,4]dioxin-6-ylmethyl)piperazine (1.7 g, 7.3 mmol), 1-hydroxybenzotriazole monohydrate (0.86 g, 5.6 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (1.29 g, 6.7 mmol) under ice cooling, and the resulting solution was stirred for 30 minutes under ice cooling and for 17 hours at room temperature. This reaction solution was concentrated under reduced pressure. Water was added to the residue, and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was dissolved in ethanol (30 mL). To the resulting solution was added maleic acid (0.32 g, 2.7 mmol), and this solution was left to stand. The precipitates were collected by filtration, to thereby yield 1.45 g of the title compound. 
         [1351]    Appearance: Pale yellow powder 
         [1352]    Melting point: 188-190° C. 
       Example 2710 
     Production of N-(6-{4-[4-(4-benzylpiperazine-1-carbonyl)piperidin-1-yl]phenoxy}pyridin-3-yl)-3,4-dichlorobenzenesulfonamide 
       [1353]    N-(6-{4-[4-(4-Benzylpiperazine-1-carbonyl)piperidin-1-yl]phenoxy}pyridin-3-yl)-3,4-dichlorobenzenesulfonamide (0.79 g) was recrystallized from ethanol (15 mL) to yield 0.67 g of the title compound. 
         [1354]    Appearance: White powder 
         [1355]    Melting point: 185-189° C. 
       Example 2711 
     Production of N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-methylphenoxy)pyridin-3-yl]-4-pyrrole-1-ylbenzamide 
       [1356]    N-[6-(4-{[2-(4-Piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-methylphenoxy)pyridin-3-yl]-4-pyrrole-1-ylbenzamide (2.49 g) was recrystallized from a mixed solvent consisting of acetone (20 mL) and diethyl ether (30 mL) to yield 2.26 g of the title compound. 
         [1357]    Appearance: Pale yellow powder 
         [1358]    Melting point: 163.1-166.5° C. 
       Example 2712 
     Production of N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]ethylamino}-2-fluorophenoxy)pyridin-3-yl]-4-trifluoromethylbenzenesulfonamide 
       [1359]    N-[6-(4-{[2-(4-Piperonylpiperazin-1-yl)-2-oxoethyl]ethylamino}-2-fluorophenoxy)pyridin-3-yl]-4-trifluoromethylbenzenesulfonamide (8.18 g) was recrystallized from a mixed solvent consisting of ethyl acetate (70 mL) and n-hexane (20 mL) to yield 6.93 g of the title compound. 
         [1360]    Appearance: White powder 
         [1361]    Melting point: 177.8-180.1° C. 
       Example 2713 
     Production of 6-(4-{4-[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl]-2-methylphenoxy}pyridine-3-sulfonyl-(4-trifluoromethylphenyl)amide 
       [1362]    6-(4-{4-[2-(4-Piperonylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl]-2-methylphenoxy}pyridine-3-sulfonyl-(4-trifluoromethylphenyl)amide (1.50 g) was recrystallized from ethanol (20 mL) to yield 1.40 g of the title compound. 
         [1363]    Appearance: White powder 
         [1364]    Melting point: 156-160° C. 
       Example 2714 
     Production of N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-methylphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide 
       [1365]    N-[6-(4-{[2-(4-Piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-methylphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide (2.1 g, 3.2 mmol) was heated to dissolve in acetone (5 mL), and to the resulting solution was then added diethyl ether (10 mL), whereby recrystallization yielded 2.0 g of the title compound. 
         [1366]    Appearance: White powder 
         [1367]    Melting point: 113-116° C. 
       Example 2715 
     Production of 3,4-dichloro-N-{3-fluoro-4-[4-(1-hydroxy-2-morpholine-4-ylethyl)phenoxy]phenyl}benzamide 
       [1368]    3,4-Dichloro-N-{3-fluoro-4-[4-(1-hydroxy-2-morpholine-4-ylethyl)phenoxy]phenyl}benzamide (5 g) was recrystallized from ethyl acetate-n-hexane to yield 4.73 g of the title compound. 
         [1369]    Appearance: White powder 
         [1370]    Melting point: 169-170° C. 
       Example 2716 
     Production of N-(6-{4-[4-(4-piperonylpiperazine-1-carbonyl)piperidine-1-carbonyl]phenoxy}pyridin-3-yl)-3,4-dichlorobenzamide 
       [1371]    To a solution of 1-{4-[5-(3,4-dichlorobenzoylamino)pyridin-2-yloxy]benzoyl}piperidine-4-carboxylic acid (7.96 g, 15.5 mmol) in DMF (160 mL) were added 1-piperonylpiperazine (3.75 g, 17.6 mmol), 1-hydroxybenzotriazole monohydrate (2.85 g, 18.6 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (3.56 g, 18.6 mmol) under ice cooling, and the resulting solution was stirred for overnight at room temperature. This reaction solution was concentrated under reduced pressure. To the residue were added water and ethyl acetate, and the resulting solution was vigorously stirred. The resulting precipitates were collected by filtration and recrystallized from a dichloromethane-methanol mixed solvent, to thereby yield 7.36 g of the title compound. 
         [1372]    Appearance: White powder 
         [1373]    Melting point: 236-238° C. 
       Example 2717 
     Production of N-{6-[(4-{4-[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}phenyl)methylamino]-pyridin-3-yl}-4-trifluoromethylbenzamide 
       [1374]    To a solution of [1-(4-{methyl[5-(4-trifluoromethylbenzoylamino)pyridin-2-yl]amino}phenyl)piperidine-4-yl]acetic acid (0.80 g, 1.6 mmol) in DMF (10 mL) were added 1-piperonylpiperazine (0.41 g, 1.9 mmol), 1-hydroxybenzotriazole monohydrate (0.24 g, 1.6 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.39 g, 2.0 mmol) under ice cooling, and the resulting solution was stirred for 3 hours at room temperature. This reaction solution was concentrated under reduced pressure. To the residue was added a saturated sodium bicarbonate solution, and extracted with dichloromethane. The dichloromethane layer was washed with a saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatography (dichloromethane:methanol=20:1). The resulting product was then recrystallized from a mixed solvent consisting of 95% ethanol-dichloromethane, to thereby yield 1.05 g of the title compound. 
         [1375]    Appearance: White powder 
         [1376]    Melting point: 210-212° C. 
       Formulation Example 1 
       [1377]    100 g of the N-[6-(4-{4-[2-(piperonyl-piperazin-1-yl)-2-oxoethyl]piperidin-1-yl}phenoxy)-pyridin-3-yl]-4-trifluoromethylbenzamide obtained in Example 319, 40 g of Avicel (Tradename, manufactured by Asahi Kasei Corporation), 30 g of cornstarch and 2 g of magnesium stearate were mixed and ground together. The resulting mixture was then formed into a sugar-coated R 10-mm-tablets using a pestle. The obtained tablets were coated with a film coating agent containing 10 g of TC-5 (Tradename, manufactured by Shin-Etsu Chemical Co., Ltd., hydroxypropylmethyl cellulose), 3 g of polyethylene glycol 6000, 40 g of castor oil and a suitable amount of ethanol, to thereby prepare a film-coated tablet. 
       Pharmacological Test 1 
     Anti-Cancer Effect (In-Vitro) on Cancer Cells 
       [1378]    Anti-proliferative effect of test compounds on human hepatic cancer cells (HuH-7), human lung cancer cells (EBC-1), human colorectal cancer cells (HCT116), human prostatic cancer cells (22Rv1), human pancreatic cancer cells (MIA PaCa-2), human stomach cancer cells (MKN45), human breast cancer cells (ZR-75-1) was checked by a sulforhodamine B method in accordance with Skehan P et al. (J. Natl. Cancer Inst. 1990 Jul. 4; 82(13): 1107-12). Explanation will be made taking HuH-7 cells as an example. 
         [1379]    HuH-7 cells were seeded on DMEM medium (Dulbeco&#39;s modified Eagle Medium) containing 10% fetal bovine serum of a 96-well microplate and cultured at 37° C. for 24 hours in the presence of 5% carbon dioxide gas (CO 2 ). Thereafter, a test compound was added to the wells and the cells were cultured for a further 5 days. After the cultivation, trichloro acetic acid was added to the wells so as to obtain a final concentration of 10%. The microplate was allowed to stand still at 4° C. for one hour to fix the cells on the wells. The microplate was washed with water to remove the medium and trichloroacetic acid and dried in the air. After the air-dry, the microplate was stored at 4° C. until it was stained with sulforhodamine B. 
         [1380]    To each of the wells, a 1% aqueous acetic acid solution containing 0.4% sulforhodamine B was added and the wells were allowed to stand still at room temperature for 20 to 30 minutes. After the supernatant was removed, each well was washed with the 1% aqueous acetic acid solution and a 10 mM aqueous Tris (Tris hydroxyaminomethane) solution was add to each well and stirred. In this manner, the dye taken in the cell was eluted. Subsequently, OD (optical density) was measured at a measurement wavelength of 492 nm and a reference wavelength of 690 nm to obtain the difference (A) in OD thus measured. Furthermore, the OD of a control well (containing no cells) was measured at a measurement wavelength of 492 nm and a reference wavelength of 690 nm to obtain the difference (B) in OD. The difference (A−B) was regarded as the cell proliferation activity of each of the wells. 
         [1381]    Anti-proliferative effect of test compounds on human chronic myelogenous leukemia cells (KU812) was determined by an MTT assay in accordance with the method described in Singh A K et al. (Cancer Lett. 1996 Oct. 1; 107(1): 109-15). To describe more specifically, KU812 cells were seeded on RPMI 1640 medium containing 10% fetal bovine serum of a 96-well microplate, cultured at 37° C. for 24 hours in the presence of a 5% carbon dioxide gas (CO 2 ). Thereafter, a test compound was added to the wells and the cells were cultured for a further 5 days. After the incubation, 10 μl of 5 mg/mL MTT (3-(4,5-dimethyl)-2,5-diphenyltetrazolium bromide) was added to the wells. After the cells were cultured for 4 hours, 100 μl of 0.01N HCl containing 10% SDS (sodium dodecyl sulfate) was added to the wells, which was further cultured overnight. 
         [1382]    Subsequently, OD was measured at a measurement wavelength of 570 nm and a reference wavelength of 690 nm to obtain the difference (A) in OD. Furthermore, OD of a control well (containing no cells) was measured at a measurement wavelength of 570 nm and a reference wavelength of 690 nm to obtain the difference (B) in OD. The difference (A−B) was regarded as the cell proliferation activity of each of the wells. 
         [1383]    The cell proliferation activity (T) at the time a test compound was added was compared to that (C) of the control (containing no test compound) and the cell proliferation suppression activity (T/C) of the test compound was computationally obtained. Based on this, the concentration (IC50) of the test compound at which the proliferation of 50% of the cells was inhibited, that is, the concentration of the test compound providing T/C=0.5, was obtained. 
         [0000]    
       
         
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 432 
               
               
                   
               
               
                   
                   
                   
                   
                   
                 MIA 
                   
                   
                   
               
               
                   
                 HuH-7 
                 EBC-1 
                 HCT116 
                 22Rv1 
                 PaCa-2 
                 MKN45 
                 ZR-75-1 
                 KU812 
               
               
                   
                 IC50 
                 IC50 
                 IC50 
                 IC50 
                 IC50 
                 IC50 
                 IC50 
                 IC50 
               
               
                 Example No. 
                 (nM) 
                 (nM) 
                 (nM) 
                 (nM) 
                 (nM) 
                 (nM) 
                 (nM) 
                 (nM) 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 276 
                 &lt;100 
                 &lt;1000 
                 &lt;1000 
                 &lt;1000 
                 &lt;100 
                 &lt;1000 
                 &lt;1000 
                 &lt;100 
               
               
                 322 
                 &lt;100 
                 &lt;100 
                 &lt;100 
                 &lt;100 
                 &lt;100 
                 &lt;100 
                 &lt;100 
                 &lt;100 
               
               
                 582 
                 &lt;100 
                 &lt;100 
                 &lt;100 
                 &lt;1000 
                 &lt;100 
                 &lt;1000 
                 &lt;1000 
                 &lt;100 
               
               
                 940 
                 &lt;100 
                 &lt;100 
                 &lt;1000 
                 &lt;1000 
                 &lt;100 
                 &lt;100 
                 &lt;1000 
                 &lt;100 
               
               
                 1039 
                 &lt;100 
                 &lt;100 
                 &lt;100 
                 &lt;100 
                 &lt;100 
                 &lt;100 
                 &lt;1000 
                 &lt;100 
               
               
                 1049 
                 &lt;100 
                 &lt;100 
                 &lt;100 
                 &lt;100 
                 &lt;100 
                 &lt;1000 
                 &lt;100 
                 &lt;100 
               
               
                 1202 
                 &lt;100 
                 &lt;100 
                 &lt;100 
                 &lt;100 
                 &lt;100 
                 &lt;100 
                 &lt;100 
                 &lt;100 
               
               
                 1503 
                 &lt;100 
                 &lt;100 
                 &lt;100 
                 &lt;100 
                 &lt;100 
                 &lt;100 
                 &lt;100 
                 &lt;100 
               
               
                 2228 
                 &lt;100 
                 &lt;100 
                 &lt;1000 
                 &lt;1000 
                 &lt;100 
                 &lt;1000 
                 &lt;1000 
                 &lt;100 
               
               
                   
               
             
          
         
       
     
       Pharmacological Test 2 
     Anti-Cancer Effect (In-Vitro) on Hepatic Cancer Cells HuH-7 
       [1384]    Human hepatic cancer cells HuH-7 were transplanted into SCID mice (a group of 6 female mice). Anti-tumor effect of test compounds according to the present invention was checked. To describe more specifically, the cancer cells were cultured in advance and a cell suspension solution containing the cancer cells in a concentration of 2.5×10 7  cells/mL was prepared. Then, 0.2 mL of the cell suspension solution was injected into the right axillary region of each of the mice to transplant the cancer cells. In this manner, cancer-bearing mice were prepared. When the tumor grew up to a diameter of 5 mm or more, the mice were divided into groups based on tumor volume. From the following day after the grouping, a 5% gum arabic suspension solution containing a test compound was orally administrated once a day for consecutive 9 days. To a control group, a 5% gum arabic suspension solution was administrated. Next day after completion of administration, the volume of a tumor was measured. The ratio in volume of a tumor at the time of grouping relative to that measured next day after completion of administration was calculated to obtain a relative tumor volume of each group. Then, the ratio (T/C %) in relative tumor volume of a control group to a test group (administrated with a test compound) was calculated and used as an index of the effect. 
         [0000]      Relative tumor volume=tumor volume measured on the next day of completion of administration/tumor volume measured at the time of grouping 
         [0000]      ( T/C  %)=(an average value of relative tumor volume of test compound administration group)/(an average value of relative tumor volume of a control group)×100 
         [0000]    
       
         
               
               
               
               
             
               
               
               
               
             
           
               
                   
                 TABLE 433 
               
               
                   
                   
               
               
                   
                   
                 Applied dose 
                   
               
               
                   
                 Compound 
                 (mg/kg/day) 
                 T/C % 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 Example 811 
                 30 
                 &lt;50 
               
               
                   
                 Example 1202 
                 100 
                 &lt;50 
               
               
                   
                 Example 1503 
                 100 
                 &lt;50 
               
               
                   
                   
               
             
          
         
       
     
       Pharmacological Test 3 
       [1385]    Anti-Proliferative effect of test compounds on human renal cancer cells (Caki-2) was checked in the same manner as in Pharmacological test 1 in accordance with the sulforhodamine B method of Skehan P et al. 
         [1386]    In addition, anti-proliferative effect of test compounds on human acute myelogenous leukemia cells (KG-1), human Burkitt&#39;s lymphoma cells (Daudi), human lymphoma cells (U937) and human multiple myeloma cells (IM-9) was checked by the MTT assay in the same manner as in Pharmacological test 1 in accordance with Singh A K et al. (Cancer Lett. 1996 Oct. 1; 107(1): 109-15). 
         [1387]    IC50 values of human renal cancer cells (Caki-2), human acute myelogenous leukemia cells (KG-1) and human multiple myeloma, cells (IM-9) are shown in Table 434. 
         [1388]    The cell proliferation activity of each of the test compounds on human Burkitt&#39;s lymphoma cells (Daudi) and human lymphoma cells (U937) was compared to that of a control (containing no test compounds) to obtain cell proliferation suppression activities (T/C) of each test compound. The results are shown in Table 435. 
         [0000]    
       
         
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                   
                 TABLE 434 
               
               
                   
                   
               
               
                   
                   
                 Caki-2 
                 IM-9 
                 KG-1 
               
               
                   
                   
                 IC50 
                 IC50 
                 IC50 
               
               
                   
                 Example No. 
                 (nM) 
                 (nM) 
                 (nM) 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 276 
                 &lt;1000 
                 &lt;1000 
                 &lt;100 
               
               
                   
                 322 
                 &lt;100 
                 &lt;100 
                 &lt;100 
               
               
                   
                 582 
                 &lt;1000 
                 &lt;100 
                 &lt;100 
               
               
                   
                 940 
                 &lt;1000 
                 &lt;100 
                 &lt;100 
               
               
                   
                 1039 
                 &lt;100 
                 &lt;100 
                 &lt;100 
               
               
                   
                 1049 
                 &lt;100 
                 &lt;100 
                 &lt;100 
               
               
                   
                 1202 
                 &lt;100 
                 &lt;100 
                 &lt;100 
               
               
                   
                 1503 
                 &lt;100 
                 &lt;100 
                 &lt;100 
               
               
                   
                 2228 
                 &lt;100 
                 &lt;100 
                 &lt;100 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                   
                 TABLE 435 
               
               
                   
                   
               
               
                   
                   
                 Applied 
                   
                   
               
               
                   
                   
                 dose 
                 Daudi 
                 U937 
               
               
                   
                 Example No. 
                 (nM) 
                 (T/C %) 
                 (T/C %) 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 322 
                 10 
                 &lt;70 
                 &lt;70 
               
               
                   
                 1202 
                 10 
                 &lt;70 
                 &lt;70 
               
               
                   
                 1503 
                 10 
                 &lt;70 
                 &lt;70