# Patent

## Title
Fungicidal pyrazoles

## Abstract

Disclosed are compounds of Formula 1, including all geometric and stereoisomers, N-oxides, and salts thereof,




wherein

    
    
        Q1 is a phenyl ring, naphthalenyl ring system, a 5- to 6-membered fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each as described with optional substituents as defined in the disclosure;
        Q2 is a phenyl ring, a naphthalenyl ring system, a 5- to 6-membered saturated, partially unsaturated or fully unsaturated heterocyclic ring, or an 8- to 10-membered heteroaromatic bicyclic ring system, each as described with optional substituents as defined in the disclosure;
        X is O, S(O)m, NR4, CR15R16, C(═O) or C(═S);
        and R1, R1a, R2, R4, R15, R16 and m are as defined in the disclosure.

Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling plant disease caused by a fungal pathogen comprising applying an effective amount of a compound or a composition of the invention. Also disclosed are compounds of Formula 2, including all geometric and stereoisomers, and salts thereof,

    
    






wherein

    
    
        X is NH; and
        Q1, Q2 and R2 are as defined for Formula 1;

which are useful as intermediates for preparing compounds of Formula 1.

## Background
This application is a divisional of application Ser. No. 13/254,205 filed Sep. 1, 2011 which is a national stage entry of PCT/US10/26003, filed Mar. 3, 2010. PCT/US10/26003 claims priority benefit from Provisional Applications 61/304,053, filed Feb. 12, 2010, and 61/157,046, filed Mar. 3, 2009.


FIELD OF THE INVENTION
This invention relates to certain pyrazoles, their N-oxides, salts and compositions, and methods of their use as fungicides.
BACKGROUND OF THE INVENTION
The control of plant diseases caused by fungal plant pathogens is extremely important in achieving high crop efficiency. Plant disease damage to ornamental, vegetable, field, cereal, and fruit crops can cause significant reduction in productivity and thereby result in increased costs to the consumer. Many products are commercially available for these purposes, but the need continues for new compounds which are more effective, less costly, less toxic, environmentally safer or have different sites of action. JP09208620 discloses N-phenylpyrazolylamine and N-pyridylpyrazolylamine derivatives as insecticides, herbicides and fungicides; however the fungicides of the present invention are not disclosed in this publication.
SUMMARY OF THE INVENTION
This invention is directed to compounds of Formula 1 (including all geometric and stereoisomers), N-oxides, and salts thereof, agricultural compositions containing them and their use as fungicides:




wherein

    
    
        Q1 is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 5 substituents independently selected from R3; or a 5- to 6-membered fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each ring or ring system containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon ring members are independently selected from C(═O) and C(═S), and the sulfur atom ring members are independently selected from S(═O)u(═NR14)v, each ring or ring system optionally substituted with up to 5 substituents independently selected from R3 on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members;
        Q2 is a phenyl ring or a naphthalenyl ring system, each ring or ring system optionally substituted with up to 5 substituents independently selected from R3; or a 5- to 6-membered saturated, partially unsaturated or fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each ring or ring system containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon ring members are independently selected from C(═O) and C(═S), and the sulfur atom ring members are independently selected from S(═O)u(═NR14)v, each ring or ring system optionally substituted with up to 5 substituents independently selected from R3 on carbon atom ring members and selected from cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members; or C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C3-C12 cycloalkyl or C3-C12 cycloalkenyl, each optionally substituted with up to 5 substituents independently selected from R3;
        X is O, S(O)m, NR4, CR15R16, C(═O) or C(═S);
        R1 is H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C7 cycloalkyl, CO2R5, C(O)NR6R7, cyano, C1-C6 alkoxy, C1-C6 haloalkoxy or C2-C5 alkoxyalkyl; or
        R1 is phenyl optionally substituted with up to 3 R8; or a five- or six-membered nitrogen-containing aromatic heterocycle optionally substituted with up to 3 substituents independently selected from R9a on carbon atom ring members and R9b on nitrogen atom ring members;
        R1a is H; or
        R1a and R1 are taken together with the carbon atom to which they are attached to form a cyclopropyl ring optionally substituted with up to 2 substituents independently selected from halogen and methyl;
        R2 is CH3, CH2CH3, halogen, cyano, cyanomethyl, halomethyl, hydroxymethyl, methoxy or methylthio; or cyclopropyl optionally substituted with up to 2 substituents independently selected from halogen and methyl;
        each R3 is independently selected from halogen, cyano, nitro, amino, methylamino, dimethylamino, formylamino, C2-C3 alkylcarbonylamino, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 haloalkylthio, C1-C3 alkylsulfinyl, C1-C3 haloalkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylsulfonyl, C1-C2 alkylsulfonyloxy, C1-C2 haloalkylsulfonyloxy, C3-C4 cycloalkyl, C3-C7 cycloalkoxy, C4-C6 alkylcycloalkyl, C4-C6 cycloalkylalkyl, C3-C7 halocycloalkyl, C2-C4 alkenyl, C2-C4 alkynyl, hydroxy, formyl, C2-C3 alkylcarbonyl, C2-C3 alkylcarbonyloxy, —SF5, —SCN, C(═S)NR19R20 or —U—V-T;
        R4 is H, formyl, C2-C5 alkenyl, C3-C5 alkynyl, C3-C7 cycloalkyl, —SO3−M+, —S(═O)tR10, —(C═W)R11, NH2 or OR21; or C1-C6 alkyl or C1-C6 haloalkyl, each optionally substituted with up to 2 R12;
        R5 is H, C1-C6 alkyl or C1-C6 haloalkyl;
        R6 and R7 are independently selected from H, C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C4-C8 cycloalkylalkyl and C4-C8 alkylcycloalkyl; or
        R6 and R7 are taken together with the nitrogen atom to which they are connected to form a four- to seven-membered nonaromatic heterocyclic ring containing ring members, in addition to the connecting ring nitrogen atom, selected from carbon atoms and optionally up to one ring member selected from O, S(O)n and NR13;
        each R8, R9a and R9b is independently selected from halogen, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy, C1-C2 haloalkoxy, cyano, nitro, SCH3, S(O)CH3 and S(O)2CH3;
        R10 is C1-C6 alkyl or C1-C6 haloalkyl;
        each R11 is independently C1-C6 alkyl, C1-C6 alkoxy, C2-C7 alkoxyalkyl, C2-C7 alkylaminoalkyl, C2-C8 dialkylaminoalkyl, C1-C6 alkylthio or C2-C7 alkylthioalkyl;
        each R12 is independently C3-C7 cycloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl or cyano;
        R13 is H, C1-C3 alkyl or C2-C3 haloalkyl;
        each R14 is independently H, cyano, C1-C3 alkyl or C1-C3 haloalkyl;
        R15 is H, C1-C4 alkyl or OR18;
        R16 is C1-C4 alkyl or OR18; or
        R15 and R16 are taken together as —OCH2CH2O—;
        each R18 is independently H, formyl, C3-C7 cycloalkyl, —SO3−M+ or —(C═W)R11; or C1-C6 alkyl or C1-C6 haloalkyl, each optionally substituted with up to 2 R12;
        each R19 and R20 is independently H or CH3;
        R21 is H, formyl, C3-C7 cycloalkyl, —SO3−M+ or —(C═W)R11; or C1-C6 alkyl or C1-C6 haloalkyl, each optionally substituted with up to 2 R12;
        each U is independently O, S(═O)w, NR22 or a direct bond;
        each V is independently C1-C6 alkylene, C2-C6 alkenylene, C3-C6 alkynylene, C3-C6 cycloalkylene or C3-C6 cycloalkenylene, wherein up to 3 carbon atoms are independently selected from C(═O), each optionally substituted with up to 5 substituents independently selected from halogen, cyano, nitro, hydroxy, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy and C1-C6 haloalkoxy;
        each T is independently cyano, NR23aR23b, OR24 or S(═O)yR25 
        each R22 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 (alkylthio)carbonyl, C2-C6 alkoxy(thiocarbonyl), C4-C8 cycloalkylcarbonyl, C4-C8 cycloalkoxycarbonyl, C4-C8 (cycloalkylthio)carbonyl or C4-C8 cycloalkoxy(thiocarbonyl);
        each R23a and R23b is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C3-C6 alkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 (alkylthio)carbonyl, C2-C6 alkoxy(thiocarbonyl), C4-C8 cycloalkylcarbonyl, C4-C8 cycloalkoxycarbonyl, C4-C8 (cycloalkylthio)carbonyl or C4-C8 cycloalkoxy(thiocarbonyl); or
        a pair of R23a and R23b attached to the same nitrogen atom are taken together with the nitrogen atom to form a 3- to 6-membered heterocyclic ring, the ring optionally substituted with up to 5 substituents independently selected from R26;
        each R24 and R25 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C3-C6 alkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 (alkylthio)carbonyl, C2-C6 alkoxy(thiocarbonyl), C4-C8 cycloalkylcarbonyl, C4-C8 cycloalkoxycarbonyl, C4-C8 (cycloalkylthio)carbonyl or C4-C8 cycloalkoxy(thiocarbonyl);
        each R26 is independently halogen, C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 alkoxy;
        each W is independently O or S;
        each M+ is independently a cation;
        m is 0, 1 or 2;
        n is 0, 1 or 2;
        t is 0, 1 or 2;
        each u and v are independently 0, 1 or 2 in each instance of S(═O)u(═NR14)v, provided that the sum of u and v is 0, 1 or 2;
        each w is independently 0, 1 or 2; and
        each y is independently 0, 1 or 2;

provided that:

        when Q2 is a phenyl ring substituted on at least one ortho position with a substituent selected from —U—V-T wherein U is a direct bond, V is C(═O) and T is NR23aR23b or OR24, then X is other than NR4.
    
    


More particularly, this invention pertains to a compound of Formula 1 (including all geometric and stereoisomers), an N-oxide or a salt thereof.
This invention also relates to a fungicidal composition comprising a compound of Formula 1, an N-oxide, or a salt thereof, and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.
This invention also relates to a fungicidal composition comprising: (a) a compound of Formula 1, an N-oxide, or a salt thereof, and (b) at least one other fungicide (e.g., at least one other fungicide having a different site of action).
This invention further relates to a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of a compound of the invention (e.g., as a composition described herein).
This invention also relates to a composition comprising a compound of Formula 1, an N-oxide, or a salt thereof, and at least one invertebrate pest control compound or agent.
The invention also relates to compounds of Formula 2 (including all geometric and stereoisomers) and salts thereof




wherein

    
    
        X is NH; and
        Q1, Q2 and R2 are as defined above for Formula 1;

provided that:

        (a) when Q2 is a phenyl ring substituted on at least one ortho position with a substituent selected from —U—V-T wherein U is a direct bond and T is NR23aR23b or OR24, then V is other than C(═O); and
        (b) when Q1 is phenyl and Q2 is 4-(trifluoromethyl)phenyl, then R2 is other than methyl;

and to use of said compounds as intermediates for preparing compounds of Formula 1. More particularly, the present invention pertains to a compound of Formula 2 or a salt thereof.

    
    




DETAILS OF THE INVENTION
As used herein, the terms “comprises,” “comprising,” “includes,” “including,” “has,” “having,” “contains”, “containing,” “characterized by” or any other variation thereof, are intended to cover a non-exclusive inclusion, subject to any limitation explicitly indicated. For example, a composition, mixture, process or method that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, mixture, process or method.
The transitional phrase “consisting of” excludes any element, step, or ingredient not specified. If in the claim, such would close the claim to the inclusion of materials other than those recited except for impurities ordinarily associated therewith. When the phrase “consisting of” appears in a clause of the body of a claim, rather than immediately following the preamble, it limits only the element set forth in that clause; other elements are not excluded from the claim as a whole.
The transitional phrase “consisting essentially of” is used to define a composition or method that includes materials, steps, features, components, or elements, in addition to those literally disclosed, provided that these additional materials, steps, features, components, or elements do not materially affect the basic and novel characteristic(s) of the claimed invention. The term “consisting essentially of” occupies a middle ground between “comprising” and “consisting of”.
Where applicants have defined an invention or a portion thereof with an open-ended term such as “comprising,” it should be readily understood that (unless otherwise stated) the description should be interpreted to also describe such an invention using the terms “consisting essentially of” or “consisting of.”
Further, unless expressly stated to the contrary, “or” refers to an inclusive or and not to an exclusive or. For example, a condition A or B is satisfied by any one of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B are true (or present).
Also, the indefinite articles “a” and “an” preceding an element or component of the invention are intended to be nonrestrictive regarding the number of instances (i.e. occurrences) of the element or component. Therefore “a” or “an” should be read to include one or at least one, and the singular word form of the element or component also includes the plural unless the number is obviously meant to be singular.
As referred to in the present disclosure and claims, “plant” includes members of Kingdom Plantae, particularly seed plants (Spermatopsida), at all life stages, including young plants (e.g., germinating seeds developing into seedlings) and mature, reproductive stages (e.g., plants producing flowers and seeds). Portions of plants include geotropic members typically growing beneath the surface of the growing medium (e.g., soil), such as roots, tubers, bulbs and corms, and also members growing above the growing medium, such as foliage (including stems and leaves), flowers, fruits and seeds.
As referred to herein, the term “seedling”, used either alone or in a combination of words means a young plant developing from the embryo of a seed.
As used herein, the term “alkylating agent” refers to a chemical compound in which a carbon-containing radical is bound through a carbon atom to leaving group such as halide or sulfonate, which is displaceable by bonding of a nucleophile to said carbon atom. Unless otherwise indicated, the term “alkylating” does not limit the carbon-containing radical to alkyl; the carbon-containing radicals in alkylating agents include the variety of carbon-bound substituent radicals specified for R1.
Generally when a molecular fragment (i.e. radical) is denoted by a series of atom symbols (e.g., C, H, N, O, S) the implicit point or points of attachment will be easily recognized by those skilled in the art. In some instances herein, particularly when alternative points of attachment are possible, the point or points of attachment may be explicitly indicated by a hyphen (“-”). For example, “-SCN” indicates that the point of attachment is the sulfur atom (i.e. thiocyanato, not isothiocyanato).
In the above recitations, the term “alkyl”, used either alone or in compound words such as “alkylthio” or “haloalkyl” includes straight-chain or branched alkyl, such as, methyl, ethyl, n-propyl, i-propyl, or the different butyl, pentyl or hexyl isomers. “Alkenyl” includes straight-chain or branched alkenes such as ethenyl, 1-propenyl, 2-propenyl, and the different butenyl isomers. “Alkenyl” also includes polyenes such as 1,2-propadienyl. “Alkynyl” includes straight-chain or branched alkynes such as ethynyl, 1-propynyl, 2-propynyl and the different butynyl isomers. “Alkenylene” denotes a straight-chain or branched alkenediyl containing one olefinic bond. Examples of “alkenylene” include CH═CH, CH2CH═CH, CH═C(CH3). “Alkynylene” denotes a straight-chain or branched alkynediyl containing one triple bond. Examples of “alkynylene” include CH2C≡C, C≡CCH2 and the different butynylene, pentynylene and hexynylene isomers.
“Alkoxy” includes, for example, methoxy, ethoxy, n-propyloxy, isopropyloxy and the different butoxy, pentoxy and hexyloxy isomers. “Alkoxyalkyl” denotes alkoxy substitution on alkyl. Examples of “alkoxyalkyl” include CH3OCH2, CH3OCH2CH2, CH3CH2OCH2, CH3CH2CH2CH2OCH2 and CH3CH2OCH2CH2. “Alkylthio” includes branched or straight-chain alkylthio moieties such as methylthio, ethylthio, and the different propylthio, butylthio, pentylthio and hexylthio isomers. “Alkylsulfinyl” includes both enantiomers of an alkylsulfinyl group. Examples of “alkylsulfinyl” include CH3S(O)—, CH3CH2S(O)—, CH3CH2CH2S(O)—, (CH3)2CHS(O)— and the different butylsulfinyl isomers. Examples of “alkylsulfonyl” include CH3S(O)2—, CH3CH2S(O)2—, CH3CH2CH2S(O)2—, (CH3)2CHS(O)2—, and the different butylsulfonyl isomers. “Alkylthioalkyl” denotes alkylthio substitution on alkyl. Examples of “alkylthioalkyl” include CH3SCH2, CH3SCH2CH2, CH3CH2SCH2, CH3CH2CH2CH2SCH2 and CH3CH2SCH2CH2. “(Alkylthio)carbonyl” denotes a straight-chain or branched alkylthio group bonded to a C(═O) moiety. Examples of “(alkylthio)carbonyl” include CH3SC(═O), CH3CH2CH2SC(═O) and (CH3)2CHSC(═O). “Alkoxy(thiocarbonyl)” denotes a straight-chain or branched alkoxy group bonded to a C(═S) moiety. Examples of “alkoxy(thiocarbonyl)” include CH3OC(═S), CH3CH2CH2OC(═S) and (CH3)2CHOC(═S). “Alkylaminoalkyl” denotes a straight-chain or branched alkyl moieties bonded to a nitrogen atom of an amino(straight-chain or branched)alkyl moiety. Examples of “alkylaminoalkyl” include CH3NHCH2—, (CH3)2CHNHCH2— and CH3NHCH(CH3)—. “Dialkylaminoalkyl” denotes two independent straight-chain or branched alkyl moieties bonded to a nitrogen atom of an amino(straight-chain or branched)alkyl moiety. Examples of “dialkylaminoalkyl” include (CH3)2NCH2—, (CH3)2CH(CH3)NCH2— and (CH3)2NCH(CH3)—. The term “alkylcarbonylamino” denotes alkyl bonded to a C(═O)NH moiety. Examples of “alkylcarbonylamino” include CH3CH2C(═O)NH and CH3CH2CH2C(═O)NH.
“Cycloalkyl” includes, for example, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. The term “alkylcycloalkyl” denotes alkyl substitution on a cycloalkyl moiety and includes, for example, ethylcyclopropyl, i-propylcyclobutyl, 3-methylcyclopentyl and 4-methylcyclohexyl. The term “cycloalkylalkyl” denotes cycloalkyl substitution on an alkyl moiety. Examples of “cycloalkylalkyl” include cyclopropylmethyl, cyclopentylethyl, and other cycloalkyl moieties bonded to straight-chain or branched alkyl groups. The term “cycloalkoxy” denotes cycloalkyl linked through an oxygen atom such as cyclopentyloxy and cyclohexyloxy. “Cycloalkenyl” includes carbocyclic rings that contain only one double bond such as cyclopentenyl and cyclohexenyl, as well as carbocyclic rings with more than one double bond such as 1,3- and 1,4-cyclohexadienyl, but are not aromatic. “Cycloalkylcarbonyl” denotes cycloalkyl bonded to a C(═O) group including, for example, cyclopropylcarbonyl and cyclopentylcarbonyl. The term “cycloalkoxycarbonyl” means cycloalkoxy bonded to a C(═O) group, for example, cyclopropyloxycarbonyl and cyclopentyloxycarbonyl. The term “cycloalkylene” denotes a cycloalkanediyl ring. Examples of “cycloalkylene” include cyclopropylene, cyclobutylene, cyclopentylene and cyclohexylene. The term “cycloalkenylene” denotes a cycloalkenediyl ring containing one olefinic bond. Examples of “cycloalkenylene” include cylopropenediyl and cyclpentenediyl.
The term “halogen”, either alone or in compound words such as “haloalkyl”, or when used in descriptions such as “alkyl substituted with halogen” includes fluorine, chlorine, bromine or iodine. Further, when used in compound words such as “haloalkyl”, or when used in descriptions such as “alkyl substituted with halogen” said alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Examples of “haloalkyl” or “alkyl substituted with halogen” include F3C—, ClCH2—, CF3CH2— and CF3CCl2—. The terms “halocycloalkyl”, “haloalkoxy”, “haloalkylthio”, and the like, are defined analogously to the term “haloalkyl”. Examples of “haloalkoxy” include CH2FO—, CHF2O—, CF3O—, CCl3CH2O—, HCF2CH2CH2O— and CF3CH2O—. Examples of “fluoroalkoxy” include CH2FO—, CHF2O—, CF3O— HCF2CH2CH2O— and CF3CH2O—. Examples of “fluoromethoxy” include CH2FO—, CHF2O— and CF3O—. Examples of “haloalkylthio” include CCl3S—, CF3S—, CCl3CH2S— and ClCH2CH2CH2S—. Examples of “haloalkylsulfinyl” include CF3S(O)—, CCl3S(O)—, CF3CH2S(O)— and CF3CF2S(O)—. Examples of “haloalkylsulfonyl” include CF3S(O)2—, CCl3S(O)2—, CF3CH2S(O)2— and CF3CF2S(O)2—.
The total number of carbon atoms in a substituent group is indicated by the “Ci-Cj” prefix where i and j are numbers from 1 to 12. For example, C1-C4 alkylsulfonyl designates methylsulfonyl through butylsulfonyl; C2 alkoxyalkyl designates CH3OCH2—; C3 alkoxyalkyl designates, for example, CH3CH(OCH3)—, CH3OCH2CH2— or CH3CH2OCH2—; and C4 alkoxyalkyl designates the various isomers of an alkyl group substituted with an alkoxy group containing a total of four carbon atoms, examples including CH3CH2CH2OCH2— and CH3CH2OCH2CH2—.
As used herein, the following definitions shall apply unless otherwise indicated. The term “optionally substituted” is used interchangeably with the phrase “substituted or unsubstituted” or with the term “(un)substituted.” Unless otherwise indicated, an optionally substituted group may have a substituent at each substitutable position of the group, and each substitution is independent of the other.
The term “unsubstituted” in connection with a group such as a ring or ring system means the group does not have any substituents other than its one or more attachments to the remainder of Formula 1. The term “optionally substituted” means that the number of substituents can be zero. Unless otherwise indicated, optionally substituted groups may be substituted with as many optional substituents as can be accommodated by replacing a hydrogen atom with a non-hydrogen substituent on any available carbon or nitrogen atom. The number of optional substituents may be restricted by an expressed limitation. For example, the phrase “optionally substituted with up to 3 substituents selected from R9a on carbon ring members” means that 0, 1, 2 or 3 substituents can be present (if the number of potential connection points allows). Similarly, the phrase “optionally substituted with up to 5 substituents selected from R3 on carbon ring members” means that 0, 1, 2, 3, 4 or 5 substituents can be present if the number of available connection points allows. When a range specified for the number of substituents (e.g., r being an integer from 0 to 4 or from 0 to 3 for 5- and 6-membered nitrogen-containing heterocycles in Exhibit A) exceeds the number of positions available for substituents on a ring (e.g., 2 positions available for (Ra)r on U-27 in Exhibit A), the actual higher end of the range is recognized to be the number of available positions.
When a compound is substituted with a substituent bearing a subscript that indicates the number of said substituents can exceed 1, said substituents (when they exceed 1) are independently selected from the group of defined substituents, e.g., (R3)p in Table 1 where p is 0, 1, 2, 3, 4 or 5. When a group contains a substituent which can be hydrogen, for example R1, R4, R5, R6, R7 or R13, then when this substituent is taken as hydrogen, it is recognized that this is equivalent to said group being unsubstituted. When a variable group is shown to be optionally attached to a position, for example (Ra)r in H-23 of Exhibit 1, wherein r may be 0, then hydrogen may be at the position even if not recited in the variable group definition. When one or more positions on a group are said to be “not substituted” or “unsubstituted”, then hydrogen atoms are attached to take up any free valency.
The variables “m”, “n”, “t”, “u”, “v”, “w” and “y” in the Summary of the Invention and corresponding parts of the patent specification relate to subscripts appearing to the right of atoms or other molecular fragments within parentheses and denote the integral number of instances present of the atoms or other molecular fragments within the parentheses. “m” relates to “S(O)m”, “n” relates to “S(O)n”, “t” relates to “—S(═O)tR10”, “u” and “v” relate to “S(═O)u(═NR14)y”, “w” relates to “S(═O)w”, and “y” relates to “S(═O)yR25. For example, “m” being 0, 1 or 2 means that “S(O)m” can be “S”, “S(O)” or “S(O)2”.
Unless otherwise indicated, a “ring” as a component of Formula 1 is carbocyclic or heterocyclic. The term “ring system” as a component of Formula 1 denotes two fused rings (e.g., a phenyl ring fused to a pyridinyl ring to form quinolinyl). The term “ring member” refers to an atom or other moiety (e.g., O, S(O), S(O)2 or S(═O)u(═NR14)v) forming the backbone of a ring or ring system.
The term “carbocyclic ring” denotes a ring wherein the atoms forming the ring backbone are selected only from carbon. Unless otherwise indicated, a carbocyclic ring can be a saturated, partially unsaturated, or fully unsaturated ring. “Saturated carbocyclic” refers to a ring having a backbone consisting of carbon atoms linked to one another by single bonds; unless otherwise specified, the remaining carbon valences are occupied by hydrogen atoms.
The terms “heterocyclic ring” or “heterocycle” denote a ring or ring system in which at least one atom forming the ring backbone is not carbon, e.g., nitrogen, oxygen or sulfur. Typically a heterocyclic ring contains no more than 4 nitrogens, no more than 2 oxygens and no more than 2 sulfurs. Unless otherwise indicated, a heterocyclic ring can be a saturated, partially unsaturated, or fully unsaturated ring. The term “saturated heterocyclic ring” refers to a heterocyclic ring containing only single bonds between ring members. In regards to degree of saturation, “a partially unsaturated heterocyclic ring” is intermediate between a saturated heterocyclic ring and a fully unsaturated heterocyclic ring (which may be aromatic). Therefore, as referred to in the present disclosure and claims, the term “partially unsaturated heterocyclic ring” denotes a heterocyclic ring comprising at least one ring member bonded to an adjacent ring member through a double bond and which conceptually potentially accommodates a number of non-cumulated double bonds between adjacent ring members (i.e. in its fully unsaturated counterpart form) greater than the number of double bonds present (i.e. in its partially unsaturated form). When a fully unsaturated heterocyclic ring satisfies Hückel's rule, then said ring is also called a “heteroaromatic ring” or “aromatic heterocyclic ring”. The terms “heteroaromatic ring system” and “heteroaromatic bicyclic ring system” denote a ring system in which at least one atom forming the ring backbone is not carbon, e.g., nitrogen, oxygen or sulfur, and at least one ring is aromatic. Unless otherwise indicated, heterocyclic rings and ring systems can be attached through any available carbon or nitrogen by replacement of a hydrogen on said carbon or nitrogen.
“Aromatic” indicates that each of the ring atoms is essentially in the same plane and has a p-orbital perpendicular to the ring plane, and that (4n+2)π electrons, where n is a positive integer, are associated with the ring to comply with Hückel's rule. The term “aromatic heterocyclic ring system” denotes a heterocyclic ring system in which at least one ring of the ring system is aromatic. The term “nonaromatic ring system” denotes a carbocyclic or heterocyclic ring system that may be fully saturated, as well as partially or fully unsaturated, provided that none of the rings in the ring system are aromatic. The term “four- to seven-membered nonaromatic heterocyclic ring” refers to rings containing four to seven ring members and which do not satisfy Hückel's rule. This term (as used where R6 and R7 are taken together) is not limited by carbon atoms only and can include ring members selected from O, S(O)n and NR13.
In the context of the present invention when an instance of Q1, Q2 or R1 comprises a phenyl or a 6-membered fully unsaturated heterocyclic ring, the ortho, meta and para positions of each ring is relative to the connection of the ring to the remainder of Formula 1.
As noted above, Q1, Q2 and R1 can be (among others) phenyl optionally substituted with one or more substituents selected from a group of substituents as defined in the Summary of the Invention. An example of phenyl optionally substituted with one to five substituents is the ring illustrated as U-57 in Exhibit A, wherein R8 is as defined in the Summary of the Invention for R8 and q is an integer from 0 to 5.
As noted above, Q1 is, inter alia, a 5- to 6-membered fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each ring or ring system containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon atom ring members are independently selected from C(═O) and C(═S), the sulfur atom ring members are independently selected from S(═O)u(═NR14)v, each ring or ring system optionally substituted with up to 5 substituents independently selected from any substituent defined in the Summary of the Invention for Q1 (e.g., a Q1 ring or ring system is optionally substituted with R3 on carbon ring members and cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members). Similarly, Q2 is, inter alia, a 5- to 6-membered saturated, partially unsaturated or fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each ring or ring system containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon atom ring members are independently selected from C(═O) and C(═S), the sulfur atom ring members are independently selected from S(═O)u(═NR14)v, each ring or ring system optionally substituted with up to 5 substituents independently selected from any substituent defined in the Summary of the Invention for Q2. As the substituents on the ring or ring system of Q1 or Q2 are optional, 0 to 5 substituents may be present, limited only by the number of available points of attachment. In these definitions of heterocyclic ring and heteroaromatic ring system, the ring members selected from up to 2 O, up to 2 S and up to 4 N atoms are optional, provided at least one ring member is not carbon (e.g., N, O or S). The definition of S(═O)u(═NR14)v allows the up to 2 sulfur ring members, to be oxidized sulfur moieties (e.g., S(═O) or S(═O)2) or unoxidized sulfur atoms (i.e. when u and v are both zero). The nitrogen atom ring members may be oxidized as N-oxides, because compounds relating to Formula 1 also include N-oxide derivatives. The up to 3 carbon atom ring members selected from C(═O) and C(═S) are in addition to the up to 4 heteroatoms selected from up to 2 O, up to 2 S and up to 4 N atoms.
Also as noted above, R1 can be (among others) 5- or 6-membered nitrogen-containing aromatic heterocycle, which may be optionally substituted with one or more substituents selected from a group of substituents as defined in the Summary of Invention.
When R1 is phenyl or a 5- or 6-membered nitrogen-containing aromatic heterocycle, it may be attached to the remainder of Formula 1 through any available carbon or nitrogen ring atom, unless otherwise described. Likewise, the ring or ring system of Q1 or Q2 may be attached to the remainder of Formula 1 through any available carbon or nitrogen ring atom, unless otherwise described.
Examples of a 5- to 6-membered fully unsaturated heterocyclic ring include the rings H-1 through H-39 illustrated in Exhibit 1, and examples of an 8- to 10-membered heteroaromatic bicyclic ring system include the ring systems B-1 through B-39 illustrated in Exhibit 2. In Exhibits 1 and 2 the variable Ra is any substituent as defined in the Summary of the Invention for Q1, Q2 or R1 (e.g., a Q1 ring or ring system is optionally substituted with R3 on carbon ring members and cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members) and r is an integer from 0 to 5 for Q1 and Q2 or from 0 to 3 for R1, limited by the number of available positions on each depicted ring or ring system.
Exhibit 1













Exhibit 2













Examples of a saturated or partially unsaturated 5- to 6-membered fully unsaturated heterocyclic ring include the rings P-1 through P-40 illustrated in Exhibit 3. In Exhibit 3 the variable Ra is any substituent as defined in the Summary of the Invention for Q2 (e.g., a Q2 ring is optionally substituted with R3 on carbon ring members and cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C2-C6 alkoxyalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminoalkyl and C3-C6 dialkylaminoalkyl on nitrogen atom ring members) and r is an integer from 0 to 5, limited by the number of available positions on each depicted ring or ring system.
Exhibit 3













Examples of a 5- or 6-membered nitrogen-containing heterocycle optionally substituted with from one or more substituents of particular note for Q1, Q2 and R1 include the rings U-1 through U-56 illustrated in Exhibit A wherein Ra is any substituent as defined in the Summary of the Invention for Q1 Q2 and R1, respectively (i.e. for Q1 and Q2:R3 on carbon atom ring members, and the recited list of possible substituents on nitrogen atom ring members; and for R1, R9a on carbon ring members and R9b on nitrogen ring members) and r is an integer ranging from 0 to 4 for Q1 and Q2 and from 0 to 3 for R1, limited by the number of available positions on each U group. Note that some U groups can only be substituted with less than 4 Ra groups (e.g., U-4 through U-43 and U-47 through U-56). As U-24, U-25, U-31, U-32, U-33, U-34, U-35, U-36, U-37 and U-38 have only one available position, for these U groups, r is limited to the integers 0 or 1, and r being 0 means that the U group is unsubstituted and a hydrogen is present at the position indicated by (Ra)r.
Exhibit A
















Although Ra groups are shown in the structures H-1 through H-39, B-1 through B-39, P-1 through P-40, and U-1 through U-57 in Exhibits 1 through 3 and Exhibit A, it is noted that they do not need to be present since they are optional substituents. The nitrogen atoms that require substitution to fill their valence are substituted with H or Ra. Note that when the attachment point between (Ra)r and the H, B, P or U group in Exhibits 1 through 3 and Exhibit A is illustrated as floating, (Ra)r can be attached to any available carbon atom or nitrogen atom of the H, B, P or U group. Note that when the attachment point on the H, B or P group in Exhibits 1 through 3 is illustrated as floating, the H, B or P group can be attached to the remainder of Formula 1 through any available carbon or nitrogen of the H, B or P group by replacement of a hydrogen atom. Of note are alternative depictions of the chemical structures shown in Exhibits 1 through 3 and Exhibit A in which the “Ra” variable substituent is replaced by “RV”, wherein the “v” superscript in “RV” does not refer to the subscript variable “v” defined in the Summary of the Invention but instead differentiates “RV” from other substituent variables beginning with “R”.
Examples of where R6 and R7 are taken together to form a four- to seven-membered nonaromatic heterocyclic ring include the rings G-1 through G-28 as illustrated in Exhibit 4. Note that when R6 and R7 are taken together to form a ring comprising a ring selected from G-25 through G-28, G2 is selected from O, S(O)n or NR13. Note that when G2 is N, the nitrogen atom can complete its valence by substitution with either H or the substituents corresponding to R13 as defined in the Summary of Invention.
Exhibit 4










A wide variety of synthetic methods are known in the art to enable preparation of aromatic and nonaromatic heterocyclic rings and ring systems; for extensive reviews see the eight volume set of Comprehensive Heterocyclic Chemistry, A. R. Katritzky and C. W. Rees editors-in-chief, Pergamon Press, Oxford, 1984 and the twelve volume set of Comprehensive Heterocyclic Chemistry II, A. R. Katritzky, C. W. Rees and E. F. V. Scriven editors-in-chief, Pergamon Press, Oxford, 1996.
Compounds of this invention can exist as one or more stereoisomers. The various stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers. One skilled in the art will appreciate that one stereoisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other stereoisomer(s) or when separated from the other stereoisomer(s). Additionally, the skilled artisan knows how to separate, enrich, and/or to selectively prepare said stereoisomers. The compounds of the invention may be present as a mixture of stereoisomers, individual stereoisomers or as an optically active form.
One skilled in the art will appreciate that not all nitrogen-containing heterocycles can form N-oxides since the nitrogen requires an available lone pair for oxidation to the oxide; one skilled in the art will recognize those nitrogen-containing heterocycles which can form N-oxides. One skilled in the art will also recognize that tertiary amines can form N-oxides. Synthetic methods for the preparation of N-oxides of heterocycles and tertiary amines are very well known by one skilled in the art including the oxidation of heterocycles and tertiary amines with peroxy acids such as peracetic and m-chloroperbenzoic acid (MCPBA), hydrogen peroxide, alkyl hydroperoxides such as t-butyl hydroperoxide, sodium perborate, and dioxiranes such as dimethyldioxirane. These methods for the preparation of N-oxides have been extensively described and reviewed in the literature, see for example: T. L. Gilchrist in Comprehensive Organic Synthesis, vol. 7, pp 748-750, S. V. Ley, Ed., Pergamon Press; M. Tisler and B. Stanovnik in Comprehensive Heterocyclic Chemistry, vol. 3, pp 18-20, A. J. Boulton and A. McKillop, Eds., Pergamon Press; M. R. Grimmett and B. R. T. Keene in Advances in Heterocyclic Chemistry, vol. 43, pp 149-161, A. R. Katritzky, Ed., Academic Press; M. Tisler and B. Stanovnik in Advances in Heterocyclic Chemistry, vol. 9, pp 285-291, A. R. Katritzky and A. J. Boulton, Eds., Academic Press; and G. W. H. Cheeseman and E. S. G. Werstiuk in Advances in Heterocyclic Chemistry, vol. 22, pp 390-392, A. R. Katritzky and A. J. Boulton, Eds., Academic Press.
One skilled in the art recognizes that some of the compounds disclosed herein can exist in equilibrium with one or more of their respective tautomeric counterparts. Unless otherwise indicated, reference to a compound by one tautomer description is to be considered to include all tautomers. For example, reference to the tautomeric form depicted by Formula 21 also includes the tautomic form depicted by Formula 22.




One skilled in the art recognizes that because in the environment and under physiological conditions salts of chemical compounds are in equilibrium with their corresponding nonsalt forms, salts share the biological utility of the nonsalt forms. Thus a wide variety of salts of the compounds of Formula 1 are useful for control of plant diseases caused by fungal plant pathogens (i.e. are agriculturally suitable). The salts of the compounds of Formula 1 include acid-addition salts with inorganic or organic acids such as hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-toluenesulfonic or valeric acids.
Compounds selected from Formula 1, geometric and stereoisomers, tautomers, N-oxides, and salts thereof, typically exist in more than one form, and Formula 1 thus includes all crystalline and non-crystalline forms of the compounds that Formula 1 represents. Non-crystalline forms include embodiments which are solids such as waxes and gums as well as embodiments which are liquids such as solutions and melts. Crystalline forms include embodiments which represent essentially a single crystal type and embodiments which represent a mixture of polymorphs (i.e. different crystalline types). The term “polymorph” refers to a particular crystalline form of a chemical compound that can crystallize in different crystalline forms, these forms having different arrangements and/or conformations of the molecules in the crystal lattice. Although polymorphs can have the same chemical composition, they can also differ in composition due the presence or absence of co-crystallized water or other molecules, which can be weakly or strongly bound in the lattice. Polymorphs can differ in such chemical, physical and biological properties as crystal shape, density, hardness, color, chemical stability, melting point, hygroscopicity, suspensibility, dissolution rate and biological availability. One skilled in the art will appreciate that a polymorph of a compound represented by Formula 1 can exhibit beneficial effects (e.g., suitability for preparation of useful formulations, improved biological performance) relative to another polymorph or a mixture of polymorphs of the same compound represented by Formula 1. Preparation and isolation of a particular polymorph of a compound represented by Formula 1 can be achieved by methods known to those skilled in the art including, for example, crystallization using selected solvents and temperatures.
Embodiments of the present invention as described in the Summary of the Invention include (where Formula 1 as used in the following Embodiments includes N-oxides and salts, geometric isomers, stereoisomers and atropisomers thereof):
Embodiment 1
A compound of Formula 1 wherein X is O, S(O)m, NR4, CR15R16 or C(═O).
Embodiment 2
A compound of Formula 1 wherein X is O, S(O)m, NR4 or CR15R16.
Embodiment 3
A compound of Formula 1 wherein X is O, NR4, CR15R16 or C(═O).
Embodiment 4
A compound of Formula 1 wherein X is O, NR4 or CR15R16.
Embodiment 5
A compound of Formula 1 wherein X is O, S(O)m or NR4.
Embodiment 6
A compound of Formula 1 wherein X is O or S(O)m.
Embodiment 7
A compound of Formula 1 wherein X is O.
Embodiment 8
A compound of Formula 1 wherein X is NR4.
Embodiment 9
A compound of Formula 1 wherein X is O or NR4.
Embodiment 10
A compound of Formula 1 wherein X is CR15R16, C(═O) or C(═S).
Embodiment 11
A compound of Formula 1 or any one of Embodiments 1 through 10 wherein when Q1 is a six-membered ring (e.g., phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl) and an R3 substituent is located at a meta position (relative to the connection of the Q1 ring to the remainder of Formula 1), then said R3 substituent is selected from F, Cl, Br and cyano (—CN).
Embodiment 11a
A compound of Formula 1 or any one of Embodiments 1 through 11 wherein when Q1 is a six-membered ring and an R3 substituent is located at a meta position (relative to the connection of the Q1 ring to the remainder of Formula 1), then said R3 substituent is F.
Embodiment 12
A compound of Formula 1 or any one of Embodiments 1 through 11a wherein when Q1 is a six-membered ring (e.g., phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl) substituted with only one R3 substituent, then said R3 substituent is attached at an ortho position (relative to the connection of the Q1 ring to the remainder of Formula 1).
Embodiment 13
A compound of Formula 1 or any one of Embodiments 1 through 12 wherein Q1 is phenyl, thienyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, naphthalenyl, quinolinyl, isoquinolinyl or quinoxalinyl, each optionally substituted with up to 5 substituents independently selected from R3.
Embodiment 14
A compound of Embodiment 13 wherein Q1 is phenyl, thienyl, pyridinyl, pyridazinyl, pyrazinyl or pyrimidinyl, each optionally substituted with up to 5 substituents independently selected from R3.
Embodiment 15
A compound of Embodiment 14 wherein Q1 is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with from 1 to 4 substituents independently selected from R3.
Embodiment 16
A compound of Embodiment 15 wherein Q1 is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with 1, 2 or 3 substituents independently selected from R3.
Embodiment 17
A compound of Embodiment 16 wherein the substituents are located at the ortho and/or para positions (relative to the connection of the Q1 ring to the remainder of Formula 1) of the phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl of Q1.
Embodiment 18
A compound of Embodiment 16 or 17 wherein Q1 is phenyl or pyridinyl, each substituted with 1, 2 or 3 substituents independently selected from R3.
Embodiment 19
A compound of Embodiment 18 wherein Q1 is phenyl or pyridinyl, each substituted with 2 or 3 substituents independently selected from R3.
Embodiment 20
A compound of Embodiment 19 wherein Q1 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R3; or phenyl substituted at the 2- and 4-positions with substituents independently selected from R3; or phenyl substituted at the 2- and 6-positions with substituents independently selected from R3.
Embodiment 21
A compound of Embodiment 20 wherein Q1 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R3; or phenyl substituted at the 2- and 4-positions with substituents independently selected from R3.
Embodiment 22
A compound of Embodiment 21 wherein Q1 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R3.
Embodiment 23
A compound of Embodiment 21 wherein Q1 is phenyl substituted at the 2- and 4-positions with substituents independently selected from R3.
Embodiment 24
A compound of Embodiment 21 wherein Q1 is phenyl substituted at the 2- and 6-positions with substituents independently selected from R3.
Embodiment 25
A compound of Embodiment 18 wherein Q1 is pyridinyl substituted with 1, 2 or 3 substituents independently selected from R3.
Embodiment 26
A compound of Embodiment 25 wherein Q1 is pyridinyl substituted with 1 or 2 substituents independently selected from R3.
Embodiment 27
A compound of Embodiment 26 wherein Q1 is pyridinyl substituted with 1 substituent independently selected from R3.
Embodiment 28
A compound of Formula 1 or any one of Embodiments 1 through 27 wherein when Q2 is a six-membered ring (e.g., phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl) and an R3 substituent is located at a meta position (relative to the connection of the Q2 ring to the remainder of Formula 1), then said R3 substituent is selected from F, Cl, Br and cyano (—CN).
Embodiment 29
A compound of Formula 1 or any one of Embodiments 1 through 28 wherein when Q2 is a six-membered ring and an R3 substituent is located at a meta position (relative to the connection of the Q2 ring to the remainder of Formula 1), then said R3 substituent is F.
Embodiment 30
A compound of Formula 1 or any one of Embodiments 1 through 29 wherein when Q2 is a six-membered ring (e.g., phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl) substituted with only one R3 substituent, then said R3 substituent is attached at an ortho position (relative to the connection of the Q2 ring to the remainder of Formula 1).
Embodiment 31
A compound of Formula 1 or any one of Embodiments 1 through 30 wherein Q2 is phenyl, thienyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, naphthalenyl, quinolinyl, isoquinolinyl or quinoxalinyl, each optionally substituted with up to 5 substituents independently selected from R3.
Embodiment 32
A compound of Embodiment 31 wherein Q2 is phenyl, thienyl, pyridinyl, pyridazinyl, pyrazinyl or pyrimidinyl, each optionally substituted with up to 5 substituents independently selected from R3.
Embodiment 33
A compound of Embodiment 32 wherein Q2 is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with from 1 to 4 substituents independently selected from R3.
Embodiment 34
A compound of any one of Embodiments 31 through 33 wherein Q2 is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with 1, 2 or 3 substituents independently selected from R3.
Embodiment 35
A compound of Embodiment 34 wherein the substituents are located at the ortho and/or para positions (relative to the connection of the Q2 ring to the remainder of Formula 1) of the phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl of Q2.
Embodiment 36
A compound of any one of Embodiments 34 or 35 wherein Q2 is phenyl or pyridinyl, each substituted with 1, 2 or 3 substituents independently selected from R3.
Embodiment 37
A compound of Embodiment 36 wherein Q2 is phenyl substituted with 1, 2 or 3 substituents independently selected from R3.
Embodiment 38
A compound of Embodiment 37 wherein Q2 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R3; or phenyl substituted at the 2- and 4-positions with substituents independently selected from R3; or phenyl substituted at the 2- and 6-positions with substituents independently selected from R3.
Embodiment 39
A compound of Embodiment 38 wherein Q2 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R3.
Embodiment 40
A compound of Embodiment 38 wherein Q2 is phenyl substituted at the 2- and 4-positions with substituents independently selected from R3.
Embodiment 41
A compound of Embodiment 38 wherein Q2 is phenyl substituted at the 2- and 6-positions with substituents independently selected from R3.
Embodiment 42
A compound of Embodiment 36 wherein Q2 is pyridinyl substituted with 1, 2 or 3 substituents independently selected from R3.
Embodiment 43
A compound of Embodiment 42 wherein Q2 is pyridinyl substituted with 1 or 2 substituents independently selected from R3.
Embodiment 44
A compound of Embodiment 43 wherein Q2 is pyridinyl substituted with 1 substituent selected from R3.
Embodiment 45
A compound of Formula 1 or any one of Embodiments 1 through 44 wherein at least one of Q1 and Q2 is phenyl optionally substituted with R3 (e.g., optionally substituted with up to 5 substituents independently selected from R3).
Embodiment 46
A compound of Embodiment 45 wherein at least one of Q1 and Q2 is phenyl substituted with 2, 3 or 4 substituents independently selected from R3.
Embodiment 47
A compound of Embodiment 46 wherein at least one Q1 and Q2 is phenyl substituted with 2 or 3 substituents independently selected from R3.
Embodiment 48
A compound of Embodiment 47 wherein each of Q1 and Q2 is phenyl substituted with 2 or 3 substituents independently selected from R3.
Embodiment 49
A compound of Formula 1 or any one of Embodiments 1 through 48 wherein R1 is H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, CO2R5, C(O)NR6R7, cyano, C1-C6 alkoxy, C1-C6 haloalkoxy or C2-C5 alkoxyalkyl; or R1 is a five- or six-membered nitrogen-containing aromatic heterocycle optionally substituted with up to 3 substituents independently selected from R9a on carbon atom ring members and R9b on nitrogen atom ring members.
Embodiment 50
A compound of Embodiment 49 wherein R1 is H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, cyano, C1-C6 alkoxy or C1-C6 haloalkoxy; or R1 is pyridinyl, pyrimidinyl, pyrazolyl or oxazolyl, each optionally substituted with up to 3 substituents independently selected from R9a on carbon atom ring members and R9b on nitrogen atom ring members.
Embodiment 51
A compound of Embodiment 50 wherein R1 is H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, CO2R5, C(O)NR6R7, cyano, C1-C6 alkoxy, C1-C6 haloalkoxy or C2-C5 alkoxyalkyl.
Embodiment 52
A compound of Embodiment 51 wherein R1 is H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C(O)NR6R7, cyano, C1-C6 alkoxy, C1-C6 haloalkoxy or C2-C5 alkoxyalkyl.
Embodiment 53
A compound of Embodiment 52 wherein R1 is H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, cyano, C1-C6 alkoxy, C1-C6 haloalkoxy or C2-C5 alkoxyalkyl.
Embodiment 54
A compound of Embodiment 53 wherein R1 is H, halogen or C1-C6 alkyl.
Embodiment 55
A compound of Embodiment 54 wherein R1 is H or CH3.
Embodiment 56
A compound of Embodiment 55 wherein R1 is H.
Embodiment 57
A compound of Formula 1 or any one of Embodiments 1 through 56 wherein R1 is other than an optionally substituted phenyl or an optionally substituted five- or six-membered nitrogen-containing aromatic heterocycle.
Embodiment 58
A compound of Formula 1 or any one of Embodiments 1 through 50 wherein R1 is other than H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C7 cycloalkyl, CO2R5, C(O)NR6R7, cyano, C1-C6 alkoxy, C1-C6 haloalkoxy or C2-C5 alkoxyalkyl.
Embodiment 59
A compound of Formula 1 or any one of Embodiments 1 through 58 wherein R1a is H.
Embodiment 60
A compound of Formula 1 or any one of Embodiments 1 through 59 wherein R2 is CH3, CH2CH3, halogen, cyano, cyanomethyl, monohalomethyl, hydroxymethyl, methoxy or methylthio; or cyclopropyl optionally substituted with up to 2 substituents independently selected from halogen and methyl.
Embodiment 61
A compound of Embodiment 60 wherein R2 is CH3, CH2CH3, Cl, Br or I.
Embodiment 62
A compound of Embodiment 61 wherein R2 is CH3, CH2CH3, Cl or Br.
Embodiment 63
A compound of Embodiment 62 wherein R2 is CH3, Cl or Br.
Embodiment 64
A compound of Embodiment 63 wherein R2 is CH3 or Cl.
Embodiment 65
A compound of Embodiment 64 wherein R2 is CH3.
Embodiment 66
A compound of Embodiment 62 wherein R2 is Cl or Br.
Embodiment 67
A compound of Embodiment 66 wherein R2 is Cl.
Embodiment 68
A compound of Formula 1 or any one of Embodiments 1 through 67 wherein R5 is H or C1-C6 alkyl.
Embodiment 69
A compound of Embodiment 68 wherein R5 is H, CH3 or CH2CH3.
Embodiment 70
A compound of Embodiment 68 wherein R5 is C1-C6 alkyl.
Embodiment 71
A compound of Embodiment 69 or 70 wherein R5 is CH3 or CH2CH3.
Embodiment 72
A compound of Formula 1 or any one of Embodiments 1 through 71 wherein when R6 is separate (i.e. not taken together with R7 to form a ring), then R6 is H or C1-C6 alkyl.
Embodiment 73
A compound of Embodiment 72 wherein R6 is H.
Embodiment 74
A compound of Formula 1 or any one of Embodiments 1 through 73 wherein when R7 is separate (i.e. not taken together with R6 to form a ring), then R7 is H, C1-C6 alkyl, C1-C6 haloalkyl or C4-C8 alkylcycloalkyl.
Embodiment 75
A compound of Embodiment 74 wherein R7 is H or C1-C6 alkyl.
Embodiment 76
A compound of Embodiment 75 wherein R7 is H.
Embodiment 77
A compound of Formula 1 or any one Embodiments 1 through 76 wherein when R6 and R7 are taken together with the nitrogen atom to which they are connected to form a nonaromatic heterocyclic ring, the ring contains ring members, in addition to the connecting nitrogen atom, selected from carbon atoms and up to one ring member selected from O and NR13.
Embodiment 78
A compound of Embodiment 77 wherein when R6 and R7 are taken together with the nitrogen atom to which they are connected to form a nonaromatic heterocyclic ring, the ring is six-membered and contains one ring member selected from O and NR13 in addition to the connecting nitrogen atom and ring members selected from carbon atoms.
Embodiment 79
A compound of Embodiment 77 wherein R6 and R7 are taken together with the nitrogen atom to which they are connected to form a piperidine ring.
Embodiment 80
A compound of Embodiment 78 wherein R6 and R7 are taken together with the nitrogen atom to which they are connected to form a piperazine or morpholine ring.
Embodiment 81
A compound of Formula 1 or any one of Embodiments 1 through 80 wherein each R8 is independently selected from halogen, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy, C1-C2 haloalkoxy, cyano and nitro.
Embodiment 82
A compound of Embodiment 81 wherein each R8 is independently selected from halogen, C1-C2 alkyl, C1-C2 alkoxy, cyano and nitro.
Embodiment 83
A compound of Embodiment 82 wherein each R8 is independently Cl or F.
Embodiment 84
A compound of Formula 1 or any one of Embodiments 1 through 83 wherein each R9a is independently selected from halogen, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy, C1-C2 haloalkoxy, cyano and nitro.
Embodiment 85
A compound of Embodiment 84 wherein each R9a is independently selected from halogen, C1-C2 alkyl, C1-C2 alkoxy, cyano and nitro.
Embodiment 86
A compound of Embodiment 85 wherein each R9a is independently selected from Cl, F, CH3, —OCH3 and cyano.
Embodiment 87
A compound of Embodiment 86 wherein each R9a is independently Cl or F.
Embodiment 88
A compound of Formula 1 or any one of Embodiments 1 through 87 wherein each R9b is independently C1-C2 alkyl.
Embodiment 89
A compound of Formula 1 or any one of Embodiments 1 through 88 wherein each R3 is independently selected from halogen, cyano, nitro, amino, methylamino, dimethylamino, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 haloalkylthio, C1-C3 alkylsulfinyl, C1-C3 haloalkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylsulfonyl, C3-C4 cycloalkyl, C(═S)NH2 and —U—V-T.
Embodiment 90
A compound of Embodiment 89 wherein each R3 is independently selected from halogen, cyano, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy and —U—V-T.
Embodiment 91
A compound of Embodiment 90 wherein each R3 is independently selected from F, Cl, Br, cyano, nitro, CH3, CF3, —OCH3, —OCHF2 and —U—V-T.
Embodiment 92
A compound of Formula 1 or any one of Embodiments 1 through 91 wherein at least one R3 substituent on the ring or ring system of Q1 or Q2 is —U—V-T.
Embodiment 93
A compound of Formula 1 or any one of Embodiments 1 through 91 wherein each R3 is other than —U—V-T.
Embodiment 94
A compound of Embodiment 89 wherein each R3 is independently selected from halogen, cyano, nitro, amino, methylamino, dimethylamino, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 haloalkylthio, C1-C3 alkylsulfinyl, C1-C3 haloalkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylsulfonyl and C3-C4 cycloalkyl.
Embodiment 95
A compound of Embodiment 94 wherein each R3 is independently selected from halogen, cyano, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkoxy and C1-C3 haloalkoxy.
Embodiment 96
A compound of Embodiment 95 wherein each R3 is independently selected from halogen, cyano, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy and C1-C3 haloalkoxy.
Embodiment 97
A compound of Embodiment 96 wherein each R3 is independently selected from F, Cl, Br, cyano, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy and C1-C2 haloalkoxy.
Embodiment 98
A compound of Embodiment 97 wherein each R3 is independently selected from F, Cl, Br, cyano, methyl, C1-C2 alkoxy and fluoromethoxy.
Embodiment 99
A compound of Embodiment 98 wherein each R3 is independently selected from F, Cl, cyano, methyl, C1-C2 alkoxy and fluoromethoxy.
Embodiment 100
A compound of Embodiment 95 wherein each R3 is independently selected from F, Cl, Br, cyano, nitro, CH3, CF3, —OCH3 and —OCHF2.
Embodiment 101
A compound of any one of Embodiments 89 through 98 or 100 wherein each R3 is independently selected from F, Cl, Br, cyano and methoxy.
Embodiment 102
A compound of Embodiment 101 wherein each R3 is independently selected from F, Cl, Br and cyano.
Embodiment 103
A compound of Embodiment 101 wherein each R3 is independently selected from F, Cl, cyano and —OCH3.
Embodiment 104
A compound of Formula 1 or any one of Embodiments 1 through 92 wherein each U is independently O or NR22.
Embodiment 105
A compound of Embodiment 104 wherein each U is independently O or NH.
Embodiment 106
A compound of Formula 1 or any one of Embodiments 1 through 92 and 104 through 105 wherein each V is C2-C4 alkylene.
Embodiment 107
A compound of Formula 1 or any one of Embodiments 1 through 92 and 104 through 106 wherein each T is independently NR23aR23b or OR24.
Embodiment 108
A compound of Formula 1 or any one of Embodiments 1 through 92 and 104 through 107 wherein each R23a and R23b is independently H, C1-C6 alkyl or C1-C6 haloalkyl.
Embodiment 109
A compound of Formula 1 or any one of Embodiments 1 through 92 and 104 through 108 wherein each R24 is independently H, C1-C6 alkyl or C1-C6 haloalkyl.
Embodiment 110
A compound of Formula 1 or any one of Embodiments 1 through 109 wherein when an R3 substituent attached to phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl of Q1 or Q2 is other than F, Cl, Br, cyano, methyl, C1-C2 alkoxy and fluoromethoxy, then said R3 substituent is attached at the para position (of the phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl ring).
Embodiment 111
A compound of Formula 1 or any one of Embodiments 1 through 110 wherein R4 is H, formyl, C3-C7 cycloalkyl or —SR10; or C1-C6 alkyl or C1-C6 haloalkyl, each optionally substituted with up to 2 R12.
Embodiment 112
A compound of Embodiment 111 wherein R4 is H, formyl, C3-C7 cycloalkyl or —SR10; or C1-C6 alkyl substituted with one R12.
Embodiment 113
A compound of Embodiment 112 wherein R4 is H, formyl, —CH2OCH3, cyclopropyl, —SCH3, —SCF3 or —CH2CN.
Embodiment 114
A compound of Embodiment 113 wherein R4 is H, formyl, cyclopropyl or —CH2CN.
Embodiment 115
A compound of Embodiment 113 wherein R4 is H, formyl, —CH2OCH3, cyclopropyl, —SCH3 or —SCF3.
Embodiment 116
A compound of Embodiment 115 wherein R4 is H, formyl or cyclopropyl.
Embodiment 117
A compound of Embodiment 114 or 116 wherein R4 is H.
Embodiment 118
A compound of Formula 1 or any one of Embodiments 1 through 117 wherein R13 is H or CH3.
Embodiment 119
A compound of Embodiment 118 wherein R13 is CH3.
Embodiment 120
A compound of Formula 1 or any one of Embodiments 1 through 119 wherein each R12 is independently C3-C7 cycloalkyl, C1-C4 alkoxy or cyano.
Embodiment 121
A compound of Embodiment 120 wherein each R12 is independently cyclopropyl, —OCH3 or cyano.
Embodiment 122
A compound of Embodiment 120 wherein each R12 is independently C3-C7 cycloalkyl or C1-C4 alkoxy.
Embodiment 123
A compound of Embodiment 122 wherein each R12 is independently cyclopropyl or —OCH3.
Embodiment 124
A compound of Formula 1 or any one of Embodiments 1 through 123 wherein R10 is CH3, CH2CH3, CF3 or CF2CF3.
Embodiment 125
A compound of Embodiment 124 wherein R10 is CH3.
Embodiment 126
A compound of Formula 1 or any one of Embodiments 1 through 125 wherein R11 is C1-C6 alkyl, C1-C6 alkoxy or C1-C6 alkylthio.
Embodiment 127
A compound of Embodiment 126 wherein R11 is CH3, CH2CH3, —OCH3, —OCH2CH3, —SCH3 or —SCH2CH3.
Embodiment 128
A compound of Embodiment 127 wherein R11 is CH3, —OCH3 or —SCH3.
Embodiment 129
A compound of Formula 1 or any one of Embodiments 1 through 128 wherein R15 is H or CH3.
Embodiment 130
A compound of Embodiment 129 wherein R15 is H.
Embodiment 131
A compound of Formula 1 or any one of Embodiments 1 through 130 wherein R16 is CH3 or OR18.
Embodiment 132
A compound of Embodiment 131 wherein R16 is OR18.
Embodiment 133
A compound of Formula 1 or any one of Embodiments 1 through 132 wherein R18 is H.
Embodiment 134
A compound of Formula 1 or any one of Embodiments 1 through 133 wherein W is O.
Embodiment 135
A compound of Formula 1 or any one of Embodiments 1 through 134 wherein M+ is a cation selected from sodium, potassium and lithium ions.
Embodiment 136
A compound of Embodiment 135 wherein M+ is a cation selected from sodium and potassium ions.
Embodiment 137
A compound of Embodiment 136 wherein M+ is a sodium ion.
Embodiment 138
A compound of Formula 1 or any one of Embodiments 1 through 137 wherein m is 0.
Embodiment 139
A compound of Formula 1 or any one of Embodiments 1 through 138 wherein n is 0.
Embodiments of this invention, including Embodiments 1-139 above as well as any other embodiments described herein, can be combined in any manner, and the descriptions of variables in the embodiments pertain not only to the compounds of Formula 1 but also to the starting compounds and intermediate compounds (e.g. compounds of Formula 2) useful for preparing the compounds of Formula 1. In addition, embodiments of this invention, including Embodiments 1-139 above as well as any other embodiments described herein, and any combination thereof, pertain to the compositions and methods of the present invention.
Combinations of Embodiments 1-139 are illustrated by:
Embodiment A
A compound of Formula 1 wherein

    
    
        Q1 is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with from 1 to 4 substituents independently selected from R3; provided that when an R3 substituent is located at a meta position, then said R3 substituent is selected from F, Cl, Br and cyano;
        Q2 is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with 1, 2 or 3 substituents independently selected from R3, provided that when an R3 substituent is located at a meta position, then said R3 substituent is selected from F, Cl, Br and cyano;
        X is O, NR4, C(═O) or CR15R16;
        R1 is H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, CO2R5, C(O)NR6R7, cyano, C1-C6 alkoxy, C1-C6 haloalkoxy or C2-C5 alkoxyalkyl;
        R1a is H;
        R2 is CH3, CH2CH3, Cl or Br;
        each R3 is independently selected from halogen, cyano, nitro, amino, methylamino, dimethylamino, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy C1-C3 alkylthio, C1-C3 haloalkylthio, C1-C3 alkylsulfinyl, C1-C3 haloalkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylsulfonyl, C3-C4 cycloalkyl, C(═S)NH2 and —U—V-T;
        R4 is H, formyl, C3-C7 cycloalkyl or —SR10; or C1-C6 alkyl or C1-C6 haloalkyl, each optionally substituted with up to 2 R12;
        R5 is C1-C6 alkyl;
        R6 is H or C1-C6 alkyl;
        R7 is H, C1-C6 alkyl, C1-C6 haloalkyl or C4-C8 alkylcycloalkyl; or
        R6 and R7 are taken together with the nitrogen atom to which they are connected to form a four- to seven-membered nonaromatic heterocyclic ring containing ring members, in addition to the connecting nitrogen atom, selected from carbon atoms and up to one ring member selected from O and NR13;
        each R12 is independently C3-C7 cycloalkyl, C1-C4 alkoxy or cyano;
        R13 is H or CH3;
        R15 is H or CH3; and
        R16 is OR18.
    
    


Embodiment B
A compound of Embodiment A wherein

    
    
        Q1 is phenyl or pyridinyl, each substituted with 1, 2 or 3 substituents independently selected from R3;
        Q2 is phenyl or pyridinyl, each substituted with 1, 2 or 3 substituents independently selected from R3;
        R1 is H, halogen or C1-C6 alkyl;
        R2 is CH3, Cl or Br;
        each R3 is independently selected from halogen, cyano, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy and —U—V-T;
        R4 is H, formyl, C3-C7 cycloalkyl or —SR10; or C1-C6 alkyl substituted with one R12;
    
    


each R12 is independently cyclopropyl, —OCH3 or cyano;

    
    
        R15 is H;
        each U is independently O or NH;
        each V is C2-C4 alkylene;
        each T is independently NR23aR23b or OR24;
        each R23a and R23b is independently H, C1-C6 alkyl or C1-C6 haloalkyl; and
        each R24 is independently H, C1-C6 alkyl or C1-C6 haloalkyl.
    
    


Embodiment C
A compound of Embodiment B wherein

    
    
        at least one of Q1 and Q2 is phenyl substituted with 2 or 3 substituents independently selected from R3;
        R1 is H or CH3;
        R2 is CH3;
        R4 is H;
        each R3 is independently selected from halogen, cyano, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy and C1-C3 haloalkoxy; and
        R18 is H.
    
    


Embodiment D
A compound of Embodiment C wherein

    
    
        Q1 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R3; or phenyl substituted at the 2- and 4-positions with substituents independently selected from R3; or phenyl substituted at the 2- and 6-positions with substituents independently selected from R3;
        Q2 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R3; or phenyl substituted at the 2- and 4-positions with substituents independently selected from R3; or phenyl substituted at the 2- and 6-positions with substituents independently selected from R3;
        X is O, NR4 or CR15R16;
        R1 is H;
        each R3 is independently selected from F, Cl, Br, cyano, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy and C1-C2 haloalkoxy; and
        R4 is H.
    
    


Embodiment E
A compound of Embodiment D wherein

    
    
        each R3 is independently selected from F, Cl, Br, cyano, methyl, C1-C2 alkoxy and fluoromethoxy.
    
    


Embodiment F
A compound of Embodiment E wherein

    
    
        X is O or NH; and
        each R3 is independently selected from F, Cl, Br, cyano and methoxy.
    
    


Specific embodiments include compounds of Formula 1 selected from the group consisting of:

    4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-N-(2,4,6-trifluorophenyl)-1H-pyrazol-5-amine (Compound 18),
    N-(4-chlorophenyl)-4-(2,6-difluoro-4-methoxyphenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 22),
    4-(2,6-difluoro-4-methoxyphenyl)-N-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 23),
    4-(2,6-difluoro-4-methoxyphenyl)-1,3-dimethyl-N-(2,4,6-trifluorophenyl)-1H-pyrazol-5-amine (Compound 24),
    N-(2,6-difluoro-4-methoxyphenyl)-4-(3,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 36),
    4-(2,4-difluorophenyl)-1,3-dimethyl-N-(2,4,6-trifluorophenyl)-1H-pyrazol-5-amine (Compound 41),
    4-[[4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]oxy]-3,5-difluorobenzonitrile (Compound 45),
    4-[[4-(2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]oxy]-3-fluorobenzonitrile (Compound 361),
    4-(2-chloro-4-fluorophenyl)-N-(2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 172),
    4-[[4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]oxy]-3-fluorobenzonitrile (Compound 118),
    3-chloro-4-[[4-(2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]oxy]benzonitrile (Compound 358),
    4-(2-chloro-4-fluorophenyl)-α-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazole-5-methanol (Compound 351),
    N,4-bis(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 175),
    N-(2-chloro-4-fluorophenyl)-4-(2-chloro-6-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 193),
    N-(2-chloro-4,6-difluorophenyl)-4-(2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 297),
    N-(2-chloro-4,6-difluorophenyl)-4-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 343),
    N-(4-chloro-2,6-difluorophenyl)-4-(2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 349),
    N-(4-chloro-2,6-difluorophenyl)-4-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 357),
    3-chloro-4-[[4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]oxy]benzonitrile (Compound 139),
    4-[[4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]amino]-3,5-difluorobenzonitrile (Compound 91),
    4-[[4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]oxy]-2,5-difluorobenzonitrile (Compound 148),
    N-(2-chloro-4-fluorophenyl)-4-(2,6-difluoro-4-methoxyphenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 87),
    α,4-bis(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazole-5-methanol (Compound 352),
    N-(4-chloro-2,6-difluorophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazole-5-amine (Compound 286),
    N-(2-chloro-4,6-difluorophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 287),
    N-(2,6-dichloro-4-fluorophenyl)-4-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 368),
    3-chloro-4-[5-[(2-chloro-4,6-difluorophenyl)amino]-1,3-dimethyl-1H-pyrazol-4-yl]-benzonitrile (Compound 332),
    3-chloro-4-[5-[(4-chloro-2,6-difluorophenyl)amino]-1,3-dimethyl-1H-pyrazol-4-yl]-benzonitrile (Compound 336),
    N-(2-bromo-4-fluorophenyl)-4-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 346),
    4-(2-chloro-4-fluorophenyl)-N-(2,4-dichloro-6-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 367),
    4-(2-chloro-4-fluorophenyl)-N-(2,6-dichloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 369),
    4-[[4-(2-bromo-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]oxy]-3-fluorobenzonitrile (Compound 284),
    N-(2-bromo-4-fluorophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 265),
    4-(2-bromo-4-fluorophenyl)-1,3-dimethyl-N-(2,4,6-trifluorophenyl)-1H-pyrazol-5-amine (Compound 266),
    N-(4-bromo-2,6-difluorophenyl)-4-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 364),
    4-[[4-(2-bromo-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]oxy]-3,5-difluorobenzonitrile (Compound 232),
    4-(2-bromo-4-fluorophenyl)-N-(2-chloro-4,6-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 292),
    4-(2-bromo-4-fluorophenyl)-N-(4-chloro-2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 360),
    N-(4-bromo-2,6-difluorophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 365),
    3-bromo-4-[[4-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]oxy]benzonitrile (Compound 372),
    3-chloro-4-[[4-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]oxy]benzonitrile (Compound 373),
    N-(2,4-dichloro-6-fluorophenyl)-4-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 374),
    N-(2,6-dichloro-4-fluorophenyl)-4-(2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 375),
    N-(2-bromo-4,6-difluorophenyl)-4-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 376),
    N-(2-bromo-4,6-difluorophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 377),
    N-(4-bromo-2,6-difluorophenyl)-4-(2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 378),
    N-(2-bromo-4,6-difluorophenyl)-4-(2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 379),
    N-(2-bromo-4,6-difluorophenyl)-4-(2-chloro-6-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 380),
    α-(4-chloro-2,6-difluorophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazole-5-methanol (Compound 381),
    4-[5-[(2-chloro-4,6-difluorophenyl)amino]-1,3-dimethyl-1H-pyrazol-4-yl]-3-fluorobenzonitrile (Compound 382),
    4-[5-[(4-chloro-2,6-difluorophenyl)amino]-1,3-dimethyl-1H-pyrazol-4-yl]-3-fluorobenzonitrile (Compound 383),
    α-(2-chloro-4,6-difluorophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazole-5-methanol (Compound 384),
    α-(2-bromo-4-fluorophenyl)-4-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazole-5-methanol (Compound 385), and
    α-(2-bromo-4-fluorophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazole-5-methanol (Compound 386).


This invention provides a fungicidal composition comprising a compound of Formula 1 (including all geometric and stereoisomers, N-oxides, and salts thereof), and at least one other fungicide. Of note as embodiments of such compositions are compositions comprising a compound corresponding to any of the compound embodiments described above.
This invention provides a fungicidal composition comprising a fungicidally effective amount of a compound of Formula 1 (including all geometric and stereoisomers, N-oxides, and salts thereof), and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents. Of note as embodiments of such compositions are compositions comprising a compound corresponding to any of the compound embodiments described above.
This invention provides a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of a compound of Formula 1 (including all geometric and stereoisomers, N-oxides, and salts thereof). Of note as embodiment of such methods are methods comprising applying a fungicidally effective amount of a compound corresponding to any of the compound embodiments describe above. Of particular note are embodiments where the compounds are applied as compositions of this invention.
Of note are compounds of Formula 1 that are compounds of Formula 1P (including all geometric and stereoisomers), N-oxides, and salts thereof, and also agricultural compositions containing them and their use as fungicides:




wherein

    
    
        Q1 and Q2 are independently phenyl, thienyl, pyridinyl, pyridazinyl, pyrazinyl or pyrimidinyl, each optionally substituted with up to 5 substituents independently selected from R3;
        X is O, S(O)m or NR4;
        R1 is H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C7 cycloalkyl, CO2R5, C(O)NR6R7, cyano, C1-C6 alkoxy, C1-C6 haloalkoxy or C2-C5 alkoxyalkyl; or
        R1 is phenyl optionally substituted with up to 3 R8; or a five- or six-membered nitrogen-containing aromatic heterocycle optionally substituted with up to 3 substituents independently selected from R9a on carbon atom ring members and R9b on nitrogen atom ring members;
        R2 is CH3, CH2CH3, cyclopropyl or halogen;
        each R3 is independently selected from halogen, cyano, nitro, amino, methylamino, dimethylamino, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 haloalkylthio, C1-C3 alkylsulfinyl, C1-C3 haloalkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylsulfonyl, C3-C4 cycloalkyl, C3-C7 cycloalkoxy, C4-C6 alkylcycloalkyl, C4-C6 cycloalkylalkyl, C3-C7 halocycloalkyl, C2-C4 alkenyl and C2-C4 alkynyl;
        R4 is H, formyl, C3-C7 cycloalkyl, —SO3−M+, —SR10 or —(C═W)R11; or C1-C6 alkyl or C1-C6 haloalkyl, each optionally substituted with up to 2 R12;
        R5 is H, C1-C6 alkyl or C1-C6 haloalkyl;
        R6 and R7 are independently selected from H, C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C4-C8 cycloalkylalkyl and C4-C8 alkylcycloalkyl; or
        R6 and R7 are taken together with the nitrogen atom to which they are connected to form a four- to seven-membered nonaromatic heterocyclic ring containing ring members, in addition to the connecting ring nitrogen atom, selected from carbon atoms and optionally up to one ring member selected from O, S(O)n and NR13;
        each R8, R9a and R9b is independently selected from halogen, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy, C1-C2 haloalkoxy, cyano, nitro, SCH3, S(O)CH3 and S(O)2CH3;
        R10 is C1-C6 alkyl or C1-C6 haloalkyl;
        R11 is C1-C6 alkyl, C1-C6 alkoxy, C2-C7 alkoxyalkyl, C2-C7 alkylaminoalkyl, C2-C8 dialkylaminoalkyl, C1-C6 alkylthio or C2-C7 alkylthioalkyl;
        each R12 is independently C3-C7 cycloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl or C1-C4 alkylsulfonyl;
        R13 is H, C1-C3 alkyl or C2-C3 haloalkyl;
        W is O or S;
        M+ is a cation;
        m is 0, 1 or 2; and
        n is 0, 1 or 2.
    
    


Accordingly of note is a compound selected from Formula 1P (including all geometric and stereoisomers), N-oxides, and salts thereof, as defined above. Also of note are counterpart embodiments that are embodiment counterparts to Embodiments 1 through 139 and Embodiments A through F wherein in said counterpart embodiments “Formula 1” is replaced by “Formula 1P” and the scope of said counterpart embodiments does not exceed the scope defined above for Formula 1P. Examples of combinations of Embodiments 1 through 139 as applied to Formula 1P are Embodiments AP, BP, CP, DP and EP: Embodiment AP. A compound of Formula 1P wherein

    
    
        Q1 is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with from 1 to 4 substituents independently selected from R3;
        Q2 is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with 1, 2 or 3 substituents independently selected from R3 
        X is O or NR4;
        R1 is H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, CO2R5, C(O)NR6R7, cyano, C1-C6 alkoxy, C1-C6 haloalkoxy or C2-C5 alkoxyalkyl; or
        R1 is a five- or six-membered nitrogen-containing aromatic heterocycle optionally substituted with up to 3 substituents independently selected from R9a on carbon atom ring members and R9b on nitrogen atom ring members;
        R2 is CH3, CH2CH3, Cl or Br;
        each R3 is independently selected from halogen, cyano, nitro, amino, methylamino, dimethylamino, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy C1-C3 alkylthio, C1-C3 haloalkylthio, C1-C3 alkylsulfinyl, C1-C3 haloalkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylsulfonyl and C3-C4 cycloalkyl;
        R4 is H, formyl, C3-C7 cycloalkyl or —SR10; or C1-C6 alkyl or C1-C6 haloalkyl, each optionally substituted with up to 2 R12;
        R5 is H or C1-C6 alkyl;
        R6 is H or C1-C6 alkyl;
        R7 is H, C1-C6 alkyl, C1-C6 haloalkyl or C4-C8 alkylcycloalkyl; or
        R6 and R7 are taken together with the nitrogen atom to which they are connected to form a four- to seven-membered nonaromatic heterocyclic ring containing ring members, in addition to the connecting nitrogen atom, selected from carbon atoms and up to one ring member selected from O and NR13;
        each R8 is independently selected from halogen, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy, C1-C2 haloalkoxy, cyano and nitro;
    
    


each R9a is independently selected from halogen, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy, C1-C2 haloalkoxy, cyano and nitro;

    
    
        each R9b is C1-C2 alkyl;
        R10 is CH3, CH2CH3, CF3 or CF2CF3;
        each R12 is independently C3-C7 cycloalkyl or C1-C4 alkoxy; and
        R13 is H or CH3.
    
    


Embodiment BP
A compound of Embodiment AP wherein

    
    
        Q1 is phenyl or pyridinyl, each substituted with 1, 2 or 3 substituents independently selected from R3;
        Q2 is phenyl or pyridinyl, each substituted with 1, 2 or 3 substituents independently selected from R3;
        X is NR4;
        R1 is H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, cyano, C1-C6 alkoxy or C1-C6 haloalkoxy;
        R2 is CH3;
        each R3 is independently selected from halogen, cyano, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkoxy and C1-C3 haloalkoxy;
        R4 is H, formyl, C3-C7 cycloalkyl or —SR10; or C1-C6 alkyl substituted with one R12;
        R10 is CH3; and
        each R12 is independently cyclopropyl or —OCH3.
    
    


Embodiment CP
A compound of Embodiment AP wherein

    
    
        Q1 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R3; or
        Q1 is phenyl substituted at the 2- and 4-positions with substituents independently selected from R3;
        Q2 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R3;
        X is O;
        R2 is CH3;
        each R3 is independently selected from F, Cl, Br, cyano, nitro, CH3, CF3, —OCH3, and —OCHF2; and
        R4 is H, formyl or cyclopropyl.
    
    


Embodiment DP
A compound of Embodiment CP wherein

    
    
        Q1 is phenyl substituted at the 2- and 4-positions with substituents independently selected from R3;
        Q2 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R3;
        each R3 is independently selected from F, Cl, cyano and —OCH3; and
        R4 is H.
    
    


Embodiment EP
A compound of Embodiment BP wherein

    
    
        Q1 is phenyl substituted at the 2- and 4-positions with substituents independently selected from R3;
        Q2 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R3;
        each R3 is independently selected from F, Cl, CN and —OCH3; and R4 is H.
    
    


Also of note is a fungicidal composition comprising a fungicidally effective amount of a compound of Formula 1P (including all geometric and stereoisomers, N-oxides, and salts thereof) or any one of counterpart embodiments that are embodiment counterparts to Embodiments 1 through 139 and Embodiments A through F (e.g., Embodiment AP, BP, CP, DP or EP), and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents. Also of note is a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of a compound of Formula 1P (including all geometric and stereoisomers, N-oxides, and salts thereof) or any one of said counterpart embodiments. Of particular note are embodiments where the compounds of Formula 1P are applied as compositions of this invention.
One or more of the following methods and variations as described in Schemes 1-24 can be used to prepare the compounds of Formula 1 (including Formula 1P). The definitions of Q1, Q2, R1, R2 and m in the compounds of Formulae 1-33 below are as defined above in the Summary of the Invention unless otherwise noted. Formulae 1a, 1b, 1c, 1d, 1e, 1f, 1g and 1h are various subsets of Formula 1; Formulae 4a, 4b and 4c are various subsets of Formula 4; Formulae 6a and 6b are various subsets of Formula 6; Formula 11a is a subset of Formula 11; Formula 13a is a subset or analog of Formula 13; and Formula 17a is a subset of Formula 17. Substituents for each subset formula are as defined for its parent formula unless otherwise noted.
As illustrated in Scheme 1, sulfoxides and sulfones of Formula 1b (i.e. Formula 1 wherein X is S(O)m and m is 1 or 2) can be made via oxidation of the linking sulfur atom on sulfides of Formula 1a (i.e. Formula 1 wherein X is S(O)m and m is 0). In this method a compound of Formula 1b wherein m is 1 (i.e. sulfoxides) or m is 2 (i.e. sulfones) is prepared by oxidizing a corresponding sulfide of Formula 1a with a suitable oxidizing agent. In a typical procedure, an oxidizing agent in an amount from 1 to 4 equivalents depending on the oxidation state of the product desired is added to a solution of the compound of Formula 1a in a solvent. Useful oxidizing agents include Oxone® (potassium peroxymonosulfate), hydrogen peroxide, sodium periodate, peracetic acid and 3-chloroperbenzoic acid. The solvent is selected with regard to the oxidizing agent employed. Aqueous ethanol or aqueous acetone is preferably used with potassium peroxymonosulfate, and dichloromethane is generally preferable with 3-chloroperbenzoic acid. Useful reaction temperatures typically range from −78 to 90° C. Particular procedures useful for oxidizing sulfides to sulfoxides and sulfones are described by Brand et al., J. Agric. Food Chem. 1984, 32, 221-226 and references cited therein.




As shown in Scheme 2, compounds of Formula 1 in which X is NH and R1a is H can be prepared by the reaction of 1H-pyrazole compounds of Formula 2 with various alkylating agents (e.g., Formula 3), such as iodoalkanes, alkylsulfonates (e.g., mesylate (OMs) or tosylate (OTs)) or trialkyl phosphates, preferably in the presence of an organic or inorganic base such as 1,8-diazabicyclo[5.4.0]undec-7-ene, potassium carbonate or potassium hydroxide, and in a solvent such as N,N-dimethylformamide, tetrahydrofuran, toluene or water.




Compounds of Formula 1 wherein CHR1R1a forms an optionally substituted cyclopropyl ring can likewise be prepared by reaction of a pyrazole of Formula 2 with an organometallic reagent, such as tricyclopropylbismuth, in the presence of a catalyst, such as copper acetate, under conditions known in the art. See, for example, J. Am. Chem. Soc. 2007, 129(1), 44-45. Of note as starting materials in the method of Scheme 2 are compounds of Formula 2 specifically disclosed in Tables 588 through 671 below.
As is shown in Scheme 3, compounds of Formula 1 can be prepared by the reaction of compounds of Formula 4 (i.e. 5-aminopyrazoles for X being NR4, 5-hydroxypyrazoles (5-pyrazolones) for X being O, or 5-mercaptopyrazoles for X being S) with aromatic compounds of Formula 5 containing a leaving group G (i.e. halogen or (halo)alkylsulfonate), optionally in the presence of a metal catalyst, and generally in the presence of a base and a polar aprotic solvent such as N,N-dimethylformamide or dimethyl sulfoxide. For example, compounds of Formula 5 in which Q2 is an electron-deficient heteroaromatic ring, or a benzene ring with electron-withdrawing substituents, react by direct displacement of the leaving group G from the ring to provide compounds of Formula 1. For compounds of Formula 5 wherein Q2 is attached through a spa-hybridized carbon atom, G is typically Cl, Br, I or a sulfonate (e.g., OS(O)2CH3). Compounds of Formula 5 are commercially available or their preparation is known in the art. Of note are embodiments of the method of Scheme 3 wherein a compound of Formula 4 is used to prepare a corresponding compound of Formula 1 specifically disclosed in Tables 85 through 252 below.




For reactions according to the method of Scheme 3 of a compound of Formula 4 wherein X is O or NR4 with a compound of Formula 5 (Q2-G) wherein Q is an aromatic or heteroaromatic ring Q lacking sufficiently electron-withdrawing substituents, or to improve reaction rate, yield or product purity, the use of a metal catalyst (e.g., metal or metal salt) in amounts ranging from catalytic up to superstoichiometric can facilitate the desired reaction. Typically for these conditions, G is Br or I or a sulfonate such as OS(O)2CF3 or OS(O)2(CF2)3CF3. For example, copper salt complexes (e.g., CuI with N,N-dimethyl-ethylenediamine, proline or bipyridyl), palladium complexes (e.g., tris(dibenzylidene-acetone)dipalladium(0)) or palladium salts (e.g., palladium acetate) with ligands such as 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (i.e. “Xantphos”), 2-dicyclohexyl-phosphino-2′,4′,6′-triisopropylbiphenyl (i.e. “Xphos”) or 2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (i.e. “BINAP”), in the presence of a base such as potassium carbonate, cesium carbonate, sodium phenoxide or sodium tert-butoxide, in a solvent such as N,N-dimethylformamide, 1,2-dimethoxyethane, dimethyl sulfoxide, 1,4-dioxane or toluene, optionally mixed with alcohols such as ethanol, can be used. Alternatively as illustrated in Scheme 4, compounds of Formula 1c (i.e. Formula 1 in which X is NR4 and R4 is H) can be prepared by reaction of compounds of Formula 6 (i.e. 5-bromopyrazoles or other pyrazoles substituted at the 5-position with a leaving group) with compounds of Formula 7 under metal-catalyzed conditions similar to those described above for Scheme 3. Compounds of Formula 7 are commercially available or their preparation is known in the art.




As shown in Scheme 5, compounds of Formula 6 wherein G is Br or I can be prepared by reaction of 5-aminopyrazoles of Formula 4a (i.e. Formula 4 wherein X is NH) under diazotization conditions either in the presence of, or followed by combination with, copper salts containing bromide or iodide. For example, addition of tert-butyl nitrite to a solution of a 5-aminopyrazole of Formula 4a in the presence of CuBr2 in a solvent such as acetonitrile provides the corresponding 5-bromopyrazole of Formula 6. Likewise, a 5-aminopyrazole of Formula 4a can be converted to a diazonium salt and then to a corresponding 5-halopyrazole of Formula 6 by treatment with sodium nitrite in solvents such as water, acetic acid or trifluoroacetic acid, in the presence of a mineral acid typically containing the same halide atom (such as aqueous HI solution for G being I), followed by treatment with the corresponding copper(I) or copper(II) salt according to general procedures well known to those skilled in the art.




As shown in Scheme 6, 5-bromopyrazoles of Formula 6a (i.e. Formula 6 wherein G is Br) can be prepared by reacting 5-hydroxypyrazoles of Formula 4b (i.e. Formula 4 wherein X is O) with phosphorus tribromide as described in Tetrahedron Lett. 2000, 41(24), 4713.




As shown in Scheme 7, 5-hydroxypyrazoles of Formula 4b can also be used to prepare 5-fluoroalkylsulfonyl (e.g, 5-trifluoromethanesulfonyl, 5-nonafluorobutylsulfonyl) pyrazoles of Formula 6b (i.e. Formula 6 wherein G is fluoroalkylsulfonyl) as described in Synlett 2004, 5, 795.




    
    
        wherein Rf is fluoroalkyl such as CF3 or (CF2)2CF3 
    
    


As shown in Scheme 8, compounds of Formula 1 can be prepared by reaction of 4-bromo or iodo pyrazoles of Formula 10 wherein X is O, NR4, C(═O) or S(O)m in which m is 2 with organometallic compounds of formula Q1-M (Formula 11) under transition-metal-catalyzed cross-coupling reaction conditions. Reaction of a 4-bromo or iodo pyrazole of Formula 10 with a boronic acid, trialkyltin, zinc or organomagnesium reagent of Formula 11 in the presence of a palladium or nickel catalyst having appropriate ligands (e.g., triphenylphosphine (PPh3), dibenzylideneacetone (dba), dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (SPhos)) and a base, if needed, affords the corresponding compound of Formula 1. For example, a substituted aryl boronic acid or derivative (e.g., Formula 11 wherein Q1 is optionally substituted phenyl or heterocyclyl and M is B(OH)2, B(OC(CH3)2C(CH3)2O)) or B(O-i-Pr)3/Li. reacts with a 4-bromo- or 4-iodopyrazole of Formula 10 in the presence of dichlorobis(triphenylphosphine) palladium(II) and aqueous base such as sodium carbonate or potassium hydroxide, in solvents such as 1,4-dioxane, 1,2-dimethoxyethane, toluene or ethyl alcohol, or under anhydrous conditions with a ligand such as phosphine oxide or phosphite ligand (e.g., diphenylphosphine oxide) and potassium fluoride in a solvent such as 1,4-dioxane (see Angewandte Chemie, International Edition 2008, 47(25), 4695-4698) to provide the corresponding compound of Formula 1.




As illustrated in Scheme 9, compounds of Formula 4a (i.e. Formula 4 wherein X is NH) can be prepared by reacting compounds of Formula 12 with compounds of Formula 11 (such as Q1-B(OH)2 (Formula 11a)) using transition-metal-catalyzed cross-coupling reaction conditions as described for the method of Scheme 8.




As illustrated in Scheme 10, pyrazoles of Formula 10 wherein X is O, S(O)2, NR4 or C(═O) and G is Br or I are readily prepared by the reaction of pyrazoles unsubstituted at the 4-position (Formula 13) with halogenating reagents such as bromine, sodium bromite, N-bromosuccinimide (NBS) or N-iodosuccinimide (NIS), in solvents such as acetic acid, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide or 1,4-dioxane, or a mixture of water with the aforementioned solvents, at temperatures ranging from ambient to the boiling point of the solvent.




Furthermore, using reaction conditions similar to those for the method of Scheme 10, compounds of Formula 13 wherein A is H or a protecting group can be converted into intermediates corresponding to Formula 10 wherein Q2 is replaced by A or a protecting group, respectively, which are useful for preparing compounds of Formula 1. Compounds of Formula 13 wherein A is H can be prepared by methods known in the art; see, for example, Synlett 2004, 5, 795-798, U.S. Pat. No. 4,256,902 and references cited therein. Furthermore, some compounds of Formula 13 wherein A is H, particularly those in which R2 is methyl, ethyl or halogen, are commercially available.
As shown in Scheme 11, compounds of Formula 13 wherein X is O, S(O)m or NR4, m is 0, and A is Q2 can be prepared from corresponding compounds of Formula 13a (i.e. Formula 13 wherein A is H) by procedures analogous those used for the method of Scheme 3. Compounds of Formula 13 wherein X is S (i.e. S(O)m wherein m is 0) can then be oxidized using procedures such as those used for the method of Scheme 1 to provide corresponding compounds of Formula 13 wherein X is S(O)2 for use in the method of Scheme 10. Compounds of Formula 13a are commercially available or can be prepared by methods known in the art.




As shown in Scheme 12, compounds of Formula 1a (i.e. Formula 1 wherein X is S(O)m and m is 0), Formula 1d (i.e. Formula 1 wherein X is CR15R16, R15 is H, R16 is OR18 and R18 is H,) and Formula 1e (i.e. Formula 1 wherein X is C(═O)) can be prepared by treatment of compounds of Formula 6 with an organometallic reagent (i.e. Formula 26) such as an alkyllithium, preferably n-butyllithium, or an alkylmagnesium reagent, preferably isopropylmagnesium chloride (optionally complexed with lithium chloride), followed by the addition of a sulfur electrophile (i.e. Formula 27) or carbonyl electrophile (i.e. Formula 28, 29 or 30). Reaction temperatures can range from −90° C. to the boiling point of the reaction solvent; temperatures of −78° C. to ambient temperature are generally preferred, with temperatures of −78 to −10° C. preferred when an alkyllithium reagent is used, and −20° C. to ambient temperature preferred with use of alkylmagnesium reagents. A variety of solvents are useful, such as toluene, ethyl ether, tetrahydrofuran or dimethoxymethane; anhydrous tetrahydrofuran is preferred. A second metallic component, such as zinc chloride, zinc bromide or a monovalent copper salt, such as copper(I) iodide or copper(I) cyanide, can advantageously be added before the electrophile in cases in which the electrophile is Q2C(O)Cl (i.e. Formula 30). The Q2-containing sulfur and carbonyl intermediates of Formulae 27, 28, 29 and 30 are commercially available or can be prepared by methods known in the art.




It will be recognized by one skilled in the art that reactions analogous to those shown in Scheme 12 can also be utilized with pyrazoles lacking a Q1 substituent, thus affording certain compounds of Formula 13 that are useful in the method outlined in Scheme 10.
General methods useful for preparing 5-aminopyrazoles of Formula 4a are well known in the art; see, for example, Journal für Praktische Chemie (Leipzig) 1911, 83, 171 and J. Am. Chem. Soc. 1954, 76, 501. Such a method is illustrated in Scheme 13 in which R2 is alkyl or cycloalkyl.




Similarly, general methods useful for preparing 5-hydroxypyrazoles of Formula 4b are well known in the art; see, for example, Annalen der Chemie 1924, 436, 88. Such a method is illustrated in Scheme 14 in which R2 is alkyl or cycloalkyl.




As shown in Scheme 15, 5-thiopyrazole compounds of Formula 4c (i.e. Formula 4 wherein X is S) can be prepared by reaction of corresponding 5-hydroxypyrazole compounds of Formula 4b with P2S5 (see, for example, Justus Liebigs Annalen der Chemie 1908, 361, 251) or with Lawesson's Reagent (2,4-bis-(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane 2,4-disulfide; see, for example, International Patent Publication WO 2005/118575) in solvents such as toluene, xylene or tetrahydrofuran.




As shown in Scheme 16, compounds of Formula 1c (i.e. Formula 1 wherein X is NR4 and R4 is H) can be prepared by condensing compounds of Formula 17 with alkylhydrazines of Formula 15 in a solvent such as ethanol or methanol and optionally in the presence of an acid or base catalyst such as acetic acid, piperidine or sodium methoxide, according to general procedures known in the art.




    
    
        wherein R32 is H or lower alkyl (e.g., CH3, CH2CH3 or (CH2)2CH3)
    
    


In a manner analogous to the method of Scheme 16, compounds of Formula 2 wherein X is NH can be similarly prepared by condensing compounds of Formula 17 with hydrazine. This method is described in Chemistry of Heterocyclic Compounds 2005, 41(1), 105-110.
As shown in Scheme 17, compounds of Formula 17 (wherein, e.g., R2 is methyl, ethyl or optionally substituted cyclopropyl and R33 is H or lower alkyl such as CH3, CH2CH3 or (CH2)2CH3) can be prepared by reaction of corresponding ketene dithioacetal compounds of Formula 18 with compounds of formula Q2-NH2 (i.e. Formula 7) optionally in the presence of a base, such as sodium hydride or ethylmagnesium chloride, in solvents such as toluene, tetrahydrofuran or dimethoxymethane, at temperatures ranging from −10° C. to the boiling point of the solvent. See, for example, J. Heterocycl. Chem. 1975, 12(1), 139. Methods useful for preparing compounds of Formula 18 are known in the art.




    
    
        wherein R33 is H or lower alkyl (e.g., CH3, CH2CH3 or (CH2)2CH3)
    
    


It is also known in the art (see, for example, Synthesis 1989, 398) that compounds of Formula 18 in which the two R33 groups are taken together as a single CH2 group (thus forming a dithietane ring) react with an stoichiometric excess amount of hydrazines of Formula 15 to afford compounds of Formula 4c, which are useful for preparation of compounds of Formula 1 in which X is S according to the method of Scheme 3.
As shown in Scheme 18, compounds of Formula 17a (i.e. tautomer of Formula 17 wherein R33 is H) can be prepared by reaction of corresponding isothiocyanate compounds of Formula 19 with arylacetone compounds of Formula 20 wherein R2 is methyl, ethyl or optionally substituted cyclopropyl; see, for example, Zhurnal Organicheskoi Khimii 1982, 18(12), 2501. Bases useful for this reaction include sodium hydride, alkoxide bases (e.g., potassium tert-butoxide or sodium ethoxide), potassium hydroxide, sodium hydroxide, potassium carbonate, or amine bases (e.g., triethylamine or N,N-diisopropylethylamine). A variety of solvents are useful, such as tetrahydrofuran, ether, toluene, N,N-dimethylformamide, alcohols (e.g., ethanol), esters (e.g., ethyl acetate or isopropyl acetate), or mixtures thereof. Solvents are chosen for compatibility with the base selected, as is well-known in the art. Reaction temperatures can range from −78° C. to the boiling point of the solvent. One useful mixture of base and solvent is potassium tert-butoxide in tetrahydrofuran, to which at −70 to 0° C. is added a combined solution of an isothiocyanate of Formula 19 and a carbonyl compound of Formula 20.




Ketothioamides of Formula 17 can be also be prepared by allowing the corresponding ketoamides to react with sulfurizing agents such as Lawesson's reagent or P2S5; see, for example, Helv. Chim. Act. 1998, 81(7), 1207.
Compounds of Formula 2 wherein X is NH and R2 is Cl or Br, which are useful for preparing compounds of Formula 1 according to the method of Scheme 2, can be prepared by reaction of corresponding compounds of Formula 31 with POCl3 or POBr3 using general procedures known in the art, as shown in Scheme 19.




As shown in Scheme 20, compounds of Formula 1f (i.e. Formula 1 wherein R1 and R1a are H and R2 is OCH3) can be prepared by reacting corresponding compounds of Formula 31 with diazomethane or iodomethane in the presence of base using general procedures known in the art, such as those described in J. Heterocyclic Chem. 1988, 1307-1310.




Compounds of Formula 1g (i.e. Formula 1 wherein R1 and R1a are H and R2 is SCH3) can be prepared by treating corresponding compounds of Formula 31 with P2S5 or Lawesson's Reagent to prepare compounds of Formula 32, which are then reacted with diazomethane or iodomethane in the presence of base using general procedures known in the art, as shown in Scheme 21.




As shown in Scheme 22, compounds of Formula 31 wherein X is NH can be prepared by condensation of corresponding isothiocyanates of Formula 19 with esters of Formula 33 wherein R33 is lower alkyl (e.g., methyl, ethyl, propyl) in the presence of a strong, non-nucleophilic base such as sodium hydride or lithium hexamethyldisilazide, in an inert solvent such as tetrahydrofuran (analogous to the method of Scheme 18), followed by reaction of the intermediate with hydrazine or an acid salt of hydrazine, such as, for example, an acetate or hydrochloride salt (analogous to the method of Scheme 16).




One skilled in the art will recognize that use of a substituted hydrazine of formula H2NNHCHR1R1a instead of unsubstituted hydrazine in the method of Scheme 22, followed by the further manipulations described for Schemes 19, 20 and 21 will also afford compounds of Formula 1.
Compounds of Formula 1c (i.e. Formula 1 wherein X is NR4 and R4 is H) in which R2 is halogen can also be prepared as shown in Scheme 23. In this method an acetonitrile compound of Formula 21 is condensed with an isothiocyanate compound of Formula 22 in the presence of a base such as sodium hydride or potassium tert-butoxide, in a solvent such as N,N-dimethylformamide or tetrahydrofuran, to afford a cyano ketoamide intermediate compound, which is then reacted with a methylating agent such as iodomethane or dimethyl sulfate, in the presence of a base to provide the corresponding compound of Formula 23. Alternatively, the methylating agent can be included in the reaction mixture with the compounds of Formulae 21 and 22 without isolation of the cyano ketoamide intermediate. One skilled in the art will recognize that compounds of Formula 23 can also be prepared by a method analogous to Scheme 17 wherein the C(O)R2 of the compound of Formula 18 is replaced by cyano. According to the method of Scheme 23, the resultant compound of Formula 23 is then reacted with an alkylhydrazine of Formula 15 to form the corresponding 3-aminopyrazole compound of Formula 24 using general procedures known in the art; see, for example, J. Chem. Soc. Perkin 1 1988, 2, 169-173 and J. Med. Chem. 2003, 46(7), 1229-1241. The amino group of the compound of Formula 24 can then be converted to R2 being halogen in Formula 1c by a diazotization reaction using conditions known in the art, such as those previously described for Scheme 5.




Analogous to the method of Scheme 23, compounds of Formula 2 wherein X is NH and R2 is halogen can be similarly prepared by condensing compounds of Formula 23 with hydrazine instead of an alkylhydrazine of Formula 15.
As shown in Scheme 24, compounds of Formula 1h (i.e. Formula 1 wherein X in NR4) can be prepared by reacting corresponding compounds of Formula 1c (i.e. Formula 1 wherein X is NH) with an electrophile comprising R4 (i.e. Formula 25) typically in the presence of a base such as NaH and a polar solvent such as N,N-dimethylformamide. In this context the expression “electrophile comprising R4” means a chemical compound capable of transferring an R4 moiety to a nucleophile (such as the nitrogen atom attached to Q2 in Formula 1c). Often electrophiles comprising R4 have the formula R4Lg wherein Lg is a nucleofuge (i.e. leaving group in nucleophilic reactions). Typical nucleofuges include halogens (e.g., Cl, Br, I) and sulfonates (e.g., OS(O)2CH3, OS(O)2CF3, OS(O)2-(4-CH3-Ph)). However, some electrophiles comprising R4 do not comprise a nucleofuge; an example is sulfur trioxide (SO3), which after deprotonation (such as by a base of the formulae M+H− wherein M+ is a cation) of the nitrogen atom attached to Q2 in Formula 1c, can bond to the nitrogen atom as a —SO3−M+ substituent.




It is recognized by one skilled in the art that various functional groups can be converted into others to provide different compounds of Formula 1. For example, compounds of Formula 1 in which R2 is methyl, ethyl or cyclopropyl can be modified by free-radical halogenation to form compounds of Formula 1 wherein R2 is halomethyl, haloethyl or halocyclopropyl. The halomethyl compounds can be used as intermediates to prepare compounds of Formula 1 wherein R2 is hydroxymethyl or cyanomethyl. Compounds of Formula 1 or intermediates for their preparation may contain aromatic nitro groups, which can be reduced to amino groups, and then be converted via reactions well known in the art such as the Sandmeyer reaction, to various halides, providing other compounds of Formula 1. By similar known reactions, aromatic amines (anilines) can be converted via diazonium salts to phenols, which can then be alkylated to prepare compounds of Formula 1 with alkoxy substituents. Likewise, aromatic halides such as bromides or iodides prepared via the Sandmeyer reaction can react with alcohols under copper-catalyzed conditions, such as the Ullmann reaction or known modifications thereof, to provide compounds of Formula 1 that contain alkoxy substituents. Additionally, some halogen groups, such as fluorine or chlorine, can be displaced with alcohols under basic conditions to provide compounds of Formula 1 containing the corresponding alkoxy substituents. The resultant alkoxy compounds can themselves be used in further reactions to prepare compounds of Formula 1 wherein R3 is —U—V-T (see, for example, PCT Publication WO 2007/149448 A2). Compounds of Formula 1 or precursors thereof in which R2 or R3 is halide, preferably bromide or iodide, are particularly useful intermediates for transition metal-catalyzed cross-coupling reactions to prepare compounds of Formula 1. These types of reactions are well documented in the literature; see, for example, Tsuji in Transition Metal Reagents and Catalysts: Innovations in Organic Synthesis, John Wiley and Sons, Chichester, 2002; Tsuji in Palladium in Organic Synthesis, Springer, 2005; and Miyaura and Buchwald in Cross Coupling Reactions: A Practical Guide, 2002; and references cited therein.
One skilled in the art will recognize that sulfide groups can be oxidized to the corresponding sulfoxides or sulfones by conditions well-known in the art. Likewise, compounds of Formula 1 wherein X is CR15R16, R15 is H, R16 is OR18 and R18 is H can be readily interconverted with corresponding compounds of Formula 1 wherein X is C(═O) by alcohol oxidation and ketone reduction reactions well known in the art. Compounds of Formula 1 wherein X is C(═O) (i.e. ketones) can be readily converted to ketals using general methods known in the art, thus providing compounds of Formula 1 wherein X is CR15R16 and R15 and R16 are taken together as —OCH2CH2O—. Compounds of Formula 1 wherein X is C(═O) can also be converted by the use of Lawesson's Reagent to prepare corresponding compounds of Formula 1 wherein X is C(═S). Furthermore, compounds of Formula 1 wherein X is CR15R16, R15 is C1-C4 alkyl, R16 is OR18, and R18 is H can be prepared by adding an alkyl Grignard reagent to the corresponding compounds of Formula 1 wherein X is C(═O).
The above reactions can also in many cases be performed in alternate sequence, such as the preparation of 1H pyrazoles for use in the reaction in Scheme 2 by reactions illustrated later for the general preparation of substituted pyrazoles. The presence of certain functional groups may not be compatible with all of these reaction conditions, and the use of protecting groups may be desirable for obtaining the desired products with improved yields and or purity.
It is recognized that some reagents and reaction conditions described above for preparing compounds of Formula 1 may not be compatible with certain functionalities present in the intermediates. In these instances, the incorporation of protection/deprotection sequences or functional group interconversions into the synthesis will aid in obtaining the desired products. The use and choice of the protecting groups will be apparent to one skilled in chemical synthesis (see, for example, Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 2nd ed.; Wiley: New York, 1991). One skilled in the art will recognize that, in some cases, after the introduction of a given reagent as it is depicted in any individual scheme, it may be necessary to perform additional routine synthetic steps not described in detail to complete the synthesis of compounds of Formula 1. One skilled in the art will also recognize that it may be necessary to perform a combination of the steps illustrated in the above schemes in an order other than that implied by the particular sequence presented to prepare the compounds of Formula 1. One skilled in the art will also recognize that compounds of Formula 1 and the intermediates described herein can be subjected to various electrophilic, nucleophilic, radical, organometallic, oxidation, and reduction reactions to add substituents or modify existing substituents.
Without further elaboration, it is believed that one skilled in the art using the preceding description can utilize the present invention to its fullest extent. The following Synthesis Examples are, therefore, to be construed as merely illustrative, and not limiting of the disclosure in any way whatsoever. Steps in the following Synthesis Examples illustrate a procedure for each step in an overall synthetic transformation, and the starting material for each step may not have necessarily been prepared by a particular preparative run whose procedure is described in other Examples or Steps. Percentages are by weight except for chromatographic solvent mixtures or where otherwise indicated. Parts and percentages for chromatographic solvent mixtures are by volume unless otherwise indicated. 1H NMR spectra are reported in ppm downfield from tetramethylsilane in CDCl3 unless otherwise noted; “s” means singlet, “m” means multiplet, “br s” means broad singlet. Mass spectra are reported as the molecular weight of the highest isotopic abundance parent ion (M+1) formed by addition of H+ (molecular weight of 1) to the molecule, observed by mass spectrometry using atmospheric pressure chemical ionization (AP+) where “amu” stands for atomic mass units.
Synthesis Example 1
Preparation of N-(3-Chlorophenyl)-4-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 1)
Step A: Preparation of α-Acetyl-2,4-difluorobenzeneacetonitrile (alternatively named methyl α-cyano-2,4-difluorobenzeneacetate)
Sodium hydride (60% in mineral oil) (1.5 g, 38 mmol) was stirred in xylenes (7 mL) under a nitrogen atmosphere at ambient temperature. A solution of anhydrous ethanol (6.3 mL, 64 mmol) in xylenes (2 mL) was added dropwise over about 20 minutes at a temperature of about 40° C. The reaction mixture was heated to 70° C., and a solution of 2,4-difluorophenylacetonitrile (3.9 g, 25 mmol), ethyl acetate (3.8 mL, 38 mmol) and xylenes (1 mL) was added dropwise over 15 min. Additional xylenes (5 mL) was added to aid stirring. The reaction mixture was heated for 2 h, then allowed to cool. Water (50 mL) was added, and the mixture was extracted with hexanes (50 mL). The aqueous phase was then acidified to pH 3-4 with 1 N aqueous HCl solution. The aqueous phase was extracted with ether (50 mL), and the ethereal extract was washed with water (25 mL) and brine, then dried over MgSO4, and concentrated to give the title compound as a viscous residue (3.3 g).
1H NMR δ 7.42 (m, 1H), 6.8-7.0 (m, 2H), 4.95 (s, 1H), 2.36 (s, 3H).
Step B: Preparation of 4-(2,4-Difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine
Acetic acid (0.5 mL, 8.3 mmol) and methylhydrazine (534 μL, 10.0 mmol) were added to a solution of the residue obtained in Step A (1.6 g, 8.5 mmol) in ethyl alcohol (8 mL). The reaction mixture was then heated at reflux for 16 h under a nitrogen atmosphere. While the reaction mixture was still warm, water was added in small portions (1 mL at a time) until a precipitate formed (about 12 mL of water total). The mixture was reheated to dissolve the solids and then allowed cooled to room temperature. The resulting precipitate was collected on a glass frit, washed with 2 to 3 mL of 50% aqueous ethyl alcohol, and dried under vacuum to obtain the compound as a white solid (0.99 g).
1H NMR δ 7.20 (m, 1H), 6.92 (m, 2H), 3.68 (s, 3H), 3.47 (br s, 2H), 2.14 (s, 3H).
Step C: Preparation of N-(3-Chlorophenyl)-4-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine
Palladium(II) acetate (90 mg, 0.40 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (460 mg, 0.80 mmol) and powdered potassium carbonate (5.5 g, 40 mmol) were combined in anhydrous 1,4-dioxane (20 mL), and the mixture was sparged with a subsurface stream of N2 gas for 10 min. 4-(2,4-Difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (i.e. the product of Step B) (0.89 g, 4.0 mmol) was added in one portion, and 1-bromo-3-chlorobenzene (0.47 mL, 4.0 mmol) was added via a syringe. The reaction mixture was heated at reflux under a nitrogen atmosphere for 3 h. Additional 1-bromo-3-chlorobenzene (0.09 mL, 0.8 mmol) was added, and heating was continued for 1 h. The reaction mixture was allowed to cool to room temperature, and then partitioned between water (40 mL) and ethyl acetate (40 mL). The organic phase was washed with additional water (40 mL), brine (40 mL), dried over MgSO4 and concentrated under reduced pressure. The residue was purified by column chromatography through 10 g of silica gel eluted with hexanes/ethyl acetate (1:1) to give the title compound, a compound of the present invention, as a solid (0.41 g).
1H NMR δ 7.2-7.3 (m, 2H), 7.10 (m, 1H), 6.9-7.0 (m, 2H), 6.70 (m, 1H), 6.58 (m, 1H), 6.52 (m, 1H), 3.64 (s, 3H), 2.14 (s, 3H). MS: 334 amu.
Synthesis Example 2
Preparation of 4-(2-Chloro-4-fluorophenyl)-N-(2,6-difluoro-4-methoxyphenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 17)
Step A: Preparation of 5-Bromo-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazole
Copper(II) bromide (3.94 g, 17.7 mmol) was added to a solution of 4-[2-chloro-4-fluorophenyl]-1,3-dimethyl-1H-pyrazol-5-amine (prepared similarly to the preparation of 4-(2,4-Difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine in Steps A and B of Synthesis Example 1) (2.4 g, 10 mmol) in acetonitrile (50 mL), and the mixture was stirred and cooled in an ice-water bath while tert-butyl nitrite (90% technical grade, 2.33 mL, 17.7 mmol) was added dropwise over 5 min. The reaction mixture was allowed to warm slowly to ambient temperature. Aqueous HCl solution (20 mL) was added, and then ethyl acetate was added (20 mL). This mixture was filtered through a 2-cm pad of Celite® diatomaceous filter aid. The filter pad was washed with ethyl acetate (20 mL), and the phases were separated. The organic phase was washed with 1.0 N aqueous hydrochloric acid solution and brine, dried over MgSO4, and concentrated to leave the title compound as an orange-brown semisolid (2.8 g).
1H NMR δ 7.18-7.25 (m, 2H), 7.04 (m, 1H), 3.89 (s, 3H), 2.14 (s, 3H).
Step B: Preparation of 4-(2-Chloro-4-fluorophenyl)-N-(2,6-difluoro-4-methoxyphenyl)-1,3-dimethyl-1H-pyrazol-5-amine
5-Bromo-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazole (i.e. the product of Step A) (0.20 g, 0.66 mmol), palladium(II) acetate (15 mg, 0.066 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (76 mg, 0.13 mmol) and powdered potassium carbonate (1.8 g, 13 mmol) were combined in anhydrous 1,4-dioxane (3 mL), and the mixture was sparged with a subsurface stream of N2 gas for 10 min. 2,6-Difluoro-4-methoxyaniline (0.22 g, 1.3 mmol) was added in one portion, and the reaction mixture was heated at reflux for 22 h. The reaction mixture was filtered through Celite® diatomaceous filter aid, and the filter pad was washed with ethyl acetate (20 mL). The filtrate was washed with water (10 mL) and brine (10 mL), dried over MgSO4, and concentrated to leave a semisolid residue. This residue was purified by column chromatography through 5 g of silica gel eluted with a gradient of hexanes/ethyl acetate (20:1 to 1:3) to give the title compound, a compound of the present invention, as a light-brown solid (48 mg).
1H NMR δ 7.0-7.1 (m, 2H), 6.85 (m, 1H), 6.26 (m, 2H), 4.84 (br s, 1H), 3.78 (s, 3H), 3.66 (s, 3H), 2.08 (s 3H). MS: 382 amu.
Synthesis Example 3
Preparation of 4-(2,6-Difluoro-4-methoxyphenyl)-1,3-dimethyl-N-(2,4,6-trifluorophenyl)-1H-pyrazol-5-amine (Compound 24)
Step A: Preparation of 2,6-Difluoro-4-methoxybenzeneacetonitrile
A solution of KCN (0.88 g, 13 mmol) dissolved in water (2 mL) was added dropwise to a water-bath-cooled solution of 2,6-difluoro-4-methoxybenzyl bromide (2.50 g, 10.5 mmol) in N,N-dimethylformamide (10 mL). The reaction mixture was stirred for 20 min. Water was added (20 mL) and then the reaction mixture was poured into saturated aqueous NaHCO3 solution (20 mL) and extracted with ether (50 mL). The organic phase was washed with water (5×25 mL), dried over MgSO4, and concentrated to give an oil, which crystallized on standing to provide the title compound as a white solid (1.9 g).
1H NMR δ 6.50 (m, 2H), 3.80 (s, 3H), 3.65 (s, 2H).
Step B: Preparation of α-Acetyl-2,6-difluoro-4-methoxybenzeneacetonitrile
Solid sodium ethoxide (4.7 g, 66 mmol) was stirred in a mixture of xylene (20 mL) and ethanol (10 mL) and heated to 50° C. A solution of 2,6-difluoro-4-methoxybenzeneacetonitrile (i.e. the product of Step A) (8.0 g, 44 mmol) in ethyl acetate (10.4 mL) was added dropwise. The reaction mixture was heated at 50° C. for 4 h and then allowed to cool to ambient temperature. The reaction mixture was poured into water (100 mL) and extracted with ethyl acetate (25 mL). The aqueous phase was acidified with 3 N aqueous HCl to pH 4 and extracted with ethyl acetate (100 mL). This organic phase was washed with water (50 mL), brine (50 mL), then dried over MgSO4, and concentrated to leave the title compound as a tan semisolid (8.0 g).
1H NMR δ 6.56 (m, 2H), 4.86 (s, 1H), 3.83 (s, 3H), 2.40 (s, 3H).
Step C: Preparation of 4-(2,6-Difluoro-4-methoxyphenyl)-1,3-dimethyl-1H-pyrazole-5-amine
α-Acetyl-2,6-difluoro-4-methoxybenzeneacetonitrile (i.e. the product of Step B) (8.03 g, 35.7 mmol) and acetic acid (5 mL) were stirred in ethanol (35 mL), and methylhydrazine (1.91 mL, 35.7 mmol) was added. The reaction mixture was heated at reflux for 16 h, cooled, and then poured into water (100 mL). The resulting mixture was extracted with ethyl acetate (100 mL). The organic phase was washed with 1 N aqueous NaOH (50 mL) and then brine (50 mL), dried over MgSO4, and concentrated to leave a solid. The solid was dissolved in methanol, and the resulting solution was warmed to 45° C. Water (25 mL) was added dropwise, and the mixture was allowed to cool. The precipitate was collected on a glass frit to give the title compound as a white solid (3.88 g).
1H NMR δ 6.55 (m, 2H), 3.81 (s, 3H), 3.67 (s, 3H), 3.43 (br s, 2H), 2.09 (s, 3H).
Step D: Preparation of 5-Bromo-4-(2,6-difluoro-4-methoxyphenyl)-1,3-dimethyl-1H-pyrazole
Copper(II) bromide (3.81 g, 16.9 mmol) was added to a solution of 4-(2,6-difluoro-4-methoxyphenyl)-1,3-dimethyl-1H-pyrazole (i.e. the product of Step C) (3.88 g, 15.4 mmol) in acetonitrile (50 mL), and the mixture was stirred and cooled in an ice-water bath while tert-butyl nitrite (90% technical grade, 3.54 mL, 26.9 mmol) was added dropwise over 5 min. The reaction mixture was allowed to warm slowly to ambient temperature. Aqueous hydrochloric acid solution (25 mL) was added, then ethyl acetate (25 mL) was added, and the resulting mixture was filtered through a 2-cm pad of Celite® diatomaceous filter aid. The filter pad was washed with ethyl acetate (50 mL), and the phases were separated. The organic phase was washed with 1 N aqueous HCl solution (25 mL) and brine (25 mL), dried over MgSO4, and concentrated. The residue was purified by column chromatography through 24 g of silica gel eluted with a gradient of hexanes/ethyl acetate (9:1 to 1:1) to give the title compound as a white solid (3.25 g).
1H NMR δ 6.54 (m, 2H), 3.88 (s, 3H), 3.83 (s, 3H), 2.16 (s, 3H).
Step E: Preparation of 4-(2,6-Difluoro-4-methoxyphenyl)-1,3-dimethyl-N-(2,4,6-trifluorophenyl)-1H-pyrazol-5-amine
5-Bromo-4-(2,6-difluoro-4-methoxyphenyl)-1,3-dimethyl-1H-pyrazole (i.e. the product of Step D) (0.30 g, 0.94 mmol), palladium(II) acetate (20 mg, 0.090 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.11 g, 0.19 mmol) and powdered potassium carbonate (2.6 g, 19 mmol) were combined in anhydrous 1,4-dioxane (4 mL), and the resulting mixture was sparged with a subsurface stream of N2 gas for 10 min. 2,4,6-Trifluoroaniline (0.28 g, 1.9 mmol) was added in one portion, and the reaction mixture was heated at reflux under nitrogen for 22 h. The reaction mixture was cooled, then filtered through Celite® diatomaceous filter aid. The filter pad was washed with ethyl acetate (20 mL), and the filtrate was washed with water (10 mL) and brine (10 mL), dried over MgSO4, and concentrated to leave a semisolid residue. The residue was purified by column chromatography through 12 g of silica gel eluted with a gradient of hexanes/ethyl acetate (20:1 to 1:3) to give the title compound, a compound of the present invention, as a semisolid (73 mg).
1H NMR (acetone-d6) δ 6.84 (br s, 1H), 6.68 (m, 2H), 6.43 (m, 2H), 3.77 (s, 3H), 3.75 (s, 3H), 1.99 (s, 3H). MS: 384 amu (AP+).
Synthesis Example 4
Preparation of 4-[[4-(2-Chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]oxy]-3,5-difluorobenzonitrile (Compound 45)
Step A: Preparation of 4-[(1,3-Dimethyl-1H-pyrazol-5-yl)oxy]-3,5-difluorobenzonitrile
Potassium carbonate (1.38 g, 10 mmol) was added to a solution of 2,4-dihydro-2,5-dimethyl-3H-pyrazol-3-one (0.70 g, 6.3 mmol) in N,N-dimethylformamide (15 mL). 3,4,5-Trifluorobenzonitrile (0.94 g, 6.0 mmol) was added, and the reaction mixture was heated at 75° C. under a nitrogen atmosphere for 16 h, then allowed to cool. The reaction mixture was partitioned between water (60 mL) and ethyl acetate (30 mL). The organic phase was washed with water (2×30 mL) and brine (30 mL), dried over MgSO4, and concentrated to give the title compound as a yellow oil (1.38 g).
1H NMR δ 7.36 (m, 2H), 5.24 (s, 1H), 3.78 (s, 3H), 2.16 (s, 3H).
Step B: Preparation of 3,5-Difluoro-4-[(4-iodo-1,3-dimethyl-1H-pyrazol-5-yl)oxy]benzonitrile
A solution of 4-[(1,3-dimethyl-1H-pyrazol-5-yl)oxy]-3,5-difluorobenzonitrile (i.e. the product of Step A) (1.38 g, 5.5 mmol) in acetonitrile (20 mL) was stirred at ambient temperature, and N-iodosuccinimide (1.35 g, 6.0 mmol) was added in one portion. The reaction mixture was heated at reflux for 2 h, cooled, and then poured into water (40 mL). The resulting mixture was extracted with ethyl acetate (40 mL). The organic phase was washed with water (20 mL) and saturated aqueous NaHCO3 solution (20 mL), dried over MgSO4, and concentrated under reduced pressure to give the title compound as a tan solid (2.1 g).
1H NMR (acetone-d6) δ 7.80 (m, 2H), 3.82 (s, 3H), 2.09 (s, 3H). MS: 376 amu (AP+).
Step C: Preparation of 4-[[4-(2-Chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]oxy]-3,5-difluorobenzonitrile
To a solution of 3,5-difluoro-4-[(4-iodo-1,3-dimethyl-1H-pyrazol-5-yl)oxy]-benzonitrile (i.e. the product of Step B) (1.0 g, 2.67 mmol) in 1,4-dioxane (6 mL) was added 2-chloro-4-fluorobenzeneboronic acid (alternatively named B-(2-chloro-4-fluorophenyl)-boronic acid) (0.93 g, 5.33 mmol), dichloro (bis)triphenylphosphine palladium(II) (alternatively named bis(triphenylphosphine)palladium(II) dichloride) (93 mg, 0.13 mmol), potassium carbonate (0.74 g, 5.33 mmol), and water (4 mL). The resulting mixture was heated at reflux for 5 h, allowed to cool, and partitioned between water (20 mL) and ethyl acetate (20 mL). The organic layer was dried over MgSO4 and concentrated. The residue was purified by chromatography on silica gel with a gradient of hexanes/ethyl acetate to obtain the title compound, a compound of the present invention, as an off-white solid (110 mg).
1H NMR δ 7.00-7.09 (m, 3H), 6.97 (m, 1H), 6.86 (m, 1H), 3.85 (s, 3H), 2.02 (s, 3H).
Synthesis Example 5
Preparation of 4-(2,4-Dichlorophenyl)-N-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 69)
Step A: Preparation of α-Acetyl-2,4-dichloro-N-(2,4-difluorophenyl)benzeneethanethioamide
2,4-Difluorophenyl isothiocyanate (0.27 mL, 2.0 mmol) was added to a stirred suspension of sodium hydride (60% in mineral oil) (112 mg, 2.8 mmol) in anhydrous tetrahydrofuran (4 mL) cooled in an ice-water bath under a nitrogen atmosphere. A solution of (2,4-dichlorophenyl)-2-propanone (570 mg, 2.8 mmol) in tetrahydrofuran (4 mL) was added dropwise over 5 min. The resultant yellow solution was stirred at 5-10° C. for 1 h. Water (10 mL) was carefully added, and the reaction mixture was extracted with ethyl acetate (10 mL). The aqueous phase was acidified to pH 3 with 1 N aqueous HCl, then extracted with ethyl acetate (20 mL). The organic extract was washed with water (10 mL) and brine (10 mL), dried over MgSO4, and concentrated to leave a solid. The solid was triturated with hexanes/ethyl acetate (2:1), collected on a glass frit, and air-dried to give the title compound as a white solid (240 mg). MS: 373 amu (AP+).
Step B: Preparation of 4-(2,4-Dichlorophenyl)-N-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine
Acetic acid (50 μL) and methylhydrazine (41 μL) were added to a stirred suspension of α-acetyl-2,4-dichloro-N-(2,4-difluorophenyl)benzeneethanethioamide (238 mg, 0.64 mmol) in ethanol (4 mL). The reaction mixture was heated at reflux for 2 h and allowed to cool. Then the reaction mixture was diluted with ethyl acetate (10 mL) and washed with 1 N aqueous NaOH (10 mL), water (10 mL) and brine (10 mL), dried over MgSO4, and concentrated to leave a solid residue. The residue was purified by column chromatography on 5 g of silica gel with a gradient of hexanes/ethyl acetate (2:1 to 1:1) to give the title compound as a solid (170 mg).
1H NMR δ 7.43 (s, 1H), 7.19 (m, 1H), 7.07 (m, 1H), 6.78 (m, 1H), 6.62 (m, 1H), 6.37 (m, 1H), 5.22 (br s, 1H), 3.70 (s, 3H), 2.18 (s, 3H). MS: 368 amu (AP+).
Synthesis Example 6
Preparation of 4-(2-Chloro-4-fluorophenyl)-α-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazole-5-methanol (Compound 351)
5-Bromo-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazole (i.e. the product of Synthesis Example 2, Step A) (0.25 g, 0.82 mmol) was dissolved in anhydrous tetrahydrofuran (12 mL), and the mixture was cooled in a dry ice/acetone bath under a nitrogen atmosphere. A cyclohexane solution of n-butyllithium (2.0 M, 0.49 mL, 0.98 mmol) was added dropwise over 5 minutes. After 15 minutes, a solution of 2,4-difluorobenzaldehyde (0.09 mL, 0.82 mmol) in anhydrous tetrahydrofuran (3 mL) was added slowly dropwise, causing the dark red-colored solution to lighten to a yellow color. After 45 minutes, the reaction mixture was quenched by the addition of saturated aqueous NH4Cl solution (−20 mL) and allowed to warm to ambient temperature. This mixture was extracted with ethyl acetate, and the organic phase was washed with saturated aqueous NH4Cl solution (25 mL) and with brine, dried over Na2SO4, and concentrated to leave a viscous residue. This residue was purified by column chromatography through silica gel eluted with a gradient of ethyl acetate in hexane (7% to 10%) to give the title product, a compound of the present invention, as a white semi-solid (109 mg).
1H NMR δ 7.5 (m, 1H), 7.1 (m, 2H), 7.0 (m, 1H), 6.85 (m, 2H), 6.0 (br s, 1H), 5.9 (s, 1H), 3.8 (s, 3H), 2.1 (s, 3H). MS: 367 amu (AP+).
Synthesis Example 7
Preparation of [4-(2-Chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl](2,4-difluorophenyl)methanone (Compound 370)
4-(2-Chloro-4-fluorophenyl)-α-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazole-5-methanol (i.e. the product of Synthesis Example 6) (90 mg, 0.25 mmol) was dissolved in dichloromethane (8 mL), and pyridinium dichromate (113 mg, 0.3 mmol) was added in one portion. The reaction mixture was stirred at ambient temperature for 16 h, and then the reaction mixture was partitioned between water (5 mL) and dichloromethane (5 mL). The organic phase was washed with additional water (5 mL) and with brine (5 mL), dried over Na2SO4 and concentrated under reduced pressure to give a viscous residue. This residue was purified by column chromatography through silica gel eluted with a gradient of ethyl acetate in hexane (25% to 30%) to give the title product, a compound of the present invention, as a pale yellow viscous oil (29 mg).
1H NMR δ 7.94 (m, 1H), 7.32 (s, 1H), 7.27 (m, 1H), 7.03 (m, 1H), 6.95 (m, 1H), 6.78 (m, 1H), 3.82 (s, 3H), 2.13 (s, 3H). MS: 365 amu (AP+).
Synthesis Example 8
Preparation of 5-(2,6-Difluoro-4-nitrophenoxy)-1,3-dimethyl-4-(2,4,6-trifluorophenyl)-1H-pyrazole (Compound 54)
Step A: Preparation of Methyl 2,4,6-trifluorobenzeneacetate
A solution of 2,4,6-trifluorobenzeneacetic acid (5.00 g, 26.3 mmol) in methanol (25 mL) was stirred at ambient temperature, and thionyl chloride (6 mL,  ̃3 eq.) was added dropwise, causing the temperature of the reaction mixture to reach 60° C. The reaction mixture was allowed to cool to ambient temperature and was stirred for 3 h. Water (25 mL) was added with ice cooling. The mixture was extracted with ethyl acetate (2×100 mL). The combined organic phases were washed with water (2×), with saturated aqueous sodium bicarbonate solution and with brine, and dried over MgSO4. Concentration provided the title product as a clear oil (5.38 g).
1H NMR δ 6.68 (m, 2H), 3.72 (s, 3H), 3.66 (s, 2H).
Step B: Preparation of Methyl α-acetyl-2,4,6-trifluorobenzeneacetate
To a commercially obtained tetrahydrofuran solution of lithium bis(trimethyl-silyl)amide (1.0 M, 21.0 mL), stirred under a nitrogen atmosphere and cooled to an internal temperature of −65° C., was added dropwise over 30 minutes a solution of methyl 2,4,6-trifluorobenzeneacetate (i.e. the product of Step A) (2.04 g, 10.0 mmol) dissolved in dry tetrahydrofuran (10 mL). The reaction mixture was stirred for an additional 30 minutes, and then while maintaining the −65° C. temperature, a solution of freshly distilled acetyl chloride (0.80 mL, 11 mmol) in dry tetrahydrofuran (3 mL) was added dropwise. The reaction mixture was allowed to warm slowly to ambient temperature, and then water (30 mL) was added. The resultant mixture was extracted with ethyl acetate (60 mL). The aqueous phase was acidified with 1 N hydrochloric acid and extracted with ethyl acetate (60 mL). Only the first extract was retained, because thin layer chromatographic analysis showed the second extract to contain apparent polar impurities besides additional desired product. The initial organic phase was further washed with 1 N hydrochloric acid, water and brine, dried over MgSO4, and concentrated to provide the title product as a clear oil (1.86 g).
1H NMR δ 6.69 (m, 2H), 3.7 (m, 1H and s, 3H), 1.87 (s, 3H); minor resonances at 13.2 ppm and 4.9 ppm indicated presence of enolic tautomer.
Step C: Preparation of 1,3-Dimethyl-4-(2,4,6-trifluorophenyl)-1H-pyrazol-5-ol
To a solution of methyl α-acetyl-2,4,6-trifluorobenzeneacetate (i.e. the product of Step B) (2.46 g, 10.0 mmol) in methanol (15 mL) was added methylhydrazine (0.665 mL, 12.5 mmol), and the mixture was stirred at ambient temperature over 3 days. Aqueous citric acid solution (1 M, 10 mL) was added, and then water (50 mL) was added. The mixture was extracted with ethyl acetate (2×50 mL). The combined organic extracts were washed with water and with brine, dried over MgSO4, and concentrated to leave a yellow solid. This solid was suspended in a small volume of ethyl acetate (about 5 mL), an equal volume of hexanes was gradually added, and the suspension was stirred for 30 minutes. The solid component was collected on a glass frit, washed with small portions of ethyl acetate/hexanes (1:1 and 1:2 v:v), and allowed to dry in air to provide a white solid (1.02 g). Evaporation of the mother liquor and treatment of the resultant residue with small volumes of ethyl acetate and hexanes as already described provided an additional 0.13 g of solid containing the title product (1.15 g total). Analysis of the combined solids by LC/MS showed a primary component of mass 242 (AP+) and a minor component, eluting later by reverse-phase LC, also having a mass of 242 (AP+). The apparent ratio of components was 94:6.
1H NMR (acetone-d6) δ 6.95 (m, 2H), 3.52 (s, 3H), 1.98 (s, 3H); 5-hydroxy resonance was not observed in this solvent.
Step D: Preparation of 5-(2,6-Difluoro-4-nitrophenoxy)-1,3-dimethyl-4-(2,4,6-trifluorophenyl)-1H-pyrazole
1,3-Dimethyl-4-(2,4,6-trifluorophenyl)-1H-pyrazol-5-ol (i.e. the product of Step C) (0.310 g, 1.28 mmol), was combined with 3,4,5-trifluoronitrobenzene (157 μL, 1.35 mmol) and potassium carbonate powder (0.27 g, 2 mmol) in dry N,N-dimethylformamide (4 mL). This mixture was stirred and heated at 80° C. for 45 minutes and then allowed to cool. The reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (2×10 mL). The organic phase was washed with water and with brine, dried over MgSO4, and concentrated to leave a viscous residue. This residue was purified by column chromatography through silica gel eluted with a gradient of ethyl acetate (30% to 100%) in hexane to give the title product, a compound of the present invention, as an off-white solid (209 mg).
1H NMR δ 7.71 (m, 2H), 6.54 (m, 2H), 3.86 (s, 3H), 2.07 (s, 3H); 400 amu (AP+).
Synthesis Example 9
Preparation of 4-[[1,3-Dimethyl-4-(2,4,6-trifluorophenyl)-1H-pyrazol-5-yl]oxy]-3,5-difluorobenzenamine (Compound 371)
5-(2,6-Difluoro-4-nitrophenoxy)-1,3-dimethyl-4-(2,4,6-trifluorophenyl)-1H-pyrazole (i.e. the product of Synthesis Example 8) (0.780 g, 1.95 mmol) was combined with iron powder (325 mesh, 0.58 g, 10 mmol) and ammonium chloride (64 mg, 1.2 mmol) in ethanol (27 mL) to which water (3 mL) had been added. The mixture was heated at reflux for 1.25 h and then allowed to cool. The reaction mixture was diluted with an equal volume of ethyl acetate and filtered through Celite filter aid. The filtrate was dried with MgSO4 and concentrated. Analysis by LC/MS showed the major component (93%) to have mass 370 amu (AP+). The residue was dissolved in anhydrous dimethyl sulfoxide (8 mL), and a commercial solution of sodium methoxide in methanol (0.45 mL of 25% solution) was added. This solution was stirred under nitrogen and heated at reflux for 1 h. Additional sodium methoxide/methanol solution (0.20 mL) was added, and heating was continued for an additional 30 minutes. The reaction mixture was allowed to cool, and it was then treated with aqueous citric acid solution (1 M, 5 mL), diluted with water (50 mL) and extracted with ethyl acetate (2×25 mL). The organic phase was washed with water (3×) and with brine, dried over MgSO4, and concentrated to leave the title product, a compound of the present invention, as a viscous oil (0.52 g).
1H NMR δ 6.29 (m, 2H), 5.95 (m, 2H), 3.80 (s, 3H), 3.75 (s, 3H), 3.55-3.75 (br s, NH2), 2.01 (s, 3H); 382 amu (AP+).
Synthesis Example 10
Preparation of 5-(4-Chloro-2,6-difluorophenoxy)-4-(2,6-difluoro-4-methoxyphenyl)-1,3-dimethyl-1H-pyrazole (Compound 58)
Copper(I) chloride (56 mg, 0.42 mmol) was added to a solution of 4-[[4-(2,6-difluoro-4-methoxyphenyl)-1,3-dimethyl-1H-pyrazol-5-yl]oxy]-3,5-difluorobenzenamine (prepared analogous to Synthesis Example 9) (132 mg, 0.346 mmol) in acetonitrile (5 mL). The stirred mixture was cooled using an ice-water bath, and tert-butyl nitrite (90% technical grade, 72 μL) was added dropwise. The reaction mixture was allowed to warm slowly to ambient temperature and stirred at room temperature overnight, and then it was heated at reflux for 1 h. Hydrochloric acid (1 N, 5 mL) was added, and the mixture was extracted with ethyl acetate ( ̃20 mL). The organic phase was washed with brine, dried over MgSO4, and concentrated. The residue was purified by column chromatography through silica gel eluted with 20% ethyl acetate in hexane to give the title product, a compound of the present invention, as a viscous oil (45 mg).
1H NMR δ 6.74 (m, 2H), 6.30 (m, 2H), 3.83 (s, 3H), 3.75 (s, 3H), 2.03 (s, 3H); 401 amu (AP+).
By the procedures described herein together with methods known in the art, the compounds disclosed in the Tables that follow can be prepared. The following abbreviations are used in the Table which follows: Me means methyl, Et means ethyl, n-Pr means n-propyl, c-Pr means cyclopropyl, Ph means phenyl, OMe (or MeO) means methoxy, OEt (or EtO) means ethoxy, —CN means cyano, and —NO2 means nitro.







TABLE 1













 











(R3)p
(R3)p
(R3)p
(R3)p
(R3)p





2-F
3-F
4-F
2-Cl
3-Cl


4-Cl
2-Br
3-Br
4-Br
2,4-di-F


2,6-di-F
2,4,6-tri-F
2,4,5-tri-F
2,3,5-tri-F
2,3,6-tri-F


2-Cl-4-F
2-F-4-Cl
2,4-di-Cl
2,6-di-Cl
2,4,6-tri-Cl


2-Br-4-F
2-I-4-F
2-Me-4-F
2-F-4-MeO
2-Cl-4-MeO


2-Br-4-MeO
2,6-di-F-4-
2-F-4-CN
2-Cl-4-CN
2-Br-4-CN



MeO





2,6-di-F-4-
2-Cl-4,5-di-F
2-Cl-4,6-di-F
2-Br-4,5-di-F
2-Br-4,6-di-F


CN






4-Cl-2,5-di-F
4-Cl-2,6-di-F
4-Br-2,5-di-F
4-Br-2,6-di-F
2,4-di-Cl-6-F


2,6-di-Cl-4-F
2,6-di-Cl-4-
2-CF3-4-F
4-Me
2,4-di-Me



MeO





2-F-4-Br
2-Cl-4-Br
2-Br-4-Cl
2-Br-4-F-6-Cl
2-Cl-4-Br-6-F





Q1 is 2,6-di-F—Ph, and R2 is Me.






The present disclosure also includes Tables 2 through 84, each of which is constructed the same as Table 1 above, except that the row heading in Table 1 (i.e. “Q1 is 2,6-di-F-Ph, and R2 is Me.”) is replaced with the respective row heading shown below. For Example, in Table 2 the row heading is “Q1 is 2,6-di-F-Ph, and R2 is Cl.”, and (R3)p is as defined in Table 1 above. Thus, the first entry in Table 2 specifically discloses 2-chloro-4-(2,6-difluorophenyl)-N-(2-fluorophenyl)-1-methyl-1H-pyrazol-5-amine. Tables 3 through 84 are constructed similarly.














Table
Row Heading









 2
Q1 is 2,6-di-F—Ph, and R2 is Cl.



 3
Q1 is 2,6-di-F—Ph, and R2 is Br.



 4
Q1 is 2,4-di-F—Ph, and R2 is Me.



 5
Q1 is 2,4-di-F—Ph, and R2 is Cl.



 6
Q1 is 2,4-di-F—Ph, and R2 is Br.



 7
Q1 is 2,4,6-tri-F—Ph, and R2 is Me.



 8
Q1 is 2,4,6-tri-F—Ph, and R2 is Cl.



 9
Q1 is 2,4,6-tri-F—Ph, and R2 is Br.



10
Q1 is 2,6-di-F-4-OMe—Ph, and R2 is Me.



11
Q1 is 2,6-di-F-4-OMe—Ph, and R2 is Cl.



12
Q1 is 2,6-di-F-4-OMe—Ph, and R2 is Br.



12A
Q1 is 2,6-di-F-4-OEt—Ph, and R2 is Me.



12B
Q1 is 2,6-di-F-4-OEt—Ph, and R2 is Cl.



12C
Q1 is 2,6-di-F-4-OEt—Ph, and R2 is Br.



13
Q1 is 2,6-di-F-4-CN—Ph, and R2 is Me.



14
Q1 is 2,6-di-F-4-CN—Ph, and R2 is Cl.



15
Q1 is 2,6-di-F-4-CN—Ph, and R2 is Br.



16
Q1 is 2-Cl-4-F—Ph, and R2 is Me.



17
Q1 is 2-Cl-4-F—Ph, and R2 is Cl.



18
Q1 is 2-Cl-4-F—Ph, and R2 is Br.



19
Q1 is 2-Cl-6-F—Ph, and R2 is Me.



20
Q1 is 2-Cl-6-F—Ph, and R2 is Cl.



21
Q1 is 2-Cl-6-F—Ph, and R2 is Br.



22
Q1 is 2-Cl-4,6-di-F—Ph, and R2 is Me.



23
Q1 is 2-Cl-4,6-di-F—Ph, and R2 is Cl.



24
Q1 is 2-Cl-4,6-di-F—Ph, and R2 is Br.



25
Q1 is 4-Cl-2,6-di-F—Ph, and R2 is Me.



26
Q1 is 4-Cl-2,6-di-F—Ph, and R2 is Cl.



27
Q1 is 4-Cl-2,6-di-F—Ph, and R2 is Br.



28
Q1 is 2-Br-4-F—Ph, and R2 is Me.



29
Q1 is 2-Br-4-F—Ph, and R2 is Cl.



30
Q1 is 2-Br-4-F—Ph, and R2 is Br.



31
Q1 is 2-Br-6-F—Ph, and R2 is Me.



32
Q1 is 2-Br-6-F—Ph, and R2 is Cl.



33
Q1 is 2-Br-6-F—Ph, and R2 is Br.



34
Q1 is 2-Me-4-F—Ph, and R2 is Me.



35
Q1 is 2-Me-4-F—Ph, and R2 is Cl.



36
Q1 is 2-Me-4-F—Ph, and R2 is Br.



37
Q1 is 2-I-4-F—Ph, and R2 is Me.



38
Q1 is 2-I-4-F—Ph, and R2 is Cl.



39
Q1 is 2-I-4-F—Ph, and R2 is Br.



40
Q1 is 2-F—Ph, and R2 is Me.



41
Q1 is 2-F—Ph, and R2 is Cl.



42
Q1 is 2-F—Ph, and R2 is Br.



43
Q1 is 2-Cl—Ph, and R2 is Me.



44
Q1 is 2-Cl—Ph, and R2 is Cl.



45
Q1 is 2-Cl—Ph, and R2 is Br.



46
Q1 is 2-Br—Ph, and R2 is Me.



47
Q1 is 2-Br—Ph, and R2 is Cl.



48
Q1 is 2-Br—Ph, and R2 is Br.



49
Q1 is 2-F-4-Cl—Ph, and R2 is Me.



50
Q1 is 2-F-4-Cl—Ph, and R2 is Cl.



51
Q1 is 2-F-4-Cl—Ph, and R2 is Br.



52
Q1 is 2,4-di-Cl—Ph, and R2 is Me.



53
Q1 is 2,4-di-Cl—Ph, and R2 is Cl.



54
Q1 is 2,4-di-Cl—Ph, and R2 is Br.



55
Q1 is 2,6-di-Cl—Ph, and R2 is Me.



56
Q1 is 2,6-di-Cl—Ph, and R2 is Cl.



57
Q1 is 2,6-di-Cl—Ph, and R2 is Br.



58
Q1 is 2-F-4-MeO—Ph, and R2 is Me.



59
Q1 is 2-F-4-MeO—Ph, and R2 is Cl.



60
Q1 is 2-F-4-MeO—Ph, and R2 is Br.



60A
Q1 is 2-F-4-EtO—Ph, and R2 is Me.



60B
Q1 is 2-F-4-EtO—Ph, and R2 is Cl.



60C
Q1 is 2-F-4-EtO—Ph, and R2 is Br.



61
Q1 is 2-Cl-4-MeO—Ph, and R2 is Me.



62
Q1 is 2-Cl-4-MeO—Ph, and R2 is Cl.



63
Q1 is 2-Cl-4-MeO—Ph, and R2 is Br.



63A
Q1 is 2-Cl-4-EtO—Ph, and R2 is Me.



63B
Q1 is 2-Cl-4-EtO—Ph, and R2 is Cl.



63C
Q1 is 2-Cl-4-EtO—Ph, and R2 is Br.



64
Q1 is 2-Br-4-MeO—Ph, and R2 is Me.



65
Q1 is 2-Br-4-MeO—Ph, and R2 is Cl.



66
Q1 is 2-Br-4-MeO—Ph, and R2 is Br.



66A
Q1 is 2-Br-4-EtO—Ph, and R2 is Me.



66B
Q1 is 2-Br-4-EtO—Ph, and R2 is Cl.



66C
Q1 is 2-Br-4-EtO—Ph, and R2 is Br.



67
Q1 is 2-F-4-CN—Ph, and R2 is Me.



68
Q1 is 2-F-4-CN—Ph, and R2 is Cl.



69
Q1 is 2-F-4-CN—Ph, and R2 is Br.



70
Q1 is 2-Cl-4-CN—Ph, and R2 is Me.



71
Q1 is 2-Cl-4-CN—Ph, and R2 is Cl.



72
Q1 is 2-Cl-4-CN—Ph, and R2 is Br.



73
Q1 is 2-Br-4-CN—Ph, and R2 is Me.



74
Q1 is 2-Br-4-CN—Ph, and R2 is Cl.



75
Q1 is 2-Br-4-CN—Ph, and R2 is Br.



76
Q1 is 2,5-di-Cl-3-pyridinyl, and R2 is Me.



77
Q1 is 2,5-di-Cl-3-pyridinyl, and R2 is Cl.



78
Q1 is 2,5-di-Cl-3-pyridinyl, and R2 is Br.



79
Q1 is 2-Cl-3-thienyl, and R2 is Me.



80
Q1 is 2-Cl-3-thienyl, and R2 is Cl.



81
Q1 is 2-Cl-3-thienyl, and R2 is Br.



82
Q1 is 2,5-di-Cl-3-thienyl, and R2 is Me.



83
Q1 is 2,5-di-Cl-3-thienyl, and R2 is Cl.



84
Q1 is 2,5-di-Cl-3-thienyl, and R2 is Br.

















TABLE 85













 











(R3)p
(R3)p
(R3)p
(R3)p
(R3)p





4-F
4-Cl
4-Br
2,4-di-F
2-Br-4-F


2,6-di-F
2,4-di-Cl
2,6-di-Cl
2-Cl-4-F
2-F-4-Cl


2-F-4-Br
2-Br-6-F
2-Cl-4-Br
2-Br-4-Cl
2-I-4-F


2-F-4-I
2-Cl-4,6-di-F
4-Cl-2,6-di-F
2-Br-4,6-di-F
4-Br-2,6-di-F


2-F-4-MeO
2-Cl-4-MeO
2,6-di-F-4-
2-F-4-CN
2-Cl-4-CN




MeO




2-Br-4-CN
2,6-di-F-4-
2-F-4-NO2
2-Cl-4-NO2
2-Br-4-NO2



CN





2,5-di-F-4-CN
4-Cl-2,5-di-F
2-Br-4,5-di-F
4-Br-2,5-di-F
2-Cl-4,5-di-F





Q1 is 2,6-di-F—Ph, X is O, R1 and R1a are both H, and R2 is Me.






The present disclosure also includes Tables 86 through 280, each of which is constructed the same as Table 85 above, except that the row heading in Table 85 (i.e. “Q1 is 2,6-di-F-Ph, X is O, R1 and R1a are both H, and R2 is Me.”) is replaced with the respective row heading shown below. For Example, in Table 86 the row heading is “Q1 is 2,6-di-F-Ph, X is O, R1 and R1a are both H, and R2 is Cl.” and (R3)p is as defined in Table 85 above. Thus, the first entry in Table 86 specifically discloses 3-chloro-4-(2,6-difluorophenyl)-5-(4-fluorophenoxy)-1-methyl-1H-pyrazole. Tables 87 through 280 are constructed similarly.











Table
Row Heading







 86
Q1 is 2,6-di-F—Ph, X is O, R1 and R1a are both H, and R2 is Cl.


 87
Q1 is 2,6-di-F—Ph, X is O, R1 and R1a are both H, and R2 is Br.


 88
Q1 is 2,4-di-F—Ph, X is O, R1 and R1a are both H, and R2 is Me.


 89
Q1 is 2,4-di-F—Ph, X is O, R1 and R1a are both H, and R2 is Cl.


 90
Q1 is 2,4-di-F—Ph, X is O, R1 and R1a are both H, and R2 is Br.


 91
Q1 is 2,4,6-tri-F—Ph, X is O, R1 and R1a are both H, and R2 is Me.


 92
Q1 is 2,4,6-tri-F—Ph, X is O, R1 and R1a are both H, and R2 is Cl.


 93
Q1 is 2,4,6-tri-F—Ph, X is O, R1 and R1a are both H, and R2 is Br.


 94
Q1 is 2,6-di-F-4-OMe—Ph, X is O, R1 and R1a are both H, and R2 is Me.


 95
Q1 is 2,6-di-F-4-OMe—Ph, X is O, R1 and R1a are both H, and R2 is Cl.


 96
Q1 is 2,6-di-F-4-OMe—Ph, X is O, R1 and R1a are both H, and R2 is Br.


 96A
Q1 is 2,6-di-F-4-OEt—Ph, X is O, R1 and R1a are both H, and R2 is Me.


 96B
Q1 is 2,6-di-F-4-OEt—Ph, X is O, R1 and R1a are both H, and R2 is Cl.


 96C
Q1 is 2,6-di-F-4-OEt—Ph, X is O, R1 and R1a are both H, and R2 is Br.


 97
Q1 is 2,6-di-F-4-CN—Ph, X is O, R1 and R1a are both H, and R2 is Me.


 98
Q1 is 2,6-di-F-4-CN—Ph, X is O, R1 and R1a are both H, and R2 is Cl.


 99
Q1 is 2,6-di-F-4-CN—Ph, X is O, R1 and R1a are both H, and R2 is Br.


100
Q1 is 2-Cl-4-F—Ph, X is O, R1 and R1a are both H, and R2 is Me.


101
Q1 is 2-Cl-4-F—Ph, X is O, R1 and R1a are both H, and R2 is Cl.


102
Q1 is 2-Cl-4-F—Ph, X is O, R1 and R1a are both H, and R2 is Br.


103
Q1 is 2-Cl-6-F—Ph, X is O, R1 and R1a are both H, and R2 is Me.


104
Q1 is 2-Cl-6-F—Ph, X is O, R1 and R1a are both H, and R2 is Cl.


105
Q1 is 2-Cl-6-F—Ph, X is O, R1 and R1a are both H, and R2 is Br.


106
Q1 is 2-Cl-4,6-di-F—Ph, X is O, R1 and R1a are both H, and R2 is Me.


107
Q1 is 2-Cl-4,6-di-F—Ph, X is O, R1 and R1a are both H, and R2 is Cl.


108
Q1 is 2-Cl-4,6-di-F—Ph, X is O, R1 and R1a are both H, and R2 is Br.


109
Q1 is 4-Cl-2,6-di-F—Ph, X is O, R1 and R1a are both H, and R2 is Me.


110
Q1 is 4-Cl-2,6-di-F—Ph, X is O, R1 and R1a are both H, and R2 is Cl.


111
Q1 is 4-Cl-2,6-di-F—Ph, X is O, R1 and R1a are both H, and R2 is Br.


112
Q1 is 2-Br-4-F—Ph, X is O, R1 and R1a are both H, and R2 is Me.


113
Q1 is 2-Br-4-F—Ph, X is O, R1 and R1a are both H, and R2 is Cl.


114
Q1 is 2-Br-4-F—Ph, X is O, R1 and R1a are both H, and R2 is Br.


115
Q1 is 2-Br-6-F—Ph, X is O, R1 and R1a are both H, and R2 is Me.


116
Q1 is 2-Br-6-F—Ph, X is O, R1 and R1a are both H, and R2 is Cl.


117
Q1 is 2-Br-6-F—Ph, X is O, R1 and R1a are both H, and R2 is Br.


118
Q1 is 2-Me-4-F—Ph, X is O, R1 and R1a are both H, and R2 is Me.


119
Q1 is 2-Me-4-F—Ph, X is O, R1 and R1a are both H, and R2 is Cl.


120
Q1 is 2-Me-4-F—Ph, X is O, R1 and R1a are both H, and R2 is Br.


121
Q1 is 2-I-4-F—Ph, X is O, R1 and R1a are both H, and R2 is Me.


122
Q1 is 2-I-4-F—Ph, X is O, R1 and R1a are both H, and R2 is Cl.


123
Q1 is 2-I-4-F—Ph, X is O, R1 and R1a are both H, and R2 is Br.


124
Q1 is 2-F—Ph, X is O, R1 and R1a are both H, and R2 is Me.


125
Q1 is 2-F—Ph, X is O, R1 and R1a are both H, and R2 is Cl.


126
Q1 is 2-F—Ph, X is O, R1 and R1a are both H, and R2 is Br.


127
Q1 is 2-Cl—Ph, X is O, R1 and R1a are both H, and R2 is Me.


128
Q1 is 2-Cl—Ph, X is O, R1 and R1a are both H, and R2 is Cl.


129
Q1 is 2-Cl—Ph, X is O, R1 and R1a are both H, and R2 is Br.


130
Q1 is 2-Br—Ph, X is O, R1 and R1a are both H, and R2 is Me.


131
Q1 is 2-Br—Ph, X is O, R1 and R1a are both H, and R2 is Cl.


132
Q1 is 2-Br—Ph, X is O, R1 and R1a are both H, and R2 is Br.


133
Q1 is 2-F-4-Cl—Ph, X is O, R1 and R1a are both H, and R2 is Me.


134
Q1 is 2-F-4-Cl—Ph, X is O, R1 and R1a are both H, and R2 is Cl.


135
Q1 is 2-F-4-Cl—Ph, X is O, R1 and R1a are both H, and R2 is Br.


136
Q1 is 2,4-di-Cl—Ph, X is O, R1 and R1a are both H, and R2 is Me.


137
Q1 is 2,4-di-Cl—Ph, X is O, R1 and R1a are both H, and R2 is Cl.


138
Q1 is 2,4-di-Cl—Ph, X is O, R1 and R1a are both H, and R2 is Br.


139
Q1 is 2,6-di-Cl—Ph, X is O, R1 and R1a are both H, and R2 is Me.


140
Q1 is 2,6-di-Cl—Ph, X is O, R1 and R1a are both H, and R2 is Cl.


141
Q1 is 2,6-di-Cl—Ph, X is O, R1 and R1a are both H, and R2 is Br.


142
Q1 is 2-F-4-MeO—Ph, X is O, R1 and R1a are both H, and R2 is Me.


143
Q1 is 2-F-4-MeO—Ph, X is O, R1 and R1a are both H, and R2 is Cl.


144
Q1 is 2-F-4-MeO—Ph, X is O, R1 and R1a are both H, and R2 is Br.


144A
Q1 is 2-F-4-EtO—Ph, X is O, R1 and R1a are both H, and R2 is Me.


144B
Q1 is 2-F-4-EtO—Ph, X is O, R1 and R1a are both H, and R2 is Cl.


144C
Q1 is 2-F-4-EtO—Ph, X is O, R1 and R1a are both H, and R2 is Br.


145
Q1 is 2-Cl-4-MeO—Ph, X is O, R1 and R1a are both H, and R2 is Me.


146
Q1 is 2-Cl-4-MeO—Ph, X is O, R1 and R1a are both H, and R2 is Cl.


147
Q1 is 2-Cl-4-MeO—Ph, X is O, R1 and R1a are both H, and R2 is Br.


147A
Q1 is 2-Cl-4-EtO—Ph, X is O, R1 and R1a are both H, and R2 is Me.


147B
Q1 is 2-Cl-4-EtO—Ph, X is O, R1 and R1a are both H, and R2 is Cl.


147C
Q1 is 2-Cl-4-EtO—Ph, X is O, R1 and R1a are both H, and R2 is Br.


148
Q1 is 2-Br-4-MeO—Ph, X is O, R1 and R1a are both H, and R2 is Me.


149
Q1 is 2-Br-4-MeO—Ph, X is O, R1 and R1a are both H, and R2 is Cl.


150
Q1 is 2-Br-4-MeO—Ph, X is O, R1 and R1a are both H, and R2 is Br.


150A
Q1 is 2-Br-4-EtO—Ph, X is O, R1 and R1a are both H, and R2 is Me.


150B
Q1 is 2-Br-4-EtO—Ph, X is O, R1 and R1a are both H, and R2 is Cl.


150C
Q1 is 2-Br-4-EtO—Ph, X is O, R1 and R1a are both H, and R2 is Br.


151
Q1 is 2-F-4-CN—Ph, X is O, R1 and R1a are both H, and R2 is Me.


152
Q1 is 2-F-4-CN—Ph, X is O, R1 and R1a are both H, and R2 is Cl.


153
Q1 is 2-F-4-CN—Ph, X is O, R1 and R1a are both H, and R2 is Br.


154
Q1 is 2-Cl-4-CN—Ph, X is O, R1 and R1a are both H, and R2 is Me.


155
Q1 is 2-Cl-4-CN—Ph, X is O, R1 and R1a are both H, and R2 is Cl.


156
Q1 is 2-Cl-4-CN—Ph, X is O, R1 and R1a are both H, and R2 is Br.


157
Q1 is 2-Br-4-CN—Ph, X is O, R1 and R1a are both H, and R2 is Me.


158
Q1 is 2-Br-4-CN—Ph, X is O, R1 and R1a are both H, and R2 is Cl.


159
Q1 is 2-Br-4-CN—Ph, X is O, R1 and R1a are both H, and R2 is Br.


160
Q1 is 2,5-di-Cl-3-pyridinyl, X is O, R1 and R1a are both H, and R2 is Me.


161
Q1 is 2,5-di-Cl-3-pyridinyl, X is O, R1 and R1a are both H, and R2 is Cl.


162
Q1 is 2,5-di-Cl-3-pyridinyl, X is O, R1 and R1a are both H, and R2 is Br.


163
Q1 is 2-Cl-3-thienyl, X is O, R1 and R1a are both H, and R2 is Me.


164
Q1 is 2-Cl-3-thienyl, X is O, R1 and R1a are both H, and R2 is Cl.


165
Q1 is 2-Cl-3-thienyl, X is O, R1 and R1a are both H, and R2 is Br.


166
Q1 is 2,5-di-Cl-3-thienyl, X is O, R1 and R1a are both H, and R2 is Me.


167
Q1 is 2,5-di-Cl-3-thienyl, X is O, R1 and R1a are both H, and R2 is Cl.


168
Q1 is 2,5-di-Cl-3-thienyl, X is O, R1 and R1a are both H, and R2 is Br.


169
Q1 is 2,6-di-F—Ph, X is S, R1 and R1a are both H, and R2 is Me.


170
Q1 is 2,6-di-F—Ph, X is S, R1 and R1a are both H, and R2 is Cl.


171
Q1 is 2,6-di-F—Ph, X is S, R1 and R1a are both H, and R2 is Br.


172
Q1 is 2,4-di-F—Ph, X is S, R1 and R1a are both H, and R2 is Me.


173
Q1 is 2,4-di-F—Ph, X is S, R1 and R1a are both H, and R2 is Cl.


174
Q1 is 2,4-di-F—Ph, X is S, R1 and R1a are both H, and R2 is Br.


175
Q1 is 2,4,6-tri-F—Ph, X is S, R1 and R1a are both H, and R2 is Me.


176
Q1 is 2,4,6-tri-F—Ph, X is S, R1 and R1a are both H, and R2 is Cl.


177
Q1 is 2,4,6-tri-F—Ph, X is S, R1 and R1a are both H, and R2 is Br.


178
Q1 is 2,6-di-F-4-OMe—Ph, X is S, R1 and R1a are both H, and R2 is Me.


179
Q1 is 2,6-di-F-4-OMe—Ph, X is S, R1 and R1a are both H, and R2 is Cl.


180
Q1 is 2,6-di-F-4-OMe—Ph, X is S, R1 and R1a are both H, and R2 is Br.


180A
Q1 is 2,6-di-F-4-OEt—Ph, X is S, R1 and R1a are both H, and R2 is Me.


180B
Q1 is 2,6-di-F-4-OEt—Ph, X is S, R1 and R1a are both H, and R2 is Cl.


180C
Q1 is 2,6-di-F-4-OEt—Ph, X is S, R1 and R1a are both H, and R2 is Br.


181
Q1 is 2,6-di-F-4-CN—Ph, X is S, R1 and R1a are both H, and R2 is Me.


182
Q1 is 2,6-di-F-4-CN—Ph, X is S, R1 and R1a are both H, and R2 is Cl.


183
Q1 is 2,6-di-F-4-CN—Ph, X is S, R1 and R1a are both H, and R2 is Br.


184
Q1 is 2-Cl-4-F—Ph, X is S, R1 and R1a are both H, and R2 is Me.


185
Q1 is 2-Cl-4-F—Ph, X is S, R1 and R1a are both H, and R2 is Cl.


186
Q1 is 2-Cl-4-F—Ph, X is S, R1 and R1a are both H, and R2 is Br.


187
Q1 is 2-Cl-6-F—Ph, X is S, R1 and R1a are both H, and R2 is Me.


188
Q1 is 2-Cl-6-F—Ph, X is S, R1 and R1a are both H, and R2 is Cl.


189
Q1 is 2-Cl-6-F—Ph, X is S, R1 and R1a are both H, and R2 is Br.


190
Q1 is 2-Cl-4,6-di-F—Ph, X is S, R1 and R1a are both H, and R2 is Me.


191
Q1 is 2-Cl-4,6-di-F—Ph, X is S, R1 and R1a are both H, and R2 is Cl.


192
Q1 is 2-Cl-4,6-di-F—Ph, X is S, R1 and R1a are both H, and R2 is Br.


193
Q1 is 4-Cl-2,6-di-F—Ph, X is S, R1 and R1a are both H, and R2 is Me.


194
Q1 is 4-Cl-2,6-di-F—Ph, X is S, R1 and R1a are both H, and R2 is Cl.


195
Q1 is 4-Cl-2,6-di-F—Ph, X is S, R1 and R1a are both H, and R2 is Br.


196
Q1 is 2-Br-4-F—Ph, X is S, R1 and R1a are both H, and R2 is Me.


197
Q1 is 2-Br-4-F—Ph, X is S, R1 and R1a are both H, and R2 is Cl.


198
Q1 is 2-Br-4-F—Ph, X is S, R1 and R1a are both H, and R2 is Br.


199
Q1 is 2-Br-6-F—Ph, X is S, R1 and R1a are both H, and R2 is Me.


200
Q1 is 2-Br-6-F—Ph, X is S, R1 and R1a are both H, and R2 is Cl.


201
Q1 is 2-Br-6-F—Ph, X is S, R1 and R1a are both H, and R2 is Br.


202
Q1 is 2-Me-4-F—Ph, X is S, R1 and R1a are both H, and R2 is Me.


203
Q1 is 2-Me-4-F—Ph, X is S, R1 and R1a are both H, and R2 is Cl.


204
Q1 is 2-Me-4-F—Ph, X is S, R1 and R1a are both H, and R2 is Br.


205
Q1 is 2-I-4-F—Ph, X is S, R1 and R1a are both H, and R2 is Me.


206
Q1 is 2-I-4-F—Ph, X is S, R1 and R1a are both H, and R2 is Cl.


207
Q1 is 2-I-4-F—Ph, X is S, R1 and R1a are both H, and R2 is Br.


208
Q1 is 2-F—Ph, X is S, R1 and R1a are both H, and R2 is Me.


209
Q1 is 2-F—Ph, X is S, R1 and R1a are both H, and R2 is Cl.


210
Q1 is 2-F—Ph, X is S, R1 and R1a are both H, and R2 is Br.


211
Q1 is 2-Cl—Ph, X is S, R1 and R1a are both H, and R2 is Me.


212
Q1 is 2-Cl—Ph, X is S, R1 and R1a are both H, and R2 is Cl.


213
Q1 is 2-Cl—Ph, X is S, R1 and R1a are both H, and R2 is Br.


214
Q1 is 2-Br—Ph, X is S, R1 and R1a are both H, and R2 is Me.


215
Q1 is 2-Br—Ph, X is S, R1 and R1a are both H, and R2 is Cl.


216
Q1 is 2-Br—Ph, X is S, R1 and R1a are both H, and R2 is Br.


217
Q1 is 2-F-4-Cl—Ph, X is S, R1 and R1a are both H, and R2 is Me.


218
Q1 is 2-F-4-Cl—Ph, X is S, R1 and R1a are both H, and R2 is Cl.


219
Q1 is 2-F-4-Cl—Ph, X is S, R1 and R1a are both H, and R2 is Br.


220
Q1 is 2,4-di-Cl—Ph, X is S, R1 and R1a are both H, and R2 is Me.


221
Q1 is 2,4-di-Cl—Ph, X is S, R1 and R1a are both H, and R2 is Cl.


222
Q1 is 2,4-di-Cl—Ph, X is S, R1 and R1a are both H, and R2 is Br.


223
Q1 is 2,6-di-Cl—Ph, X is S, R1 and R1a are both H, and R2 is Me.


224
Q1 is 2,6-di-Cl—Ph, X is S, R1 and R1a are both H, and R2 is Cl.


225
Q1 is 2,6-di-Cl—Ph, X is S, R1 and R1a are both H, and R2 is Br.


226
Q1 is 2-F-4-MeO—Ph, X is S, R1 and R1a are both H, and R2 is Me.


227
Q1 is 2-F-4-MeO—Ph, X is S, R1 and R1a are both H, and R2 is Cl.


228
Q1 is 2-F-4-MeO—Ph, X is S, R1 and R1a are both H, and R2 is Br.


228A
Q1 is 2-F-4-EtO—Ph, X is S, R1 and R1a are both H, and R2 is Me.


228B
Q1 is 2-F-4-EtO—Ph, X is S, R1 and R1a are both H, and R2 is Cl.


228C
Q1 is 2-F-4-EtO—Ph, X is S, R1 and R1a are both H, and R2 is Br.


229
Q1 is 2-Cl-4-MeO—Ph, X is S, R1 and R1a are both H, and R2 is Me.


230
Q1 is 2-Cl-4-MeO—Ph, X is S, R1 and R1a are both H, and R2 is Cl.


231
Q1 is 2-Cl-4-MeO—Ph, X is S, R1 and R1a are both H, and R2 is Br.


231A
Q1 is 2-Cl-4-EtO—Ph, X is S, R1 and R1a are both H, and R2 is Me.


231B
Q1 is 2-Cl-4-EtO—Ph, X is S, R1 and R1a are both H, and R2 is Cl.


231C
Q1 is 2-Cl-4-EtO—Ph, X is S, R1 and R1a are both H, and R2 is Br.


232
Q1 is 2-Br-4-MeO—Ph, X is S, R1 and R1a are both H, and R2 is Me.


233
Q1 is 2-Br-4-MeO—Ph, X is S, R1 and R1a are both H, and R2 is Cl.


234
Q1 is 2-Br-4-MeO—Ph, X is S, R1 and R1a are both H, and R2 is Br.


234A
Q1 is 2-Br-4-EtO—Ph, X is S, R1 and R1a are both H, and R2 is Me.


234B
Q1 is 2-Br-4-EtO—Ph, X is S, R1 and R1a are both H, and R2 is Cl.


234C
Q1 is 2-Br-4-EtO—Ph, X is S, R1 and R1a are both H, and R2 is Br.


235
Q1 is 2-F-4-CN—Ph, X is S, R1 and R1a are both H, and R2 is Me.


236
Q1 is 2-F-4-CN—Ph, X is S, R1 and R1a are both H, and R2 is Cl.


237
Q1 is 2-F-4-CN—Ph, X is S, R1 and R1a are both H, and R2 is Br.


238
Q1 is 2-Cl-4-CN—Ph, X is S, R1 and R1a are both H, and R2 is Me.


239
Q1 is 2-Cl-4-CN—Ph, X is S, R1 and R1a are both H, and R2 is Cl.


240
Q1 is 2-Cl-4-CN—Ph, X is S, R1 and R1a are both H, and R2 is Br.


241
Q1 is 2-Br-4-CN—Ph, X is S, R1 and R1a are both H, and R2 is Me.


242
Q1 is 2-Br-4-CN—Ph, X is S, R1 and R1a are both H, and R2 is Cl.


243
Q1 is 2-Br-4-CN—Ph, X is S, R1 and R1a are both H, and R2 is Br.


244
Q1 is 2,5-di-Cl-3-pyridinyl, X is S, R1 and R1a are both H, and R2 is Me.


245
Q1 is 2,5-di-Cl-3-pyridinyl, X is S, R1 and R1a are both H, and R2 is Cl.


246
Q1 is 2,5-di-Cl-3-pyridinyl, X is S, R1 and R1a are both H, and R2 is Br.


247
Q1 is 2-Cl-3-thienyl, X is S, R1 and R1a are both H, and R2 is Me.


248
Q1 is 2-Cl-3-thienyl, X is S, R1 and R1a are both H, and R2 is Cl.


249
Q1 is 2-Cl-3-thienyl, X is S, R1 and R1a are both H, and R2 is Br.


250
Q1 is 2,5-di-Cl-3-thienyl, X is S, R1 and R1a are both H, and R2 is Me.


251
Q1 is 2,5-di-Cl-3-thienyl, X is S, R1 and R1a are both H, and R2 is Cl.


252
Q1 is 2,5-di-Cl-3-thienyl, X is S, R1 and R1a are both H, and R2 is Br.


253
Q1 is 2,6-di-F—Ph, X is NH, R1 and R1a form c-Pr, and R2 is Me.


254
Q1 is 2,4-di-F—Ph, X is O, R1 is Et, R1a is H, and R2 is Cl.


255
Q1 is 2,4,6-tri-F—Ph, X is S, R1 and R1a are both H, and R2 is Et.


256
Q1 is 2,6-di-F-4-OMe—Ph, X is CHOH, R1 and R1a are both H, and R2 is CF3.


257
Q1 is 2,6-di-F-4-CN—Ph, X is NH, R1 is CH═CH2, R1a is H, and R2 is Cl.


258
Q1 is 2-Cl-4-F—Ph, X is CHOH, X is O, R1 is c-Pr, R1a is H, and R2 is Br.


259
Q1 is 2-Cl-6-F—Ph, X is S, R1 and R1a form c-Pr, and R2 is Me.


260
Q1 is 2-Cl-4,6-di-F—Ph, X is CHOH, R1 is c-Pr, R1a is H, and R2 is Cl.


261
Q1 is 4-Cl-2,6-di-F—Ph, X is NH, X is NH, R1 is Et, R1a is H, and R2 is Br.


262
Q1 is 2-Br-4-F—Ph, X is O, R1 and R1a are both H, and R2 is Et.


263
Q1 is 2-Br-6-F—Ph, X is S, R1 is CH2CH═CH2, R1a is H, and R2 is Cl.


264
Q1 is 2-Me-4-F—Ph, X is CHOH, R1 and R1a are both H, and R2 is c-Pr.


265
Q1 is 2-I-4-F—Ph, X is NH, R1 is CH2CF3, R1a is H, and R2 is Me.


266
Q1 is 2-F—Ph, X is O, R1 is CH2F, R1a is H, and R2 is Cl.


267
Q1 is 2-Cl—Ph, X is S, R1 and R1a are both H, and R2 is CH2Cl.


268
Q1 is 2-Br—Ph, X is CHCH3, R1 and R1a are both H, and R2 is Me.


269
Q1 is 2-F-4-Cl—Ph, X is C(CH3)OH, R1 and R1a are both H, and R2 is Me.


270
Q1 is 2,4-di-Cl—Ph, X is O, R1 is Et, R1a is H, and R2 is Br.


271
Q1 is 2,6-di-Cl—Ph, X is S, R1 and R1a are both H, and R2 is OMe.


272
Q1 is 2-F-4-MeO—Ph, X is CHOCH3, R1 and R1a are both H, and R2 is Cl.


273
Q1 is 2-Cl-4-MeO—Ph, X is NH, R1 and R1a form c-Pr, and R2 is Br.


274
Q1 is 2-Br-4-MeO—Ph, X is O, R1 is n-Pr, R1a is H, and R2 is Me.


275
Q1 is 2-F-4-CN—Ph, X is NH, R1 is CH2C≡CH, R1a is H, and R2 is Cl.


276
Q1 is 2-Cl-4-CN—Ph, X is C(OCH3)2, R1 and R1a are both H, and R2 is Br.


277
Q1 is 2-Br-4-CN—Ph, X is NH, R1 and R1a form c-Pr, and R2 is Me.


278
Q1 is 2,5-di-Cl-3-pyridinyl, X is O, R1 is c-Pr, R1a is H, and R2 is Cl.


279
Q1 is 2-Cl-3-thienyl, X is S, R1 and R1a are both H, and R2 is Et.


280
Q1 is 2,5-di-Cl-3-thienyl, X is CHOH, R1 is Et, R1a is H, and R2 is Me.
















TABLE 281













 











(R3)p
(R3)p
(R3)p
(R3)p
(R3)p





4-F
4-Cl
4-Br
4-Me
2,4-di-F


2,6-di-F
2,4-di-Cl
2,6-di-Cl
2-Cl-4-F
2-F-4-Cl


2-F-4-Br
2-Br-6-F
2-Cl-4-Br
2-Br-4-Cl
2-I-4-F


2-F-4-I
2-Cl-4,6-di-F
4-Cl-2,6-di-F
2-Br-4,6-di-F
4-Br-2,6-di-F


2-Br-4-F
2-Me-4-F
2,4,6-tri-F
2-Cl-4,5-di-F
4-Cl-2,5-di-F


2-F-4-CN
2-Cl-4-CN
2-Br-4-CN
2,6-diF-4-CN
2-F-4-MeO


2-Cl-4-MeO
2-Br-4-MeO
2,6-di-F-4-MeO
4-Br-2,5-di-F
2-Br-4,5-di-F





Q1 is 2,6-di-F—Ph, X is CHOH, and R2 is Me.






The present disclosure also includes Tables 282 through 448, each of which is constructed the same as Table 281 above, except that the row heading in Table 281 (i.e. “Q1 is 2,6-di-F-Ph, X is CHOH, and R2 is Me.”) is replaced with the respective row heading shown below. For Example, in Table 282 the row heading is “Q1 is 2,6-di-F-Ph, X is CHOH, and R2 is Cl.” and (R3)p is as defined in Table 281 above. Thus, the first entry in Table 282 specifically discloses 3-chloro-4-(2,6-difluorophenyl)-α-(4-fluorophenyl)-1-methyl-1H-pyrazole-5-methanol. Tables 283 through 448 are constructed similarly.














Table
Row Heading









282
Q1 is 2,6-di-F—Ph, X is CHOH, and R2 is Cl.



283
Q1 is 2,6-di-F—Ph, X is CHOH, and R2 is Br.



284
Q1 is 2,4-di-F—Ph, X is CHOH, and R2 is Me.



285
Q1 is 2,4-di-F—Ph, X is CHOH, and R2 is Cl.



286
Q1 is 2,4-di-F—Ph, X is CHOH, and R2 is Br.



287
Q1 is 2,4,6-tri-F—Ph, X is CHOH, and R2 is Me.



288
Q1 is 2,4,6-tri-F—Ph, X is CHOH, and R2 is Cl.



289
Q1 is 2,4,6-tri-F—Ph, X is CHOH, and R2 is Br.



290
Q1 is 2,6-di-F-4-OMe—Ph, X is CHOH, and R2 is Me.



291
Q1 is 2,6-di-F-4-OMe—Ph, X is CHOH, and R2 is Cl.



292
Q1 is 2,6-di-F-4-OMe—Ph, X is CHOH, and R2 is Br.



292A
Q1 is 2,6-di-F-4-OEt—Ph, X is CHOH, and R2 is Me.



292B
Q1 is 2,6-di-F-4-OEt—Ph, X is CHOH, and R2 is Cl.



292C
Q1 is 2,6-di-F-4-OEt—Ph, X is CHOH, and R2 is Br.



293
Q1 is 2,6-di-F-4-CN—Ph, X is CHOH, and R2 is Me.



294
Q1 is 2,6-di-F-4-CN—Ph, X is CHOH, and R2 is Cl.



295
Q1 is 2,6-di-F-4-CN—Ph, X is CHOH, and R2 is Br.



296
Q1 is 2-Cl-4-F—Ph, X is CHOH, and R2 is Me.



297
Q1 is 2-Cl-4-F—Ph, X is CHOH, and R2 is Cl.



298
Q1 is 2-Cl-4-F—Ph, X is CHOH, and R2 is Br.



299
Q1 is 2-Cl-6-F—Ph, X is CHOH, and R2 is Me.



300
Q1 is 2-Cl-6-F—Ph, X is CHOH, and R2 is Cl.



301
Q1 is 2-Cl-6-F—Ph, X is CHOH, and R2 is Br.



302
Q1 is 2-Cl-4,6-di-F—Ph, X is CHOH, and R2 is Me.



303
Q1 is 2-Cl-4,6-di-F—Ph, X is CHOH, and R2 is Cl.



304
Q1 is 2-Cl-4,6-di-F—Ph, X is CHOH, and R2 is Br.



305
Q1 is 4-Cl-2,6-di-F—Ph, X is CHOH, and R2 is Me.



306
Q1 is 4-Cl-2,6-di-F—Ph, X is CHOH, and R2 is Cl.



307
Q1 is 4-Cl-2,6-di-F—Ph, X is CHOH, and R2 is Br.



308
Q1 is 2-Br-4-F—Ph, X is CHOH, and R2 is Me.



309
Q1 is 2-Br-4-F—Ph, X is CHOH, and R2 is Cl.



310
Q1 is 2-Br-4-F—Ph, X is CHOH, and R2 is Br.



311
Q1 is 2-Br-6-F—Ph, X is CHOH, and R2 is Me.



312
Q1 is 2-Br-6-F—Ph, X is CHOH, and R2 is Cl.



313
Q1 is 2-Br-6-F—Ph, X is CHOH, and R2 is Br.



314
Q1 is 2-Me-4-F—Ph, X is CHOH, and R2 is Me.



315
Q1 is 2-Me-4-F—Ph, X is CHOH, and R2 is Cl.



316
Q1 is 2-Me-4-F—Ph, X is CHOH, and R2 is Br.



317
Q1 is 2-I-4-F—Ph, X is CHOH, and R2 is Me.



318
Q1 is 2-I-4-F—Ph, X is CHOH, and R2 is Cl.



319
Q1 is 2-I-4-F—Ph, X is CHOH, and R2 is Br.



320
Q1 is 2-F—Ph, X is CHOH, and R2 is Me.



321
Q1 is 2-F—Ph, X is CHOH, and R2 is Cl.



322
Q1 is 2-F—Ph, X is CHOH, and R2 is Br.



323
Q1 is 2-Cl—Ph, X is CHOH, and R2 is Me.



324
Q1 is 2-Cl—Ph, X is CHOH, and R2 is Cl.



325
Q1 is 2-Cl—Ph, X is CHOH, and R2 is Br.



326
Q1 is 2-Br—Ph, X is CHOH, and R2 is Me.



327
Q1 is 2-Br—Ph, X is CHOH, and R2 is Cl.



328
Q1 is 2-Br—Ph, X is CHOH, and R2 is Br.



329
Q1 is 2-F-4-Cl—Ph, X is CHOH, and R2 is Me.



330
Q1 is 2-F-4-Cl—Ph, X is CHOH, and R2 is Cl.



331
Q1 is 2-F-4-Cl—Ph, X is CHOH, and R2 is Br.



332
Q1 is 2,4-di-Cl—Ph, X is CHOH, and R2 is Me.



333
Q1 is 2,4-di-Cl—Ph, X is CHOH, and R2 is Cl.



334
Q1 is 2,4-di-Cl—Ph, X is CHOH, and R2 is Br.



335
Q1 is 2,6-di-Cl—Ph, X is CHOH, and R2 is Me.



336
Q1 is 2,6-di-Cl—Ph, X is CHOH, and R2 is Cl.



337
Q1 is 2,6-di-Cl—Ph, X is CHOH, and R2 is Br.



338
Q1 is 2-F-4-MeO—Ph, X is CHOH, and R2 is Me.



339
Q1 is 2-F-4-MeO—Ph, X is CHOH, and R2 is Cl.



340
Q1 is 2-F-4-MeO—Ph, X is CHOH, and R2 is Br.



340A
Q1 is 2-F-4-EtO—Ph, X is CHOH, and R2 is Me.



340B
Q1 is 2-F-4-EtO—Ph, X is CHOH, and R2 is Cl.



340C
Q1 is 2-F-4-EtO—Ph, X is CHOH, and R2 is Br.



341
Q1 is 2-Cl-4-MeO—Ph, X is CHOH, and R2 is Me.



342
Q1 is 2-Cl-4-MeO—Ph, X is CHOH, and R2 is Cl.



343
Q1 is 2-Cl-4-MeO—Ph, X is CHOH, and R2 is Br.



343A
Q1 is 2-Cl-4-EtO—Ph, X is CHOH, and R2 is Me.



343B
Q1 is 2-Cl-4-EtO—Ph, X is CHOH, and R2 is Cl.



343C
Q1 is 2-Cl-4-EtO—Ph, X is CHOH, and R2 is Br.



344
Q1 is 2-Br-4-MeO—Ph, X is CHOH, and R2 is Me.



345
Q1 is 2-Br-4-MeO—Ph, X is CHOH, and R2 is Cl.



346
Q1 is 2-Br-4-MeO—Ph, X is CHOH, and R2 is Br.



346A
Q1 is 2-Br-4-EtO—Ph, X is CHOH, and R2 is Me.



346B
Q1 is 2-Br-4-EtO—Ph, X is CHOH, and R2 is Cl.



346C
Q1 is 2-Br-4-EtO—Ph, X is CHOH, and R2 is Br.



347
Q1 is 2-F-4-CN—Ph, X is CHOH, and R2 is Me.



348
Q1 is 2-F-4-CN—Ph, X is CHOH, and R2 is Cl.



349
Q1 is 2-F-4-CN—Ph, X is CHOH, and R2 is Br.



350
Q1 is 2-Cl-4-CN—Ph, X is CHOH, and R2 is Me.



351
Q1 is 2-Cl-4-CN—Ph, X is CHOH, and R2 is Cl.



352
Q1 is 2-Cl-4-CN—Ph, X is CHOH, and R2 is Br.



353
Q1 is 2-Br-4-CN—Ph, X is CHOH, and R2 is Me.



354
Q1 is 2-Br-4-CN—Ph, X is CHOH, and R2 is Cl.



355
Q1 is 2-Br-4-CN—Ph, X is CHOH, and R2 is Br.



356
Q1 is 2,5-di-Cl-3-pyridinyl, X is CHOH, and R2 is Me.



357
Q1 is 2,5-di-Cl-3-pyridinyl, X is CHOH, and R2 is Cl.



358
Q1 is 2,5-di-Cl-3-pyridinyl, X is CHOH, and R2 is Br.



359
Q1 is 2-Cl-3-thienyl, X is CHOH, and R2 is Me.



360
Q1 is 2-Cl-3-thienyl, X is CHOH, and R2 is Cl.



361
Q1 is 2-Cl-3-thienyl, X is CHOH, and R2 is Br.



362
Q1 is 2,5-di-Cl-3-thienyl, X is CHOH, and R2 is Me.



363
Q1 is 2,5-di-Cl-3-thienyl, X is CHOH, and R2 is Cl.



364
Q1 is 2,5-di-Cl-3-thienyl, X is CHOH, and R2 is Br.



365
Q1 is 2,6-di-F—Ph, X is C(O), and R2 is Cl.



366
Q1 is 2,6-di-F—Ph, X is C(O), and R2 is Cl.



367
Q1 is 2,6-di-F—Ph, X is C(O), and R2 is Br.



368
Q1 is 2,4-di-F—Ph, X is C(O), and R2 is Me.



369
Q1 is 2,4-di-F—Ph, X is C(O), and R2 is Cl.



370
Q1 is 2,4-di-F—Ph, X is C(O), and R2 is Br.



371
Q1 is 2,4,6-tri-F—Ph, X is C(O), and R2 is Me.



372
Q1 is 2,4,6-tri-F—Ph, X is C(O), and R2 is Cl.



373
Q1 is 2,4,6-tri-F—Ph, X is C(O), and R2 is Br.



374
Q1 is 2,6-di-F-4-OMe—Ph, X is C(O), and R2 is Me.



375
Q1 is 2,6-di-F-4-OMe—Ph, X is C(O), and R2 is Cl.



376
Q1 is 2,6-di-F-4-OMe—Ph, X is C(O), and R2 is Br.



376A
Q1 is 2,6-di-F-4-OEt—Ph, X is C(O), and R2 is Me.



376B
Q1 is 2,6-di-F-4-OEt—Ph, X is C(O), and R2 is Cl.



376C
Q1 is 2,6-di-F-4-OEt—Ph, X is C(O), and R2 is Br.



377
Q1 is 2,6-di-F-4-CN—Ph, X is C(O), and R2 is Me.



378
Q1 is 2,6-di-F-4-CN—Ph, X is C(O), and R2 is Cl.



379
Q1 is 2,6-di-F-4-CN—Ph, X is C(O), and R2 is Br.



380
Q1 is 2-Cl-4-F—Ph, X is C(O), and R2 is Me.



381
Q1 is 2-Cl-4-F—Ph, X is C(O), and R2 is Cl.



382
Q1 is 2-Cl-4-F—Ph, X is C(O), and R2 is Br.



383
Q1 is 2-Cl-6-F—Ph, X is C(O), and R2 is Me.



384
Q1 is 2-Cl-6-F—Ph, X is C(O), and R2 is Cl.



385
Q1 is 2-Cl-6-F—Ph, X is C(O), and R2 is Br.



386
Q1 is 2-Cl-4,6-di-F—Ph, X is C(O), and R2 is Me.



387
Q1 is 2-Cl-4,6-di-F—Ph, X is C(O), and R2 is Cl.



388
Q1 is 2-Cl-4,6-di-F—Ph, X is C(O), and R2 is Br.



389
Q1 is 4-Cl-2,6-di-F—Ph, X is C(O), and R2 is Me.



390
Q1 is 4-Cl-2,6-di-F—Ph, X is C(O), and R2 is Cl.



391
Q1 is 4-Cl-2,6-di-F—Ph, X is C(O), and R2 is Br.



392
Q1 is 2-Br-4-F—Ph, X is C(O), and R2 is Me.



393
Q1 is 2-Br-4-F—Ph, X is C(O), and R2 is Cl.



394
Q1 is 2-Br-4-F—Ph, X is C(O), and R2 is Br.



395
Q1 is 2-Br-6-F—Ph, X is C(O), and R2 is Me.



396
Q1 is 2-Br-6-F—Ph, X is C(O), and R2 is Cl.



397
Q1 is 2-Br-6-F—Ph, X is C(O), and R2 is Br.



398
Q1 is 2-Me-4-F—Ph, X is C(O), and R2 is Me.



399
Q1 is 2-Me-4-F—Ph, X is C(O), and R2 is Cl.



400
Q1 is 2-Me-4-F—Ph, X is C(O), and R2 is Br.



401
Q1 is 2-I-4-F—Ph, X is C(O), and R2 is Me.



402
Q1 is 2-I-4-F—Ph, X is C(O), and R2 is Cl.



403
Q1 is 2-I-4-F—Ph, X is C(O), and R2 is Br.



404
Q1 is 2-F—Ph, X is C(O), and R2 is Me.



405
Q1 is 2-F—Ph, X is C(O), and R2 is Cl.



406
Q1 is 2-F—Ph, X is C(O), and R2 is Br.



407
Q1 is 2-Cl—Ph, X is C(O), and R2 is Me.



408
Q1 is 2-Cl—Ph, X is C(O), and R2 is Cl.



409
Q1 is 2-Cl—Ph, X is C(O), and R2 is Br.



410
Q1 is 2-Br—Ph, X is C(O), and R2 is Me.



411
Q1 is 2-Br—Ph, X is C(O), and R2 is Cl.



412
Q1 is 2-Br—Ph, X is C(O), and R2 is Br.



413
Q1 is 2-F-4-Cl—Ph, X is C(O), and R2 is Me.



414
Q1 is 2-F-4-Cl—Ph, X is C(O), and R2 is Cl.



415
Q1 is 2-F-4-Cl—Ph, X is C(O), and R2 is Br.



416
Q1 is 2,4-di-Cl—Ph, X is C(O), and R2 is Me.



417
Q1 is 2,4-di-Cl—Ph, X is C(O), and R2 is Cl.



418
Q1 is 2,4-di-Cl—Ph, X is C(O), and R2 is Br.



419
Q1 is 2,6-di-Cl—Ph, X is C(O), and R2 is Me.



420
Q1 is 2,6-di-Cl—Ph, X is C(O), and R2 is Cl.



421
Q1 is 2,6-di-Cl—Ph, X is C(O), and R2 is Br.



422
Q1 is 2-F-4-MeO—Ph, X is C(O), and R2 is Me.



423
Q1 is 2-F-4-MeO—Ph, X is C(O), and R2 is Cl.



424
Q1 is 2-F-4-MeO—Ph, X is C(O), and R2 is Br.



424A
Q1 is 2-F-4-EtO—Ph, X is C(O), and R2 is Me.



424B
Q1 is 2-F-4-EtO—Ph, X is C(O), and R2 is Cl.



424C
Q1 is 2-F-4-EtO—Ph, X is C(O), and R2 is Br.



425
Q1 is 2-Cl-4-MeO—Ph, X is C(O), and R2 is Me.



426
Q1 is 2-Cl-4-MeO—Ph, X is C(O), and R2 is Cl.



427
Q1 is 2-Cl-4-MeO—Ph, X is C(O), and R2 is Br.



427A
Q1 is 2-Cl-4-EtO—Ph, X is C(O), and R2 is Me.



427B
Q1 is 2-Cl-4-EtO—Ph, X is C(O), and R2 is Cl.



427C
Q1 is 2-Cl-4-EtO—Ph, X is C(O), and R2 is Br.



428
Q1 is 2-Br-4-MeO—Ph, X is C(O), and R2 is Me.



429
Q1 is 2-Br-4-MeO—Ph, X is C(O), and R2 is Cl.



430
Q1 is 2-Br-4-MeO—Ph, X is C(O), and R2 is Br.



430A
Q1 is 2-Br-4-EtO—Ph, X is C(O), and R2 is Me.



430B
Q1 is 2-Br-4-EtO—Ph, X is C(O), and R2 is Cl.



430C
Q1 is 2-Br-4-EtO—Ph, X is C(O), and R2 is Br.



431
Q1 is 2-F-4-CN—Ph, X is C(O), and R2 is Me.



432
Q1 is 2-F-4-CN—Ph, X is C(O), and R2 is Cl.



433
Q1 is 2-F-4-CN—Ph, X is C(O), and R2 is Br.



434
Q1 is 2-Cl-4-CN—Ph, X is C(O), and R2 is Me.



435
Q1 is 2-Cl-4-CN—Ph, X is C(O), and R2 is Cl.



436
Q1 is 2-Cl-4-CN—Ph, X is C(O), and R2 is Br.



437
Q1 is 2-Br-4-CN—Ph, X is C(O), and R2 is Me.



438
Q1 is 2-Br-4-CN—Ph, X is C(O), and R2 is Cl.



439
Q1 is 2-Br-4-CN—Ph, X is C(O), and R2 is Br.



440
Q1 is 2,5-di-Cl-3-pyridinyl, X is C(O), and R2 is Me.



441
Q1 is 2,5-di-Cl-3-pyridinyl, X is C(O), and R2 is Cl.



442
Q1 is 2,5-di-Cl-3-pyridinyl, X is C(O), and R2 is Br.



443
Q1 is 2-Cl-3-thienyl, X is C(O), and R2 is Me.



444
Q1 is 2-Cl-3-thienyl, X is C(O), and R2 is Cl.



445
Q1 is 2-Cl-3-thienyl, X is C(O), and R2 is Br.



446
Q1 is 2,5-di-Cl-3-thienyl, X is C(O), and R2 is Me.



447
Q1 is 2,5-di-Cl-3-thienyl, X is C(O), and R2 is Cl.



448
Q1 is 2,5-di-Cl-3-thienyl, X is C(O), and R2 is Br.

















TABLE 449













 










Q2
Q2
Q2
Q2





2-Cl-3-pyridinyl
6-Cl-3-pyridinyl
2,6-di-Cl-3-pyridinyl
3-Cl-2-pyridinyl


3,5-di-Cl-2-pyridinyl
3,5-di-F-2-pyridinyl
5-Me-2-pyridinyl
5-CN-2-pyridinyl


5-pyrimidinyl
2-Cl-5-pyrimidinyl
1,3-di-Me-5-pyrazolyl
5-Me-2-thiazolyl


5-Cl-2-pyridinyl
3,5-di-Cl-4-pyridinyl
tetrahydro-2H-pyran-4-yl
quinolin-2-yl





Q1 is 2,6-di-F—Ph, and X is NH.






The present disclosure also includes Tables 450 through 587, each of which is constructed the same as Table 449 above, except that the row heading in Table 449 (i.e. “Q1 is 2,6-di-F-Ph, and X is NH.”) is replaced with the respective row heading shown below. For Example, in Table 450 the row heading is “Q1 is 2,4-di-F-Ph, and X is NH.” and Q2 is as defined in Table 449 above. Thus, the first entry in Table 450 specifically discloses 2-chloro-N-[4-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]-3-pyridinamine. Tables 451 through 587 are constructed similarly.














Table
Row Heading









450
Q1 is 2,4-di-F—Ph, and X is NH.



451
Q1 is 2,4,6-tri-F—Ph, and X is NH.



452
Q1 is 2,6-di-F-4-OMe—Ph, and X is NH.



453
Q1 is 2,6-di-F-4-CN—Ph, and X is NH.



454
Q1 is 2-Cl-4-F—Ph, and X is NH.



455
Q1 is 2-Cl-6-F—Ph, and X is NH.



456
Q1 is 2-Cl-4,6-di-F—Ph, and X is NH.



457
Q1 is 4-Cl-2,6-di-F—Ph, and X is NH.



458
Q1 is 2-Br-4-F—Ph, and X is NH.



459
Q1 is 2-Br-6-F—Ph, and X is NH.



460
Q1 is 2-Me-4-F—Ph, and X is NH.



461
Q1 is 2-I-4-F—Ph, and X is NH.



462
Q1 is 2-F—Ph, and X is NH.



463
Q1 is 2-Cl—Ph, and X is NH.



464
Q1 is 2-Br—Ph, and X is NH.



465
Q1 is 2-F-4-Cl—Ph, and X is NH.



466
Q1 is 2,4-di-Cl—Ph, and X is NH.



467
Q1 is 2,6-di-Cl—Ph, and X is NH.



468
Q1 is 2-F-4-MeO—Ph, and X is NH.



469
Q1 is 2-Cl-4-MeO—Ph, and X is NH.



470
Q1 is 2-Br-4-MeO—Ph, and X is NH.



471
Q1 is 2-F-4-CN—Ph, and X is NH.



472
Q1 is 2-Cl-4-CN—Ph, and X is NH.



473
Q1 is 2-Br-4-CN—Ph, and X is NH.



474
Q1 is 2,5-di-Cl-3-pyridinyl, and X is NH.



475
Q1 is 2-Cl-3-thienyl, and X is NH.



476
Q1 is 2,5-di-Cl-3-thienyl, and X is NH.



477
Q1 is 2,6-di-F—Ph, and X is O.



478
Q1 is 2,4-di-F—Ph, and X is O.



479
Q1 is 2,4,6-tri-F—Ph, and X is O.



480
Q1 is 2,6-di-F-4-OMe—Ph, and X is O.



481
Q1 is 2,6-di-F-4-CN—Ph, and X is O.



482
Q1 is 2-Cl-4-F—Ph, and X is O.



483
Q1 is 2-Cl-6-F—Ph, and X is O.



484
Q1 is 2-Cl-4,6-di-F—Ph, and X is O.



485
Q1 is 4-Cl-2,6-di-F—Ph, and X is O.



486
Q1 is 2-Br-4-F—Ph, and X is O.



487
Q1 is 2-Br-6-F—Ph, and X is O.



488
Q1 is 2-Me-4-F—Ph, and X is O.



489
Q1 is 2-I-4-F—Ph, and X is O.



490
Q1 is 2-F—Ph, and X is O.



491
Q1 is 2-Cl—Ph, and X is O.



492
Q1 is 2-Br—Ph, and X is O.



493
Q1 is 2-F-4-Cl—Ph, and X is O.



494
Q1 is 2,4-di-Cl—Ph, and X is O.



495
Q1 is 2,6-di-Cl—Ph, and X is O.



496
Q1 is 2-F-4-MeO—Ph, and X is O.



497
Q1 is 2-Cl-4-MeO—Ph, and X is O.



498
Q1 is 2-Br-4-MeO—Ph, and X is O.



499
Q1 is 2-F-4-CN—Ph, and X is O.



500
Q1 is 2-Cl-4-CN—Ph, and X is O.



501
Q1 is 2-Br-4-CN—Ph, and X is O.



502
Q1 is 2,5-di-Cl-pyridin-3-yl, and X is O.



503
Q1 is 2-Cl-thien-3-yl, and X is O.



504
Q1 is 2,5-di-Cl-thien-3-yl, and X is O.



505
Q1 is 2,6-di-F—Ph, and X is S.



506
Q1 is 2,4-di-F—Ph, and X is S.



507
Q1 is 2,4,6-tri-F—Ph, and X is S.



508
Q1 is 2,6-di-F-4-OMe—Ph, and X is S.



509
Q1 is 2,6-di-F-4-CN—Ph, and X is S.



510
Q1 is 2-Cl-4-F—Ph, and X is S.



511
Q1 is 2-Cl-6-F—Ph, and X is S.



512
Q1 is 2-Cl-4,6-di-F—Ph, and X is S.



513
Q1 is 4-Cl-2,6-di-F—Ph, and X is S.



514
Q1 is 2-Br-4-F—Ph, and X is S.



515
Q1 is 2-Br-6-F—Ph, and X is S.



516
Q1 is 2-Me-4-F—Ph, and X is S.



517
Q1 is 2-I-4-F—Ph, and X is S.



518
Q1 is 2-F—Ph, and X is S.



519
Q1 is 2-Cl—Ph, and X is S.



520
Q1 is 2-Br—Ph, and X is S.



521
Q1 is 2-F-4-Cl—Ph, and X is S.



522
Q1 is 2,4-di-Cl—Ph, and X is S.



523
Q1 is 2,6-di-Cl—Ph, and X is S.



524
Q1 is 2-F-4-MeO—Ph, and X is S.



525
Q1 is 2-Cl-4-MeO—Ph, and X is S.



526
Q1 is 2-Br-4-MeO—Ph, and X is S.



527
Q1 is 2-F-4-CN—Ph, and X is S.



528
Q1 is 2-Cl-4-CN—Ph, and X is S.



529
Q1 is 2-Br-4-CN—Ph, and X is S.



530
Q1 is 2,5-di-Cl-3-pyridinyl, and X is S.



531
Q1 is 2-Cl-3-thienyl, and X is S.



532
Q1 is 2,5-di-Cl-3-thienyl, and X is S.



533
Q1 is 2,6-di-F—Ph, and X is CHOH.



534
Q1 is 2,4-di-F—Ph, and X is CHOH.



535
Q1 is 2,4,6-tri-F—Ph, and X is CHOH.



536
Q1 is 2,6-di-F-4-OMe—Ph, and X is CHOH.



537
Q1 is 2,6-di-F-4-CN—Ph, and X is CHOH.



538
Q1 is 2-Cl-4-F—Ph, and X is CHOH.



539
Q1 is 2-Cl-6-F—Ph, and X is CHOH.



540
Q1 is 2-Cl-4,6-di-F—Ph, and X is CHOH.



541
Q1 is 4-Cl-2,6-di-F—Ph, and X is CHOH.



542
Q1 is 2-Br-4-F—Ph, and X is CHOH.



543
Q1 is 2-Br-6-F—Ph, and X is CHOH.



544
Q1 is 2-Me-4-F—Ph, and X is CHOH.



545
Q1 is 2-I-4-F—Ph, and X is CHOH.



546
Q1 is 2-F—Ph, and X is CHOH.



547
Q1 is 2-Cl—Ph, and X is CHOH.



548
Q1 is 2-Br—Ph, and X is CHOH.



549
Q1 is 2-F-4-Cl—Ph, and X is CHOH.



550
Q1 is 2,4-di-Cl—Ph, and X is CHOH.



551
Q1 is 2,6-di-Cl—Ph, and X is CHOH.



552
Q1 is 2-F-4-MeO—Ph, and X is CHOH.



553
Q1 is 2-Cl-4-MeO—Ph, and X is CHOH.



554
Q1 is 2-Br-4-MeO—Ph, and X is CHOH.



555
Q1 is 2-F-4-CN—Ph, and X is CHOH.



556
Q1 is 2-Cl-4-CN—Ph, and X is CHOH.



557
Q1 is 2-Br-4-CN—Ph, and X is CHOH.



558
Q1 is 2,5-di-Cl-pyridin-3-yl, and X is CHOH.



559
Q1 is 2,5-di-Cl-thien-3-yl, and X is CHOH.



560
Q1 is 2,6-di-F—Ph, and X is C(O).



561
Q1 is 2,4-di-F—Ph, and X is C(O).



562
Q1 is 2,4,6-tri-F—Ph, and X is C(O).



563
Q1 is 2,6-di-F-4-OM-Ph e, and X is C(O).



564
Q1 is 2,6-di-F-4-CN—Ph, and X is C(O).



565
Q1 is 2-Cl-4-F—Ph, and X is C(O).



566
Q1 is 2-Cl-6-F—Ph, and X is C(O).



567
Q1 is 2-Cl-4,6-di-F—Ph, and X is C(O).



568
Q1 is 4-Cl-2,6-di-F—Ph, and X is C(O).



569
Q1 is 2-Br-4-F—Ph, and X is C(O).



570
Q1 is 2-Br-6-F—Ph, and X is C(O).



571
Q1 is 2-Me-4-F—Ph, and X is C(O).



572
Q1 is 2-I-4-F—Ph, and X is C(O).



573
Q1 is 2-F—Ph, and X isC(O).



574
Q1 is 2-Cl—Ph, and X is C(O).



575
Q1 is 2-Br—Ph, and X is C(O).



576
Q1 is 2-F-4-Cl—Ph, and X is C(O).



577
Q1 is 2,4-di-Cl—Ph, and X is C(O).



578
Q1 is 2,6-di-Cl—Ph, and X is C(O).



579
Q1 is 2-F-4-MeO—Ph, and X is C(O).



580
Q1 is 2-Cl-4-MeO—Ph, and X is C(O).



581
Q1 is 2-Br-4-MeO—Ph, and X is C(O).



582
Q1 is 2-F-4-CN—Ph, and X is C(O).



583
Q1 is 2-Cl-4-CN—Ph, and X is C(O).



584
Q1 is 2-Br-4-CN—Ph, and X is C(O).



585
Q1 is 2,5-di-Cl-3-pyridinyl, and X is C(O).



586
Q1 is 2-Cl-3-thienyl, and X is C(O).



587
O1 is 2,5-di-Cl-3-thienyl, and X is C(O).

















TABLE 588













 











(R3)p
(R3)p
(R3)p
(R3)p
(R3)p





2-F
3-F
4-F
2-Cl
3-Cl


4-Cl
2-Br
3-Br
4-Br
2,4-di-F


2,6-di-F
2,4,6-tri-F
2,4,5-tri-F
2,3,5-tri-F
2,3,6-tri-F


2-Cl-4-F
2-F-4-Cl
2,4-di-Cl
2,6-di-Cl
2,4,6-tri-Cl


2-Br-4-F
2-I-4-F
2-Me-4-F
2-F-4-MeO
2-Cl-4-MeO


2-Br-4-MeO
2,6-di-F-4-
2-F-4-CN
2-Cl-4-CN
2-Br-4-CN



MeO





2,6-di-F-4-
2-Cl-4,5-di-F
2-Cl-4,6-di-F
2-Br-4,5-di-F
2-Br-4,6-di-F


CN






4-Cl-2,5-di-F
4-Cl-2,6-di-F
4-Br-2,5-di-F
4-Br-2,6-di-F
2,4-di-Cl-6-F


2,6-di-Cl-4-F
2,6-di-Cl-4-
2-CF3-4-F
4-Me
2,4-di-Me



MeO





2-F-4-Br
2-Cl-4-Br
2-Br-4-Cl
2-Br-4-F-6-Cl
2-Cl-4-Br-6-F





Q1 is 2,6-di-F—Ph, and R2 is Me.






The present disclosure also includes Tables 589 through 671, each of which is constructed the same as Table 588 above, except that the row heading in Table 588 (i.e. “Q1 is 2,6-di-F-Ph, and R2 is Me.”) is replaced with the respective row heading shown below. For Example, in Table 589 the row heading is “Q1 is 2,6-di-F-Ph, and R2 is Cl.”, and (R3)p is as defined in Table 588 above. Thus, the first entry in Table 589 specifically discloses 5-chloro-4-(2,6-difluorophenyl)-N-(2-fluorophenyl)-1H-pyrazol-3-amine. Tables 589 through 671 are constructed similarly.














Table
Row Heading









589
Q1 is 2,6-di-F—Ph, and R2 is Cl.



590
Q1 is 2,6-di-F—Ph, and R2 is Br.



591
Q1 is 2,4-di-F—Ph, and R2 is Me.



592
Q1 is 2,4-di-F—Ph, and R2 is Cl.



593
Q1 is 2,4-di-F—Ph, and R2 is Br.



594
Q1 is 2,4,6-tri-F—Ph, and R2 is Me.



595
Q1 is 2,4,6-tri-F—Ph, and R2 is Cl.



596
Q1 is 2,4,6-tri-F—Ph, and R2 is Br.



597
Q1 is 2,6-di-F-4-OMe—Ph, and R2 is Me.



598
Q1 is 2,6-di-F-4-OMe—Ph, and R2 is Cl.



599
Q1 is 2,6-di-F-4-OMe—Ph, and R2 is Br.



599A
Q1 is 2,6-di-F-4-OEt—Ph, and R2 is Me.



599B
Q1 is 2,6-di-F-4-OEt—Ph, and R2 is Cl.



599C
Q1 is 2,6-di-F-4-OEt—Ph, and R2 is Br.



600
Q1 is 2,6-di-F-4-CN—Ph, and R2 is Me.



601
Q1 is 2,6-di-F-4-CN—Ph, and R2 is Cl.



602
Q1 is 2,6-di-F-4-CN—Ph, and R2 is Br.



603
Q1 is 2-Cl-4-F—Ph, and R2 is Me.



604
Q1 is 2-Cl-4-F—Ph, and R2 is Cl.



605
Q1 is 2-Cl-4-F—Ph, and R2 is Br.



606
Q1 is 2-Cl-6-F—Ph, and R2 is Me.



607
Q1 is 2-Cl-6-F—Ph, and R2 is Cl.



608
Q1 is 2-Cl-6-F—Ph, and R2 is Br.



609
Q1 is 2-Cl-4,6-di-F—Ph, and R2 is Me.



610
Q1 is 2-Cl-4,6-di-F—Ph, and R2 is Cl.



611
Q1 is 2-Cl-4,6-di-F—Ph, and R2 is Br.



612
Q1 is 4-Cl-2,6-di-F—Ph, and R2 is Me.



613
Q1 is 4-Cl-2,6-di-F—Ph, and R2 is Cl.



614
Q1 is 4-Cl-2,6-di-F—Ph, and R2 is Br.



615
Q1 is 2-Br-4-F—Ph, and R2 is Me.



616
Q1 is 2-Br-4-F—Ph, and R2 is Cl.



617
Q1 is 2-Br-4-F—Ph, and R2 is Br.



618
Q1 is 2-Br-6-F—Ph, and R2 is Me.



619
Q1 is 2-Br-6-F—Ph, and R2 is Cl.



620
Q1 is 2-Br-6-F—Ph, and R2 is Br.



621
Q1 is 2-Me-4-F—Ph, and R2 is Me.



622
Q1 is 2-Me-4-F—Ph, and R2 is Cl.



623
Q1 is 2-Me-4-F—Ph, and R2 is Br.



624
Q1 is 2-I-4-F—Ph, and R2 is Me.



625
Q1 is 2-I-4-F—Ph, and R2 is Cl.



626
Q1 is 2-I-4-F—Ph, and R2 is Br.



627
Q1 is 2-F—Ph, and R2 is Me.



628
Q1 is 2-F—Ph, and R2 is Cl.



629
Q1 is 2-F—Ph, and R2 is Br.



630
Q1 is 2-Cl—Ph, and R2 is Me.



631
Q1 is 2-Cl—Ph, and R2 is Cl.



632
Q1 is 2-Cl—Ph, and R2 is Br.



633
Q1 is 2-Br—Ph, and R2 is Me.



634
Q1 is 2-Br—Ph, and R2 is Cl.



635
Q1 is 2-Br—Ph, and R2 is Br.



636
Q1 is 2-F-4-Cl—Ph, and R2 is Me.



637
Q1 is 2-F-4-Cl—Ph, and R2 is Cl.



638
Q1 is 2-F-4-Cl—Ph, and R2 is Br.



639
Q1 is 2,4-di-Cl—Ph, and R2 is Me.



640
Q1 is 2,4-di-Cl—Ph, and R2 is Cl.



641
Q1 is 2,4-di-Cl—Ph, and R2 is Br.



642
Q1 is 2,6-di-Cl—Ph, and R2 is Me.



643
Q1 is 2,6-di-Cl—Ph, and R2 is Cl.



644
Q1 is 2,6-di-Cl—Ph, and R2 is Br.



645
Q1 is 2-F-4-MeO—Ph, and R2 is Me.



646
Q1 is 2-F-4-MeO—Ph, and R2 is Cl.



647
Q1 is 2-F-4-MeO—Ph, and R2 is Br.



647A
Q1 is 2-F-4-EtO—Ph, and R2 is Me.



647B
Q1 is 2-F-4-EtO—Ph, and R2 is Cl.



647C
Q1 is 2-F-4-EtO—Ph, and R2 is Br.



648
Q1 is 2-Cl-4-MeO—Ph, and R2 is Me.



649
Q1 is 2-Cl-4-MeO—Ph, and R2 is Cl.



650
Q1 is 2-Cl-4-MeO—Ph, and R2 is Br.



650A
Q1 is 2-Cl-4-EtO—Ph, and R2 is Me.



650B
Q1 is 2-Cl-4-EtO—Ph, and R2 is Cl.



650C
Q1 is 2-Cl-4-EtO—Ph, and R2 is Br.



651
Q1 is 2-Br-4-MeO—Ph, and R2 is Me.



652
Q1 is 2-Br-4-MeO—Ph, and R2 is Cl.



653
Q1 is 2-Br-4-MeO—Ph, and R2 is Br.



653A
Q1 is 2-Br-4-EtO—Ph, and R2 is Me.



653B
Q1 is 2-Br-4-EtO—Ph, and R2 is Cl.



653C
Q1 is 2-Br-4-EtO—Ph, and R2 is Br.



654
Q1 is 2-F-4-CN—Ph, and R2 is Me.



655
Q1 is 2-F-4-CN—Ph, and R2 is Cl.



656
Q1 is 2-F-4-CN—Ph, and R2 is Br.



657
Q1 is 2-Cl-4-CN—Ph, and R2 is Me.



658
Q1 is 2-Cl-4-CN—Ph, and R2 is Cl.



659
Q1 is 2-Cl-4-CN—Ph, and R2 is Br.



660
Q1 is 2-Br-4-CN—Ph, and R2 is Me.



661
Q1 is 2-Br-4-CN—Ph, and R2 is Cl.



662
Q1 is 2-Br-4-CN—Ph, and R2 is Br.



663
Q1 is 2,5-di-Cl-3-pyridinyl, and R2 is Me.



664
Q1 is 2,5-di-Cl-3-pyridinyl, and R2 is Cl.



665
Q1 is 2,5-di-Cl-3-pyridinyl, and R2 is Br.



666
Q1 is 2-Cl-3-thienyl, and R2 is Me.



667
Q1 is 2-Cl-3-thienyl, and R2 is Cl.



668
Q1 is 2-Cl-3-thienyl, and R2 is Br.



669
Q1 is 2,5-di-Cl-3-thienyl, and R2 is Me.



670
Q1 is 2,5-di-Cl-3-thienyl, and R2 is Cl.



671
Q1 is 2,5-di-Cl-3-thienyl, and R2 is Br.










The compounds of Tables 588 through 671 illustrate compounds of Formula 2 wherein X is NH, which are useful intermediates to prepare compounds of Formula 1 using the method of Scheme 2.







TABLE 672













 










Q1
Q1
Q1
Q1





2,6-di-F—Ph
2-Cl-4,6-di-F—Ph
2-Cl—Ph
2-Br-4-





MeO—Ph


2,4-di-F—Ph
4-Cl-2,6-di-F—Ph
2-Br—Ph
2-F-4-CN—Ph


2,4,6-tri-F—Ph
2-Br-4-F—Ph
2-F-4-Cl—Ph
2-Cl-4-CN—Ph


2,6-di-F-4-OMe—Ph
2-Br-6-F—Ph
2,4-di-Cl—Ph
2-Br-4-CN—Ph


2,6-di-F-4-CN—Ph
2-Me-4-F—Ph
2,6-di-Cl—Ph
2,5-di-Cl-3-





pyridinyl


2-Cl-4-F—Ph
2-I-4-F—Ph
2-F-4-MeO—Ph
2-Cl-3-thienyl


2-Cl-6-F—Ph
2-F—Ph
2-Cl-4-
2,5-di-Cl-3-




MeO—Ph
thienyl


2,6-di-F-4-EtO—Ph
2-F-4-EtO—Ph
2-Cl-4-EtO—Ph
2-Br-4-EtO—Ph





G1 is —OH.






The present disclosure also includes Tables 673 through 676, each of which is constructed the same as Table 672 above, except that the row heading in Table 672 (i.e. “G1 is —OH.”) is replaced with the respective row heading shown below. For Example, in Table 673 the row heading is “G1 is —SH.”, and Q1 is as defined in Table 672 above. Thus, the first entry in Table 673 specifically discloses 4-(2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-thiol. Tables 674 through 676 are constructed similarly.














Table
Row Heading









673
G1 is —SH.



674
G1 is Cl.



675
G1 is Br.



675A
G1 is I.



676
G1 is —NH2.










The compounds of Tables 672 and 673 illustrate compounds of Formula 4 wherein X is O or S, R1 and R1a are each H, and R2 is CH3, which are useful intermediates to prepare compounds of Formula 1 using the method of Scheme 3. The compounds of Table 672 further illustrate compounds of Formula 4b wherein R1 and R1a are each H, and R2 is CH3, which are useful intermediates to prepare intermediate compounds of Formula 6a using the method of Scheme 6 and to prepare intermediate compounds of Formula 6b using the method of Scheme 7. Tables 674 and 675 illustrate compounds of Formula 6 wherein G is Cl or Br, and R1a are each H, and R2 is CH3 which are useful intermediates to prepare compounds of Formula 1c using the method of Scheme 4. Table 676 illustrates compounds of Formula 4a wherein R1 and R1a are each H, and R2 is CH3, which are useful intermediates to prepare intermediate compounds of Formula 6 using the method of Scheme 5.







TABLE 677













 











(R3)p
(R3)p
(R3)p
(R3)p
(R3)p





2-F
3-F
4-F
2-Cl
3-Cl


4-Cl
2-Br
3-Br
4-Br
2,4-di-F


2,6-di-F
2,4,6-tri-F
2,4,5-tri-F
2,3,5-tri-F
2,3,6-tri-F


2-Cl-4-F
2-F-4-Cl
2,4-di-Cl
2,6-di-Cl
2,4,6-tri-Cl


2-Br-4-F
2-I-4-F
2-Me-4-F
2-F-4-MeO
2-Cl-4-MeO


2-Br-4-MeO
2,6-di-F-4-
2-F-4-CN
2-Cl-4-CN
2-Br-4-CN



MeO





2,6-di-F-4-
2-Cl-4,5-di-F
2-Cl-4,6-di-F
2-Br-4,5-di-F
2-Br-4,6-di-F


CN






4-Cl-2,5-di-F
4-Cl-2,6-di-F
4-Br-2,5-di-F
4-Br-2,6-di-F
2,4-di-Cl-6-F


2,6-di-Cl-4-F
2,6-di-Cl-4-
2-CF3-4-F
4-Me
2,4-di-Me



MeO





2-F-4-Br
2-Cl-4-Br
2-Br-4-Cl
2-Br-4-F-6-Cl
2-Cl-4-Br-6-F





Q1 is 2,6-di-F—Ph, and R32 is Me.






The present disclosure also includes Tables 678 through 704, each of which is constructed the same as Table 677 above, except that the row heading in Table 677 (i.e. “Q1 is 2,6-di-F-Ph.”) is replaced with the respective row heading shown below. For Example, in Table 2 the row heading is “Q1 is 2,4-di-F-Ph.”, and (R3)p is as defined in Table 677 above. Thus, the first entry in Table 678 specifically discloses 3-(2,6-difluorophenyl)-4-[(2,4-difluorophenyl)amino]-4-(methylthio)-3-buten-2-one. Tables 679 through 704 are constructed similarly.














Table
Row Heading









678
Q1 is 2,4-di-F—Ph, and R32 is Me.



679
Q1 is 2,4,6-tri-F—Ph, and R32 is Me.



680
Q1 is 2,6-di-F-4-OMe—Ph, and R32 is Me.



680A
Q1 is 2,6-di-F-4-OEt—Ph, and R32 is Me.



681
Q1 is 2,6-di-F-4-CN—Ph, and R32 is Me.



682
Q1 is 2-Cl-4-F—Ph, and R32 is Me.



683
Q1 is 2-Cl-6-F—Ph, and R32 is Me.



684
Q1 is 2-Cl-4,6-di-F—Ph, and R32 is Me.



685
Q1 is 4-Cl-2,6-di-F—Ph, and R32 is Me.



686
Q1 is 2-Br-4-F—Ph, and R32 is Me.



687
Q1 is 2-Br-6-F—Ph, and R32 is Me.



688
Q1 is 2-Me-4-F—Ph, and R32 is Me.



689
Q1 is 2-I-4-F—Ph, and R32 is Me.



690
Q1 is 2-F—Ph, and R32 is Me.



691
Q1 is 2-Cl—Ph, and R32 is Me.



692
Q1 is 2-Br—Ph, and R32 is Me.



693
Q1 is 2-F-4-Cl—Ph, and R32 is Me.



694
Q1 is 2,4-di-Cl—Ph, and R32 is Me.



695
Q1 is 2,6-di-Cl—Ph, and R32 is Me.



696
Q1 is 2-F-4-MeO—Ph, and R32 is Me.



696A
Q1 is 2-F-4-EtO—Ph, and R32 is Me.



697
Q1 is 2-Cl-4-MeO—Ph, and R32 is Me.



697A
Q1 is 2-Cl-4-EtO—Ph, and R32 is Me.



698
Q1 is 2-Br-4-MeO—Ph, and R32 is Me.



698A
Q1 is 2-Br-4-EtO—Ph, and R32 is Me.



699
Q1 is 2-F-4-CN—Ph, and R32 is Me.



700
Q1 is 2-Cl-4-CN—Ph, and R32 is Me.



701
Q1 is 2-Br-4-CN—Ph, and R32 is Me.



702
Q1 is 2,5-di-Cl-3-pyridinyl, and R32 is Me.



703
Q1 is 2-Cl-3-thienyl, and R32 is Me.



704
Q1 is 2,5-di-Cl-3-thienyl, and R32 is Me.



705
Q1 is 2,6-di-F—Ph, and R32 is Et.



706
Q1 is 2,4-di-F—Ph, and R32 is Et.



707
Q1 is 2,4,6-tri-F—Ph, and R32 is Et.



708
Q1 is 2,6-di-F-4-OMe—Ph, and R32 is Et.



708A
Q1 is 2,6-di-F-4-OEt—Ph, and R32 is Et.



709
Q1 is 2,6-di-F-4-CN—Ph, and R32 is Et.



710
Q1 is 2-Cl-4-F—Ph, and R32 is Et.



711
Q1 is 2-Cl-6-F—Ph, and R32 is Et.



712
Q1 is 2-Cl-4,6-di-F—Ph, and R32 is Et.



713
Q1 is 4-Cl-2,6-di-F—Ph, and R32 is Et.



714
Q1 is 2-Br-4-F—Ph, and R32 is Et.



715
Q1 is 2-Br-6-F—Ph, and R32 is Et.



716
Q1 is 2-Me-4-F—Ph, and R32 is Et.



717
Q1 is 2-I-4-F—Ph, and R32 is Et,



718
Q1 is 2-F—Ph, and R32 is Et.



719
Q1 is 2-Cl—Ph, and R32 is Et.



720
Q1 is 2-Br—Ph, and R32 is Et.



721
Q1 is 2-F-4-Cl—Ph, and R32 is Et.



722
Q1 is 2,4-di-Cl—Ph, and R32 is Et.



723
Q1 is 2,6-di-Cl—Ph, and R32 is Et.



724
Q1 is 2-F-4-MeO—Ph, and R32 is Et.



724A
Q1 is 2-F-4-EtO—Ph, and R32 is Et.



725
Q1 is 2-Cl-4-MeO—Ph, and R32 is Et.



725A
Q1 is 2-Cl-4-EtO—Ph, and R32 is Et.



726
Q1 is 2-Br-4-MeO—Ph, and R32 is Et.



726A
Q1 is 2-Br-4-EtO—Ph, and R32 is Et.



727
Q1 is 2-F-4-CN—Ph, and R32 is Et.



728
Q1 is 2-Cl-4-CN—Ph, and R32 is Et.



729
Q1 is 2-Br-4-CN—Ph, and R32 is Et.



730
Q1 is 2,5-di-Cl-3-pyridinyl, and R32 is Et.



731
Q1 is 2-Cl-3-thienyl, and R32 is Et.



732
Q1 is 2,5-di-Cl-3-thienyl, and R32 is Et.



733
Q1 is 2,6-di-F—Ph, and R32 is n-Pr.



734
Q1 is 2,4-di-F—Ph, and R32 is n-Pr.



735
Q1 is 2,4,6-tri-F—Ph, and R32 is n-Pr.



736
Q1 is 2,6-di-F-4-OMe—Ph, and R32 is n-Pr.



736A
Q1 is 2,6-di-F-4-OEt—Ph, and R32 is n-Pr.



737
Q1 is 2,6-di-F-4-CN—Ph, and R32 is n-Pr.



738
Q1 is 2-Cl-4-F—Ph, and R32 is n-Pr.



739
Q1 is 2-Cl-6-F—Ph, and R32 is n-Pr.



740
Q1 is 2-Cl-4,6-di-F—Ph, and R32 is n-Pr.



741
Q1 is 4-Cl-2,6-di-F—Ph, and R32 is n-Pr.



742
Q1 is 2-Br-4-F—Ph, and R32 is n-Pr.



743
Q1 is 2-Br-6-F—Ph, and R32 is n-Pr.



744
Q1 is 2-Me-4-F—Ph, and R32 is n-Pr.



745
Q1 is 2-I-4-F—Ph, and R32 is n-Pr.



746
Q1 is 2-F—Ph, and R32 is n-Pr.



747
Q1 is 2-Cl—Ph, and R32 is n-Pr.



748
Q1 is 2-Br—Ph, and R32 is n-Pr.



749
Q1 is 2-F-4-Cl—Ph, and R32 is n-Pr.



750
Q1 is 2,4-di-Cl—Ph, and R32 is n-Pr.



751
Q1 is 2,6-di-Cl—Ph, and R32 is n-Pr.



752
Q1 is 2-F-4-MeO—Ph, and R32 is n-Pr.



752A
Q1 is 2-F-4-EtO—Ph, and R32 is n-Pr.



753
Q1 is 2-Cl-4-MeO—Ph, and R32 is n-Pr.



753A
Q1 is 2-Cl-4-EtO—Ph, and R32 is n-Pr.



754
Q1 is 2-Br-4-MeO—Ph, and R32 is n-Pr.



754A
Q1 is 2-Br-4-EtO—Ph, and R32 is n-Pr.



755
Q1 is 2-F-4-CN—Ph, and R32 is n-Pr.



756
Q1 is 2-Cl-4-CN—Ph, and R32 is n-Pr.



757
Q1 is 2-Br-4-CN—Ph, and R32 is n-Pr.



758
Q1 is 2,5-di-Cl-3-pyridinyl, and R32 is n-Pr.



759
Q1 is 2-Cl-3-thienyl, and R32 is n-Pr.



760
Q1 is 2,5-di-Cl-3-thienyl, and R32 is n-Pr.










The compounds of Tables 677 through 760 illustrate compounds of Formula 17 wherein R2 is CH3, which are useful intermediates to prepare compounds of Formula 1c using the method of Scheme 16.







TABLE 761













 










Q1
Q1
Q1
Q1





2,6-di-F—Ph
2-Cl-4,6-di-F—Ph
2-Cl—Ph
2-Br-4-





MeO—Ph


2,4-di-F—Ph
4-Cl-2,6-di-F—Ph
2-Br—Ph
2-F-4-CN—Ph


2,4,6-tri-F—Ph
2-Br-4-F—Ph
2-F-4-Cl—Ph
2-Cl-4-CN—Ph


2,6-di-F-4-OMe—Ph
2-Br-6-F—Ph
2,4-di-Cl—Ph
2-Br-4-CN—Ph


2,6-di-F-4-CN—Ph
2-Me-4-F—Ph
2,6-di-Cl—Ph
2,5-di-Cl-3-





pyridinyl


2-Cl-4-F—Ph
2-I-4-F—Ph
2-F-4-MeO—Ph
2-Cl-3-thienyl


2-Cl-6-F—Ph
2-F—Ph
2-Cl-4-
2,5-di-Cl-3-




MeO—Ph
thienyl


2,6-di-F-4-EtO—Ph
2-F-4-EtO—Ph
2-Cl-4-EtO—Ph
2-Br-4-EtO—Ph





Each R33 is Me.






The present disclosure also includes Tables 762 through 764, each of which is constructed the same as Table 761 above, except that the row heading in Table 761 (i.e. “Each R33 is Me.”) is replaced with the respective row heading shown below. For Example, in Table 762 the row heading is “Each R33 is Et.”, and Q1 is as defined in Table 761 above. Thus, the first entry in Table 762 specifically discloses 3-(2,6-difluorophenyl)-4,4-bis(ethylthio)-3-buten-2-one. Tables 763 and 764 are constructed similarly.














Table
Row Heading









762
Each R33 is Et.



763
Each R33 is n-Pr.



764
The two R33 are taken together as —CH2—.










The compounds of Tables 761 through 763 illustrate compounds of Formula 18 wherein R2 is CH3, which are useful intermediates to prepare intermediate compounds of Formula 17 using the method of Scheme 17. The compounds of Table 764 illustrate compounds of Formula 18 wherein R2 is CH3, which are useful intermediates to prepare intermediate compounds of Formula 4c using the method described below Scheme 17.







TABLE 765













 










Q1
Q1
Q1
Q1





2,6-di-F—Ph
2-Cl-4,6-di-F—Ph
2-Cl—Ph
2-Br-4-





MeO—Ph


2,4-di-F—Ph
4-Cl-2,6-di-F—Ph
2-Br—Ph
2-F-4-CN—Ph


2,4,6-tri-F—Ph
2-Br-4-F—Ph
2-F-4-Cl—Ph
2-Cl-4-CN—Ph


2,6-di-F-4-OMe—Ph
2-Br-6-F—Ph
2,4-di-Cl—Ph
2-Br-4-CN—Ph


2,6-di-F-4-CN—Ph
2-Me-4-F—Ph
2,6-di-Cl—Ph
2,5-di-Cl-3-





pyridinyl


2-Cl-4-F—Ph
2-I-4-F—Ph
2-F-4-MeO—Ph
2-Cl-3-thienyl


2-Cl-6-F—Ph
2-F—Ph
2-Cl-4-
2,5-di-Cl-3-




MeO—Ph
thienyl


2,6-di-F-4-EtO—Ph
2-F-4-EtO—Ph
2-Cl-4-EtO—Ph
2-Br-4-EtO—Ph





B1 is Me.






The present disclosure also includes Tables 766 through 769, each of which is constructed the same as Table 765 above, except that the row heading in Table 765 (i.e. “B1 is Me.”) is replaced with the respective row heading shown below. For Example, in Table 766 the row heading is “B1 is Et.”, and Q1 is as defined in Table 765 above. Thus, the first entry in Table 766 specifically discloses ethyl α-acetyl-2,6-difluorobenzeneacetate. Tables 767 through 769 are constructed similarly.














Table
Row Heading









766
B1 is Et.



767
B1 is is n-Pr.



768
B1 is Ph.



769
B1 is CH2Ph.










The compounds of Tables 765 through 769 illustrate compounds of Formula 16 wherein R2 is CH3, which are useful intermediates to prepare intermediate compounds of Formula 4b using the method of Scheme 14.
Formulation/Utility
A compound of this invention will generally be used as a fungicidal active ingredient in a composition, i.e. formulation, with at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, which serves as a carrier. The formulation or composition ingredients are selected to be consistent with the physical properties of the active ingredient, mode of application and environmental factors such as soil type, moisture and temperature.
Useful formulations include both liquid and solid compositions. Liquid compositions include solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions and/or suspoemulsions) and the like, which optionally can be thickened into gels. The general types of aqueous liquid compositions are soluble concentrate, suspension concentrate, capsule suspension, concentrated emulsion, microemulsion and suspo-emulsion. The general types of nonaqueous liquid compositions are emulsifiable concentrate, microemulsifiable concentrate, dispersible concentrate and oil dispersion.
The general types of solid compositions are dusts, powders, granules, pellets, prills, pastilles, tablets, filled films (including seed coatings) and the like, which can be water-dispersible (“wettable”) or water-soluble. Films and coatings formed from film-forming solutions or flowable suspensions are particularly useful for seed treatment. Active ingredient can be (micro)encapsulated and further formed into a suspension or solid formulation; alternatively the entire formulation of active ingredient can be encapsulated (or “overcoated”). Encapsulation can control or delay release of the active ingredient. An emulsifiable granule combines the advantages of both an emulsifiable concentrate formulation and a dry granular formulation. High-strength compositions are primarily used as intermediates for further formulation.
Sprayable formulations are typically extended in a suitable medium before spraying. Such liquid and solid formulations are formulated to be readily diluted in the spray medium, usually water. Spray volumes can range from about from about one to several thousand liters per hectare, but more typically are in the range from about ten to several hundred liters per hectare. Sprayable formulations can be tank mixed with water or another suitable medium for foliar treatment by aerial or ground application, or for application to the growing medium of the plant. Liquid and dry formulations can be metered directly into drip irrigation systems or metered into the furrow during planting. Liquid and solid formulations can be applied onto seeds of crops and other desirable vegetation as seed treatments before planting to protect developing roots and other subterranean plant parts and/or foliage through systemic uptake.
The formulations will typically contain effective amounts of active ingredient, diluent and surfactant within the following approximate ranges which add up to 100 percent by weight.













Weight Percent











Active





Ingredient
Diluent
Surfactant














Water-Dispersible and Water-
0.001-90
0-99.999
0-15


soluble Granules, Tablets and


Powders


Oil Dispersions, Suspensions,
   1-50
40-99   
0-50


Emulsions, Solutions


(including Emulsifiable


Concentrates)


Dusts
   1-25
70-99   
0-5 


Granules and Pellets
0.001-95
5-99.999
0-15


High Strength Compositions
  90-99
0-10   
0-2 









Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, gypsum, cellulose, titanium dioxide, zinc oxide, starch, dextrin, sugars (e.g., lactose, sucrose), silica, talc, mica, diatomaceous earth, urea, calcium carbonate, sodium carbonate and bicarbonate, and sodium sulfate. Typical solid diluents are described in Watkins et al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, N.J.
Liquid diluents include, for example, water, N,N-dimethylalkanamides (e.g., N,N-dimethylformamide), limonene, dimethyl sulfoxide, N-alkylpyrrolidones (e.g., N-methylpyrrolidinone), ethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, propylene carbonate, butylene carbonate, paraffins (e.g., white mineral oils, normal paraffins, isoparaffins), alkylbenzenes, alkylnaphthalenes, glycerine, glycerol triacetate, sorbitol, triacetin, aromatic hydrocarbons, dearomatized aliphatics, alkylbenzenes, alkylnaphthalenes, ketones such as cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4-methyl-2-pentanone, acetates such as isoamyl acetate, hexyl acetate, heptyl acetate, octyl acetate, nonyl acetate, tridecyl acetate and isobornyl acetate, other esters such as alkylated lactate esters, dibasic esters and γ-butyrolactone, and alcohols, which can be linear, branched, saturated or unsaturated, such as methanol, ethanol, n-propanol, isopropyl alcohol, n-butanol, isobutyl alcohol, n-hexanol, 2-ethylhexanol, n-octanol, decanol, isodecyl alcohol, isooctadecanol, cetyl alcohol, lauryl alcohol, tridecyl alcohol, oleyl alcohol, cyclohexanol, tetrahydrofurfuryl alcohol, diacetone alcohol and benzyl alcohol. Liquid diluents also include glycerol esters of saturated and unsaturated fatty acids (typically C6-C22), such as plant seed and fruit oils (e.g, oils of olive, castor, linseed, sesame, corn (maize), peanut, sunflower, grapeseed, safflower, cottonseed, soybean, rapeseed, coconut and palm kernel), animal-sourced fats (e.g., beef tallow, pork tallow, lard, cod liver oil, fish oil), and mixtures thereof. Liquid diluents also include alkylated fatty acids (e.g., methylated, ethylated, butylated) wherein the fatty acids may be obtained by hydrolysis of glycerol esters from plant and animal sources, and can be purified by distillation. Typical liquid diluents are described in Marsden, Solvents Guide, 2nd Ed., Interscience, New York, 1950.
The solid and liquid compositions of the present invention often include one or more surfactants. When added to a liquid, surfactants (also known as “surface-active agents”) generally modify, most often reduce, the surface tension of the liquid. Depending on the nature of the hydrophilic and lipophilic groups in a surfactant molecule, surfactants can be useful as wetting agents, dispersants, emulsifiers or defoaming agents.
Surfactants can be classified as nonionic, anionic or cationic. Nonionic surfactants useful for the present compositions include, but are not limited to: alcohol alkoxylates such as alcohol alkoxylates based on natural and synthetic alcohols (which may be branched or linear) and prepared from the alcohols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof; amine ethoxylates, alkanolamides and ethoxylated alkanolamides; alkoxylated triglycerides such as ethoxylated soybean, castor and rapeseed oils; alkylphenol alkoxylates such as octylphenol ethoxylates, nonylphenol ethoxylates, dinonyl phenol ethoxylates and dodecyl phenol ethoxylates (prepared from the phenols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); block polymers prepared from ethylene oxide or propylene oxide and reverse block polymers where the terminal blocks are prepared from propylene oxide; ethoxylated fatty acids; ethoxylated fatty esters and oils; ethoxylated methyl esters; ethoxylated tristyrylphenol (including those prepared from ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); fatty acid esters, glycerol esters, lanolin-based derivatives, polyethoxylate esters such as polyethoxylated sorbitan fatty acid esters, polyethoxylated sorbitol fatty acid esters and polyethoxylated glycerol fatty acid esters; other sorbitan derivatives such as sorbitan esters; polymeric surfactants such as random copolymers, block copolymers, alkyd peg (polyethylene glycol) resins, graft or comb polymers and star polymers; polyethylene glycols (pegs); polyethylene glycol fatty acid esters; silicone-based surfactants; and sugar-derivatives such as sucrose esters, alkyl polyglycosides and alkyl polysaccharides.
Useful anionic surfactants include, but are not limited to: alkylaryl sulfonic acids and their salts; carboxylated alcohol or alkylphenol ethoxylates; diphenyl sulfonate derivatives; lignin and lignin derivatives such as lignosulfonates; maleic or succinic acids or their anhydrides; olefin sulfonates; phosphate esters such as phosphate esters of alcohol alkoxylates, phosphate esters of alkylphenol alkoxylates and phosphate esters of styryl phenol ethoxylates; protein-based surfactants; sarcosine derivatives; styryl phenol ether sulfate; sulfates and sulfonates of oils and fatty acids; sulfates and sulfonates of ethoxylated alkylphenols; sulfates of alcohols; sulfates of ethoxylated alcohols; sulfonates of amines and amides such as N,N-alkyltaurates; sulfonates of benzene, cumene, toluene, xylene, and dodecyl and tridecylbenzenes; sulfonates of condensed naphthalenes; sulfonates of naphthalene and alkyl naphthalene; sulfonates of fractionated petroleum; sulfosuccinamates; and sulfosuccinates and their derivatives such as dialkyl sulfosuccinate salts.
Useful cationic surfactants include, but are not limited to: amides and ethoxylated amides; amines such as N-alkyl propanediamines, tripropylenetriamines and dipropylenetetramines, and ethoxylated amines, ethoxylated diamines and propoxylated amines (prepared from the amines and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); amine salts such as amine acetates and diamine salts; quaternary ammonium salts such as quaternary salts, ethoxylated quaternary salts and diquaternary salts; and amine oxides such as alkyldimethylamine oxides and bis-(2-hydroxyethyl)-alkylamine oxides.
Also useful for the present compositions are mixtures of nonionic and anionic surfactants or mixtures of nonionic and cationic surfactants. Nonionic, anionic and cationic surfactants and their recommended uses are disclosed in a variety of published references including McCutcheon's Emulsifiers and Detergents, annual American and International Editions published by McCutcheon's Division, The Manufacturing Confectioner Publishing Co.; Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964; and A. S. Davidson and B. Milwidsky, Synthetic Detergents, Seventh Edition, John Wiley and Sons, New York, 1987.
Compositions of this invention may also contain formulation auxiliaries and additives, known to those skilled in the art as formulation aids (some of which may be considered to also function as solid diluents, liquid diluents or surfactants). Such formulation auxiliaries and additives may control: pH (buffers), foaming during processing (antifoams such polyorganosiloxanes), sedimentation of active ingredients (suspending agents), viscosity (thixotropic thickeners), in-container microbial growth (antimicrobials), product freezing (antifreezes), color (dyes/pigment dispersions), wash-off (film formers or stickers), evaporation (evaporation retardants), and other formulation attributes. Film formers include, for example, polyvinyl acetates, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohols, polyvinyl alcohol copolymers and waxes. Examples of formulation auxiliaries and additives include those listed in McCutcheon's Volume 2: Functional Materials, annual International and North American editions published by McCutcheon's Division, The Manufacturing Confectioner Publishing Co.; and PCT Publication WO 03/024222.
The compound of Formula 1 and any other active ingredients are typically incorporated into the present compositions by dissolving the active ingredient in a solvent or by grinding in a liquid or dry diluent. Solutions, including emulsifiable concentrates, can be prepared by simply mixing the ingredients. If the solvent of a liquid composition intended for use as an emulsifiable concentrate is water-immiscible, an emulsifier is typically added to emulsify the active-containing solvent upon dilution with water. Active ingredient slurries, with particle diameters of up to 2,000 μm can be wet milled using media mills to obtain particles with average diameters below 3 μm. Aqueous slurries can be made into finished suspension concentrates (see, for example, U.S. Pat. No. 3,060,084) or further processed by spray drying to form water-dispersible granules. Dry formulations usually require dry milling processes, which produce average particle diameters in the 2 to 10 μm range. Dusts and powders can be prepared by blending and usually grinding (such as with a hammer mill or fluid-energy mill). Granules and pellets can be prepared by spraying the active material upon preformed granular carriers or by agglomeration techniques. See Browning, “Agglomeration”, Chemical Engineering, Dec. 4, 1967, pp 147-48, Perry's Chemical Engineer's Handbook, 4th Ed., McGraw-Hill, New York, 1963, pages 8-57 and following, and WO 91/13546. Pellets can be prepared as described in U.S. Pat. No. 4,172,714. Water-dispersible and water-soluble granules can be prepared as taught in U.S. Pat. No. 4,144,050, U.S. Pat. No. 3,920,442 and DE 3,246,493. Tablets can be prepared as taught in U.S. Pat. No. 5,180,587, U.S. Pat. No. 5,232,701 and U.S. Pat. No. 5,208,030. Films can be prepared as taught in GB 2,095,558 and U.S. Pat. No. 3,299,566.
For further information regarding the art of formulation, see T. S. Woods, “The Formulator's Toolbox—Product Forms for Modern Agriculture” in Pesticide Chemistry and Bioscience, The Food-Environment Challenge, T. Brooks and T. R. Roberts, Eds., Proceedings of the 9th International Congress on Pesticide Chemistry, The Royal Society of Chemistry, Cambridge, 1999, pp. 120-133. See also U.S. Pat. No. 3,235,361, Col. 6, line 16 through Col. 7, line 19 and Examples 10-41; U.S. Pat. No. 3,309,192, Col. 5, line 43 through Col. 7, line 62 and Examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167 and 169-182; U.S. Pat. No. 2,891,855, Col. 3, line 66 through Col. 5, line 17 and Examples 1-4; Klingman, Weed Control as a Science, John Wiley and Sons, Inc., New York, 1961, pp 81-96; Hance et al., Weed Control Handbook, 8th Ed., Blackwell Scientific Publications, Oxford, 1989; and Developments in formulation technology, PJB Publications, Richmond, UK, 2000.
In the following Examples, all percentages are by weight and all formulations are prepared in conventional ways. Compound numbers refer to compounds in Index Table A. Without further elaboration, it is believed that one skilled in the art using the preceding description can utilize the present invention to its fullest extent. The following Examples are, therefore, to be construed as merely illustrative, and not limiting of the disclosure in any way whatsoever. Percentages are by weight except where otherwise indicated.
Example A
High Strength Concentrate
















Compound 18
98.5%



silica aerogel
0.5%



synthetic amorphous fine silica
1.0%










Example B
Wettable Powder
















Compound 22
65.0%



dodecylphenol polyethylene glycol ether
2.0%



sodium ligninsulfonate
4.0%



sodium silicoaluminate
6.0%



montmorillonite (calcined)
23.0%










Example C
Granule













Compound 23
10.0%


attapulgite granules (low volatile matter, 0.71/0.30 mm;
90.0%


U.S.S. No. 25-50 sieves)









Example D
Extruded Pellet
















Compound 24
25.0%



anhydrous sodium sulfate
10.0%



crude calcium ligninsulfonate
5.0%



sodium alkylnaphthalenesulfonate
1.0%



calcium/magnesium bentonite
59.0%










Example E
Emulsifiable Concentrate
















Compound 36
10.0%



polyoxyethylene sorbitol hexoleate
20.0%



C6-C10 fatty acid methyl ester
70.0%










Example F
Microemulsion
















Compound 41
5.0%



polyvinylpyrrolidone-vinyl acetate copolymer
30.0%



alkylpolyglycoside
30.0%



glyceryl monooleate
15.0%



water
20.0%










Example G
Seed Treatment
















Compound 45
20.00%



polyvinylpyrrolidone-vinyl acetate copolymer
5.00%



montan acid wax
5.00%



calcium ligninsulfonate
1.00%



polyoxyethylene/polyoxypropylene block copolymers
1.00%



stearyl alcohol (POE 20)
2.00%



polyorganosilane
0.20%



colorant red dye
0.05%



water
65.75%










Formulations such as those in the Formulation Table are typically diluted with water to form aqueous compositions before application. Aqueous compositions for direct applications to the plant or portion thereof (e.g., spray tank compositions) typically at least about 1 ppm or more (e.g., from 1 ppm to 100 ppm) of the compound(s) of this invention.
The compounds of this invention are useful as plant disease control agents. The present invention therefore further comprises a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof to be protected, or to the plant seed to be protected, an effective amount of a compound of the invention or a fungicidal composition containing said compound. The compounds and/or compositions of this invention provide control of diseases caused by a broad spectrum of fungal plant pathogens in the Basidiomycete, Ascomycete, Oomycete and Deuteromycete classes. They are effective in controlling a broad spectrum of plant diseases, particularly foliar pathogens of ornamental, turf, vegetable, field, cereal, and fruit crops. These pathogens include: Oomycetes, including Phytophthora diseases such as Phytophthora infestans, Phytophthora megasperma, Phytophthora parasitica, Phytophthora cinnamomi and Phytophthora capsici, Pythium diseases such as Pythium aphanidermatum, and diseases in the Peronosporaceae family such as Plasmopara viticola, Peronospora spp. (including Peronospora tabacina and Peronospora parasitica), Pseudoperonospora spp. (including Pseudoperonospora cubensis) and Bremia lactucae; Ascomycetes, including Alternaria diseases such as Alternaria solani and Alternaria brassicae, Guignardia diseases such as Guignardia bidwell, Venturia diseases such as Venturia inaequalis, Septoria diseases such as Septoria nodorum and Septoria tritici, powdery mildew diseases such as Erysiphe spp. (including Erysiphe graminis and Erysiphe polygoni), Uncinula necatur, Sphaerotheca fuligena and Podosphaera leucotricha, Pseudocercosporella herpotrichoides, Botrytis diseases such as Botrytis cinerea, Monilinia fructicola, Sclerotinia diseases such as Sclerotinia sclerotiorum, Magnaporthe grisea, Phomopsis viticola, Helminthosporium diseases such as Helminthosporium tritici repentis, Pyrenophora teres, anthracnose diseases such as Glomerella or Colletotrichum spp. (such as Colletotrichum graminicola and Colletotrichum orbiculare), and Gaeumannomyces graminis; Basidiomycetes, including rust diseases caused by Puccinia spp. (such as Puccinia recondite, Puccinia striiformis, Puccinia hordei, Puccinia graminis and Puccinia arachidis), Hemileia vastatrix and Phakopsora pachyrhizi; other pathogens including Rutstroemia floccosum (also known as Sclerontina homoeocarpa); Rhizoctonia spp. (such as Rhizoctonia solani); Fusarium diseases such as Fusarium roseum, Fusarium graminearum and Fusarium oxysporum; Verticillium dahliae; Sclerotium rolfsii; Rynchosporium secalis; Cercosporidium personatum, Cercospora arachidicola and Cercospora beticola; and other genera and species closely related to these pathogens. In addition to their fungicidal activity, the compositions or combinations also have activity against bacteria such as Erwinia amylovora, Xanthomonas campestris, Pseudomonas syringae, and other related species.
Plant disease control is ordinarily accomplished by applying an effective amount of a compound of this invention either pre- or post-infection, to the portion of the plant to be protected such as the roots, stems, foliage, fruit, seeds, tubers or bulbs, or to the media (soil or sand) in which the plants to be protected are growing. The compounds can also be applied to seeds to protect the seeds and seedlings developing from the seeds. The compounds can also be applied through irrigation water to treat plants.
Accordingly, this aspect of the present invention can also be described as a method for protecting a plant or plant seed from diseases caused by fungal pathogens comprising applying a fungicidally effective amount of a compound of Formula 1, an N-oxide, or salt thereof to the plant (or portion thereof) or plant seed (directly or through the environment (e.g., growing medium) of the plant or plant seed).
Rates of application for these compounds can be influenced by many factors of the environment and should be determined under actual use conditions. Foliage can normally be protected when treated at a rate of from less than about 1 g/ha to about 5,000 g/ha of active ingredient. Seed and seedlings can normally be protected when seed is treated at a rate of from about 0.1 to about 10 g per kilogram of seed.
Compounds of this invention can also be mixed with one or more other biologically active compounds or agents including fungicides, insecticides, nematocides, bactericides, acaricides, herbicides, herbicide safeners, growth regulators such as insect molting inhibitors and rooting stimulants, chemosterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants, plant nutrients, other biologically active compounds or entomopathogenic bacteria, virus or fungi to form a multi-component pesticide giving an even broader spectrum of agricultural protection. Thus the present invention also pertains to a composition comprising a fungicidally effective amount of a compound of Formula 1 and a biologically effective amount of at least one additional biologically active compound or agent and can further comprise at least one of a surfactant, a solid diluent or a liquid diluent. The other biologically active compounds or agents can be formulated in compositions comprising at least one of a surfactant, solid or liquid diluent. For mixtures of the present invention, one or more other biologically active compounds or agents can be formulated together with a compound of Formula 1, to form a premix, or one or more other biologically active compounds or agents can be formulated separately from the compound of Formula 1, and the formulations combined together before application (e.g., in a spray tank) or, alternatively, applied in succession.
As mentioned in the Summary of the Invention, one aspect of the present invention is a fungicidal composition comprising (i.e. a mixture or combination of) a compound of Formula 1, an N-oxide, or a salt thereof (i.e. component a), and at least one other fungicide (i.e. component b).
Of note is a composition which, in addition to the Formula 1 compound of component (a), includes as component (b) at least one fungicidal compound selected from the group consisting of the classes (b1) methyl benzimidazole carbamate (MBC) fungicides; (b2) dicarboximide fungicides; (b3) demethylation inhibitor (DMI) fungicides; (b4) phenylamide fungicides; (b5) amine/morpholine fungicides; (b6) phospholipid biosynthesis inhibitor fungicides; (b7) carboxamide fungicides; (b8) hydroxy(2-amino-)pyrimidine fungicides; (b9) anilinopyrimidine fungicides; (b10) N-phenyl carbamate fungicides; (b11) quinone outside inhibitor (QoI) fungicides; (b12) phenylpyrrole fungicides; (b13) quinoline fungicides; (b14) lipid peroxidation inhibitor fungicides; (b15) melanin biosynthesis inhibitors-reductase (MBI-R) fungicides; (b16) melanin biosynthesis inhibitors-dehydratase (MBI-D) fungicides; (b17) hydroxyanilide fungicides; (b18) squalene-epoxidase inhibitor fungicides; (b19) polyoxin fungicides; (b20) phenylurea fungicides; (b21) quinone inside inhibitor (QiI) fungicides; (b22) benzamide fungicides; (b23) enopyranuronic acid antibiotic fungicides; (b24) hexopyranosyl antibiotic fungicides; (b25) glucopyranosyl antibiotic: protein synthesis fungicides; (b26) glucopyranosyl antibiotic: trehalase and inositol biosynthesis fungicides; (b27) cyanoacetamideoxime fungicides; (b28) carbamate fungicides; (b29) oxidative phosphorylation uncoupling fungicides; (b30) organo tin fungicides; (b31) carboxylic acid fungicides; (b32) heteroaromatic fungicides; (b33) phosphonate fungicides; (b34) phthalamic acid fungicides; (b35) benzotriazine fungicides; (b36) benzene-sulfonamide fungicides; (b37) pyridazinone fungicides; (b38) thiophene-carboxamide fungicides; (b39) pyrimidinamide fungicides; (b40) carboxylic acid amide (CAA) fungicides; (b41) tetracycline antibiotic fungicides; (b42) thiocarbamate fungicides; (b43) benzamide fungicides; (b44) host plant defense induction fungicides; (b45) multi-site contact activity fungicides; (b46) fungicides other than classes (b1) through (b45); and salts of compounds of classes (b1) through (b46).
Further descriptions of these classes of fungicidal compounds are provided below.
(b1) “Methyl benzimidazole carbamate (MBC) fungicides” (FRAC (Fungicide Resistance Action Committee) code 1) inhibit mitosis by binding to β-tubulin during microtubule assembly. Inhibition of microtubule assembly can disrupt cell division, transport within the cell and cell structure. Methyl benzimidazole carbamate fungicides include benzimidazole and thiophanate fungicides. The benzimidazoles include benomyl, carbendazim, fuberidazole and thiabendazole. The thiophanates include thiophanate and thiophanate-methyl.
(b2) “Dicarboximide fungicides” (FRAC code 2) are proposed to inhibit a lipid peroxidation in fungi through interference with NADH cytochrome c reductase. Examples include chlozolinate, iprodione, procymidone and vinclozolin.
(b3) “Demethylation inhibitor (DMI) fungicides” (FRAC code 3) inhibit C14-demethylase which plays a role in sterol production. Sterols, such as ergosterol, are needed for membrane structure and function, making them essential for the development of functional cell walls. Therefore, exposure to these fungicides result in abnormal growth and eventually death of sensitive fungi. DMI fungicides are divided between several chemical classes: azoles (including triazoles and imidazoles), pyrimidines, piperazines and pyridines. The triazoles include azaconazole, bitertanol, bromuconazole, cyproconazole, difenoconazole, diniconazole (including diniconazole-M), epoxiconazole, etaconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, prothioconazole, quinconazole, simeconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triticonazole and uniconazole. The imidazoles include clotrimazole, econazole, imazalil, isoconazole, miconazole, oxpoconazole, prochloraz, pefurazoate and triflumizole. The pyrimidines include fenarimol, nuarimol and triarimol. The piperazines include triforine. The pyridines include buthiobate and pyrifenox. Biochemical investigations have shown that all of the above mentioned fungicides are DMI fungicides as described by K. H. Kuck et al. in Modern Selective Fungicides—Properties, Applications and Mechanisms of Action, H. Lyr (Ed.), Gustav Fischer Verlag: New York, 1995, 205-258.
(b4) “Phenylamide fungicides” (FRAC code 4) are specific inhibitors of RNA polymerase in Oomycete fungi. Sensitive fungi exposed to these fungicides show a reduced capacity to incorporate uridine into rRNA. Growth and development in sensitive fungi is prevented by exposure to this class of fungicide. Phenylamide fungicides include acylalanine, oxazolidinone and butyrolactone fungicides. The acylalanines include benalaxyl, benalaxyl-M, furalaxyl, metalaxyl, metalaxyl-M (also known as mefenoxam). The oxazolidinones include oxadixyl. The butyrolactones include ofurace.
(b5) “Amine/morpholine fungicides” (FRAC code 5) inhibit two target sites within the sterol biosynthetic pathway, Δ8→Δ7 isomerase and Δ14 reductase. Sterols, such as ergosterol, are needed for membrane structure and function, making them essential for the development of functional cell walls. Therefore, exposure to these fungicides results in abnormal growth and eventually death of sensitive fungi. Amine/morpholine fungicides (also known as non-DMI sterol biosynthesis inhibitors) include morpholine, piperidine and spiroketal-amine fungicides. The morpholines include aldimorph, dodemorph, fenpropimorph, tridemorph and trimorphamide. The piperidines include fenpropidin and piperalin. The spiroketal-amines include spiroxamine.
(b6) “Phospholipid biosynthesis inhibitor fungicides” (FRAC code 6) inhibit growth of fungi by affecting phospholipid biosynthesis. Phospholipid biosynthesis fungicides include phosphorothiolate and dithiolane fungicides. The phosphorothiolates include edifenphos, iprobenfos and pyrazophos. The dithiolanes include isoprothiolane.
(b7) “Carboxamide fungicides” (FRAC code 7) inhibit Complex II (succinate dehydrogenase) fungal respiration by disrupting a key enzyme in the Krebs Cycle (TCA cycle) named succinate dehydrogenase. Inhibiting respiration prevents the fungus from making ATP, and thus inhibits growth and reproduction. Carboxamide fungicides include benzamide, furan carboxamide, oxathiin carboxamide, thiazole carboxamide, pyrazole carboxamide and pyridine carboxamide. The benzamides include benodanil, flutolanil and mepronil. The furan carboxamides include fenfuram. The oxathiin carboxamides include carboxin and oxycarboxin. The thiazole carboxamides include thifluzamide. The pyrazole carboxamides include bixafen, furametpyr, isopyrazam, fluxapyroxad, sedaxane (N-[2-(1S,2R)-[1,1′-bicyclopropyl]-2-ylphenyl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide) and penflufen (N-[2-(1,3-dimethylbutyl)phenyl]-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide (PCT Patent Publication WO 2003/010149)). The pyridine carboxamides include boscalid.
(b8) “Hydroxy(2-amino-)pyrimidine fungicides” (FRAC code 8) inhibit nucleic acid synthesis by interfering with adenosine deaminase. Examples include bupirimate, dimethirimol and ethirimol.
(b9) “Anilinopyrimidine fungicides” (FRAC code 9) are proposed to inhibit biosynthesis of the amino acid methionine and to disrupt the secretion of hydrolytic enzymes that lyse plant cells during infection. Examples include cyprodinil, mepanipyrim and pyrimethanil.
(b10) “N-Phenyl carbamate fungicides” (FRAC code 10) inhibit mitosis by binding to β-tubulin and disrupting microtubule assembly. Inhibition of microtubule assembly can disrupt cell division, transport within the cell and cell structure. Examples include diethofencarb.
(b11) “Quinone outside inhibitor (QoI) fungicides” (FRAC code 11) inhibit Complex III mitochondrial respiration in fungi by affecting ubiquinol oxidase. Oxidation of ubiquinol is blocked at the “quinone outside” (Qo) site of the cytochrome bc1 complex, which is located in the inner mitochondrial membrane of fungi Inhibiting mitochondrial respiration prevents normal fungal growth and development. Quinone outside inhibitor fungicides (also known as strobilurin fungicides) include methoxyacrylate, methoxycarbamate, oximinoacetate, oximinoacetamide, oxazolidinedione, dihydrodioxazine, imidazolinone and benzylcarbamate fungicides. The methoxyacrylates include azoxystrobin, enestroburin (SYP-Z071) and picoxystrobin. The methoxycarbamates include pyraclostrobin and pyrametostrobin. The oximinoacetates include kresoxim-methyl, pyraoxystrobin and trifloxystrobin. The oximinoacetamides include dimoxystrobin, metominostrobin, orysastrobin, α-[methoxyimino]-N-methyl-2-[[[1-[3-(trifluoromethyl)phenyl]ethoxy]imino]-methyl]benzeneacetamide and 2-[[[3-(2,6-dichlorophenyl)-1-methyl-2-propen-1-ylidene]-amino]oxy]methyl]-α-(methoxyimino)-N-methylbenzeneacetamide. The oxazolidinediones include famoxadone. The dihydrodioxazines include fluoxastrobin. The imidazolinones include fenamidone. The benzylcarbamates include pyribencarb.
(b12) “Phenylpyrrole fungicides” (FRAC code 12) inhibit a MAP protein kinase associated with osmotic signal transduction in fungi. Fenpiclonil and fludioxonil are examples of this fungicide class.
(b13) “Quinoline fungicides” (FRAC code 13) are proposed to inhibit signal transduction by affecting G-proteins in early cell signaling. They have been shown to interfere with germination and/or appressorium formation in fungi that cause powder mildew diseases. Quinoxyfen is an example of this class of fungicide.
(b14) “Lipid peroxidation inhibitor fungicides” (FRAC code 14) are proposed to inhibit lipid peroxidation which affects membrane synthesis in fungi. Members of this class, such as etridiazole, may also affect other biological processes such as respiration and melanin biosynthesis. Lipid peroxidation fungicides include aromatic carbon and 1,2,4-thiadiazole fungicides. The aromatic carbon fungicides include biphenyl, chloroneb, dicloran, quintozene, tecnazene and tolclofos-methyl. The 1,2,4-thiadiazole fungicides include etridiazole.
(b15) “Melanin biosynthesis inhibitors-reductase (MBI-R) fungicides” (FRAC code 16.1) inhibit the naphthal reduction step in melanin biosynthesis. Melanin is required for host plant infection by some fungi. Melanin biosynthesis inhibitors-reductase fungicides include isobenzofuranone, pyrroloquinolinone and triazolobenzothiazole fungicides. The isobenzofuranones include fthalide. The pyrroloquinolinones include pyroquilon. The triazolobenzothiazoles include tricyclazole.
(b16) “Melanin biosynthesis inhibitors-dehydratase (MBI-D) fungicides” (FRAC code 16.2) inhibit scytalone dehydratase in melanin biosynthesis. Melanin in required for host plant infection by some fungi. Melanin biosynthesis inhibitors-dehydratase fungicides include cyclopropanecarboxamide, carboxamide and propionamide fungicides. The cyclopropanecarboxamides include carpropamid. The carboxamides include diclocymet. The propionamides include fenoxanil.
(b17) “Hydroxyanilide fungicides (FRAC code 17) inhibit C4-demethylase which plays a role in sterol production. Examples include fenhexamid.
(b18) “Squalene-epoxidase inhibitor fungicides” (FRAC code 18) inhibit squalene-epoxidase in ergosterol biosynthesis pathway. Sterols such as ergosterol are needed for membrane structure and function, making them essential for the development of functional cell walls. Therefore exposure to these fungicides results in abnormal growth and eventually death of sensitive fungi. Squalene-epoxidase inhibitor fungicides include thiocarbamate and allylamine fungicides. The thiocarbamates include pyributicarb. The allylamines include naftifine and terbinafine.
(b19) “Polyoxin fungicides” (FRAC code 19) inhibit chitin synthase. Examples include polyoxin.
(b20) “Phenylurea fungicides” (FRAC code 20) are proposed to affect cell division. Examples include pencycuron.
(b21) “Quinone inside inhibitor (QiI) fungicides” (FRAC code 21) inhibit Complex III mitochondrial respiration in fungi by affecting ubiquinol reductase. Reduction of ubiquinol is blocked at the “quinone inside” (Qi) site of the cytochrome bc1 complex, which is located in the inner mitochondrial membrane of fungi. Inhibiting mitochondrial respiration prevents normal fungal growth and development. Quinone inside inhibitor fungicides include cyanoimidazole and sulfamoyltriazole fungicides. The cyanoimidazoles include cyazofamid. The sulfamoyltriazoles include amisulbrom.
(b22) “Benzamide fungicides” (FRAC code 22) inhibit mitosis by binding to β-tubulin and disrupting microtubule assembly Inhibition of microtubule assembly can disrupt cell division, transport within the cell and cell structure. Examples include zoxamide.
(b23) “Enopyranuronic acid antibiotic fungicides” (FRAC code 23) inhibit growth of fungi by affecting protein biosynthesis. Examples include blasticidin-S.
(b24) “Hexopyranosyl antibiotic fungicides” (FRAC code 24) inhibit growth of fungi by affecting protein biosynthesis. Examples include kasugamycin.
(b25) “Glucopyranosyl antibiotic: protein synthesis fungicides” (FRAC code 25) inhibit growth of fungi by affecting protein biosynthesis. Examples include streptomycin.
(b26) “Glucopyranosyl antibiotic: trehalase and inositol biosynthesis fungicides” (FRAC code 26) inhibit trehalase in inositol biosynthesis pathway. Examples include validamycin.
(b27) “Cyanoacetamideoxime fungicides (FRAC code 27) include cymoxanil.
(b28) “Carbamate fungicides” (FRAC code 28) are considered multi-site inhibitors of fungal growth. They are proposed to interfere with the synthesis of fatty acids in cell membranes, which then disrupts cell membrane permeability. Propamacarb, propamacarb-hydrochloride, iodocarb, and prothiocarb are examples of this fungicide class.
(b29) “Oxidative phosphorylation uncoupling fungicides” (FRAC code 29) inhibit fungal respiration by uncoupling oxidative phosphorylation. Inhibiting respiration prevents normal fungal growth and development. This class includes 2,6-dinitroanilines such as fluazinam, pyrimidonehydrazones such as ferimzone and dinitrophenyl crotonates such as dinocap, meptyldinocap and binapacryl.
(b30) “Organo tin fungicides” (FRAC code 30) inhibit adenosine triphosphate (ATP) synthase in oxidative phosphorylation pathway. Examples include fentin acetate, fentin chloride and fentin hydroxide.
(b31) “Carboxylic acid fungicides” (FRAC code 31) inhibit growth of fungi by affecting deoxyribonucleic acid (DNA) topoisomerase type II (gyrase). Examples include oxolinic acid.
(b32) “Heteroaromatic fungicides” (FRAC code 32) are proposed to affect DNA/ribonucleic acid (RNA) synthesis. Heteroaromatic fungicides include isoxazole and isothiazolone fungicides. The isoxazoles include hymexazole and the isothiazolones include octhilinone.
(b33) “Phosphonate fungicides” (FRAC code 33) include phosphorous acid and its various salts, including fosetyl-aluminum.
(b34) “Phthalamic acid fungicides” (FRAC code 34) include teclofthalam.
(b35) “Benzotriazine fungicides” (FRAC code 35) include triazoxide.
(b36) “Benzene-sulfonamide fungicides” (FRAC code 36) include flusulfamide.
(b37) “Pyridazinone fungicides” (Fungicide Resistance Action Committee (FRAC) code 37) include diclomezine.
(b38) “Thiophene-carboxamide fungicides” (FRAC code 38) are proposed to affect ATP production. Examples include silthiofam.
(b39) “Pyrimidinamide fungicides” (FRAC code 39) inhibit growth of fungi by affecting phospholipid biosynthesis and include diflumetorim.
(b40) “Carboxylic acid amide (CAA) fungicides” (FRAC code 40) are proposed to inhibit phospholipid biosynthesis and cell wall deposition Inhibition of these processes prevents growth and leads to death of the target fungus. Carboxylic acid amide fungicides include cinnamic acid amide, valinamide carbamate and mandelic acid amide fungicides. The cinnamic acid amides include dimethomorph and flumorph. The valinamide carbamates include benthiavalicarb, benthiavalicarb-isopropyl, iprovalicarb and valifenalate (valiphenal). The mandelic acid amides include mandipropamid, N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(methylsulfonyl)-amino]butanamide and N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-methoxyphenyl]-ethyl]-3-methyl-2-[(ethylsulfonyl)amino]butanamide.
(b41) “Tetracycline antibiotic fungicides” (FRAC code 41) inhibit growth of fungi by affecting complex 1 nicotinamide adenine dinucleotide (NADH) oxidoreductase. Examples include oxytetracycline.
(b42) “Thiocarbamate fungicides (b42)” (FRAC code 42) include methasulfocarb.
(b43) “Benzamide fungicides” (FRAC code 43) inhibit growth of fungi by delocalization of spectrin-like proteins. Examples include acylpicolide fungicides such as fluopicolide and fluopyram.
(b44) “Host plant defense induction fungicides” (FRAC code P) induce host plant defense mechanisms. Host plant defense induction fungicides include benzo-thiadiazole, benzisothiazole and thiadiazole-carboxamide fungicides. The benzo-thiadiazoles include acibenzolar-S-methyl. The benzisothiazoles include probenazole. The thiadiazole-carboxamides include tiadinil and isotianil.
(b45) “Multi-site contact fungicides” inhibit fungal growth through multiple sites of action and have contact/preventive activity. This class of fungicides includes: (b45.1) “copper fungicides” (FRAC code M1)”, (b45.2) “sulfur fungicides” (FRAC code M2), (b45.3) “dithiocarbamate fungicides” (FRAC code M3), (b45.4) “phthalimide fungicides” (FRAC code M4), (b45.5) “chloronitrile fungicides” (FRAC code M5), (b45.6) “sulfamide fungicides” (FRAC code M6), (b45.7) “guanidine fungicides” (FRAC code M7), (b45.8) “triazine fungicides” (FRAC code M8) and (b45.9) “quinone fungicides” (FRAC code M9). “Copper fungicides” are inorganic compounds containing copper, typically in the copper(II) oxidation state; examples include copper oxychloride, copper sulfate and copper hydroxide, including compositions such as Bordeaux mixture (tribasic copper sulfate). “Sulfur fungicides” are inorganic chemicals containing rings or chains of sulfur atoms; examples include elemental sulfur. “Dithiocarbamate fungicides” contain a dithiocarbamate molecular moiety; examples include mancozeb, metiram, propineb, ferbam, maneb, thiram, zineb and ziram. “Phthalimide fungicides” contain a phthalimide molecular moiety; examples include folpet, captan and captafol. “Chloronitrile fungicides” contain an aromatic ring substituted with chloro and cyano; examples include chlorothalonil. “Sulfamide fungicides” include dichlofluanid and tolyfluanid. “Guanidine fungicides” include dodine, guazatine and imoctadine, including iminoctadine albesilate and iminoctadine triacetate. “Triazine fungicides” include anilazine. “Quinone fungicides” include dithianon.
(b46) “Fungicides other than fungicides of classes (b1) through (b45)” include certain fungicides whose mode of action may be unknown. These include: (b46.1) “thiazole carboxamide fungicides” (FRAC code U5), (b46.2) “phenyl-acetamide fungicides” (FRAC code U6), (b46.3) “quinazolinone fungicides” (FRAC code U7) and (b46.4) “benzophenone fungicides” (FRAC code U8). The thiazole carboxamides include ethaboxam. The phenyl-acetamides include cyflufenamid and N-[[(cyclopropylmethoxy)amino][6-(difluoromethoxy)-2,3-difluorophenyl]-methylene]benzeneacetamide. The quinazolinones include proquinazid and 2-butoxy-6-iodo-3-propyl-4H-1-benzopyran-4-one. The benzophenones include metrafenone and pyriofenone. The (b46) class also includes bethoxazin, neo-asozin (ferric methanearsonate), fenpyrazamine, pyrrolnitrin, quinomethionate, tebufloquin, N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(methylsulfonyl)amino]butanamide, N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(ethylsulfonyl)amino]-butanamide, 2-[[2-fluoro-5-(trifluoromethyl)phenyl]thio]-2-[3-(2-methoxyphenyl)-2-thiazolidinylidene]acetonitrile, 3-[5-(4-chlorophenyl)-2,3-dimethyl-3-isoxazolidinyl]pyridine, 4-fluorophenyl N-[1-[[[1-(4-cyanophenyl)ethyl]sulfonyl]methyl]propyl]carbamate, 5-chloro-6-(2,4,6-trifluorophenyl)-7-(4-methylpiperidin-1-yl) [1,2,4]triazolo[1,5-a]pyrimidine, N-(4-chloro-2-nitrophenyl)-N-ethyl-4-methylbenzenesulfonamide, N-[[(cyclopropylmethoxy)-amino][6-(difluoromethoxy)-2,3-difluorophenyl]methylene]benzene acetamide, N′-[4-[4-chloro-3-(trifluoromethyl)phenoxy]-2,5-dimethylphenyl]-N-ethyl-N-methylmethanimidamide and 1-[(2-propenylthio)carbonyl]-2-(1-methylethyl)-4-(2-methylphenyl)-5-amino-1H-pyrazol-3-one.
Therefore of note is a mixture (i.e. composition) comprising as component (a) a compound of Formula 1 (or an N-oxide or salt thereof) and as component (b) at least one fungicidal compound selected from the group consisting of the aforedescribed classes (b1) through (b46). Also of note are embodiments wherein component (b) comprises at least one fungicide from each of two different groups selected from (b1) through (b46). Also of note is a composition comprising said mixture (in fungicidally effective amount) and further comprising at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents. Of particular note is a mixture (i.e. composition) comprising a compound of Formula 1 and at least one fungicidal compound selected from the group of specific compounds listed above in connection with classes (b1) through (b46). Also of particular note is a composition comprising said mixture (in fungicidally effective amount) and further comprising at least one additional surfactant selected from the group consisting of surfactants, solid diluents and liquid diluents.
Examples of other biologically active compounds or agents with which compounds of this invention can be formulated are: insecticides such as abamectin, acephate, acetamiprid, acetoprole, aldicarb, amidoflumet (S-1955), amitraz, avermectin, azadirachtin, azinphos-methyl, bifenthrin, bifenazate, bistrifluron, buprofezin, carbofuran, cartap, chinomethionat, chlorfenapyr, chlorfluazuron, chlorantraniliprole (DPX-E2Y45), chlorpyrifos, chlorpyrifos-methyl, chlorobenzilate, chromafenozide, clothianidin, cyantraniliprole (3-bromo-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6-[(methylamino)-carbonyl]phenyl]-1H-pyrazole-5-carboxamide), cyflumetofen, cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda-cyhalothrin, cyhexatin, cypermethrin, cyromazine, deltamethrin, diafenthiuron, diazinon, dicofol, dieldrin, dienochlor, diflubenzuron, dimefluthrin, dimethoate, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, etoxazole, fenamiphos, fenazaquin, fenbutatin oxide, fenothiocarb, fenoxycarb, fenpropathrin, fenpyroximate, fenvalerate, fipronil, flonicamid, flubendiamide, flucythrinate, tau-fluvalinate, flufenerim (UR-50701), flufenoxuron, fonophos, halofenozide, hexaflumuron, hexythiazox, hydramethylnon, imicyafos, imidacloprid, indoxacarb, isofenphos, lufenuron, malathion, metaflumizone, metaldehyde, methamidophos, methidathion, methomyl, methoprene, methoxychlor, methoxyfenozide, metofluthrin, monocrotophos, nitenpyram, nithiazine, novaluron (XDE-007), noviflumuron, oxamyl, parathion, parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, profluthrin, propargite, prothiocarb, protrifenbute, pymetrozine, pyrafluprole, pyrethrin, pyridaben, pyridalyl, pyrifluquinazon, pyriprole, pyriproxyfen, rotenone, ryanodine, spinetoram, spinosad, spiridiclofen, spiromesifen (BSN 2060), spirotetramat, sulprofos, tebufenozide, tebufenpyrad, teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tolfenpyrad, tralomethrin, triazamate, trichlorfon, triflumuron; nematocides such as aldicarb, imicyafos, oxamyl and fenamiphos; bactericides such as streptomycin; acaricides such as amitraz, chinomethionat, chlorobenzilate, cyenopyrafen, cyhexatin, dicofol, dienochlor, etoxazole, fenazaquin, fenbutatin oxide, fenpropathrin, fenpyroximate, hexythiazox, propargite, pyridaben and tebufenpyrad; and biological agents including entomopathogenic bacteria, such as Bacillus thuringiensis subsp. aizawai, Bacillus thuringiensis subsp. kurstaki, and the encapsulated delta-endotoxins of Bacillus thuringiensis (e.g., Cellcap, MPV, MPVII); entomopathogenic fungi, such as green muscardine fungus; and entomopathogenic virus including baculovirus, nucleopolyhedro virus (NPV) such as HzNPV, AfNPV; and granulosis virus (GV) such as CpGV.
General references for agricultural protectants (i.e. insecticides, fungicides, nematocides, acaricides, herbicides and biological agents) include The Pesticide Manual, 13th Edition, C. D. S. Tomlin, Ed., British Crop Protection Council, Farnham, Surrey, U.K., 2003 and The BioPesticide Manual, 2nd Edition, L. G. Copping, Ed., British Crop Protection Council, Farnham, Surrey, U.K., 2001.
For embodiments where one or more of these various mixing partners are used, the weight ratio of these various mixing partners (in total) to the compound of Formula 1 (or an N-oxide or salt thereof) is typically between about 1:3000 and about 3000:1. Of note are weight ratios between about 1:300 and about 300:1 (for example ratios between about 1:30 and about 30:1). One skilled in the art can easily determine through simple experimentation the biologically effective amounts of active ingredients necessary for the desired spectrum of biological activity. It will be evident that including these additional components may expand the spectrum of diseases controlled beyond the spectrum controlled by the compound of Formula 1 alone.
In certain instances, combinations of a compound of this invention with other biologically active (particularly fungicidal) compounds or agents (i.e. active ingredients) can result in a greater-than-additive (i.e. synergistic) effect. Reducing the quantity of active ingredients released in the environment while ensuring effective pest control is always desirable. When synergism of fungicidal active ingredients occurs at application rates giving agronomically satisfactory levels of fungal control, such combinations can be advantageous for reducing crop production cost and decreasing environmental load.
Compounds of this invention and compositions thereof can be applied to plants genetically transformed to express proteins toxic to invertebrate pests (such as Bacillus thuringiensis delta-endotoxins). The effect of the exogenously applied fungicidal compounds of this invention may be synergistic with the expressed toxin proteins.
Of note is a combination of a compound of Formula 1 (or an N-oxide or salt thereof) with at least one other fungicidal active ingredient. Of particular note is such a combination where the other fungicidal active ingredient has different site of action from the compound of Formula 1. In certain instances, a combination with at least one other fungicidal active ingredient having a similar spectrum of control but a different site of action will be particularly advantageous for resistance management. Thus, a composition of the present invention can further comprise a biologically effective amount of at least one additional fungicidal active ingredient having a similar spectrum of control but a different site of action.
Of particular note are compositions which in addition to a compound of Formula 1 include at least one compound selected from the group consisting of (1) alkylenebis(dithiocarbamate) fungicides; (2) cymoxanil; (3) phenylamide fungicides; (4) pyrimidinone fungicides; (5) chlorothalonil; (6) carboxamides acting at complex II of the fungal mitochondrial respiratory electron transfer site; (7) quinoxyfen; (8) metrafenone or pyriofenone; (9) cyflufenamid; (10) cyprodinil; (11) copper compounds; (12) phthalimide fungicides; (13) fosetyl-aluminum; (14) benzimidazole fungicides; (15) cyazofamid; (16) fluazinam; (17) iprovalicarb; (18) propamocarb; (19) validomycin; (20) dichlorophenyl dicarboximide fungicides; (21) zoxamide; (22) fluopicolide; (23) mandipropamid; (24) carboxylic acid amides acting on phospholipid biosynthesis and cell wall deposition; (25) dimethomorph; (26) non-DMI sterol biosynthesis inhibitors; (27) inhibitors of demethylase in sterol biosynthesis; (28) bc1 complex fungicides; and salts of compounds of (1) through (28).
Further descriptions of classes of fungicidal compounds are provided below.
Pyrimidinone fungicides (group (4)) include compounds of Formula A1




wherein M forms a fused phenyl, thiophene or pyridine ring; Ra14 is C1-C6 alkyl; Ra15 is C1-C6 alkyl or C1-C6 alkoxy; Ra16 is halogen; and Ra17 is hydrogen or halogen.

Pyrimidinone fungicides are described in PCT Patent Application Publication WO 94/26722 and U.S. Pat. Nos. 6,066,638, 6,245,770, 6,262,058 and 6,277,858. Of note are pyrimidinone fungicides selected from the group: 6-bromo-3-propyl-2-propyloxy-4(3H)-quinazolinone, 6,8-diiodo-3-propyl-2-propyloxy-4(3H)-quinazolinone, 6-iodo-3-propyl-2-propyloxy-4(3H)-quinazolinone (proquinazid), 6-chloro-2-propoxy-3-propylthieno[2,3-d]pyrimidin-4(3H)-one, 6-bromo-2-propoxy-3-propylthieno[2,3-d]pyrimidin-4(3H)-one, 7-bromo-2-propoxy-3-propylthieno[3,2-d]pyrimidin-4(3H)-one, 6-bromo-2-propoxy-3-propylpyrido[2,3-d]pyrimidin-4(3H)-one, 6,7-dibromo-2-propoxy-3-propylthieno[3,2-d]pyrimidin-4(3H)-one, and 3-(cyclopropylmethyl)-6-iodo-2-(propylthio)pyrido-[2,3-d]pyrimidin-4(3H)-one.
Sterol biosynthesis inhibitors (group (27)) control fungi by inhibiting enzymes in the sterol biosynthesis pathway. Demethylase-inhibiting fungicides have a common site of action within the fungal sterol biosynthesis pathway, involving inhibition of demethylation at position 14 of lanosterol or 24-methylene dihydrolanosterol, which are precursors to sterols in fungi. Compounds acting at this site are often referred to as demethylase inhibitors, DMI fungicides, or DMIs. The demethylase enzyme is sometimes referred to by other names in the biochemical literature, including cytochrome P-450 (14DM). The demethylase enzyme is described in, for example, J. Biol. Chem. 1992, 267, 13175-79 and references cited therein. DMI fungicides are divided between several chemical classes: azoles (including triazoles and imidazoles), pyrimidines, piperazines and pyridines. The triazoles include azaconazole, bromuconazole, cyproconazole, difenoconazole, diniconazole (including diniconazole-M), epoxiconazole, etaconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, prothioconazole, quinconazole, simeconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triticonazole and uniconazole. The imidazoles include clotrimazole, econazole, imazalil, isoconazole, miconazole, oxpoconazole, prochloraz and triflumizole. The pyrimidines include fenarimol, nuarimol and triarimol. The piperazines include triforine. The pyridines include buthiobate and pyrifenox. Biochemical investigations have shown that all of the above mentioned fungicides are DMI fungicides as described by K. H. Kuck et al. in Modern Selective Fungicides—Properties, Applications and Mechanisms of Action, H. Lyr (Ed.), Gustav Fischer Verlag: New York, 1995, 205-258.
bc1 Complex Fungicides (group 28) have a fungicidal mode of action which inhibits the bc1 complex in the mitochondrial respiration chain. The bc1 complex is sometimes referred to by other names in the biochemical literature, including complex III of the electron transfer chain, and ubihydroquinone:cytochrome c oxidoreductase. This complex is uniquely identified by Enzyme Commission number EC1.10.2.2. The bc1 complex is described in, for example, J. Biol. Chem. 1989, 264, 14543-48; Methods Enzymol. 1986, 126, 253-71; and references cited therein. Strobilurin fungicides such as azoxystrobin, dimoxystrobin, enestroburin (SYP-Z071), fluoxastrobin, kresoxim-methyl, metominostrobin, orysastrobin, picoxystrobin, pyraclostrobin and trifloxystrobin are known to have this mode of action (H. Sauter et al., Angew. Chem. Int. Ed. 1999, 38, 1328-1349). Other fungicidal compounds that inhibit the bc1 complex in the mitochondrial respiration chain include famoxadone and fenamidone.
Alkylenebis(dithiocarbamate)s (group (1)) include compounds such as mancozeb, maneb, propineb and zineb. Phenylamides (group (3)) include compounds such as metalaxyl, benalaxyl, furalaxyl and oxadixyl. Carboxamides (group (6)) include compounds such as boscalid, carboxin, fenfuram, flutolanil, fluxapyroxad, furametpyr, mepronil, oxycarboxin, thifluzamide, penthiopyrad and penflufen (N-[2-(1,3-dimethylbutyl)phenyl]-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide (PCT Patent Publication WO 2003/010149)), and are known to inhibit mitochondrial function by disrupting complex II (succinate dehydrogenase) in the respiratory electron transport chain. Copper compounds (group (11)) include compounds such as copper oxychloride, copper sulfate and copper hydroxide, including compositions such as Bordeaux mixture (tribasic copper sulfate). Phthalimides (group (12)) include compounds such as folpet and captan. Benzimidazole fungicides (group (14)) include benomyl and carbendazim. Dichlorophenyl dicarboximide fungicides (group (20)) include chlozolinate, dichlozoline, iprodione, isovaledione, myclozolin, procymidone and vinclozolin.
Non-DMI sterol biosynthesis inhibitors (group (26)) include morpholine and piperidine fungicides. The morpholines and piperidines are sterol biosynthesis inhibitors that have been shown to inhibit steps in the sterol biosynthesis pathway at a point later than the inhibitions achieved by the DMI sterol biosynthesis (group (27)). The morpholines include aldimorph, dodemorph, fenpropimorph, tridemorph and trimorphamide. The piperidines include fenpropidin.
Examples of component (b) fungicides include acibenzolar-S-methyl, aldimorph, ametoctradin, amisulbrom, anilazine, azaconazole, azoxystrobin, benalaxyl, benalaxyl-M, benodanil, benomyl, benthiavalicarb, benthiavalicarb-isopropyl, bethoxazin, binapacryl, biphenyl, bitertanol, bixafen, blasticidin-S, boscalid, bromuconazole, bupirimate, carboxin, carpropamid, captafol, captan, carbendazim, chloroneb, chlorothalonil, chlozolinate, clotrimazole, copper salts such as Bordeaux mixture (tribasic copper sulfate), copper hydroxide and copper oxychloride, cyazofamid, cyflufenamid, cymoxanil, cyproconazole, cyprodinil, dichlofluanid, diclocymet, diclomezine, dicloran, diethofencarb, difenoconazole, diflumetorim, dimethirimol, dimethomorph, dimoxystrobin, diniconazole, diniconazole-M, dinocap, dithianon, dodemorph, dodine, edifenphos, enestroburin, epoxiconazole, ethaboxam, ethirimol, etridiazole, famoxadone, fenamidone, fenarimol, fenbuconazole, fenfuram, fenhexamid, fenoxanil, fenpiclonil, fenpropidin, fenpropimorph, fenpyrazamine, fentin acetate, fentin chloride, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, flumetover, flumorph, fluopicolide (also known as picobenzamid), fluopyram, fluoroimide, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, flutianil (2-[[2-fluoro-5-(trifluoromethyl)phenyl]thio]-2-[3-(2-methoxyphenyl)-2-thiazolidinylidene]acetonitrile), flutolanil, flutriafol, fluxapyroxad, folpet, fosetyl-aluminum, fuberidazole, furalaxyl, furametpyr, hexaconazole, hymexazol, guazatine, imazalil, imibenconazole, iminoctadine, iodocarb, ipconazole, iprobenfos, iprodione, iprovalicarb, isoprothiolane, isopyrazam, isotianil, kasugamycin, kresoxim-methyl, mancozeb, mandipropamid, maneb, mepronil, meptyldinocap, metalaxyl, metalaxyl-M, metconazole, methasulfocarb, metiram, metominostrobin, mepanipyrim, metrafenone, myclobutanil, naftifine, neo-asozin (ferric methanearsonate), nuarimol, octhilinone, ofurace, orysastrobin, oxadixyl, oxolinic acid, oxpoconazole, oxycarboxin, oxytetracycline, penconazole, pencycuron, penflufen, penthiopyrad, pefurazoate, phosphorous acid and salts, phthalide, picoxystrobin, piperalin, polyoxin, probenazole, prochloraz, procymidone, propamocarb, propamocarb-hydrochloride, propiconazole, propineb, proquinazid, prothioconazole, pyraclostrobin, pyrametostrobin, pyraoxystrobin, pyrazophos, pyribencarb, pyributicarb, pyrifenox, pyrimethanil, pyriofenone, pyroquilon, pyrrolnitrin, quinomethionate, quinoxyfen, quintozene, sedaxane, silthiofam, simeconazole, spiroxamine, streptomycin, sulfur, tebuconazole, tebufloquin, tecloftalam, tecnazene, terbinafine, tetraconazole, thiabendazole, thifluzamide, thiophanate, thiophanate-methyl, thiram, tiadinil, tolclofos-methyl, tolylfluanid, triadimefon, triadimenol, triazoxide, tricyclazole, tridemorph, triflumizole, tricyclazole, trifloxystrobin, triforine, trimorphamide, triticonazole, uniconazole, validamycin, valifenalate (valiphenal), vinclozolin, zineb, ziram, zoxamide, N-[4-[4-chloro-3-(trifluoromethyl)phenoxy]-2,5-dimethylphenyl]-N-ethyl-N-methylmethanimidamide, 5-chloro-6-(2,4,6-trifluorophenyl)-7-(4-methylpiperidin-1-yl) [1,2,4]triazolo[1,5-a]pyrimidine (BAS600), penflufen (N-[2-(1,3-dimethylbutyl)phenyl]-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide), N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(methylsulfonyl)amino]butanamide, N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(ethylsulfonyl)amino]butanamide, 2-butoxy-6-iodo-3-propyl-4H-1-benzopyran-4-one, 3-[5-(4-chlorophenyl)-2,3-dimethyl-3-isoxazolidinyl]-pyridine, 4-fluorophenyl N-[1-[[[1-(4-cyanophenyl)ethyl]sulfonyl]methyl]propyl]carbamate, N-[[(cyclopropylmethoxy)amino][6-(difluoromethoxy)-2,3-difluorophenyl]methylene]benzeneacetamide, α-(methoxyimino)-N-methyl-2-[[[1-[3-(trifluoro-methyl)phenyl]ethoxy]imino]methyl]benzeneacetamide, N-[4-[4-chloro-3-(trifluoro-methyl)phenoxy]-2,5-dimethylphenyl]-N-ethyl-N-methylmethanimidamide, N-(4-chloro-2-nitrophenyl)-N-ethyl-4-methylbenzenesulfonamide, 2-[[[[3-(2,6-dichlorophenyl)-1-methyl-2-propen-1-ylidene]amino]oxy]methyl]-α-(methoxyimino)-N-methylbenzeneacetamide, 1-[(2-propenylthio)carbonyl]-2-(1-methylethyl)-4-(2-methylphenyl)-5-amino-1H-pyrazol-3-one, ethyl-6-octyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-ylamine, pentyl N-[4-[[[[(1-methyl-1H-tetrazol-5-yl)phenylmethylene]amino]oxy]methyl]-2-thiazolyl]carbamate and pentyl N-[6-[[[[(1-methyl-1H-tetrazol-5-yl)phenylmethylene]amino]oxy]methyl]-2-pyridinyl]carbamate
Of note are combinations of compounds of Formula 1 (or an N-oxide or salt thereof) (i.e. Component (a) in compositions) with azoxystrobin, kresoxim-methyl, trifloxystrobin, pyraclostrobin, picoxystrobin, pyrametostrobin, pyraoxystrobin, dimoxystrobin, metominostrobin/fenominostrobin, carbendazim, chlorothalonil, quinoxyfen, metrafenone, cyflufenamid, fenpropidine, fenpropimorph, bromuconazole, cyproconazole, difenoconazole, epoxiconazole, fenbuconazole, flusilazole, fluxapyroxad, hexaconazole, ipconazole, metconazole, penconazole, propiconazole, proquinazid, prothioconazole, pyriofenone, tebuconazole, triticonazole, famoxadone, prochloraz, penthiopyrad and boscalid (nicobifen) (i.e. as Component (b) in compositions).
Preferred for better control of plant diseases caused by fungal plant pathogens (e.g., lower use rate or broader spectrum of plant pathogens controlled) or resistance management are mixtures of a compound of this invention with a fungicide selected from the group: azoxystrobin, kresoxim-methyl, trifloxystrobin, pyraclostrobin, picoxystrobin, pyrametostrobin, pyraoxystrobin, dimoxystrobin, metominostrobin/fenominostrobin, quinoxyfen, metrafenone, cyflufenamid, fenpropidine, fenpropimorph, cyproconazole, epoxiconazole, flusilazole, metconazole, propiconazole, proquinazid, prothioconazole, pyriofenone, tebuconazole, triticonazole, famoxadone and penthiopyrad.
Tables A1 through A54 list specific combinations of a Component (b) compound with Component (a) (compound numbers refer to compounds in Index Table A) illustrative of the mixtures, compositions and methods of the present invention. In Table A1, each line below the column headings “Component (a)” and “Component (b)” specifically discloses a combination (i.e. mixture) of Component (a), which is Compound 22, with a Component (b) fungicide. The entries under the heading “Illustrative Ratios” disclose three specific weight ratios of Component (b) to Component (a) for the disclosed mixture. For example, the first line of Table A1 discloses a mixture of Compound 22 with acibenzolar-S-methyl and lists weight ratios of acibenzolar-S-methyl to Compound 22 of 1:1, 1:4 or 1:17.









TABLE A1





Component (a)
Component (b)
Illustrative Ratios(*)



















Compound 22
acibenzolar-S-methyl
1:1
1:4
 1:18


Compound 22
aldimorph
7:1
3:1
1:1


Compound 22
ametoctradin
3:1
1:1
1:3


Compound 22
amisulbrom
1:1
1:2
1:6


Compound 22
anilazine
22:1 
8:1
4:1


Compound 22
azaconazole
2:1
1:2
1:4


Compound 22
azoxystrobin
3:1
1:1
1:3


Compound 22
benalaxyl
1:1
1:2
1:6


Compound 22
benalaxyl-M
1:1
1:3
1:8


Compound 22
benodanil
4:1
2:1
1:2


Compound 22
benomyl
11:1 
4:1
1:1


Compound 22
benthiavalicarb
1:1
1:4
 1:12


Compound 22
benthiavalicarb-isopropyl
1:1
1:4
 1:12


Compound 22
bethoxazin
15:1 
5:1
2:1


Compound 22
binapacryl
15:1 
5:1
2:1


Compound 22
biphenyl
15:1 
5:1
2:1


Compound 22
bitertanol
3:1
1:1
1:2


Compound 22
bixafen
2:1
1:1
1:3


Compound 22
blasticidin-S
1:4
 1:12
 1:30


Compound 22
Bordeaux mixture (tribasic copper sulfate)
45:1 
15:1 
5:1


Compound 22
boscalid
4:1
2:1
1:2


Compound 22
bromuconazole
3:1
1:1
1:3


Compound 22
bupirimate
1:3
 1:10
 1:30


Compound 22
captafol
15:1 
5:1
2:1


Compound 22
captan
15:1 
5:1
2:1


Compound 22
carbendazim
11:1 
4:1
2:1


Compound 22
carboxin
4:1
2:1
1:2


Compound 22
carpropamid
3:1
1:1
1:3


Compound 22
chloroneb
100:1 
35:1 
14:1 


Compound 22
chlorothalonil
15:1 
5:1
2:1


Compound 22
chlozolinate
11:1 
4:1
2:1


Compound 22
clotrimazole
3:1
1:1
1:3


Compound 22
copper hydroxide
45:1 
15:1 
5:1


Compound 22
copper oxychloride
45:1 
15:1 
5:1


Compound 22
cyazofamid
1:1
1:2
1:6


Compound 22
cyflufenamid
1:2
1:6
 1:24


Compound 22
cymoxanil
1:1
1:2
1:5


Compound 22
cyproconazole
1:1
1:2
1:6


Compound 22
cyprodinil
4:1
2:1
1:2


Compound 22
dichlofluanid
15:1 
5:1
2:1


Compound 22
diclocymet
15:1 
5:1
2:1


Compound 22
diclomezine
3:1
1:1
1:3


Compound 22
dicloran
15:1 
5:1
2:1


Compound 22
diethofencarb
7:1
2:1
1:2


Compound 22
difenoconazole
1:1
1:3
 1:12


Compound 22
diflumetorim
15:1 
5:1
2:1


Compound 22
dimethirimol
1:3
1:8
 1:30


Compound 22
dimethomorph
3:1
1:1
1:2


Compound 22
dimoxystrobin
2:1
1:1
1:4


Compound 22
diniconazole
1:1
1:3
1:8


Compound 22
diniconazole-M
1:1
1:3
 1:12


Compound 22
dinocap
2:1
1:1
1:3


Compound 22
dithianon
5:1
2:1
1:2


Compound 22
dodemorph
7:1
3:1
1:1


Compound 22
dodine
10:1 
4:1
2:1


Compound 22
edifenphos
3:1
1:1
1:3


Compound 22
enestroburin
2:1
1:1
1:4


Compound 22
epoxiconazole
1:1
1:3
1:7


Compound 22
ethaboxam
2:1
1:1
1:3


Compound 22
ethirimol
7:1
3:1
1:1


Compound 22
etridiazole
7:1
2:1
1:2


Compound 22
famoxadone
2:1
1:1
1:4


Compound 22
fenamidone
2:1
1:1
1:4


Compound 22
fenarimol
1:2
1:7
 1:24


Compound 22
fenbuconazole
1:1
1:3
 1:10


Compound 22
fenfuram
4:1
1:1
1:2


Compound 22
fenhexamid
10:1 
4:1
2:1


Compound 22
fenoxanil
15:1 
4:1
1:1


Compound 22
fenpiclonil
15:1 
5:1
2:1


Compound 22
fenpropidin
7:1
2:1
1:1


Compound 22
fenpropimorph
7:1
2:1
1:1


Compound 22
fenpyrazamine
3:1
1:1
1:3


Compound 22
fentin salt such as fentin acetate, fentin chloride or fentin
3:1
1:1
1:3



hydroxide


Compound 22
ferbam
30:1 
10:1 
4:1


Compound 22
ferimzone
7:1
2:1
1:2


Compound 22
fluazinam
3:1
1:1
1:2


Compound 22
fludioxonil
2:1
1:1
1:4


Compound 22
flumetover
3:1
1:1
1:2


Compound 22
flumorph
3:1
1:1
1:3


Compound 22
fluopicolide
1:1
1:2
1:6


Compound 22
fluopyram
3:1
1:1
1:3


Compound 22
fluoroimide
37:1 
14:1 
5:1


Compound 22
fluoxastrobin
1:1
1:2
1:6


Compound 22
fluquinconazole
1:1
1:2
1:4


Compound 22
flusilazole
3:1
1:1
1:3


Compound 22
flusulfamide
15:1 
5:1
2:1


Compound 22
flutianil
1:1
1:2
1:6


Compound 22
flutolanil
4:1
1:1
1:2


Compound 22
flutriafol
1:1
1:2
1:4


Compound 22
fluxapyroxad
2:1
1:1
1:3


Compound 22
folpet
15:1 
5:1
2:1


Compound 22
fosetyl-aluminum
30:1 
12:1 
5:1


Compound 22
fuberidazole
11:1 
4:1
2:1


Compound 22
furalaxyl
1:1
1:2
1:6


Compound 22
furametpyr
15:1 
5:1
2:1


Compound 22
guazatine
15:1 
5:1
2:1


Compound 22
hexaconazole
1:1
1:2
1:5


Compound 22
hymexazol
75:1 
25:1 
9:1


Compound 22
imazalil
1:1
1:2
1:5


Compound 22
imibenconazole
1:1
1:2
1:5


Compound 22
iminoctadine
15:1 
4:1
1:1


Compound 22
iodocarb
15:1 
5:1
2:1


Compound 22
ipconazole
1:1
1:2
1:5


Compound 22
iprobenfos
15:1 
5:1
2:1


Compound 22
iprodione
15:1 
5:1
2:1


Compound 22
iprovalicarb
2:1
1:1
1:3


Compound 22
isoprothiolane
45:1 
15:1 
5:1


Compound 22
isopyrazam
2:1
1:1
1:3


Compound 22
isotianil
2:1
1:1
1:3


Compound 22
kasugamycin
1:2
1:7
 1:24


Compound 22
kresoxim-methyl
2:1
1:1
1:4


Compound 22
mancozeb
22:1 
7:1
3:1


Compound 22
mandipropamid
2:1
1:1
1:4


Compound 22
maneb
22:1 
7:1
3:1


Compound 22
mepanipyrim
6:1
2:1
1:1


Compound 22
mepronil
1:1
1:2
1:6


Compound 22
meptyldinocap
2:1
1:1
1:3


Compound 22
metalaxyl
1:1
1:2
1:6


Compound 22
metalaxyl-M
1:1
1:4
 1:12


Compound 22
metconazole
1:1
1:2
1:6


Compound 22
methasulfocarb
15:1 
5:1
2:1


Compound 22
metiram
15:1 
5:1
2:1


Compound 22
metominostrobin
3:1
1:1
1:3


Compound 22
metrafenone
2:1
1:1
1:4


Compound 22
myclobutanil
1:1
1:3
1:8


Compound 22
naftifine
15:1 
5:1
2:1


Compound 22
neo-asozin (ferric methanearsonate)
15:1 
5:1
2:1


Compound 22
nuarimol
3:1
1:1
1:3


Compound 22
octhilinone
15:1 
4:1
1:1


Compound 22
ofurace
1:1
1:2
1:6


Compound 22
orysastrobin
3:1
1:1
1:3


Compound 22
oxadixyl
1:1
1:2
1:6


Compound 22
oxolinic acid
7:1
2:1
1:2


Compound 22
oxpoconazole
1:1
1:2
1:5


Compound 22
oxycarboxin
4:1
1:1
1:2


Compound 22
oxytetracycline
3:1
1:1
1:3


Compound 22
pefurazoate
15:1 
5:1
2:1


Compound 22
penconazole
1:2
1:6
 1:15


Compound 22
pencycuron
11:1 
4:1
2:1


Compound 22
penthiopyrad
2:1
1:1
1:3


Compound 22
phosphorous acid or a salt thereof
15:1 
6:1
2:1


Compound 22
phthalide
15:1 
6:1
2:1


Compound 22
picoxystrobin
1:1
1:2
1:5


Compound 22
piperalin
3:1
1:1
1:3


Compound 22
polyoxin
3:1
1:1
1:3


Compound 22
probenazole
3:1
1:1
1:3


Compound 22
prochloraz
7:1
2:1
1:2


Compound 22
procymidone
11:1 
4:1
2:1


Compound 22
propamocarb or propamocarb-hydrochloride
10:1 
4:1
2:1


Compound 22
propiconazole
1:1
1:2
1:5


Compound 22
propineb
11:1 
4:1
2:1


Compound 22
proquinazid
1:1
1:3
 1:12


Compound 22
prothiocarb
3:1
1:1
1:3


Compound 22
prothioconazole
1:1
1:2
1:5


Compound 22
pyraclostrobin
2:1
1:1
1:4


Compound 22
pyrametostrobin
2:1
1:1
1:4


Compound 22
pyraoxystrobin
2:1
1:1
1:4


Compound 22
pyrazophos
15:1 
4:1
1:1


Compound 22
pyribencarb
4:1
1:1
1:2


Compound 22
pyributicarb
15:1 
4:1
1:1


Compound 22
pyrifenox
3:1
1:1
1:3


Compound 22
pyrimethanil
3:1
1:1
1:2


Compound 22
pyriofenone
2:1
1:1
1:4


Compound 22
pyroquilon
3:1
1:1
1:3


Compound 22
pyrrolnitrin
15:1 
5:1
2:1


Compound 22
quinomethionate
15:1 
5:1
2:1


Compound 22
quinoxyfen
1:1
1:2
1:6


Compound 22
quintozene
15:1 
5:1
2:1


Compound 22
silthiofam
2:1
1:1
1:4


Compound 22
simeconazole
1:1
1:2
1:5


Compound 22
spiroxamine
5:1
2:1
1:2


Compound 22
streptomycin
3:1
1:1
1:3


Compound 22
sulfur
75:1 
25:1 
9:1


Compound 22
tebuconazole
1:1
1:2
1:5


Compound 22
tebufloquin
3:1
1:1
1:3


Compound 22
tecloftalam
15:1 
5:1
2:1


Compound 22
tecnazene
15:1 
5:1
2:1


Compound 22
terbinafine
15:1 
5:1
2:1


Compound 22
tetraconazole
1:1
1:2
1:5


Compound 22
thiabendazole
11:1 
4:1
2:1


Compound 22
thifluzamide
3:1
1:1
1:3


Compound 22
thiophanate
11:1 
4:1
2:1


Compound 22
thiophanate-methyl
11:1 
4:1
2:1


Compound 22
thiram
37:1 
14:1 
5:1


Compound 22
tiadinil
2:1
1:1
1:3


Compound 22
tolclofos-methyl
37:1 
14:1 
5:1


Compound 22
tolylfluanid
15:1 
5:1
2:1


Compound 22
triadimefon
1:1
1:2
1:5


Compound 22
triadimenol
1:1
1:2
1:5


Compound 22
triazoxide
15:1 
5:1
2:1


Compound 22
tricyclazole
3:1
1:1
1:3


Compound 22
tridemorph
7:1
2:1
1:1


Compound 22
trifloxystrobin
2:1
1:1
1:4


Compound 22
triflumizole
3:1
1:1
1:3


Compound 22
triforine
3:1
1:1
1:3


Compound 22
trimorphamide
7:1
2:1
1:2


Compound 22
triticonazole
1:1
1:2
1:5


Compound 22
uniconazole
1:1
1:2
1:5


Compound 22
validamycin
3:1
1:1
1:3


Compound 22
valifenalate (valiphenal)
2:1
1:1
1:4


Compound 22
vinclozolin
15:1 
6:1
2:1


Compound 22
zineb
37:1 
14:1 
5:1


Compound 22
ziram
37:1 
14:1 
5:1


Compound 22
zoxamide
2:1
1:1
1:4


Compound 22
5-chloro-6-(2,4,6-trifluorophenyl)-7-(4-methylpiperidin-1-
1:1
1:2
1:6



yl)[1,2,4]triazolo[1,5-a]pyrimidine


Compound 22
Penflufen (N-[2-(1,3-dimethylbutyl)phenyl]-5-fluoro-1,3-
2:1
1:1
1:3



dimethyl-1H-pyrazole-4-carboxamide)


Compound 22
N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-
2:1
1:1
1:4



methoxyphenyl]ethyl]-3-methyl-2-



[(methylsulfonyl)amino]butanamide


Compound 22
N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-
2:1
1:1
1:4



methoxyphenyl]ethyl]-3-methyl-2-



[(ethylsulfonyl)amino]butanamide


Compound 22
2-butoxy-6-iodo-3-propyl-4H-1-benzopyran-4-one
1:1
1:3
 1:12


Compound 22
3-[5-(4-chlorophenyl)-2,3-dimethyl-3-
3:1
1:1
1:3



isoxazolidinyl]pyridine


Compound 22
4-fluorophenyl N-[1-[[[1-(4-
2:1
1:1
1:4



cyanophenyl)ethyl]sulfonyl]methyl]propyl]carbamate


Compound 22
N-[[(cyclopropylmethoxy)amino][6-(difluoromethoxy)-2,3-
1:2
1:7
 1:24



difluorophenyl]methylene]benzeneacetamide


Compound 22
α-[methoxyimino]-N-methyl-2-[[[1-[3-
3:1
1:1
1:3



(trifluoromethyl)phenyl]ethoxy]imino]methyl]-



benzeneacetamide


Compound 22
N′-[4-[4-chloro-3-(trifluoromethyl)phenoxy]-2,5-
3:1
1:1
1:3



dimethylphenyl]-N-ethyl-N-methylmethanimidamide


Compound 22
N-(4-chloro-2-nitrophenyl)-N-ethyl-4-
3:1
1:1
1:3



methylbenzenesulfonamide


Compound 22
2-[[[3-(2,6-dichlorophenyl)-1-methyl-2-propen-1-
3:1
1:1
1:3



ylidene]amino]oxy]methyl]-α-(methoxyimino)-N-



methylbenzeneacetamide


Compound 22
pentyl N-[4-[[[[(1-methyl-1H-tetrazol-5-yl)phenyl-
3:1
1:1
1:3



methylene]amino]oxy]methyl]-2-thiazolyl]carbamate


Compound 22
pentyl N-[6-[[[[(1-methyl-1H-tetrazol-5-yl)phenyl-
3:1
1:1
1:3



methylene]amino]oxy]methyl]-2-pyridinyl]carbamate





(*)Ratios of Component (b) relative to Component (a) by weight.






Tables A2 through A54 are each constructed the same as Table A1 above except that entries below the “Component (a)” column heading are replaced with the respective Component (a) Column Entry shown below. Thus, for example, in Table A2 the entries below the “Component (a)” column heading all recite “Compound 18”, and the first line below the column headings in Table A2 specifically discloses a mixture of Compound 18 with acibenzolar-S-methyl. Tables A3 through A54 are constructed similarly.













Table Number
Component (a) Column Entries








A2
Compound 18



A3
Compound 23



A4
Compound 24



A5
Compound 36



A6
Compound 41



A7
Compound 45



A8
Compound 87



A9
Compound 91



A10
Compound 118



A11
Compound 139



A12
Compound 148



A13
Compound 172



A14
Compound 175



A15
Compound 193



A16
Compound 232



A17
Compound 265



A18
Compound 266



A19
Compound 284



A20
Compound 286



A21
Compound 287



A22
Compound 292



A23
Compound 297



A24
Compound 332



A25
Compound 336



A26
Compound 343



A27
Compound 346



A28
Compound 349



A29
Compound 351



A30
Compound 352



A31
Compound 357



A32
Compound 358



A33
Compound 360



A34
Compound 361



A35
Compound 364



A36
Compound 365



A37
Compound 367



A38
Compound 368



A39
Compound 369



A40
Compound 372



A41
Compound 373



A42
Compound 374



A43
Compound 375



A44
Compound 376



A45
Compound 377



A46
Compound 378



A47
Compound 379



A48
Compound 380



A49
Compound 381



A50
Compound 382



A51
Compound 383



A52
Compound 384



A53
Compound 385



A54
Compound 386









Table B1 lists specific combinations of a Component (b) compound with Component (a) illustrative of the mixtures, compositions and methods of the present invention. The first column of Table B1 lists the specific Component (b) compound (e.g., “acibenzolar-S-methyl” in the first line). The second, third and fourth columns of Table B1 lists ranges of weight ratios for rates at which the Component (b) compound is typically applied to a field-grown crop relative to Component (a) (e.g., “2:1 to 1:180” of acibenzolar-S-methyl relative to Component (a) by weight). Thus, for example, the first line of Table B1 specifically discloses the combination of acibenzolar-S-methyl with Component (a) is typically applied in a weight ratio between 2:1 to 1:180. The remaining lines of Table B1 are to be construed similarly. Table B1 thus supplements the specific ratios disclosed in Tables A1 through A54 with ranges of ratios for these combinations.










TABLE B1






Typical
More Typical
Most Typical


Component (b)
Weight Ratio
Weight Ratio
Weight Ratio







acibenzolar-S-methyl
2:1 to 1:180
1:1 to 1:60
1:1 to 1:18


aldimorph
30:1 to 1:3
10:1 to 1:1
7:1 to 1:1


ametoctradin
9:1 to 1:18
3:1 to 1:6
3:1 to 1:3


amisulbrom
6:1 to 1:18
2:1 to 1:6
1:1 to 1:6


anilazine
90:1 to 2:1
30:1 to 4:1
22:1 to 4:1


azaconazole
7:1 to 1:18
2:1 to 1:6
2:1 to 1:4


azoxystrobin
9:1 to 1:12
3:1 to 1:4
3:1 to 1:3


benalaxyl
4:1 to 1:18
1:1 to 1:6
1:1 to 1:6


benalaxyl-M
4:1 to 1:36
1:1 to 1:12
1:1 to 1:8


benodanil
18:1 to 1:6
6:1 to 1:2
4:1 to 1:2


benomyl
45:1 to 1:4
15:1 to 1:1
11:1 to 1:1


benthiavalicarb or benthiavalicarb-
2:1 to 1:36
1:1 to 1:12
1:1 to 1:12


isopropyl





bethoxazin
150:1 to 1:36
50:1 to 1:12
15:1 to 2:1


binapacryl
150:1 to 1:36
50:1 to 1:12
15:1 to 2:1


biphenyl
150:1 to 1:36
50:1 to 1:12
15:1 to 2:1


bitertanol
15:1 to 1:5
5:1 to 1:2
3:1 to 1:2


bixafen
12:1 to 1:9
4:1 to 1:3
2:1 to 1:3


blasticidin-S
3:1 to 1:90
1:1 to 1:30
1:4 to 1:30


boscalid
18:1 to 1:6
6:1 to 1:2
4:1 to 1:2


bromuconazole
15:1 to 1:9
5:1 to 1:3
3:1 to 1:3


bupirimate
3:1 to 1:90
1:1 to 1:30
1:3 to 1:30


captafol
90:1 to 1:4
30:1 to 1:2
15:1 to 2:1


captan
90:1 to 1:4
30:1 to 1:2
15:1 to 2:1


carbendazim
45:1 to 1:4
15:1 to 1:2
11:1 to 2:1


carboxin
18:1 to 1:6
6:1 to 1:2
4:1 to 1:2


carpropamid
15:1 to 1:9
5:1 to 1:3
3:1 to 1:3


chloroneb
300:1 to 2:1
100:1 to 4:1
100:1 to 14:1


chlorothalonil
90:1 to 1:4
30:1 to 1:2
15:1 to 2:1


chlozolinate
45:1 to 1:2
15:1 to 2:1
11:1 to 2:1


clotrimazole
15:1 to 1:9
5:1 to 1:3
3:1 to 1:3


copper salts such as Bordeaux mixture
450:1 to 1:1
150:1 to 4:1
45:1 to 5:1


(tribasic copper sulfate), copper





oxychloride, copper sulfate and copper





hydroxide





cyazofamid
4:1 to 1:18
1:1 to 1:6
1:1 to 1:6


cyflufenamid
1:1 to 1:90
1:2 to 1:30
1:2 to 1:24


cymoxanil
6:1 to 1:18
2:1 to 1:6
1:1 to 1:5


cyproconazole
4:1 to 1:18
1:1 to 1:6
1:1 to 1:6


cyprodinil
22:1 to 1:9
7:1 to 1:3
4:1 to 1:2


dichlofluanid
150:1 to 1:36
50:1 to 1:12
15:1 to 2:1


diclocymet
150:1 to 1:36
50:1 to 1:12
15:1 to 2:1


diclomezine
15:1 to 1:9
5:1 to 1:3
3:1 to 1:3


dicloran
150:1 to 1:36
50:1 to 1:12
15:1 to 2:1


diethofencarb
22:1 to 1:9
7:1 to 1:3
7:1 to 1:2


difenoconazole
4:1 to 1:36
1:1 to 1:12
1:1 to 1:12


diflumetorim
150:1 to 1:36
50:1 to 1:12
15:1 to 2:1


dimethirimol
3:1 to 1:90
1:1 to 1:30
1:3 to 1:30


dimethomorph
9:1 to 1:6
3:1 to 1:2
3:1 to 1:2


dimoxystrobin
9:1 to 1:18
3:1 to 1:6
2:1 to 1:4


diniconazole
3:1 to 1:36
1:1 to 1:12
1:1 to 1:8


diniconazole M
3:1 to 1:90
1:1 to 1:30
1:1 to 1:12


dinocap
7:1 to 1:9
2:1 to 1:3
2:1 to 1:3


dithianon
15:1 to 1:4
5:1 to 1:2
5:1 to 1:2


dodemorph
30:1 to 1:3
10:1 to 1:1
7:1 to 1:1


dodine
30:1 to 1:2
10:1 to 2:1
10:1 to 2:1


edifenphos
30:1 to 1:9
10:1 to 1:3
3:1 to 1:3


enestroburin
9:1 to 1:18
3:1 to 1:6
2:1 to 1:4


epoxiconazole
3:1 to 1:36
1:1 to 1:12
1:1 to 1:7


ethaboxam
7:1 to 1:9
2:1 to 1:3
2:1 to 1:3


ethirimol
30:1 to 1:3
10:1 to 1:1
7:1 to 1:1


etridiazole
30:1 to 1:9
10:1 to 1:3
7:1 to 1:2


famoxadone
9:1 to 1:18
3:1 to 1:6
2:1 to 1:4


fenamidone
6:1 to 1:18
2:1 to 1:6
2:1 to 1:4


fenarimol
3:1 to 1:90
1:1 to 1:30
1:2 to 1:24


fenbuconazole
3:1 to 1:30
1:1 to 1:10
1:1 to 1:10


fenfuram
18:1 to 1:6
6:1 to 1:2
4:1 to 1:2


fenhexamid
30:1 to 1:2
10:1 to 2:1
10:1 to 2:1


fenoxanil
150:1 to 1:36
50:1 to 1:12
15:1 to 1:1


fenpiclonil
75:1 to 1:9
25:1 to 1:3
15:1 to 2:1


fenpropidin
30:1 to 1:3
10:1 to 1:1
7:1 to 1:1


fenpropimorph
30:1 to 1:3
10:1 to 1:1
7:1 to 1:1


fenpyrazamine
100:1 to 1:100
10:1 to 1:10
3:1 to 1:3


fentin salt such as the acetate, chloride or
15:1 to 1:9
5:1 to 1:3
3:1 to 1:3


hydroxide





ferbam
300:1 to 1:2
100:1 to 2:1
30:1 to 4:1


ferimzone
30:1 to 1:5
10:1 to 1:2
7:1 to 1:2


fluazinam
22:1 to 1:5
7:1 to 1:2
3:1 to 1:2


fludioxonil
7:1 to 1:12
2:1 to 1:4
2:1 to 1:4


flumetover
9:1 to 1:6
3:1 to 1:2
3:1 to 1:2


flumorph
9:1 to 1:18
3:1 to 1:6
3:1 to 1:3


fluopicolide
3:1 to 1:18
1:1 to 1:6
1:1 to 1:6


fluopyram
15:1 to 1:90
5:1 to 1:30
3:1 to 1:3


fluoromide
150:1 to 2:1
50:1 to 4:1
37:1 to 5:1


fluoxastrobin
4:1 to 1:18
1:1 to 1:6
1:1 to 1:6


fluquinconazole
4:1 to 1:12
1:1 to 1:4
1:1 to 1:4


flusilazole
15:1 to 1:9
5:1 to 1:3
3:1 to 1:3


flusulfamide
90:1 to 1:2
30:1 to 2:1
15:1 to 2:1


flutianil
7:1 to 1:36
2:1 to 1:12
1:1 to 1:6


flutolanil
18:1 to 1:6
6:1 to 1:2
4:1 to 1:2


flutriafol
4:1 to 1:12
1:1 to 1:4
1:1 to 1:4


fluxapyroxad
12:1 to 1:9
4:1 to 1:3
2:1 to 1:3


folpet
90:1 to 1:4
30:1 to 1:2
15:1 to 2:1


fosetyl-aluminum
225:1 to 2:1
75:1 to 5:1
30:1 to 5:1


fuberidazole
45:1 to 1:4
15:1 to 1:2
11:1 to 2:1


furalaxyl
15:1 to 1:45
5:1 to 1:15
1:1 to 1:6


furametpyr
150:1 to 1:36
50:1 to 1:12
15:1 to 2:1


guazatine or iminoctadine
150:1 to 1:36
50:1 to 1:12
15:1 to 2:1


hexaconazole
15:1 to 1:36
5:1 to 1:12
1:1 to 1:5


hymexazol
225:1 to 2:1
75:1 to 4:1
75:1 to 9:1


imazalil
7:1 to 1:18
2:1 to 1:6
1:1 to 1:5


imibenconazole
15:1 to 1:36
5:1 to 1:12
1:1 to 1:5


iodocarb
150:1 to 1:36
50:1 to 1:12
15:1 to 2:1


ipconazole
15:1 to 1:36
5:1 to 1:12
1:1 to 1:5


iprobenfos
150:1 to 1:36
50:1 to 1:12
15:1 to 2:1


iprodione
120:1 to 1:2
40:1 to 2:1
15:1 to 2:1


iprovalicarb
9:1 to 1:9
3:1 to 1:3
2:1 to 1:3


isoprothiolane
150:1 to 2:1
50:1 to 4:1
45:1 to 5:1


isopyrazam
12:1 to 1:9
4:1 to 1:3
2:1 to 1:3


isotianil
12:1 to 1:9
4:1 to 1:3
2:1 to 1:3


kasugamycin
7:1 to 1:90
2:1 to 1:30
1:2 to 1:24


kresoxim-methyl
7:1 to 1:18
2:1 to 1:6
2:1 to 1:4


mancozeb
180:1 to 1:3
60:1 to 2:1
22:1 to 3:1


mandipropamid
6:1 to 1:18
2:1 to 1:6
2:1 to 1:4


maneb
180:1 to 1:3
60:1 to 2:1
22:1 to 3:1


mepanipyrim
18:1 to 1:3
6:1 to 1:1
6:1 to 1:1


mepronil
7:1 to 1:36
2:1 to 1:12
1:1 to 1:6


meptyldinocap
7:1 to 1:9
2:1 to 1:3
2:1 to 1:3


metalaxyl
15:1 to 1:45
5:1 to 1:15
1:1 to 1:6


metalaxyl-M
7:1 to 1:90
2:1 to 1:30
1:1 to 1:12


metconazole
3:1 to 1:18
1:1 to 1:6
1:1 to 1:6


methasulfocarb
150:1 to 1:36
50:1 to 1:12
15:1 to 1:1


metiram
150:1 to 1:36
50:1 to 1:12
15:1 to 1:1


metominostrobin
9:1 to 1:12
3:1 to 1:4
3:1 to 1:3


metrafenone
6:1 to 1:12
2:1 to 1:4
2:1 to 1:4


myclobutanil
5:1 to 1:26
1:1 to 1:9
1:1 to 1:8


naftifine
150:1 to 1:36
50:1 to 1:12
15:1 to 2:1


neo-asozin (ferric methanearsonate)
150:1 to 1:36
50:1 to 1:12
15:1 to 2:1


nuarimol
15:1 to 1:9
5:1 to 1:3
3:1 to 1:3


octhilinone
150:1 to 1:36
50:1 to 1:12
15:1 to 1:1


ofurace
15:1 to 1:45
5:1 to 1:15
1:1 to 1:6


orysastrobin
9:1 to 1:12
3:1 to 1:4
3:1 to 1:3


oxadixyl
15:1 to 1:45
5:1 to 1:15
1:1 to 1:6


oxolinic acid
30:1 to 1:9
10:1 to 1:3
7:1 to 1:2


oxpoconazole
15:1 to 1:36
5:1 to 1:12
1:1 to 1:5


oxycarboxin
18:1 to 1:6
6:1 to 1:2
4:1 to 1:2


oxytetracycline
15:1 to 1:9
5:1 to 1:3
3:1 to 1:3


pefurazoate
150:1 to 1:36
50:1 to 1:12
15:1 to 2:1


penconazole
1:1 to 1:45
1:2 to 1:15
1:2 to 1:15


pencycuron
150:1 to 1:2
50:1 to 2:1
11:1 to 2:1


penthiopyrad
12:1 to 1:9
4:1 to 1:3
2:1 to 1:3


phosphorous acid and salts thereof
150:1 to 1:36
50:1 to 1:12
15:1 to 2:1


phthalide
150:1 to 1:36
50:1 to 1:12
15:1 to 2:1


picoxystrobin
7:1 to 1:18
2:1 to 1:6
1:1 to 1:5


piperalin
15:1 to 1:9
5:1 to 1:3
3:1 to 1:3


polyoxin
15:1 to 1:9
5:1 to 1:3
3:1 to 1:3


probenazole
15:1 to 1:9
5:1 to 1:3
3:1 to 1:3


prochloraz
22:1 to 1:4
7:1 to 1:1
7:1 to 1:2


procymidone
45:1 to 1:3
15:1 to 1:1
11:1 to 2:1


propamocarb or propamocarb-
30:1 to 1:2
10:1 to 2:1
10:1 to 2:1


hydrochloride





propiconazole
4:1 to 1:18
1:1 to 1:6
1:1 to 1:5


propineb
45:1 to 1:2
15:1 to 2:1
11:1 to 2:1


proquinazid
3:1 to 1:36
1:1 to 1:12
1:1 to 1:12


prothiocarb
9:1 to 1:18
3:1 to 1:6
3:1 to 1:3


prothioconazole
6:1 to 1:18
2:1 to 1:6
1:1 to 1:5


pyraclostrobin
9:1 to 1:18
3:1 to 1:6
2:1 to 1:4


pyrametostrobin
9:1 to 1:18
3:1 to 1:6
2:1 to 1:4


pyraoxystrobin
9:1 to 1:18
3:1 to 1:6
2:1 to 1:4


pyrazophos
150:1 to 1:36
50:1 to 1:12
15:1 to 1:1


pyribencarb
15:1 to 1:6
5:1 to 1:2
4:1 to 1:2


pyrifenox
15:1 to 1:9
5:1 to 1:3
3:1 to 1:3


pyrimethanil
30:1 to 1:6
10:1 to 1:2
3:1 to 1:2


pyriofenone
6:1 to 1:12
2:1 to 1:4
2:1 to 1:4


pyroquilon
15:1 to 1:9
5:1 to 1:3
3:1 to 1:3


pyrrolnitrin
150:1 to 1:36
50:1 to 1:12
15:1 to 2:1


quinmethionate
150:1 to 1:36
50:1 to 1:12
15:1 to 2:1


quinoxyfen
4:1 to 1:18
1:1 to 1:6
1:1 to 1:6


quintozene
150:1 to 1:36
50:1 to 1:12
15:1 to 2:1


silthiofam
7:1 to 1:18
2:1 to 1:6
2:1 to 1:4


simeconazole
15:1 to 1:36
5:1 to 1:12
1:1 to 1:5


spiroxamine
22:1 to 1:4
7:1 to 1:2
5:1 to 1:2


streptomycin
15:1 to 1:9
5:1 to 1:3
3:1 to 1:3


sulfur
300:1 to 3:1
100:1 to 9:1
75:1 to 9:1


tebuconazole
7:1 to 1:18
2:1 to 1:6
1:1 to 1:5


tebufloquin
100:1 to 1:100
10:1 to 1:10
3:1 to 1:3


tecloftalam
150:1 to 1:36
50:1 to 1:12
15:1 to 2:1


tecnazene
150:1 to 1:36
50:1 to 1:12
15:1 to 2:1


terbinafine
150:1 to 1:36
50:1 to 1:12
15:1 to 2:1


tetraconazole
15:1 to 1:36
5:1 to 1:12
1:1 to 1:5


thiabendazole
45:1 to 1:4
15:1 to 1:2
11:1 to 2:1


thifluzamide
15:1 to 1:9
5:1 to 1:3
3:1 to 1:3


thiophanate
45:1 to 1:3
15:1 to 2:1
11:1 to 2:1


thiophanate-methyl
45:1 to 1:3
15:1 to 2:1
11:1 to 2:1


thiram
150:1 to 1:2
50:1 to 2:1
37:1 to 5:1


tiadinil
12:1 to 1:9
4:1 to 1:3
2:1 to 1:3


tolclofos-methyl
150:1 to 1:2
50:1 to 2:1
37:1 to 5:1


tolylfluanid
150:1 to 1:36
50:1 to 1:12
15:1 to 2:1


triadimefon
15:1 to 1:36
5:1 to 1:12
1:1 to 1:5


triadimenol
15:1 to 1:36
5:1 to 1:12
1:1 to 1:5


triazoxide
150:1 to 1:36
50:1 to 1:12
15:1 to 2:1


tricyclazole
15:1 to 1:9
5:1 to 1:3
3:1 to 1:3


tridemorph
30:1 to 1:3
10:1 to 1:1
7:1 to 1:1


trifloxystrobin
6:1 to 1:18
2:1 to 1:6
2:1 to 1:4


triflumizole
15:1 to 1:9
5:1 to 1:3
3:1 to 1:3


triforine
15:1 to 1:9
5:1 to 1:3
3:1 to 1:3


trimorphamide
45:1 to 1:9
15:1 to 1:3
7:1 to 1:2


triticonazole
15:1 to 1:36
5:1 to 1:12
1:1 to 1:5


uniconazole
15:1 to 1:36
5:1 to 1:12
1:1 to 1:5


validamycin
150:1 to 1:36
50:1 to 1:12
3:1 to 1:3


valifenalate (valiphenal)
6:1 to 1:18
2:1 to 1:6
2:1 to 1:4


vinclozolin
120:1 to 1:2
40:1 to 2:1
15:1 to 2:1


zineb
150:1 to 1:2
50:1 to 2:1
37:1 to 5:1


ziram
150:1 to 1:2
50:1 to 2:1
37:1 to 5:1


zoxamide
6:1 to 1:18
2:1 to 1:6
2:1 to 1:4


5-chloro-6-(2,4,6-trifluorophenyl)-7-(4-
15:1 to 1:36
5:1 to 1:12
1:1 to 1:6


methylpiperidin-1-yl)[1,2,4]triazolo[1,5-





a]pyrimidine





penflufen(N-[2-(1,3-
12:1 to 1:9
4:1 to 1:3
2:1 to 1:3


dimethylbutyl)phenyl]-5-fluoro-1,3-





dimethyl-1H-pyrazole-4-carboxamide)





N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-
6:1 to 1:18
2:1 to 1:6
2:1 to 1:4


yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-





2-[(methylsulfonyl)amino]butanamide





N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-
6:1 to 1:18
2:1 to 1:6
2:1 to 1:4


yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-





2-[(ethylsulfonyl)amino]butanamide





2-butoxy-6-iodo-3-propyl-4H-1-
3:1 to 1:36
1:1 to 1:12
1:1 to 1:12


benzopyran-4-one





3-[5-(4-chlorophenyl)-2,3-dimethyl-3-
15:1 to 1:9
5:1 to 1:3
3:1 to 1:3


isoxazolidinyl]pyridine





4-fluorophenyl N-[1-[[[1-(4-
6:1 to 1:18
2:1 to 1:6
2:1 to 1:4


cyanophenyl)ethyl]sulfonyl]methyl]propyl]





carbamate





N-[[(cyclopropylmethoxy)amino][6-
1:1 to 1:90
1:2 to 1:30
1:2 to 1:24


(difluoromethoxy)-2,3-





difluorophenyl]methylene]benzene-





acetamide





α-[methoxyimino]-N-methyl-2-[[[1-[3-
9:1 to 1:18
3:1 to 1:6
3:1 to 1:3


(trifluoromethyl)phenyl]ethoxy]imino]-





methyl]benzeneacetamide





N′-[4-[4-chloro-3-
15:1 to 1:18
5:1 to 1:6
3:1 to 1:3


(trifluoromethyl)phenoxy]-2,5-





dimethylphenyl]-N-ethyl-N-





methylmethanimidamide





N-(4-chloro-2-nitrophenyl)-N-ethyl-4-
15:1 to 1:18
5:1 to 1:6
3:1 to 1:3


methylbenzenesulfonamide





2-[[[3-(2,6-dichlorophenyl)-1-methyl-2-
9:1 to 1:18
3:1 to 1:6
3:1 to 1:3


propen-1-ylidene]amino]oxy]methyl]-α-





(methoxyimino)-N-





methylbenzeneacetamide





pentyl N-[4-[[[[(1-methyl-1H-tetrazol-5-
9:1 to 1:18
3:1 to 1:6
3:1 to 1:3


yl)phenylmethylene]amino]oxy]methyl]-2-





thiazolyl]carbamate





pentyl N-[6-[[[[(1-methyl-1H-tetrazol-5-
9:1 to 1:18
3:1 to 1:6
3:1 to 1:3


yl)phenylmethylene]amino]oxy]methyl]-2-





pyridinyl]carbamate









As already noted, the present invention includes embodiments wherein in the composition comprising components (a) and (b), component (b) comprises at least one fungicide from each of two groups selected from (b1) through (b46). Tables C1 through C54 list specific mixtures (compound numbers refer to compounds in Index Table A) to illustrate embodiments wherein component (b) includes at least one fungicide from each of two groups selected from (b1) through (b46). In Table C1, each line below the column headings “Component (a)” and “Component (b)” specifically discloses a mixture of Component (a), which is Compound 22, with at least two Component (b) fungicides. The entries under the heading “Illustrative Ratios” disclose three specific weight ratios of Component (a) to each Component (b) fungicide in sequence for the disclosed mixture. For example, the first line discloses a mixture of Compound 22 with cyproconazole and azoxystrobin and lists weight ratios of Compound 22 to cyproconazole to azoxystrobin of 1:1:1, 2:1:1 or 3:1:1.









TABLE C1





Component (a)
Component (b)
Illustrative Ratios(*)





















Compound 22
cyproconazole
azoxystrobin

1:1:1
2:1:1
3:1:1


Compound 22
cyproconazole
kresoxim-methyl

1:1:1
2:1:1
3:1:1


Compound 22
cyproconazole
picoxystrobin

1:1:1
2:1:1
3:1:1


Compound 22
cyproconazole
pyraclostrobin

1:1:1
2:1:1
3:1:1


Compound 22
cyproconazole
trifloxystrobin

1:1:1
2:1:1
3:1:1


Compound 22
cyproconazole
bixafen

1:1:2
2:1:2
3:1:2


Compound 22
cyproconazole
boscalid

1:1:2
2:1:2
3:1:2


Compound 22
cyproconazole
cyflufenamid

1:2:1
2:2:1
3:2:1


Compound 22
cyproconazole
fluopyram

1:1:2
2:1:2
3:1:2


Compound 22
cyproconazole
isopyrazam

1:1:2
2:1:2
3:1:2


Compound 22
cyproconazole
metrafenone

1:1:2
2:1:2
3:1:2


Compound 22
cyproconazole
penthiopyrad

1:1:2
2:1:2
3:1:2


Compound 22
cyproconazole
proquinazid

1:1:1
2:1:1
3:1:1


Compound 22
cyproconazole
quinoxyfen

1:1:1
2:1:1
3:1:1


Compound 22
cyproconazole
sedaxane

1:1:2
2:1:2
3:1:2


Compound 22
cyproconazole
picoxystrobin
proquinazid
1:1:1:1
2:1:1:1
3:1:1:1


Compound 22
cyproconazole
trifloxystrobin
proquinazid
1:1:1:1
2:1:1:1
3:1:1:1


Compound 22
difenconazole
azoxystrobin

1:1:1
2:1:1
3:1:1


Compound 22
difenconazole
kresoxim-methyl

1:1:1
2:1:1
3:1:1


Compound 22
difenconazole
picoxystrobin

1:1:1
2:1:1
3:1:1


Compound 22
difenconazole
pyraclostrobin

1:1:1
2:1:1
3:1:1


Compound 22
difenconazole
trifloxystrobin

1:1:1
2:1:1
3:1:1


Compound 22
difenconazole
bixafen

1:1:2
2:1:2
3:1:2


Compound 22
difenconazole
boscalid

1:1:2
2:1:2
3:1:2


Compound 22
difenconazole
cyflufenamid

1:2:1
2:2:1
3:2:1


Compound 22
difenconazole
fluopyram

1:1:2
2:1:2
3:1:2


Compound 22
difenconazole
isopyrazam

1:1:2
2:1:2
3:1:2


Compound 22
difenconazole
metrafenone

1:1:2
2:1:2
3:1:2


Compound 22
difenconazole
penthiopyrad

1:1:2
2:1:2
3:1:2


Compound 22
difenconazole
proquinazid

1:1:1
2:1:1
3:1:1


Compound 22
difenconazole
quinoxyfen

1:1:1
2:1:1
3:1:1


Compound 22
difenconazole
sedaxane

1:1:2
2:1:2
3:1:2


Compound 22
difenconazole
picoxystrobin
proquinazid
1:1:1:1
2:1:1:1
3:1:1:1


Compound 22
difenconazole
trifloxystrobin
proquinazid
1:1:1:1
2:1:1:1
3:1:1:1


Compound 22
epoxiconazole
azoxystrobin

1:1:1
2:1:1
3:1:1


Compound 22
epoxiconazole
kresoxim-methyl

1:1:1
2:1:1
3:1:1


Compound 22
epoxiconazole
picoxystrobin

1:1:1
2:1:1
3:1:1


Compound 22
epoxiconazole
pyraclostrobin

1:1:1
2:1:1
3:1:1


Compound 22
epoxiconazole
trifloxystrobin

1:1:1
2:1:1
3:1:1


Compound 22
epoxiconazole
bixafen

1:1:2
2:1:2
3:1:2


Compound 22
epoxiconazole
boscalid

1:1:2
2:1:2
3:1:2


Compound 22
epoxiconazole
cyflufenamid

1:2:1
2:2:1
3:2:1


Compound 22
epoxiconazole
fluopyram

1:1:2
2:1:2
3:1:2


Compound 22
epoxiconazole
isopyrazam

1:1:2
2:1:2
3:1:2


Compound 22
epoxiconazole
metrafenone

1:1:2
2:1:2
3:1:2


Compound 22
epoxiconazole
penthiopyrad

1:1:2
2:1:2
3:1:2


Compound 22
epoxiconazole
proquinazid

1:1:1
2:1:1
3:1:1


Compound 22
epoxiconazole
quinoxyfen

1:1:1
2:1:1
3:1:1


Compound 22
epoxiconazole
sedaxane

1:1:2
2:1:2
3:1:2


Compound 22
epoxiconazole
picoxystrobin
proquinazid
1:1:1:1
2:1:1:1
3:1:1:1


Compound 22
epoxiconazole
trifloxystrobin
proquinazid
1:1:1:1
2:1:1:1
3:1:1:1


Compound 22
metconazole
azoxystrobin

1:1:1
2:1:1
3:1:1


Compound 22
metconazole
kresoxim-methyl

1:1:1
2:1:1
3:1:1


Compound 22
metconazole
picoxystrobin

1:1:1
2:1:1
3:1:1


Compound 22
metconazole
pyraclostrobin

1:1:1
2:1:1
3:1:1


Compound 22
metconazole
trifloxystrobin

1:1:1
2:1:1
3:1:1


Compound 22
metconazole
bixafen

1:1:2
2:1:2
3:1:2


Compound 22
metconazole
boscalid

1:1:2
2:1:2
3:1:2


Compound 22
metconazole
cyflufenamid

1:2:1
2:2:1
3:2:1


Compound 22
metconazole
fluopyram

1:1:2
2:1:2
3:1:2


Compound 22
metconazole
isopyrazam

1:1:2
2:1:2
3:1:2


Compound 22
metconazole
metrafenone

1:1:2
2:1:2
3:1:2


Compound 22
metconazole
penthiopyrad

1:1:2
2:1:2
3:1:2


Compound 22
metconazole
proquinazid

1:1:1
2:1:1
3:1:1


Compound 22
metconazole
quinoxyfen

1:1:1
2:1:1
3:1:1


Compound 22
metconazole
sedaxane

1:1:2
2:1:2
3:1:2


Compound 22
metconazole
picoxystrobin
proquinazid
1:1:1:1
2:1:1:1
3:1:1:1


Compound 22
metconazole
trifloxystrobin
proquinazid
1:1:1:1
2:1:1:1
3:1:1:1


Compound 22
myclobutanil
azoxystrobin

1:1:1
2:1:1
3:1:1


Compound 22
myclobutanil
kresoxim-methyl

1:1:1
2:1:1
3:1:1


Compound 22
myclobutanil
picoxystrobin

1:1:1
2:1:1
3:1:1


Compound 22
myclobutanil
pyraclostrobin

1:1:1
2:1:1
3:1:1


Compound 22
myclobutanil
trifloxystrobin

1:1:1
2:1:1
3:1:1


Compound 22
myclobutanil
bixafen

1:1:2
2:1:2
3:1:2


Compound 22
myclobutanil
boscalid

1:1:2
2:1:2
3:1:2


Compound 22
myclobutanil
cyflufenamid

1:2:1
2:2:1
3:2:1


Compound 22
myclobutanil
fluopyram

1:1:2
2:1:2
3:1:2


Compound 22
myclobutanil
isopyrazam

1:1:2
2:1:2
3:1:2


Compound 22
myclobutanil
metrafenone

1:1:2
2:1:2
3:1:2


Compound 22
myclobutanil
penthiopyrad

1:1:2
2:1:2
3:1:2


Compound 22
myclobutanil
proquinazid

1:1:1
2:1:1
3:1:1


Compound 22
myclobutanil
quinoxyfen

1:1:1
2:1:1
3:1:1


Compound 22
myclobutanil
sedaxane

1:1:2
2:1:2
3:1:2


Compound 22
myclobutanil
picoxystrobin
proquinazid
1:1:1:1
2:1:1:1
3:1:1:1


Compound 22
myclobutanil
trifloxystrobin
proquinazid
1:1:1:1
2:1:1:1
3:1:1:1


Compound 22
prothioconazole
azoxystrobin

1:1:1
2:1:1
3:1:1


Compound 22
prothioconazole
kresoxim-methyl

1:1:1
2:1:1
3:1:1


Compound 22
prothioconazole
picoxystrobin

1:1:1
2:1:1
3:1:1


Compound 22
prothioconazole
pyraclostrobin

1:1:1
2:1:1
3:1:1


Compound 22
prothioconazole
trifloxystrobin

1:1:1
2:1:1
3:1:1


Compound 22
prothioconazole
bixafen

1:1:2
2:1:2
3:1:2


Compound 22
prothioconazole
boscalid

1:1:2
2:1:2
3:1:2


Compound 22
prothioconazole
cyflufenamid

1:2:1
2:2:1
3:2:1


Compound 22
prothioconazole
fluopyram

1:1:2
2:1:2
3:1:2


Compound 22
prothioconazole
isopyrazam

1:1:2
2:1:2
3:1:2


Compound 22
prothioconazole
metrafenone

1:1:2
2:1:2
3:1:2


Compound 22
prothioconazole
penthiopyrad

1:1:2
2:1:2
3:1:2


Compound 22
prothioconazole
proquinazid

1:1:1
2:1:1
3:1:1


Compound 22
prothioconazole
quinoxyfen

1:1:1
2:1:1
3:1:1


Compound 22
prothioconazole
sedaxane

1:1:2
2:1:2
3:1:2


Compound 22
prothioconazole
picoxystrobin
proquinazid
1:1:1:1
2:1:1:1
3:1:1:1


Compound 22
prothioconazole
trifloxystrobin
proquinazid
1:1:1:1
2:1:1:1
3:1:1:1


Compound 22
tebuconazole
azoxystrobin

1:1:1
2:1:1
3:1:1


Compound 22
tebuconazole
kresoxim-methyl

1:1:1
2:1:1
3:1:1


Compound 22
tebuconazole
picoxystrobin

1:1:1
2:1:1
3:1:1


Compound 22
tebuconazole
pyraclostrobin

1:1:1
2:1:1
3:1:1


Compound 22
tebuconazole
trifloxystrobin

1:1:1
2:1:1
3:1:1


Compound 22
tebuconazole
bixafen

1:1:2
2:1:2
3:1:2


Compound 22
tebuconazole
boscalid

1:1:2
2:1:2
3:1:2


Compound 22
tebuconazole
cyflufenamid

1:2:1
2:2:1
3:2:1


Compound 22
tebuconazole
fluopyram

1:1:2
2:1:2
3:1:2


Compound 22
tebuconazole
isopyrazam

1:1:2
2:1:2
3:1:2


Compound 22
tebuconazole
metrafenone

1:1:2
2:1:2
3:1:2


Compound 22
tebuconazole
penthiopyrad

1:1:2
2:1:2
3:1:2


Compound 22
tebuconazole
proquinazid

1:1:1
2:1:1
3:1:1


Compound 22
tebuconazole
quinoxyfen

1:1:1
2:1:1
3:1:1


Compound 22
tebuconazole
sedaxane

1:1:2
2:1:2
3:1:2


Compound 22
tebuconazole
picoxystrobin
proquinazid
1:1:1:1
2:1:1:1
3:1:1:1


Compound 22
tebuconazole
trifloxystrobin
proquinazid
1:1:1:1
2:1:1:1
3:1:1:1





(*)Ratios of Component (a) relative to Component (b) in sequence, by weight.






Tables C2 through C54 are each constructed the same as Table C1 above except that entries below the “Component (a)” column heading are replaced with the respective Component (a) Column Entry shown below. Thus, for example, in Table C2 the entries below the “Component (a)” column heading all recite “Compound 18”, and the first line in below the column headings in Table C2 specifically discloses a mixture of Compound 18 with cyproconazole and azoxystrobin, and the illustrative weight ratios of 1:1:1, 2:1:1 and 3:1:1 of Compound 18:cyproconazole:azoxystrobin. Tables C3 through C54 are constructed similarly.













Table Number
Component (a) Column Entries








C2
Compound 18



C3
Compound 23



C4
Compound 24



C5
Compound 36



C6
Compound 41



C7
Compound 45



C8
Compound 87



C9
Compound 91



C10
Compound 118



C11
Compound 139



C12
Compound 148



C13
Compound 172



C14
Compound 175



C15
Compound 193



C16
Compound 232



C17
Compound 265



C18
Compound 266



C19
Compound 284



C20
Compound 286



C21
Compound 287



C22
Compound 292



C23
Compound 297



C24
Compound 332



C25
Compound 336



C26
Compound 343



C27
Compound 346



C28
Compound 349



C29
Compound 351



C30
Compound 352



C31
Compound 357



C32
Compound 358



C33
Compound 360



C34
Compound 361



C35
Compound 364



C36
Compound 365



C37
Compound 367



C38
Compound 368



C39
Compound 369



C40
Compound 372



C41
Compound 373



C42
Compound 374



C43
Compound 375



C44
Compound 376



C45
Compound 377



C46
Compound 378



C47
Compound 379



C48
Compound 380



C49
Compound 381



C50
Compound 382



C51
Compound 383



C52
Compound 384



C53
Compound 385



C54
Compound 386









As mentioned in the Summary of the Invention, one aspect of the present invention is a composition comprising (i.e. a mixture or combination of) a compound of Formula 1, an N-oxide, or a salt thereof, and at least one invertebrate pest control compound or agent (e.g., insecticide, acaricide). Of note is a composition comprising component (a) and at least one (i.e. one or more) invertebrate pest control compound or agent, which then can be subsequently combined with component (b) to provide a composition comprising components (a) and (b) and the one or more invertebrate pest control compounds or agents. Alternatively without first mixing with component (b), a biologically effective amount of the composition comprising component (a) with at least one invertebrate pest control agent can be applied to a plant or plant seed (directly or through the environment of the plant or plant seed) to protect the plant or plant seed from diseases caused by fungal pathogens and injury caused by invertebrate pests.
For embodiments where one or more of invertebrate pest control compounds are used, the weight ratio of these compounds (in total) to the component (a) compounds is typically between about 1:3000 and about 3000:1. Of note are weight ratios between about 1:300 and about 300:1 (for example ratios between about 1:30 and about 30:1). One skilled in the art can easily determine through simple experimentation the biologically effective amounts of active ingredients necessary for the desired spectrum of biological activity.
Of note is a composition of the present invention which comprises in addition to a component (a) compound, alone or in combination with fungicidal component (b), at least one invertebrate pest control compound or agent selected from the group consisting of abamectin, acephate, acetamiprid, acetoprole, aldicarb, amidoflumet, amitraz, avermectin, azadirachtin, azinphos-methyl, bifenthrin, bifenazate, bistrifluron, buprofezin, carbofuran, cartap, chinomethionat, chlorfenapyr, chlorfluazuron, chlorantraniliprole, chlorpyrifos, chlorpyrifos-methyl, chlorobenzilate, chromafenozide, clothianidin, cyantraniliprole, cyflumetofen, cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda-cyhalothrin, cyhexatin, cypermethrin, cyromazine, deltamethrin, diafenthiuron, diazinon, dicofol, dieldrin, dienochlor, diflubenzuron, dimefluthrin, dimethoate, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, etoxazole, fenamiphos, fenazaquin, fenbutatin oxide, fenothiocarb, fenoxycarb, fenpropathrin, fenpyroximate, fenvalerate, fipronil, flonicamid, flubendiamide, flucythrinate, tau-fluvalinate, flufenerim, flufenoxuron, fonophos, halofenozide, hexaflumuron, hexythiazox, hydramethylnon, imicyafos, imidacloprid, indoxacarb, isofenphos, lufenuron, malathion, meperfluthrin, metaflumizone, metaldehyde, methamidophos, methidathion, methomyl, methoprene, methoxychlor, methoxyfenozide, metofluthrin, monocrotophos, nitenpyram, nithiazine, novaluron, noviflumuron, oxamyl, parathion, parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, profluthrin, propargite, protrifenbute, pymetrozine, pyrafluprole, pyrethrin, pyridaben, pyridalyl, pyrifluquinazon, pyriprole, pyriproxyfen, rotenone, ryanodine, spinetoram, spinosad, spiridiclofen, spiromesifen, spirotetramat, sulfoxaflor, sulprofos, tebufenozide, tebufenpyrad, teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, tetramethylfluthin, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tolfenpyrad, tralomethrin, triazamate, trichlorfon, triflumuron, Bacillus thuringiensis subsp. aizawai, Bacillus thuringiensis subsp. kurstaki, nucleopolyhedro viruses, encapsulated delta-endotoxins of Bacillus thuringiensis, baculoviruses, entomopathogenic bacteria, entomopathogenic viruses and entomopathogenic fungi.
In certain instances, combinations of a compound of Formula 1 or an N-oxide or salt thereof (i.e. component (a)), alone or in mixture with fungicidal component (b), with other biologically active (particularly invertebrate pest control) compounds or agents (i.e. active ingredients) can result in a greater-than-additive (i.e. synergistic) effect. Reducing the quantity of active ingredients released in the environment while ensuring effective pest control is always desirable. When synergism of invertebrate pest control active ingredients occurs at application rates giving agronomically satisfactory levels of invertebrate pest control, such combinations can be advantageous for reducing crop production cost and decreasing environmental load.
Table D1 lists specific combinations of invertebrate pest control agents with Compound 22 (identified in Index Table A) as a component (a) compound illustrative of mixtures and compositions comprising these active ingredients and methods using them according to the present invention. The second column of Table D1 lists the specific invertebrate pest control agents (e.g., “Abamectin” in the first line). The third column of Table D1 lists the mode of action (if known) or chemical class of the invertebrate pest control agents. The fourth column of Table D1 lists embodiment(s) of ranges of weight ratios for rates at which the invertebrate pest control agent is typically applied relative to Compound 22 alone or in combination with fungicidal component (b) (e.g., “50:1 to 1:50” of abamectin relative to a Compound 22 by weight). Thus, for example, the first line of Table D1 specifically discloses the combination of Compound 22 with abamectin is typically applied in a weight ratio between 50:1 to 1:50. The remaining lines of Table D1 are to be construed similarly.










TABLE D1






Invertebrate Pest Control
Mode of Action or Chemical
Typical


Component (a)
Agent
Class
Weight Ratio







Compound 22
Abamectin
macrocyclic lactones
50:1 to 1:50


Compound 22
Acetamiprid
neonicotinoids
150:1 to 1:200


Compound 22
Amitraz
octopamine receptor ligands
200:1 to 1:100


Compound 22
Avermectin
macrocyclic lactones
50:1 to 1:50


Compound 22
Azadirachtin
ecdysone agonists
100:1 to 1:120


Compound 22
Beta-cyfluthrin
sodium channel modulators
150:1 to 1:200


Compound 22
Bifenthrin
sodium channel modulators
100:1 to 1:10


Compound 22
Buprofezin
chitin synthesis inhibitors
500:1 to 1:50


Compound 22
Cartap
nereistoxin analogs
100:1 to 1:200


Compound 22
Chlorantraniliprole
ryanodine receptor ligands
100:1 to 1:120


Compound 22
Chlorfenapyr
mitochondrial electron transport
300:1 to 1:200




inhibitors



Compound 22
Chlorpyrifos
cholinesterase inhibitors
500:1 to 1:200


Compound 22
Clothianidin
neonicotinoids
100:1 to 1:400


Compound 22
Cyantraniliprole
ryanodine receptor ligands
100:1 to 1:120


Compound 22
Cyfluthrin
sodium channel modulators
150:1 to 1:200


Compound 22
Cyhalothrin
sodium channel modulators
150:1 to 1:200


Compound 22
Cypermethrin
sodium channel modulators
150:1 to 1:200


Compound 22
Cyromazine
chitin synthesis inhibitors
400:1 to 1:50


Compound 22
Deltamethrin
sodium channel modulators
50:1 to 1:400


Compound 22
Dieldrin
cyclodiene insecticides
200:1 to 1:100


Compound 22
Dinotefuran
neonicotinoids
150:1 to 1:200


Compound 22
Diofenolan
molting inhibitor
150:1 to 1:200


Compound 22
Emamectin
macrocyclic lactones
50:1 to 1:10


Compound 22
Endosulfan
cyclodiene insecticides
200:1 to 1:100


Compound 22
Esfenvalerate
sodium channel modulators
100:1 to 1:400


Compound 22
Ethiprole
GABA-regulated chloride channel
200:1 to 1:100




blockers



Compound 22
Fenothiocarb

150:1 to 1:200


Compound 22
Fenoxycarb
juvenile hormone mimics
500:1 to 1:100


Compound 22
Fenvalerate
sodium channel modulators
150:1 to 1:200


Compound 22
Fipronil
GABA-regulated chloride channel
150:1 to 1:100




blockers



Compound 22
Flonicamid

200:1 to 1:100


Compound 22
Flubendiamide
ryanodine receptor ligands
100:1 to 1:120


Compound 22
Flufenoxuron
chitin synthesis inhibitors
200:1 to 1:100


Compound 22
Hexaflumuron
chitin synthesis inhibitors
300:1 to 1:50


Compound 22
Hydramethylnon
mitochondrial electron transport
150:1 to 1:250




inhibitors



Compound 22
Imidacloprid
neonicotinoids
1000:1 to 1:1000


Compound 22
Indoxacarb
sodium channel modulators
200:1 to 1:50


Compound 22
Lambda-cyhalothrin
sodium channel modulators
50:1 to 1:250


Compound 22
Lufenuron
chitin synthesis inhibitors
500:1 to 1:250


Compound 22
Meperfluthrin
Sodium channel modulators
100:1 to 1:400


Compound 22
Metaflumizone

200:1 to 1:200


Compound 22
Methomyl
cholinesterase inhibitors
500:1 to 1:100


Compound 22
Methoprene
juvenile hormone mimics
500:1 to 1:100


Compound 22
Methoxyfenozide
ecdysone agonists
50:1 to 1:50


Compound 22
Nitenpyram
neonicotinoids
150:1 to 1:200


Compound 22
Nithiazine
neonicotinoids
150:1 to 1:200


Compound 22
Novaluron
chitin synthesis inhibitors
500:1 to 1:150


Compound 22
Oxamyl
cholinesterase inhibitors
200:1 to 1:200


Compound 22
Pymetrozine

200:1 to 1:100


Compound 22
Pyrethrin
sodium channel modulators
100:1 to 1:10


Compound 22
Pyridaben
mitochondrial electron transport
200:1 to 1:100




inhibitors



Compound 22
Pyridalyl

200:1 to 1:100


Compound 22
Pyriproxyfen
juvenile hormone mimics
500:1 to 1:100


Compound 22
Ryanodine
ryanodine receptor ligands
100:1 to 1:120


Compound 22
Spinetoram
macrocyclic lactones
150:1 to 1:100


Compound 22
Spinosad
macrocyclic lactones
500:1 to 1:10


Compound 22
Spirodiclofen
lipid biosynthesis inhibitors
200:1 to 1:200


Compound 22
Spiromesifen
lipid biosynthesis inhibitors
200:1 to 1:200


Compound 22
Sulfoxaflor

200:1 to 1:200


Compound 22
Tebufenozide
ecdysone agonists
500:1 to 1:250


Compound 22
Tetramethylfluthrin
Sodium channel modulators
100:1 to 1:400


Compound 22
Thiacloprid
neonicotinoids
100:1 to 1:200


Compound 22
Thiamethoxam
neonicotinoids
1250:1 to 1:1000


Compound 22
Thiodicarb
cholinesterase inhibitors
500:1 to 1:400


Compound 22
Thiosultap-sodium

150:1 to 1:100


Compound 22
Tralomethrin
sodium channel modulators
150:1 to 1:200


Compound 22
Triazamate
cholinesterase inhibitors
250:1 to 1:100


Compound 22
Triflumuron
chitin synthesis inhibitors
200:1 to 1:100


Compound 22
Bacillus thuringiensis
biological agents
50:1 to 1:10


Compound 22
Bacillus thuringiensis delta-
biological agents
50:1 to 1:10



endotoxin




Compound 22
NPV (e.g., Gemstar)
biological agents
50:1 to 1:10









Tables D2 through D54 are each constructed the same as Table D1 above except that entries below the “Component (a)” column heading are replaced with the respective Component (a) Column Entry shown below. Thus, for example, in Table D2 the entries below the “Component (a)” column heading all recite “Compound 18”, and the first line in below the column headings in Table D2 specifically discloses a mixture of Compound 18 with abamectin. Tables D3 through D54 are constructed similarly.













Table Number
Component (a) Column Entries








D2
Compound 18



D3
Compound 23



D4
Compound 24



D5
Compound 36



D6
Compound 41



D7
Compound 45



D8
Compound 87



D9
Compound 91



D10
Compound 118



D11
Compound 139



D12
Compound 148



D13
Compound 172



D14
Compound 175



D15
Compound 193



D16
Compound 232



D17
Compound 265



D18
Compound 266



D19
Compound 284



D20
Compound 286



D21
Compound 287



D22
Compound 292



D23
Compound 297



D24
Compound 332



D25
Compound 336



D26
Compound 343



D27
Compound 346



D28
Compound 349



D29
Compound 351



D30
Compound 352



D31
Compound 357



D32
Compound 358



D33
Compound 360



D34
Compound 361



D35
Compound 364



D35
Compound 365



D37
Compound 367



D38
Compound 368



D39
Compound 369



D40
Compound 372



D41
Compound 373



D42
Compound 374



D43
Compound 375



D44
Compound 376



D45
Compound 377



D46
Compound 378



D47
Compound 379



D48
Compound 380



D49
Compound 381



D50
Compound 382



D51
Compound 383



D52
Compound 384



D53
Compound 385



D54
Compound 386









One embodiment of invertebrate pest control agents (e.g., insecticides and acaricides) for mixing with compounds of Formula 1 (and N-oxides and salts thereof) include sodium channel modulators such as bifenthrin, cypermethrin, cyhalothrin, lambda-cyhalothrin, cyfluthrin, beta-cyfluthrin, deltamethrin, dimefluthrin, esfenvalerate, fenvalerate, indoxacarb, metofluthrin, profluthrin, pyrethrin and tralomethrin; cholinesterase inhibitors such as chlorpyrifos, methomyl, oxamyl, thiodicarb and triazamate; neonicotinoids such as acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, nithiazine, thiacloprid and thiamethoxam; insecticidal macrocyclic lactones such as spinetoram, spinosad, abamectin, avermectin and emamectin; GABA (γ-aminobutyric acid)-regulated chloride channel blockers such as endosulfan, ethiprole and fipronil; chitin synthesis inhibitors such as buprofezin, cyromazine, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron and triflumuron; juvenile hormone mimics such as diofenolan, fenoxycarb, methoprene and pyriproxyfen; octopamine receptor ligands such as amitraz; ecdysone agonists such as azadirachtin, methoxyfenozide and tebufenozide; ryanodine receptor ligands such as ryanodine, anthranilic diamides such as chlorantraniliprole, cyantraniliprole and flubendiamide; nereistoxin analogs such as cartap; mitochondrial electron transport inhibitors such as chlorfenapyr, hydramethylnon and pyridaben; lipid biosynthesis inhibitors such as spirodiclofen and spiromesifen; cyclodiene insecticides such as dieldrin; cyflumetofen; fenothiocarb; flonicamid; metaflumizone; pyrafluprole; pyridalyl; pyriprole; pymetrozine; spirotetramat; and thiosultap-sodium. One embodiment of biological agents for mixing with compounds of component (a) include nucleopolyhedro virus such as HzNPV and AfNPV; Bacillus thuringiensis and encapsulated delta-endotoxins of Bacillus thuringiensis such as Cellcap, MPV and MPVII; as well as naturally occurring and genetically modified viral insecticides including members of the family Baculoviridae as well as entomophagous fungi. Of note is a composition comprising component (a) and at least one additional biologically active compound or agent selected from the Invertebrate Pest Control Agents listed in Table D1 above.
The following TESTS demonstrate the control efficacy of compounds of this invention on specific pathogens. The pathogen control protection afforded by the compounds is not limited, however, to these species. See Index Table A for compound descriptions. The following abbreviations are used in the Index Tables which follow: Me is methyl, Ph is phenyl, OMe is methoxy, —CN is cyano, —NO2 is nitro. Also, “pyridin-2-yl” is synonymous with “2-pyridinyl”, “pyridin-3-yl” is synonymous with “3-pyridinyl”, and “pyrimidin-5-yl” is synonymous with 5-pyrimidinyl”. The abbreviation “Ex.” stands for “Example” and is followed by a number indicating in which example the compound is prepared. “Cmpd No.” means compound number. Mass spectra (M.S.) are reported as the molecular weight of the highest isotopic abundance parent ion (M+1) formed by addition of H+ (molecular weight of 1) to the molecule, observed by mass spectrometry using atmospheric pressure chemical ionization (AP+).







INDEX TABLE A













 













Cmpd








No.
R1
R2
Q1
Q2
X
M.S





 1 (Ex. 1)
H
Me
2,4-di-F—Ph
3-Cl—Ph
NH
**


 2
H
Me
2,4-di-F—Ph
3,5-di-OMe—Ph
NH
360


 3
H
Me
2,4-di-F—Ph
3-Cl—Ph
NMe
*


 4
H
Me
4-Cl—Ph
2,4-di-F—Ph
NH
334


 5
H
Me
4-Cl—Ph
3,5-di-F—Ph
NH
334


 6
H
Me
4-Cl—Ph
3,5-di-F—Ph
NMe
348


 7
H
Me
2-Cl-4-F—Ph
3-Cl-4-F—Ph
NH
369


 8
H
Me
2-Cl-4-F—Ph
3-F—Ph
NH
334


 9
H
Me
2-Cl-4-F—Ph
3,5-di-F—Ph
NH
352


 10
H
Me
4-Cl—Ph
2,3,5-tri-F—Ph
NH
352


 11
H
Me
2-Cl-4-F—Ph
4-F—Ph
NH
334


 12
H
Me
2-Cl-4-F—Ph
2-F—Ph
NH
334


 13
H
Me
2-Cl-4-F—Ph
2,4-di-F—Ph
NH
352


 14
H
Me
2,4,6-tri-F—Ph
3-F-4-Cl—Ph
NH
370


 15
H
Me
2-F-4-OMe—Ph
4-Cl—Ph
O
347


 16
H
Me
3,5-di-OMe—Ph
4-Cl—Ph
O
359


 17 (Ex. 2)
H
Me
2-Cl-4-F—Ph
2,6-di-F-4-OMe—Ph
NH
**


 18
H
Me
2-Cl-4-F—Ph
2,4,6-tri-F—Ph
NH
370


 19
H
Me
2-Cl-4-F—Ph
4-Cl—Ph
NH
350


 20
H
Me
2-Cl-4-F—Ph
2-F-4-NO2—Ph
O
380


 21
H
Me
2-Cl-4-F—Ph
2-F-4-OMe—Ph
O
365


 22
H
Me
2,6-di-F-4-OMe—Ph
4-Cl—Ph
NH
364


 23
H
Me
2,6-di-F-4-OMe—Ph
2,4-di-F—Ph
NH
366


 24 (Ex. 3)
H
Me
2,6-di-F-4-OMe—Ph
2,4,6-tri-F—Ph
NH
**


 25
H
Me
3-Cl—Ph
2,6-di-F-4-OMe—Ph
NH
364


 26
H
Me
2,4,6-tri-F—Ph
4-NO2—Ph
O
364


 27
H
Me
2,4,6-tri-F—Ph
4-Cl—Ph
O
353


 28
H
Me
4-Cl—Ph
2,4,6-tri-F—Ph
NH
352


 29
H
Me
4-Cl—Ph
2,6-di-F-4-OMe—Ph
NH
364


 30
H
Me
2,4,6-tri-F—Ph
2,6-di-Cl-4-CF3—Ph
O
455


 31
H
Me
2,4,6-tri-F—Ph
2,6-di-F-4-CN—Ph
O
380


 32
H
Me
2,4,6-tri-F—Ph
2-Cl-4-NO2—Ph
O
398


 33
H
Me
4-Cl—Ph
2,6-di-F—Ph
NH
334


 34
H
Me
2,6-di-F-4-OMe—Ph
6-Cl-pyridin-3-yl
NH
365


 35
H
Me
3,4-di-F—Ph
2,4,6-tri-F—Ph
NH
354


 36
H
Me
3,4-di-F—Ph
2,6-di-F-4-OMe—Ph
NH
366


 37
H
Me
2,6-di-F—Ph
3,5-di-OMe—Ph
NH
360


 38
H
Me
2,4,6-tri-F—Ph
2,4-di-Cl—Ph
O
387


 39
H
Me
2,4,6-tri-F—Ph
5-Cl-pyridin-2-yl
O
354


 40
H
Me
2,6-di-F-4-OMe—Ph
2,4-di-Cl—Ph
O
399


 41
H
Me
2,4-di-F—Ph
2,4,6-tri-F—Ph
NH
354


 42
H
Me
2,4-di-F—Ph
2,6-di-F-4-OMe—Ph
NH
366


 43
H
Me
3-F—Ph
2,6-di-F-4-CN—Ph
O
344


 44
H
Me
4-Cl—Ph
2,6-di-F-4-CN—Ph
O
360


 45 (Ex. 4)
H
Me
2-Cl-4-F—Ph
2,6-di-F-4-CN—Ph
O
**


 46
H
Me
2-F-4-OMe—Ph
2,6-di-F-4-CN—Ph
O
374


 47
H
Me
2,6-di-F-4-OMe—Ph
5-Cl-pyridin-2-yl
O
366


 48
H
Me
2,6-di-F-4-OMe—Ph
3,4-di-F—Ph
NH
366


 49
H
Me
2,6-di-F-4-OMe—Ph
3-F-4-Cl—Ph
NH
382


 50
H
Me
2,6-di-F-4-OMe—Ph
4-Me—Ph
NH
344


 51
H
Me
2,6-di-F-4-OMe—Ph
2,4-di-OMe—Ph
NH
390


 52
H
Me
4-Me—Ph
2-Cl-4-NO2—Ph
O
358


 53
Ph
Me
2,4,6-tri-F—Ph
2,6-di-F-4-NO2—Ph
O
476


 54 (Ex. 8)
H
Me
2,4,6-tri-F—Ph
2,6-di-F-4-NO2—Ph
O
**


 55
H
Me
4-Me—Ph
2-Cl-4-OMe—Ph
O
343


 56
H
Me
4-Cl—Ph
4-OMe—Ph
NH
328


 57
H
Me
2,4-di-Cl—Ph
2,4-di-OMe—Ph
NH
392


 58 (Ex. 10)
H
Me
2,6-di-F-4-OMe—Ph
2,6-di-F-4-Cl—Ph
O
**


 59
H
Me
2,6-di-F-4-OMe—Ph
2,4-di-OMe-6-Cl—Ph
NH
424


 60
H
Me
4-Cl—Ph
2-Cl-4-OMe—Ph
NH
362


 61
Me
Me
4-Cl—Ph
2,6-di-F—Ph
NH
348


 62
H
Me
2,4-di-Cl—Ph
2,6-di-F-4-OMe—Ph
NH
398


 63
Me
Me
2,6-di-F—Ph
3,5-di-OMe—Ph
NH
374


 64
H
Me
2,4,6-tri-F—Ph
3,5-di-Cl-pyridin-2-yl
O
388


 65
—CO2Et
Me
2,4,6-tri-F—Ph
2,6-di-F, 4-NO2—Ph
O
472


 66
H
Me
2,6-di-F-4-OMe—Ph
5-Me-pyridin-2-yl
NH
345


 67
H
Me
2-Cl-4-F—Ph
5-CN-pyridin-2-yl
NH
342


 68
—CO2H
Me
2,4,6-tri-F—Ph
2,6-di-F-4-NO2—Ph
O
444


 69 (Ex. 5)
H
Me
2,4-di-Cl—Ph
2,4-di-F—Ph
NH
**


 70
Me
Me
2,4-di-Cl—Ph
2,4-di-F—Ph
NH
382


 71
H
Me
2-Cl-4-F—Ph
2-F-4-(NHC(O)Me)—Ph
O
392


 72
H
Me
2,4-di-F—Ph
3,4-di-OMe—Ph
NH
360


 73
H
Me
2-Cl-4-F—Ph
3,5-di-Cl-pyridin-2-yl
NH
387


 74
H
Me
2,4-di-Cl—Ph
3,4-di-OMe—Ph
NH
392


 75
H
Me
2,4-di-Cl—Ph
2,4,6-tri-F—Ph
NH
386


 76
H
Me
2,4-di-F—Ph
6-Cl-pyridin-3-yl
NH
331


 77
H
Me
2,6-di-F-4-OMe—Ph
2,6-di-F-4-NH2—Ph
O
382


 78
H
Me
2,4,6-tri-F—Ph
2,6-di-F-4-OMe—Ph
NH
384


 79
H
Me
4-Me—Ph
2,4,6-tri-F—Ph
NH
332


 80
H
Me
4-Me—Ph
2,6-di-F-4-OMe—Ph
NH
344


 81
H
Me
2,6-di-F-4-OMe—Ph
5-Cl-2,4-di-OMe—Ph
NH
424


 82
H
Me
2,6-di-F-4-OMe—Ph
2,6-di-F-4-CN—Ph
NH
391


 83
H
Me
2,6-di-F-4-OMe—Ph
2,6-di-F-4-OMe—Ph
NH
396


 84
H
Me
2,6-di-F-4-OMe—Ph
2,6-di-F—Ph
O
367


 85
H
Me
3,5-di-OMe—Ph
2,6-di-F-4-CN—Ph
O
386


 86
H
Me
6-Cl-pyridin-3-yl
2,6-di-F-4-CN—Ph
O
361


 87
H
Me
2,6-di-F-4-OMe—Ph
2-Cl-4-F—Ph
NH
382


 88
H
Me
2,6-di-F-4-OMe—Ph
4-F-2-Me—Ph
NH
362


 89
H
Me
4-F-2-OMe—Ph
2,6-di-F-4-CN—Ph
O
374


 90
H
Me
2,6-di-F-4-OMe—Ph
4-Br-2,6-di-F—Ph
O
447


 91
H
Me
2-Cl-4-F—Ph
2,6-di-F-4-CN—Ph
NH
377


 92
H
Me
2,4,6-tri-F—Ph
2,6-di-F-4-CN—Ph
NH
379


 93
H
Me
2,4,6-tri-F—Ph
3,4-di-OMe—Ph
NH
378


 94
H
Me
2,4,6-tri-F—Ph
6-OMe-pyridin-3-yl
NH
349


 95
H
Me
2,6-di-F-4-OMe—Ph
6-OMe-pyridin-3-yl
NH
361


 96
H
Me
2,4,6-tri-F—Ph
2-F-4-CN—Ph
O
362


 97
H
Me
4-F-2-Me—Ph
2,6-di-F-4-CN—Ph
O
358


 98
H
Me
2,4,6-tri-F—Ph
2-Cl-4-CN—Ph
O
378


 99
H
Me
2,4,6-tri-F—Ph
2,5-di-F-4-CN—Ph
O
380


100
H
Me
2,4,6-tri-F—Ph
5-Cl-2,4-di-OMe—Ph
NH
412


101
H
Me
2,4,6-tri-F—Ph
3,5-di-Cl-pyridin-2-yl
NH
386


102
H
Me
2,6-di-F-4-OMe—Ph
3,5-di-Cl-pyridin-2-yl
NH
398


103
H
Me
2,6-di-F-4-OH—Ph
2,4-di-F—Ph
NH
352


104
H
Me
2-Cl-4-OMe—Ph
2,4,6-tri-F—Ph
NH
382


105
H
Me
2,6-di-F-4-OS(O)2CF3
2,4-di-F—Ph
NH
484


106
H
Me
2,6-di-F-4-CN—Ph
2,4-di-F—Ph
NH
361


107
H
Me
2-Cl-4-F—Ph
2,6-di-Cl-pyridin-3-yl
NH
386


108
H
c-Pr
2-Cl-4-F—Ph
2,4-di-F—Ph
NH
378


109
H
Me
2,4,6-tri-F—Ph
3,5-di-F-pyridin-2-yl
NH
355


110
H
Me
2,6-di-F-4-CN—Ph
4-Cl—Ph
NH
***


111
H
Me
2,6-di-F-4-CN—Ph
4-F—Ph
NH
***


112
H
Me
2,6-di-F-4-CN—Ph
2-Cl-4-F—Ph
NH
***


113
H
Me
2,6-di-F-4-CN—Ph
3-F-4-OMe—Ph
NH
***


114
H
Me
2,6-di-F-4-CN—Ph
3,4-di-F—Ph
NH
***


115
H
Me
2,6-di-F-4-CN—Ph
3-Cl—Ph
NH
***


116
H
Me
2-Cl-4-F—Ph
3-F-5-CN—Ph
O
360


117
H
Me
2,6-di-F-4-OMe—Ph
2-Cl-4-CN—Ph
NH
389


118
H
Me
2-Cl-4-F—Ph
2-F-4-CN—Ph
O
360


119
H
Me
2-Cl-4-F—Ph
2-Cl-4-NO2—Ph
O
396


120
H
Me
2,4,6-tri-F—Ph
2-F-4-CN—Ph
NH
361


121
H
Me
2-Cl-4-F—Ph
2,6-di-F-4-NO2—Ph
O
398


122
H
Me
2-Cl-4-F—Ph
4-F-2-NO2—Ph
O
380


123
H
Me
2,6-di-F-4-CN—Ph
3,4-di-Cl—Ph
NH
***


124
H
Me
2,6-di-F-4-CN—Ph
4-Me—Ph
NH
***


125
H
Me
2,6-di-F-4-CN—Ph
4-Cl-3-F—Ph
NH
***


126
H
Me
2,6-di-F-4-CN—Ph
4-OMe—Ph
NH
***


127
H
Me
2,6-di-F-4-CN—Ph
4-F-3-OMe—Ph
NH
373


128
H
Me
2,6-di-F-4-OMe—Ph
3,5-di-F-pyridin-2-yl
NH
367


129
H
Me
2,4,6-tri-F—Ph
4-Cl-3-F—Ph
O
***


130
H
Me
2,4,6-tri-F—Ph
4-Br-3-F—Ph
O
***


131
H
Me
2,4,6-tri-F—Ph
3-F-4-NO2—Ph
O
***


132
H
Me
2-Cl-4-F—Ph
3,4,5-tri-F—Ph
NH
370


133
H
Me
2,6-di-F-4-CN—Ph
2,4,6-tri-F—Ph
NH
***


134
H
Me
2,6-di-F-4-CN—Ph
2,6-di-F-4-OMe—Ph
NH
***


135
H
Me
2,4,6-tri-F—Ph
3-Me-4-NO2—Ph
O
***


136
H
Me
2,6-di-F-4-CN—Ph
3-F—Ph
NH
***


137
H
Me
2,6-di-F-4-CN—Ph
2,5-di-F—Ph
NH
***


138
H
Me
2,6-di-F-4-CN—Ph
2,4,5-tri-F—Ph
NH
***


139
H
Me
2-Cl-4-F—Ph
2-Cl-4-CN—Ph
O
376


140
H
Me
2,6-di-F-4-OMe—Ph
2,6-di-F-4-CN—Ph
O
392


141
H
Me
2,6-di-F-4-OEt—Ph
2,4-di-F—Ph
NH
380


142
H
Me
2,6-di-F-4-CN—Ph
5-Cl-2-F—Ph
NH
***


143
H
Me
2,6-di-F-4-CN—Ph
4-Cl-2-F—Ph
NH
***


144
H
Me
2,6-di-F-4-CN—Ph
3-Cl-2-F—Ph
NH
***


145
H
Me
2,6-di-F-4-CN—Ph
2,3-di-F—Ph
NH
***


146
H
Me
2,6-di-F-4-CN—Ph
2,5-di-Cl—Ph
NH
***


147
H
Me
2,6-di-F-4-CN—Ph
2,3-di-Cl—Ph
NH
***


148
H
Me
2-Cl-4-F—Ph
2,5-di-F-4-CN—Ph
O
378


149
H
Me
2-Cl-4-F—Ph
4-F-2-CN—Ph
O
360


150
H
Me
2-Cl-4-F—Ph
2-Cl-4,5-di-CN—Ph
O
401


151
H
Me
2,4,6-tri-F—Ph
3-OMe-4-NO2—Ph
O
***


152
H
Me
2,6-di-F-4-OMe—Ph
4-Cl-3-F—Ph
O
383


153
H
Me
2,6-di-F-4-OMe—Ph
4-Br-3-F—Ph
O
429


154
H
Me
2-Cl-4-F—Ph
3,5-di-F-pyridin-2-yl
NH
353


155
H
Me
2-Cl-4-OMe—Ph
2,6-di-F-4-CN—Ph
O
390


156
H
Me
2,4,6-tri-F—Ph
3-CN-4-NO2—Ph
O
***


157
H
Me
2,4,6-tri-F—Ph
4-Cl-3-Me—Ph
O
***


158
H
Me
2-Cl-4-F—Ph
2,6-di-F-4-OMe—Ph
NEt
410


159
H
Me
2-Cl-4-F—Ph
2,6-di-F-4-OMe—Ph
NCH2CH═CH2
422


160
H
Me
2-Cl-4-OMe—Ph
2,4-di-F—Ph
NH
364


161
H
Me
2-Cl-4-OMe—Ph
2,6-di-F—Ph
NH
364


162
H
Me
2-Cl-4-F—Ph
2-Cl-4-CN—Ph
NH
375


163
H
Me
2,4,6-tri-F—Ph
2-Cl-4,5-di-CN—Ph
O
403


164
H
Me
2,4,6-tri-F—Ph
4-Cl-3-OMe—Ph
O
***


165
H
Me
2,4,6-tri-F—Ph
4-Br-3-Me—Ph
O
***


166
H
Me
2,4,6-tri-F—Ph
4-Br-3-OMe—Ph
O
429


167
H
Me
2,4,6-tri-F—Ph
2,3,5-tri-F—Ph
O
373


168
H
Me
2-Cl-4-F—Ph
3,4-di-CN—Ph
O
367


169
H
Me
2,4,6-tri-F—Ph
3,4-di-CN—Ph
O
369


170
H
Me
2,4-di-F—Ph
2,6-di-F-4-CN—Ph
O
362


171
H
Me
2-Cl-4-F—Ph
2,3,6-tri-F—Ph
NH
370


172
H
Me
2-Cl-4-F—Ph
2,6-di-F—Ph
NH
352


173
H
Me
2-Cl-4-F—Ph
2,5-di-F—Ph
NH
352


174
H
Me
2-Cl-4-OMe—Ph
2,3,6-tri-F—Ph
NH
382


175
H
Me
2-Cl-4-F—Ph
2-Cl-4-F—Ph
NH
368


176
H
Me
2-Cl-4-OMe—Ph
2,5-di-F—Ph
NH
364


177
H
Me
2-Cl-6-F—Ph
2,4-di-F—Ph
NH
352


178
H
Me
2,6-di-F—Ph
2,4-di-F—Ph
NH
***


179
H
Me
2,6-di-F—Ph
2,4-di-Cl—Ph
NH
***


180
H
Me
2,6-di-F—Ph
2-F-4-OMe—Ph
NH
***


181
H
Me
2-F—Ph
2,4-di-F—Ph
NH
318


182
H
Me
2-F—Ph
2,4,6-tri-F—Ph
NH
336


183
H
Me
2-F—Ph
2,6-di-F-4-OMe—Ph
NH
348


184
H
Me
2-F—Ph
4-F—Ph
NH
300


185
H
Me
2,6-di-F-4-OMe—Ph
4-Cl-3-Me—Ph
O
379


186
H
Me
2,6-di-F-4-OMe—Ph
4-Br-3-Me—Ph
O
***


187
H
Me
2,4,6-tri-F—Ph
3-F-4-Me—Ph
O
***


188
H
Me
2,6-di-F-4-OMe—Ph
3-F-4-Me_Ph
O
363


189
H
Me
2-Cl-4-F—Ph
3,5-di-F-pyridin-2-yl
O
354


190
H
Me
2-Cl-6-F—Ph
2,6-di-F-4-OMe—Ph
NH
382


191
H
Me
2-Cl-6-F—Ph
2,4,6-tri-F—Ph
NH
369


192
H
Me
2-Cl-6-F—Ph
2,6-di-F-4-CN—Ph
NH
377


193
H
Me
2-Cl-6-F—Ph
2-Cl-4-F—Ph
NH
368


194
H
Me
2,4-di-F—Ph
4-F—Ph
NH
***


195
H
Me
2,4-di-F—Ph
4-Cl—Ph
NH
***


196
H
Me
2,6-di-F—Ph
2-F-4-CN—Ph
NH
343


197
H
Me
2,6-di-F—Ph
2,5-di-F—Ph
NH
***


198
H
Me
2,6-di-F—Ph
2,3-di-F—Ph
NH
***


199
H
Me
2,6-di-F—Ph
4-F-2-OMe—Ph
NH
***


200
H
Me
2,6-di-F—Ph
3-OMe—Ph
NH
***


201
H
Me
2,6-di-F—Ph
2-Cl-4-OMe—Ph
NH
***


202
H
Me
2,3-di-F—Ph
2,4-di-F—Ph
NH
336


203
H
Me
2,3-di-F—Ph
2,4,6-tri-F—Ph
NH
354


204
H
Me
2,3-di-F—Ph
2,6-di-F-4-OMe—Ph
NH
366


205
H
Me
2,3-di-F—Ph
4-F—Ph
NH
318


206
H
Me
2,6-di-F-4-OMe—Ph
4-Cl—Ph
O
365


207
H
Me
2,4-di-F—Ph
2-Cl-4-F—Ph
NH
***


208
H
Me
2,6-di-F-4-OMe—Ph
2,4-di-F—Ph
CHOH
381


209
H
Me
2,4,6-tri-F—Ph
3,4-di-Me—Ph
O
***


210
H
Me
2,6-di-F-4-OMe—Ph
3,4-di-Me—Ph
O
***


211
H
Me
2,6-di-F-4-OMe—Ph
4-Cl-3-OMe—Ph
O
***


212
H
Me
2,6-di-F-4-OMe—Ph
4-Br-3-OMe—Ph
O
***


213
H
Me
2,4,6-tri-F—Ph
3-OMe—Ph
O
349


214
H
Me
2,4-di-F—Ph
2,3-di-F—Ph
NH
***


215
H
Me
2,6-di-F—Ph
2-Cl-5-OMe—Ph
NH
***


216
H
Me
2,6-di-F—Ph
2-F-5-OMe—Ph
NH
***


217
H
Me
2,4,6-tri-F—Ph
3-OMe-4-Me—Ph
O
***


218
H
Me
2,6-di-F-4-OMe—Ph
4-Cl-3-CN—Ph
O
***


219
H
Me
2,4,6-tri-F—Ph
3-Me—Ph
O
333


220
H
Me
2,6-di-F-4-OMe—Ph
3-Me—Ph
O
345


221
H
Me
2,6-di-F-4-OMe—Ph
3-OMe—Ph
O
361


222
H
Me
2,4,6-tri-F—Ph
3-CN—Ph
O
344


223
H
Me
2,6-di-F-4-OMe—Ph
3-CN—Ph
O
356


224
H
Me
2,4,6-tri-F—Ph
4-Cl-3-CN—Ph
O
***


225
H
Me
2,4,6-tri-F—Ph
4-Br-3-CN—Ph
O
***


226
H
Me
2,4-di-F—Ph
2,5-di-F—Ph
NH
***


227
H
Me
2,4-di-F—Ph
2-Cl-5-OMe—Ph
NH
***


228
H
Me
2,4-di-F—Ph
2-F-4-OMe—Ph
NH
***


229
H
Me
2,4-di-F—Ph
2,4,5-tri-F—Ph
NH
***


230
H
Me
2,4-di-F—Ph
2,4-di-F—Ph
NH
336


231
H
Me
2,4-di-F—Ph
2,3-di-Cl—Ph
NH
***


232
H
Me
2-Br-4-F—Ph
2,6-di-F-4-CN—Ph
O
423


233
H
Me
2-Br-4-F—Ph
2,5-di-F-4-CN—Ph
O
423


234
H
Me
2-Cl-4-F—Ph
4-F-3-CN—Ph
NH
359


235
H
Me
2-Cl-4-F—Ph
2-Cl-5-CN—Ph
NH
375


236
H
Me
2-CF3—Ph
2-Cl-4-F—Ph
NH
384


237
H
Me
2-CF3—Ph
4-F—Ph
NH
350


238
H
Me
2-CF3—Ph
2,4-di-F—Ph
NH
368


239
H
Me
2-CF3—Ph
2,4,6-tri-F—Ph
NH
386


240
H
Me
2-CF3—Ph
2,6-di-F-4-OMe—Ph
NH
398


241
H
Me
2,4,6-tri-F—Ph
3-Cl-pyridin-2-yl
NH
353


242
H
Me
2,4-di-F—Ph
2-Cl-4-OMe—Ph
NH
***


243
H
Me
2,4-di-F—Ph
2,4-di-Cl—Ph
NH
***


244
H
Me
2,4-di-F—Ph
2-F-5-OMe—Ph
NH
***


245
H
Me
2,4-di-F—Ph
2,5-di-Cl—Ph
NH
***


246
H
Me
2,4-di-F—Ph
2-F-4-CN—Ph
NH
***


247
H
Me
2,6-di-F—Ph
2,6-di-F—Ph
NH
***


248
H
Me
2-Br—Ph
2,4,6-tri-F—Ph
NH
398


249
H
Me
2,6-di-F-4-OMe—Ph
3-OMe-4-Me—Ph
O
***


250
H
Me
2,4,6-tri-F—Ph
3-CN-4-Me—Ph
O
***


251
H
Me
2-CF3—Ph
3,5-di-Cl-pyridin-2-yl
NH
401


252
H
Me
2-Cl-6-F—Ph
3,5-di-Cl-pyridin-2-yl
NH
387


253
H
Me
2-F-6-CF3—Ph
2-Cl-4-F—Ph
NH
402


254
H
Me
2-F-6-CF3—Ph
4-F—Ph
NH
368


255
H
Me
2-F-6-CF3—Ph
2,4-di-F—Ph
NH
368


256
H
Me
2,4-di-F—Ph
2,6-di-F—Ph
NH
***


257
H
Me
2,6-di-F—Ph
2,6-di-F-4-OMe—Ph
NH
***


258
H
Me
2,6-di-F-4-OMe—Ph
4-Br-3-CN—Ph
O
***


259
H
Me
2,6-di-F-4-OMe—Ph
3-CN-4-Me—Ph
O
***


260
H
Me
2-Br-4-F—Ph
3-F-5-CF3-pyridin-2-yl
O
449


261
H
Me
2-Br-4-F—Ph
3-Cl-5-CF3-pyridin-2-yl
O
465


262
H
Me
2-F-6-CF3—Ph
2,4,6-tri-F—Ph
NH
404


263
H
Me
2-F-6-CF3—Ph
2,6-di-F-4-OMe—Ph
NH
416


264
H
Me
2-F-6-CF3—Ph
3,5-di-F-pyridin-2-yl
NH
387


265
H
Me
2-Cl-4-F—Ph
2-Br-4-F—Ph
NH
413


266
H
Me
2-Br-4-F—Ph
2,4,6-tri-F—Ph
NH
415


267
H
Me
2-Cl-4-OMe—Ph
3,5-di-Cl-pyridin-2-yl
NH
399


268
H
Me
2-Cl-4-F—Ph
2-Cl-pyrimidin-5-yl
NH
***


269
H
Me
2-Cl-4-F—Ph
2-Me-pyrimidin-5-yl
NH
***


270
H
Me
2-Cl-4-F—Ph
pyrimidin-5-yl
NH
***


271
H
Me
2-Cl—Ph
2,6-di-F-4-CN—Ph
O
***


272
H
Me
2-Br—Ph
2,6-di-F-4-CN—Ph
O
***


273
H
Me
2,3-di-Cl—Ph
2,6-di-F-4-CN—Ph
O
***


274
H
Me
2,3-di-F—Ph
2,6-di-F-4-CN—Ph
O
***


275
H
Me
2,5-di-Cl—Ph
2,6-di-F-4-CN—Ph
O
***


276
H
Me
2-Cl-5-F—Ph
2,6-di-F-4-CN—Ph
O
***


277
H
Me
2-Cl-5-OMe—Ph
2,6-di-F-4-CN—Ph
O
***


278
H
Me
2-F-5-OMe—Ph
2,6-di-F-4-CN—Ph
O
***


279
H
Me
2-Cl-6-F—Ph
3,5-di-F-pyridin-2-yl
NH
353


280
H
Me
2-CF3—Ph
3,5-di-F-pyridin-2-yl
NH
369


281
H
Me
2,4-di-F—Ph
2-Cl-3-OMe—Ph
NH
***


282
H
Me
2-Cl-4-OMe—Ph
2,4-di-Cl—Ph
NH
397


283
H
Me
2-Cl-6-F—Ph
2,4-di-Cl—Ph
NH
386


284
H
Me
2-Br-4-F—Ph
2-F-4-CN—Ph
O
406


285
H
Me
2-Br-4-F—Ph
2-Cl-4-CN—Ph
O
422


286
H
Me
2-Cl-4-F—Ph
4-Cl-2,6-di-F—Ph
NH
386


287
H
Me
2-Cl-4-F—Ph
2-Cl-4,6-di-F—Ph
NH
386


288
H
Me
2-Cl-4-F—Ph
4-OMe—Ph
NH
346


289
H
Me
2,6-di-F—Ph
2-Cl-3-OMe—Ph
NH
***


290
H
Me
2,4-di-F—Ph
2,6-di-F-4-CN—Ph
NH
***


291
H
Me
2,4-di-F—Ph
2-Cl-5-CN—Ph
NH
***


292
H
Me
2-Br-4-F—Ph
2-Cl-4,6-di-F—Ph
NH
431


293
H
Me
2-Cl-4-F—Ph
2,4,6-tri-F—Ph
NMe
***


294
H
Me
2-Cl-4-F—Ph
2,4,6-tri-F—Ph
NEt
***


295
H
Me
2-Br-4-F—Ph
3,5-di-Cl-pyridin-2-yl
NH
430


296
H
Me
2-Cl-4-F—Ph
2,6-di-Cl-4-OMe—Ph
NH
413


297
H
Me
2,6-di-F—Ph
2-Cl-4,6-di-F—Ph
NH
370


298
H
Me
2-Cl-6-F—Ph
2-Cl-4,6-di-F—Ph
NH
386


299
H
Me
2-Cl-4-F—Ph
2,4-di-Cl—Ph
NH
383


300
H
Me
2,6-di-F—Ph
2,4,6-tri-F—Ph
NH
***


301
H
Me
2,6-di-F—Ph
2,6-di-F-4-CN—Ph
NH
***


302
H
Me
2,3-di-Cl—Ph
2,4-di-F—Ph
NH
368


303
H
Me
2,3-di-Cl—Ph
3,5-di-Cl-pyridin-2-yl
NH
400


304
H
Me
2-Cl-4-F—Ph
2,4,6-tri-F—Ph
NS(O)2Me
***


305
H
Me
2-F—Ph
2,6-di-F-4-CN—Ph
O
***


306
H
Me
2-CF3—Ph
2,6-di-F-4-CN—Ph
O
***


307
H
Me
2-Cl-5-CF3—Ph
2,6-di-F-4-CN—Ph
O
***


308
H
Me
2-Cl-pyridin-3-yl
2,6-di-F-4-CN—Ph
O
***


309
H
Me
2-Cl-4-F—Ph
2,4,6-tri-F—Ph
NCH2OMe
***


310
H
Me
2-Cl-4-OMe—Ph
2-F-4-CN—Ph
O
372


311
H
Me
2-Cl-4-OMe—Ph
2-Cl-4-CN—Ph
O
388


312
H
Me
2-Br-4-F—Ph
2,4-di-F—Ph
NH
398


313
H
Me
2-Br-4-F—Ph
2-Br-4-F—Ph
NH
458


314
H
Me
2-Br-4-F—Ph
2-Cl-4-F—Ph
NH
414


315
H
Me
2-Cl—Ph
2,4-di-F—Ph
NH
334


316
H
Me
2-Br-4-F—Ph
2,6-di-Cl-4-F—Ph
NH
448


317
H
Me
2-Br-4-F—Ph
4-OMe—Ph
NH
392


318
H
Me
2-Br-4-OMe—Ph
2-Cl-4-CN—Ph
O
433


319
H
Me
2-Br-4-OMe—Ph
2-F-4-CN—Ph
O
418


320
H
Me
2-Cl—Ph
3,5-di-Cl-pyridin-2-yl
NH
368


321
H
Me
2,6-di-F—Ph
3,5-di-Cl-pyridin-2-yl
NH
369


322
H
Me
2-Cl-4-F—Ph
2-Cl-4-OMe—Ph
NH
380


323
H
Me
2-Br-4-F—Ph
2,6-di-Cl-4-OMe—Ph
NH
459


324
H
Me
2-Br-4-F—Ph
2-Cl-4-OMe—Ph
NH
425


325
H
Me
2-Cl-4-F—Ph
2-Cl-4-OEt—Ph
NH
394


326
H
Me
2-Cl-4-F—Ph
2,4,6-tri-F—Ph
NCH2CN
409


327
H
Me
2,6-di-Cl—Ph
2,4-di-Cl—Ph
NH
***


328
H
Me
2,4-di-F—Ph
3,5-di-Cl-pyridin-2-yl
NH
369


329
H
Me
2,5-di-F—Ph
2,6-di-F-4-CN—Ph
O
***


330
H
Me
2-Cl-4,6-di-F—Ph
2,6-di-F-4-CN—Ph
NH
395


331
H
Me
2-Cl-4-CN—Ph
2,4-di-F—Ph
NH
359


332
H
Me
2-Cl-4-CN—Ph
2-Cl-4,6-di-F—Ph
NH
393


333
H
Me
2,6-di-Cl—Ph
4-OMe—Ph
NH
***


334
H
Me
2,6-di-Cl—Ph
2-Cl-4-F—Ph
NH
***


335
H
Me
2-Cl-4-CN—Ph
2,6-di-F—Ph
NH
359


336
H
Me
2-Cl-4-CN—Ph
4-Cl-2,6-di-F—Ph
NH
393


337
H
Me
2,6-di-Cl—Ph
4-F—Ph
NH
***


338
H
Me
2-Cl-4-CN—Ph
2-Cl-4-F—Ph
NH
375


339
H
Me
2,6-di-Cl—Ph
2,4-di-F—Ph
NH
***


340
H
Me
2,6-di-Cl—Ph
2-Br-4-F—Ph
NH
***


341
H
Me
2,6-di-Cl—Ph
2,6-di-Cl-4-F—Ph
NH
***


342
H
Me
2-Cl-6-F—Ph
2-F-4-CN—Ph
O
360


343
H
Me
2,4-di-F—Ph
2-Cl-4,6-di-F—Ph
NH
369


344
H
Me
2-Cl-4-F—Ph
2-F-4-NO2—Ph
NH
380


345
H
Me
2-Cl-4-F—Ph
2-F-5-NO2—Ph
NH
380


346
H
Me
2,4-di-F—Ph
2-Br-4-F—Ph
NH
398


347
H
Me
4-Cl-2-F—Ph
2-F-4-CN—Ph
O
360


348
H
Me
2,4-di-F—Ph
2-Br-6-Cl-4-F—Ph
NH
432


349
H
Me
2,6-di-F—Ph
4-Cl-2,6-di-F—Ph
NH
370


350
H
Me
2-Cl-4-F—Ph
4-F—Ph
CHOH
349


351 (Ex. 6)
H
Me
2-Cl-4-F—Ph
2,4-di-F—Ph
CHOH
**


352
H
Me
2-Cl-4-F—Ph
2-Cl-4-F—Ph
CHOH
383


353
H
Me
2,4-di-Cl—Ph
2,6-di-F—Ph
NH
***


354
H
Me
2,4-di-Cl—Ph
2-Cl-4-F—Ph
NH
***


355
H
Me
2,4-di-Cl—Ph
4-OMe—Ph
NH
***


356
H
Me
2-Cl-4-F—Ph
2,3,6-tri-F—Ph
CHOH
385


357
H
Me
2,4-di-F—Ph
4-Cl-2,6-di-F—Ph
NH
370


358
H
Me
2,6-di-F—Ph
2-Cl-4-CN—Ph
O
360


359
H
Me
2,4-di-F—Ph
2-F-4-CN—Ph
O
376


360
H
Me
2-Br-4-F—Ph
4-Cl-2,6-di-F—Ph
NH
432


361
H
Me
2,6-di-F—Ph
2-F-4-CN—Ph
O
344


362
H
Me
2,4-di-Cl—Ph
2-Cl-4-CN—Ph
O
394


363
H
Me
2,4-di-Cl—Ph
2,6-di-Cl-4-F—Ph
NH
***


364
H
Me
2,4-di-F—Ph
4-Br-2,6-di-F—Ph
NH
416


365
H
Me
2-Cl-4-F—Ph
4-Br-2,6-di-F—Ph
NH
432


366
H
Me
2-Cl-4-F—Ph
4-Br-2-F—Ph
NH
414


367
H
Me
2-Cl-4-F—Ph
2,4-di-Cl-6-F—Ph
NH
402


368
H
Me
2,4-di-F—Ph
2,4-di-Cl-6-F—Ph
NH



369
H
Me
2-Cl-4-F—Ph
2,4-di-Cl-6-F—Ph
NH



370 (Ex. 7)
H
Me
2-Cl-4-F—Ph
2,4-di-F—Ph
C(═O)
**


371 (Ex. 9)
H
Me
2,4,6-tri-F—Ph
2,6-di-F-4-NH2—Ph
O
**


372
H
Me
2,4-di-F—Ph
2-Br-4-CN—Ph
O



373
H
Me
2,4-di-F—Ph
2-Cl-4-CN—Ph
O



374
H
Me
2,4-di-F—Ph
2,4-di-Cl-6-F—Ph
NH
386


375
H
Me
2,4-di-F—Ph
2,6-di-Cl-4-F—Ph
NH



376
H
Me
2,4-di-F—Ph
2-Br-4,6-di-F—Ph
NH
416


377
H
Me
2-Cl-4-F—Ph
2-Br-4,6-di-F—Ph
NH
432


378
H
Me
2,6-di-F—Ph
4-Br-2,6-di-F—Ph
NH



379
H
Me
2,6-di-F—P
2-Br-4,6-di-F—Ph
NH



380
H
Me
2-Cl-6-F—Ph
2-Br-4,6-di-F—Ph
NH



381
H
Me
2-Cl-4-F—Ph
2,6-di-F-4-Cl—Ph
CHOH
402


382
H
Me
2-F-4-CN—Ph
2-Cl-4,6-di-F—Ph
NH



383
H
Me
2-F-4-CN—Ph
2,6-di-F-4-Cl—Ph
NH



384
H
Me
2-Cl-4-F—Ph
2-Cl-4,6-di-F—Ph
CHOH



385
H
Me
2,4-di-F—Ph
2-Br-4-F—Ph
CHOH



386
H
Me
2-Cl-4-F—Ph
2-Br-4-F—Ph
CHOH



387
H
Me
2-Cl-4-OH—Ph
2,4-di-F—Ph
NH
350


388
H
Me
2-Cl-4-OCH2CN—Ph
2,4-di-F—Ph
NH
389


389
H
Me
2,4-di-F—Ph
4-Br-4-F—Ph
NH
396


390
H
Me
2,4-di-F—Ph
4-Br-2,6-di-Cl—Ph
NH
448


391
H
Me
2,4-di-Cl—Ph
2-Cl-4,6-di-F—Ph
NH
***


392
H
Me
2,4-di-Cl—Ph
4-Cl-2,6-di-F—Ph
NH
***


393
H
Me
2-Cl-4-F—Ph
4-OEt
NH
360


394
H
Me
2-Cl-4-F—Ph
4-Cl-2-F
O
369


395
H
Me
2,4-di-F—Ph
2-F-4-CN—Ph
O
344


396
H
Me
2,4-di-F—Ph
2-Cl-2-F—Ph
NH
352


397
H
Me
2,4-di-F—Ph
2,4-di-Cl-6-F—Ph
NH
386


398
H
Me
2,6-di-F—Ph
4-Cl-2-F—Ph
NH
352


399
H
Me
2,6-di-F-4-(OCH2CH2CH2NMe2)—Ph
2-F-4-CN—Ph
O
445


400
H
Me
4-Cl—Ph
2,6-di-F—Ph
NH
334


401
H
Me
2-Cl-4-F—Ph
4-Cl-2,5-di-F—Ph
NH
386


402
H
Me
2-Br-4-F—Ph
4-Br-2,6-di-F—Ph
NH
474


403
H
Me
2-Cl-4-F—Ph
4-Br-2,6-di-Cl—Ph
NH
464


404
H
Me
2-Cl-4-F—Ph
2-Cl-4,5-di-F—Ph
NH
386


405
H
Me
2,4-di-F—Ph
2,4,6-tri-Cl—Ph
NH
404


406
H
Me
2,4-di-F—Ph
2-Br-4,6-di-F—Ph
NH
416


407
H
Me
2,4-di-F—Ph
4-Br-2-Cl—Ph
NH
414


408
H
Me
2-Br-4-F—Ph
4-Br-2,6-di-Cl—Ph
NH
508


409
H
Me
2-Br-4-F—Ph
4-Br-2-F—Ph
NH
458


410
H
Me
2-Cl-4-F—Ph
2,4,6-tri-Cl—Ph
NH
420


411
H
Me
2-Cl-4-F—Ph
2-Br-4,6-di-F—Ph
NH
432


412
H
Me
2-Cl-4-F—Ph
4-Br-2-Cl—Ph
NH
430


413
H
Me
2-Br-4-F—Ph
4-Br-2-Cl—Ph
NH
474


414
H
Me
2-Br-4-F—Ph
2,4,6-tri-Cl—Ph
NH
464


415
H
Me
2,4-di-F—Ph
4-F-2-I—Ph
NH
444


416
H
Me
2,4-di-F—Ph
2,4,6-tri-Me—Ph
NH
342


417
H
Me
2-Cl-4-F—Ph
4-Cl-2,5-di-F—Ph
NH
386


418
H
Me
2-Cl-4-F—Ph
2-Cl-4,5-di-F—Ph
NH
386


419
H
Me
2-Cl-4-F—Ph
2,4-di-F—Ph
CHOAc
409


420
H
Me
2-Cl-4-F—Ph
pyridin-2-yl
CHOH
332


421
H
Me
2-Cl-4-F—Ph
4-Cl-2-F—Ph
CHOH
384


422
H
Me
2-Cl-4-F—Ph
2,4,6-tri-F—Ph
CHOH
385


423
H
Me
2-Cl-4-F—Ph
2-F-4-CN—Ph
CHOH
374


424
H
Me
2,4-di-F—Ph
4-Cl-2-F-6-I—Ph
NH
478


425
H
Me
2-Cl-4-(OCH2CH2CH2NHMe)—Ph
2,4-di-F—Ph
NH
421


426
H
Me
2-Cl-4-(OCH2CH2CH2OMe)—Ph
2,4-di-F—Ph
NH
422


427
H
Et
2-Cl-4-F—Ph
2,4-di-F—Ph
NH
366


428
H
Et
2-Cl-4-F—Ph
2,4-di-F—Ph
CHOH
382





*1H NMR data found in Index Table B


**AP+ data or 1H NMR data found in the Synthesis Examples


***MP data found in Index Table C














INDEX TABLE B





Cmpd No.
1H NMR Data (CDCl3 solution unless indicated otherwise)a







3
δ 7.11 (m, 1H), 6.99 (m, 1H), 6.75-6.85 (m, 3H), 6.58 (m,



1H), 6.40 (m, 1H), 3.58 (s, 3H), 3.07 (s, 3H), 2.21 (s, 3H).





a1H NMR data are in ppm downfield from tetramethylsilane. Couplings are designated by (s)-singlet and (m)-multiplet.















INDEX TABLE C






Cmpd No.
Melting Pointb








110
85-87



111
165-167



112
80-82



113
135-137



114
147-149



115
168-170



123
171-173



124
135-137



125
138-140



126
142-144



129
127-130



130
129-131



131
129-133



133
160-162



134
228-230



135
112-117



136
152-154



137
165-167



138
171-173



142
186-188



143
93-95



144
176-178



145
142-144



146
145-147



147
60-62



151
150-158



156
107-114



157
 96-101



164
106-110



165
111-113



178
110-112



179
105-107



180
130-132



186
78-84



187
107-113



194
133-135



195
 98-100



197
115-117



198
106-108



199
134-136



200
139-141



201
109-111



207
57-59



209
92-96



210
73-77



211
110-114



212
130-134



214
105-107



215
90-92



216
152-154



217
72-76



218
112-117



224
132-135



225
123-126



226
139-141



227
 99-102



228
133-135



229
144-146



231
108-110



242
91-93



243
82-84



244
95-97



245
73-75



246
182-184



247
156-158



249
83-87



250
126-129



256
171-173



257
172-174



258
121-124



259
 97-100



268
178-180



269
80-85



270
172-176



271
132-135



272
132-134



273
152-153



274
141-143



275
168-171



276
115-117



277
131-134



278
112-114



281
49-52



289
148-150



290
181-183



291
146-149



293
116-118



294
113-115



300
178-180



301
168-170



304
186-191



305
101-105



306
134-138



307
161-166



308
142-145



309
118-123



327
118-120



329
 98-100



333
177-179



334
117-119



337
186-188



339
135-136



340
137-139



341
151-153



353
169-171



354
111-113



355
90-92



363
229-231



391
181-183



392
155-157





bMelting point data are ° C.






BIOLOGICAL EXAMPLES OF THE INVENTION
General protocol for preparing test suspensions for Tests A-J: the test compounds were first dissolved in acetone in an amount equal to 3% of the final volume and then suspended at the desired concentration (in ppm) in acetone and purified water (50/50 mix by volume) containing 250 ppm of the surfactant Trem® 014 (polyhydric alcohol esters). The resulting test suspensions were then used in Tests A-J. Spraying a 200 ppm test suspension to the point of run-off on the test plants was the equivalent of a rate of 500 g/ha. Unless otherwise indicated, the rating values indicate a 200 ppm test suspension was used. (An asterisk “*” next to the rating value indicates a 40 ppm test suspension was used.)
Test A
Grape seedlings were inoculated with a spore suspension of Plasmopara viticola (the causal agent of grape downy mildew) and incubated in a saturated atmosphere at 20° C. for 24 h. After a short drying period, the test suspension was sprayed to the point of run-off on the grape seedlings and then moved to a growth chamber at 20° C. for 4 days, after which time the test units were placed back into a saturated atmosphere at 20° C. for 24 h. Upon removal, visual disease ratings were made.
Test B
The test suspension was sprayed to the point of run-off on tomato seedlings. The following day the seedlings were inoculated with a spore suspension of Botrytis cinerea (the causal agent of tomato Botrytis) and incubated in saturated atmosphere at 20° C. for 48 h, and then moved to a growth chamber at 24° C. for 3 additional days, after which time visual disease ratings were made.
Test C
The test suspension was sprayed to the point of run-off on tomato seedlings. The following day the seedlings were inoculated with a spore suspension of Alternaria solani (the causal agent of tomato early blight) and incubated in a saturated atmosphere at 27° C. for 48 h, and then moved to a growth chamber at 20° C. for 5 days, after which time visual disease ratings were made.
Test D
The test suspension was sprayed to the point of run-off on tomato seedlings. The following day the seedlings were inoculated with a spore suspension of Phytophthora infestans (the causal agent of tomato late blight) and incubated in a saturated atmosphere at 20° C. for 24 h, and then moved to a growth chamber at 20° C. for 5 days, after which time visual disease ratings were made.
Test E
The test suspension was sprayed to the point of run-off on creeping bent grass (Agrostis sp.) seedlings. The following day the seedlings were inoculated with a bran and mycelial slurry of Rhizoctonia solani (the causal agent of turf brown patch) and incubated in a saturated atmosphere at 27° C. for 48 h, and then moved to a growth chamber at 27° C. for 3 days, after which time disease ratings were made.
Test F
The test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore suspension of Septoria nodorum (the causal agent of Septoria glume blotch) and incubated in a saturated atmosphere at 24° C. for 48 h, and then moved to a growth chamber at 20° C. for 6 days, after which time visual disease ratings were made.
Test G
The test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore suspension of Septoria tritici (the causal agent of wheat leaf blotch) and incubated in saturated atmosphere at 24° C. for 48 h. and then the seedlings were moved to a growth chamber at 20° C. for 19 additional days, after which time visual disease ratings were made.
Test H
Wheat seedlings were inoculated with a spore suspension of Puccinia recondita f. sp. tritici (the causal agent of wheat leaf rust) and incubated in a saturated atmosphere at 20° C. for 24 h, and then moved to a growth chamber at 20° C. for 2 days. At the end of this time the test suspension was sprayed to the point of run-off, and then the seedlings were moved to a growth chamber at 20° C. for 6 days after which time visual disease ratings were made.
Test I
The test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore suspension of Puccinia recondita f. sp. tritici (the causal agent of wheat leaf rust) and incubated in a saturated atmosphere at 20° C. for 24 h, and then moved to a growth chamber at 20° C. for 7 days, after which time visual disease ratings were made
Test J
The test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore dust of Erysiphe graminis f. sp. tritici, (the causal agent of wheat powdery mildew) and incubated in a growth chamber at 20° C. for 8 days, after which time visual disease ratings were made.
Results for Tests A-J are given in Table A. In the Table, a rating of 100 indicates 100% disease control and a rating of 0 indicates no disease control (relative to the controls). A dash (-) indicates no test results.

















TABLE A





Cmpd No.
Test A
Test B
Test C
Test D
Test E
Test F
Test G
Test H
Test I
Test J

























1
0
99
 0
0
47
0
99
—
 0
98


2
8
 1
 0
0
 0
0
 0
—
 0
 0


3
6
 0
25
9
 0
0
13
—
 0
99


4
29 
87
46
0
 0
0
98
—
53
97


5
36 
 0
25
0
 0
0
 0
—
 0
 0


6
65 
10
23
0
 0
0
 0
—
 0
93


7
29 
99
 0
0
63
0
100 
—
74
92


8
55 
99
54
0
99
0
100 
—
97
99


9
—
99
 0
0
55
0
100 
—
98
97


10
—
47
 0
0
 0
0
 0
—
 0
 0


11
—
99
99
0
99
0
100 
—
99
100 


12
—
99
93
0
99
0
100 
—
99
100 


13
—
99
100 
0
98
64 
100 
—
100 
99


14
—
98
 0
—
—
0
99
—
99
98


15
—
99
67
—
—
73 
99
—
98
99


16
—
60
 0
—
—
0
47
48 
28
 0


17
—
100 
100 
—
—
93 
97
96 
100 
100 


18
—
99
100 
—
—
99 
95
99 
100 
100 


19
—
100 
85
—
—
0
96
0
92
98


20
—
100 
99
—
—
100 
100 
79 
100 
99


21
—
98
100 
—
—
97 
—
—
100 
99


22
—
90
85
—
—
90 
94
9
94
100 


23
—
98
100 
—
—
99 
93
92 
100 
100 


24
—
98
100 
—
—
0
94
9
97
100 


25
—
100 
 0
—
—
0
100 
0
94
79


26
—
99
83
—
—
0
100 
0
99
100 


27
—
99
88
—
—
0
95
0
25
87


28
—
99
 0
—
—
0
96
7
91
 0


29
—
94
 0
—
—
0
98
0
46
 0


30
—
 7
 0
—
—
0
41
0
79
 0


31
—
 99*
 98*
—
—
 0*
 47*
15*
 79*
 60*


32
—
99
 0
—
—
0
96
0
99
97


33
—
 0
 0
—
—
0
95
0
18
 0


34
—
100*
 97*
—
—
 0*
 96*
 0*
 76*
 0*


35
—
100 
 0
—
—
0
95
0
97
100 


36
—
100 
 0
—
—
0
96
0
96
98


37
0
 0
 0
0
0
0
 3
—
 0
 0


38
—
99
 9
—
—
0
97
0
99
99


39
—
100 
99
—
—
0
99
99 
99
99


40
—
99
 0
—
—
0
94
92 
99
99


41
—
100 
99
—
—
90 
94
0
100 
99


42
—
100 
 0
—
—
0
93
0
94
82


43
—
76
 0
—
—
0
97
66 
82
99


44
—
82
 0
—
—
0
96
7
 9
 0


45
—
100 
100 
—
—
100 
100 
7
100 
100 


46
—
99
100 
—
—
99 
100 
37 
100 
99


47
—
100*
 87*
—
—
 0*
 99*
37*
 96*
 99*


48
—
100 
78
—
—
0
99
0
98
98


49
—
100 
17
—
—
35 
99
0
89
79


50
—
99
57
—
—
0
100 
0
98
99


51
—
100 
 0
—
—
0
100 
0
89
78


52
—
54
 0
—
—
0
97
0
92
64


53
—
 0
 0
—
—
0
 0
0
 0
 0


54
—
96
 0
—
—
0
41
0
95
95


55
—
 6
 0
—
—
0
98
0
41
73


56
—
43
 0
—
—
0
99
0
28
64


57
—
98
 0
—
—
0
94
85 
85
 0


58
—
98
100 
—
—
89 
98
82 
100 
100 


59
—
94
 0
—
—
0
88
0
68
 0


60
—
75
 0
—
—
0
97
59 
79
 0


61
—
97
 0
—
—
0
99
0
38
73


62
—
99
98
—
—
84 
98
98 
99
99


63
—
 0
 0
—
—
0
 0
0
 0
 0


64
—
97
80
—
—
0
100 
0
95
98


65
—
 0
 0
—
—
0
 1
0
58
 0


66
—
100 
99
—
—
0
100 
6
100 
99


67
—
95
 0
—
—
0
99
24 
95
86


68
—
 0
 0
—
—
0
 0
6
 0
 0


69
—
100 
73
—
—
60 
99
91 
99
100 


70
—
99
 0
—
—
0
99
41 
85
98


71
—
93
 0
—
—
0
96
0
91
67


72
—
 0
 0
—
—
0
 0
59 
 0
 0


73
—
100 
99
—
—
64 
100 
88 
100 
99


74
—
 0
 0
—
—
0
25
4
 0
 0


75
—
100 
98
—
—
98 
99
95 
99
97


76
—
100 
 0
—
—
0
98
6
 0
 0


77
—
99
 0
—
—
0
95
6
97
 0


78
—
99
82
—
—
0
98
0
89
91


79
—
99
 0
—
—
0
99
0
55
 0


80
—
100 
 0
—
—
0
99
18 
86
89


81
—
97
 0
—
—
0
 0
0
27
 0


82
—
100 
100 
—
—
40 
99
0
68
13


83
—
100 
100 
—
—
89 
99
99 
96
94


84
—
100 
100 
—
—
78 
100 
98 
100 
99


85
—
 0
 0
—
—
0
17
0
19
 0


86
—
 0
 0
—
—
0
48
0
 0
 0


87
—
100 
100 
—
—
95 
98
85 
99
100 


88
—
100 
100 
—
—
99 
98
95 
99
100 


89
—
99
 0
—
—
0
99
0
 0
97


90
—
99
95
—
—
84 
100 
0
98
100 


91
—
100 
99
—
—
95 
99
0
100 
100 


92
—
100 
100 
—
—
99 
100 
41 
99
100 


93
—
41
 0
—
—
0
77
0
 9
 0


94
—
99
70
—
—
29 
98
0
 9
 0


95
—
99
16
—
—
0
97
0
 0
 0


96
—
99
99
—
—
99 
100 
9
99
100 


97
—
100 
99
—
—
95 
100 
0
99
99


98
—
100 
17
—
—
69 
100 
26 
99
99


99
—
100 
99
—
—
100 
99
40 
100 
100 


100
—
38
 0
—
—
0
48
0
41
 0


101
—
100 
99
—
—
100 
100 
99 
99
100 


102
—
100 
100 
—
—
98 
99
0
100 
98


103
—
100 
64
—
—
0
95
0
91
 0


104
—
100 
99
—
—
97 
99
99 
99
100 


105
—
23
 0
—
—
0
73
9
 0
72


106
—
100 
99
—
—
90 
100 
82 
99
100 


107
—
 99*
 0*
—
—
 0*
 99*
 8*
 24*
 0*


108
—
97
 0
—
—
0
98
0
16
97


109
—
100 
99
—
—
97 
100 
99 
100 
100 


110
—
99
66
—
—
98 
99
0
97
94


111
—
99
75
—
—
90 
99
0
97
99


112
—
100 
98
—
—
99 
99
53 
100 
100 


113
—
99
47
—
—
0
100 
8
95
48


114
—
99
24
—
—
69 
99
8
99
84


115
—
99
 0
—
—
0
100 
0
91
 0


116
—
100 
94
—
—
73 
100 
16 
97
99


117
—
99
97
—
—
82 
100 
11 
98
97


118
—
100 
100 
—
—
98 
100 
99 
100 
99


119
—
100 
 0
—
—
0
100 
16 
99
96


120
—
100 
99
—
—
94 
100 
0
99
99


121
—
100 
86
—
—
82 
99
83 
100 
97


122
—
 0
 0
—
—
0
 0
11 
 0
 0


123
—
99
 0
—
—
40 
99
—
80
 0


124
—
100 
78
—
—
60 
99
—
96
94


125
—
100 
67
—
—
60 
99
—
92
 0


126
—
99
96
—
—
60 
100 
0
94
 0


127
—
70
 0
—
—
0
99
0
68
 0


128
—
100 
100 
—
—
97 
99
66 
100 
100 


129
—
99
 0
—
—
0
96
0
 0
 0


130
—
97
 0
—
—
0
99
0
19
 0


131
—
99
 0
—
—
0
98
0
86
94


132
—
99
 0
—
—
0
100 
0
94
92


133
—
100 
100 
—
—
60 
99
0
100 
94


134
—
99
 0
—
—
0
99
0
41
 0


135
—
 0
 0
—
—
0
97
16 
74
95


136
—
99
71
—
—
86 
99
0
99
100 


137
—
96
97
—
—
78 
99
8
100 
100 


138
—
99
96
—
—
84 
99
38 
100 
98


139
—
100 
86
—
—
100 
100 
69 
99
100 


140
—
99
94
—
—
87 
99
0
96
97


141
—
99
99
—
—
98 
100 
0
99
100 


142
—
33
13
—
—
20 
99
0
95
90


143
—
99
99
—
—
100 
100 
63 
100 
100 


144
—
99
 9
—
—
40 
99
0
98
91


145
—
96
98
—
—
100 
100 
88 
100 
100 


146
—
99
 0
—
—
0
99
0
97
56


147
—
99
88
—
—
100 
100 
0
98
92


148
—
99
99
—
—
100 
100 
61 
100 
99


149
—
100 
98
—
—
100 
100 
99 
100 
100 


150
—
19
 0
—
—
60 
 7
0
74
50


151
—
99
 9
—
—
0
96
0
54
64


152
—
100 
82
—
—
87 
99
9
97
99


153
—
100 
 0
—
—
73 
100 
0
96
98


154
—
99
99
—
—
97 
100 
41 
100 
100 


155
—
100 
99
—
—
100 
100 
92 
100 
99


156
—
94
 0
—
—
0
73
0
41
47


157
—
 0
 0
—
—
0
 0
0
54
73


158
—
100 
 0
—
—
0
99
18 
99
98


159
—
99
 0
—
—
0
100 
74 
99
100 


160
—
98
99
—
—
0
99
8
100 
100 


161
—
98
100 
—
—
0
100 
95 
100 
98


162
—
99
 0
—
—
0
99
8
98
94


163
—
 0
 9
—
—
0
83
0
88
 0


164
—
49
57
—
—
0
99
15 
 9
97


165
—
 0
 0
—
—
0
52
8
 0
99


166
—
 0
 0
—
—
0
97
0
68
96


167
—
75
 0
—
—
0
 0
0
 0
 0


168
—
14
 0
—
—
0
33
0
 0
 0


169
—
24
 0
—
—
0
85
0
 0
 0


170
—
100 
99
—
—
99 
98
0
100 
99


171
—
100 
97
—
—
0
97
68 
99
100 


172
—
100 
100 
—
—
87 
100 
0
99
100 


173
—
100 
86
—
—
0
98
0
83
100 


174
—
100 
99
—
—
0
96
0
97
99


175
—
100 
99
—
—
82 
96
93 
99
100 


176
—
100 
71
—
—
0
96
0
68
100 


177
—
100 
100 
—
—
73 
98
0
83
100 


178
—
100 
100 
—
—
80 
98
0
83
100 


179
—
100 
99
—
—
73 
95
0
93
100 


180
—
100 
99
—
—
0
98
0
68
100 


181
—
94
44
—
—
0
100 
0
60
98


182
—
97
99
—
—
87 
100 
0
95
99


183
—
97
100 
—
—
67 
99
27 
94
99


184
—
97
 0
—
—
0
99
0
82
98


185
—
 0
 0
—
—
0
100 
0
74
98


186
—
 0
 0
—
—
0
99
0
54
93


187
—
33
 0
—
—
0
20
0
 9
13


188
—
87
 0
—
—
0
100 
0
97
97


189
—
99
100 
—
—
80 
100 
99 
99
98


190
—
99
99
—
—
80 
100 
94 
100 
99


191
—
98
100 
—
—
0
100 
0
97
99


192
—
97
100 
—
—
73 
100 
0
99
99


193
—
99
100 
—
—
0
100 
32 
99
100 


194
—
97
86
—
—
0
99
0
91
99


195
—
100 
97
—
—
60 
100 
0
98
97


196
—
99
94
—
—
73 
100 
9
98
98


197
—
97
 0
—
—
95 
99
0
79
96


198
—
97
68
—
—
0
100 
0
94
97


199
—
99
86
—
—
0
99
0
68
98


200
—
82
 0
—
—
0
97
0
 0
94


201
—
99
97
—
—
20 
100 
18 
97
99


202
—
99
 0
—
—
0
99
0
28
99


203
—
99
 0
—
—
0
98
0
96
100 


204
—
100*
 77*
—
—
 0*
 99*
 0*
 86*
 99*


205
—
100 
17
—
—
0
99
0
91
100 


206
—
99
99
—
—
84 
99
41 
99
100 


207
—
100 
93
—
—
64 
100 
0
99
100 


208
—
100 
100 
—
—
99 
100 
0
99
99


209
—
 0
 0
—
—
0
 0
0
 0
97


210
—
 0
 0
—
—
0
100 
99 
94
99


211
—
77
 0
—
—
0
99
0
17
96


212
—
 0
17
—
—
—
98
0
—
—


213
—
97
30
—
—
0
85
94 
96
100 


214
—
98
51
—
—
0
100 
9
99
100 


215
—
89
 0
—
—
0
98
0
94
99


216
—
96
 0
—
—
0
76
0
26
99


217
—
75
 0
—
—
0
83
40 
79
99


218
—
94
 0
—
—
0
99
17 
92
87


219
—
70
 0
—
—
0
 0
17 
 0
 0


220
—
98
97
—
—
40 
98
40 
99
100 


221
—
98
94
—
—
82 
100 
17 
99
100 


222
—
99
99
—
—
0
100 
88 
99
100 


223
—
96
 9
—
—
99 
100 
0
100 
100 


224
—
99
51
—
—
0
100 
17 
91
100 


225
—
65
 0
—
—
0
99
0
79
98


226
—
99
 0
—
—
0
96
28 
91
100 


227
—
87
 0
—
—
0
99
0
74
98


228
—
99
99
—
—
0
99
0
80
99


229
—
99
17
—
—
0
99
0
91
98


230
—
99
99
—
—
0
100 
0
97
100 


231
—
98
34
—
—
0
100 
0
86
100 


232
—
100 
99
—
—
99 
100 
0
100 
100 


233
—
100 
99
—
—
99 
100 
0
100 
100 


234
—
99
 0
—
—
0
99
0
92
84


235
—
84
 0
—
—
0
17
0
 0
79


236
—
97
 0
—
—
0
96
0
68
97


237
—
99
 0
—
—
0
97
0
68
97


238
—
99
 0
—
—
0
 0
53 
 9
43


239
—
99
95
—
—
0
67
0
68
100 


240
—
100 
99
—
—
0
99
0
99
100 


241
—
99
99
—
—
0
100 
97 
100 
100 


242
—
99
37
—
—
0
100 
0
91
100 


243
—
100 
64
—
—
0
100 
0
97
100 


244
—
82
 0
—
—
0
91
0
 0
96


245
—
90
 0
—
—
0
97
0
68
93


246
—
99
51
—
—
0
100 
0
80
100 


247
—
100 
99
—
—
60 
100 
0
99
100 


248
—
99
26
—
—
73 
100 
0
99
100 


249
—
40
 0
—
—
0
99
0
96
100 


250
—
98
 0
—
—
0
77
0
86
100 


251
—
99
 0
—
—
0
98
0
86
100 


252
—
100 
97
—
—
0
100 
0
100 
100 


253
—
99
 0
—
—
0
 0
0
 0
76


254
—
100 
 0
—
—
0
84
0
 0
64


255
—
100 
 0
—
—
0
 0
0
 0
39


256
—
99
99
—
—
96 
100 
0
99
100 


257
—
100 
99
—
—
0
100 
0
97
98


258
—
41
 9
—
—
0
89
0
68
90


259
—
98
 9
—
—
0
100 
0
86
97


260
—
 0
 0
—
—
0
 0
0
 0
 0


261
—
 0
 0
—
—
0
 0
0
 0
47


262
—
99
51
—
—
0
 0
0
68
99


263
—
100 
98
—
—
0
100 
0
98
100 


264
—
100 
98
—
—
0
92
0
99
98


265
—
100 
99
—
—
78 
100 
90 
100 
100 


266
—
100 
100 
—
—
98 
100 
0
100 
100 


267
—
100 
79
—
—
60 
100 
0
96
93


268
—
95
93
—
—
0
99
0
74
 0


269
—
80
 0
—
—
0
67
8
 0
 0


270
—
92
86
—
—
0
91
8
 0
81


271
—
100 
99
—
—
99 
100 
0
99
98


272
—
100 
97
—
—
99 
99
0
99
99


273
—
 0
 0
—
—
0
72
0
27
43


274
—
 8
 0
—
—
0
96
8
 0
69


275
—
97
46
—
—
0
99
8
97
99


276
—
100 
99
—
—
98 
100 
31 
100 
100 


277
—
100 
 0
—
—
0
100 
0
96
98


278
—
99
 0
—
—
0
99
0
82
100 


279
—
100 
99
—
—
0
100 
8
98
100 


280
—
99
 0
—
—
0
96
8
18
87


281
—
98
44
—
—
0
—
0
94
98


282
—
99
98
—
—
0
—
0
99
100 


283
—
99
65
—
—
0
—
9
99
100 


284
—
99
99
—
—
100 
—
28 
100 
100 


285
—
98
 0
—
—
60 
—
9
99
99


286
—
 98*
 85*
—
—
60*
—
100* 
100*
100*


288
9
99
52
0
92
0
—
—
74
92


289
—
100 
 0
—
—
0
99
0
96
97


290
—
100 
99
—
—
87 
100 
0
100 
100 


291
—
99
 0
—
—
0
98
0
85
43


292
—
100 
99
—
—
96 
100 
92 
100 
100 


293
0
97
47
0
99
0
—
—
94
99


294
0
98
 0
0
80
0
—
—
 0
84


296
—
99
 0
—
—
0
100 
0
99
—


297
—
100 
99
—
—
90 
100 
0
100 
100 


298
—
100 
93
—
—
87 
100 
0
100 
100 


299
—
100 
95
—
—
51 

41 
100 
100 


300
—
100 
99
—
—
82 
100 
9
99
100 


301
—
99
87
—
—
87 
100 
0
98
99


302
—
 99*
 0*
—
—
 0*
 99*
 0*
 18*
 97*


303
—
99
 0
—
—
0
98
0
92
71


304
—
 0
 0
—
 0
0
16
—
 0
 0


305
—
99
99
—
—
94 
100 
0
99
99


306
—
 7
 0
—
—
0
93
0
28
64


307
—
 0
 0
—
—
0
 0
0
 0
 0


308
—
81
 0
—
—
0
98
9
100 
 0


309
—
97
61
—
92
60 
100 
—
 0
99


310
—
100 
99
—
—
99 
100 
0
99
96


311
—
100 
 0
—
—
60 
100 
0
99
91


313
—
100 
97
—
—
51 
100 
91 
100 
100 


314
—
100 
95
—
—
0
100 
94 
100 
100 


315
—
99
99
—
—
0
100 
0
96
100 


316
—
99
 0
—
—
0
—
9
99
96


318
—
99
 0
—
—
0
100 
0
97
89


319
—
92
88
—
—
100 
100 
0
99
95


320
—
99
67
—
—
0
100 
0
99
98


321
—
100 
99
—
—
78 
100 
9
99
100 


322
—
100 
93
—
—
0
100 
99 
100 
100 


323
—
98
 0
—
—
0
98
0
94
—


324
—
99
83
—
—
0
100 
63 
99
99


325
—
100 
 0
—
—
0
100 
0
97
99


326
8
99
99
0
99
73 
100 
—
99
94


327
—
99
 0
—
—
0
100 
0
96
99


328
—
100 
86
—
—
0
100 
0
98
100 


329
—
100 
99
—
—
69 
100 
0
100 
100 


331
—
100 
80
—
—
73 
100 
8
100 
97


333
—
100 
 0
—
—
0
100 
9
74
 0


334
—
100 
 0
—
—
0
100 
0
97
100 


336
—
100 
97
—
—
95 
100 
94 
100 
99


337
—
99
 0
—
—
0
99
9
41
98


338
—
100 
37
—
—
40 
100 
8
100 
99


339
—
100 
 0
—
—
0
100 
0
98
100 


340
—
99
 0
—
—
0
100 
0
91
100 


341
—
99
 0
—
—
0
99
0
99
93


342
—
100 
33
—
—
99 
100 
0
100 
100 


343
—
100 
100 
—
—
97 
100 
91 
100 
100 


344
—
100 
40
—
—
87 
100 
62 
100 
100 


345
—
 0
 0
—
—
0
67
0
 9
 0


348
—
100 
80
—
—
94 
100 
19 
100 
100 


350
—
99
 9
—
—
0
—
9
96
 0


351
—
100 
99
—
—
92 
—
96 
100 
99


353
—
97
17
—
—
0
99
3
99
99


354
—
99
 0
—
—
0
100 
82 
98
100 


355
—
99
 0
—
—
0
100 
3
91
 0


356
—
100 
 0
—
—
0
—
100 
100 
 0


357
—
100 
86
—
—
87 
100 
0
99
100 


358
—
99
 0
—
—
0
100 
0
97
97


359
—
100 
99
—
—
97 
100 
0
100 
99


360
—
100 
97
—
—
95 
100 
79 
100 
100 


361
—
100 
90
—
—
0
100 
0
100 
100 


362
—
100 
 0
—
—
0
100 
0
96
96


363
—
65
 0
—
—
0
99
0
96
43


364
—
99
97
—
—
88 
100 
0
99
100 


365
—
100 
99
—
—
64 
100 
74 
100 
100 


366
—
100 
58
—
—
0
100 
9
99
100 


367
—
100 
100 
—
—
100 
—
100 
100 
100 


369
—
100 
66
—
—
0
—
17 
100 
99


389
—
100 
 9
—
—
0
—
68 
98
99


391
—
100 
99
—
—
73 
—
31 
99
99


403
—
99
 0
—
—
0
—
99 
100 
99





“Cmpd No.” means compound number and refers to the same compound number as in Index Table A.

## Claims

1. A compound selected from Formula 1, N-oxides and salts thereof,




wherein
Q1 is a phenyl ring optionally substituted with up to 5 substituents independently selected from R3 
Q2 is pyridinyl substituted with 1, 2 or 3 substituents independently selected form R3;
X is NR4;
R1 is H, C1-C6 alkyl or CO2R5;
R1a is H;
R2 is CH3, CH2CH3, halogen or cyano;
each R3 is independently selected from halogen, cyano, nitro, amino, methylamino, dimethylamino, formylamino, C2-C3 alkylcarbonylamino, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 haloalkylthio, C1-C3 alkylsulfinyl, C1-C3 haloalkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylsulfonyl, C1-C2 alkylsulfonyloxy, C1-C2 haloalkylsulfonyloxy, C3-C4 cycloalkyl, C3-C7 cycloalkoxy, C4-C6 alkylcycloalkyl, C4-C6 cycloalkylalkyl, C3-C7 halocycloalkyl, C2-C4 alkenyl, C2-C4 alkynyl, hydroxy, formyl, C2-C3 alkylcarbonyl, C2-C3 alkylcarbonyloxy, —SF5, —SCN, C(═S)NR19R20 and —U—V-T;
R4 is H;
R5 is H, C1-C6 alkyl or C1-C6 haloalkyl;
each R19 and R20 is independently H or CH3;
each U is independently O, S(═O)w, NR22 or a direct bond;
each V is independently C1-C6 alkylene, C2-C6 alkenylene, C3-C6 alkynylene, C3-C6 cycloalkylene or C3-C6 cycloalkenylene, wherein up to 3 carbon atoms are independently selected from C(═O), each optionally substituted with up to 5 substituents independently selected from halogen, cyano, nitro, hydroxy, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy and C1-C6 haloalkoxy;
each T is independently cyano, NR23aR23b, OR24 or S(═O)yR25;
each R22 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 (alkylthio)carbonyl, C2-C6 alkoxy(thiocarbonyl), C4-C8 cycloalkylcarbonyl, C4-C8 cycloalkoxycarbonyl, C4-C8 (cycloalkylthio)carbonyl or C4-C8 cycloalkoxy(thiocarbonyl);
each R23a and R23b is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C3-C6 alkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 (alkylthio)carbonyl, C2-C6 alkoxy(thiocarbonyl), C4-C8 cycloalkylcarbonyl, C4-C8 cycloalkoxycarbonyl, C4-C8 (cycloalkylthio)carbonyl or C4-C8 cycloalkoxy(thiocarbonyl); or
a pair of R23a and R23b attached to the same nitrogen atom are taken together with the nitrogen atom to form a 3- to 6-membered heterocyclic ring, the ring optionally substituted with up to 5 substituents independently selected from R26;
each R24 and R25 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C3-C6 alkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C2-C6 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 (alkylthio)carbonyl, C2-C6 alkoxy(thiocarbonyl), C4-C8 cycloalkylcarbonyl, C4-C8 cycloalkoxycarbonyl, C4-C8 (cycloalkylthio)carbonyl or C4-C8 cycloalkoxy(thiocarbonyl);
each R26 is independently halogen, C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 alkoxy;
each w is independently 0, 1 or 2; and
each y is independently 0, 1 or 2.

2. A compound of claim 1 wherein:
Q1 is phenyl substituted with from 1 to 4 substituents independently selected from R3; provided that when an R3 substituent is located at a meta position, then said R3 substituent is selected from F, Cl, Br and cyano;
Q2 is pyridinyl substituted with 1, 2 or 3 substituents independently selected from R3, provided that when an R3 substituent is located at a meta position, then said R3 substituent is selected from F, Cl, Br and cyano;
R2 is CH3, CH2CH3, Cl or Br;
each R3 is independently selected from halogen, cyano, nitro, amino, methylamino, dimethylamino, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy C1-C3 alkylthio, C1-C3 haloalkylthio, C1-C3 alkylsulfinyl, C1-C3 haloalkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylsulfonyl, C3-C4 cycloalkyl, C(═S)NH2 and —U—V-T; and
R5 is C1-C6 alkyl.

3. A compound of claim 2 wherein
Q1 is phenyl substituted with 1, 2 or 3 substituents independently selected from R3;
R2 is CH3, Cl or Br;
each R3 is independently selected from halogen, cyano, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy and —U—V-T;
each U is independently O or NH;
each V is C2-C4 alkylene;
each T is independently NR23a R23b or OR24;
each R23a and R23b is independently H, C1-C6 alkyl or C1-C6 haloalkyl; and
each R24 is independently H, C1-C6 alkyl or C1-C6 haloalkyl.

4. A compound of claim 3 wherein
Q1 is phenyl substituted with 2 or 3 substituents independently selected from R3;
R2 is CH3; and
each R3 is independently selected from halogen, cyano, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy and C1-C3 haloalkoxy.

5. A compound of claim 4 wherein
Q1 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R3; or phenyl substituted at the 2- and 4-positions with substituents independently selected from R3; or phenyl substituted at the 2- and 6-positions with substituents independently selected from R3;
and
each R3 is independently selected from F, Cl, Br, cyano, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy and C1-C2 haloalkoxy.

6. A compound of claim 5 wherein
each R3 is independently selected from F, Cl, Br, cyano, methyl, C1-C2 alkoxy and fluoromethoxy.

7. A compound of claim 6 wherein
each R3 is independently selected from F, Cl, Br, cyano and methoxy.

8. A fungicidal composition comprising (a) a compound of claim 1; and (b) at least one other fungicide.

9. A fungicidal composition comprising: (a) a compound of claim 1; and (b) at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.

10. A method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of a compound of claim 1.

11. A composition comprising a compound of claim 1, and at least one invertebrate pest control compound or agent.

12. A compound selected from Formula 1, N-oxides and salts thereof,




wherein
Q1 is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R3; or phenyl substituted at the 2- and 4-positions with substituents independently selected from R3; or phenyl substituted at the 2- and 6-positions with substituents independently selected from R3;
Q2 is selected from




wherein Ra is independently selected from R3; and r is an integer ranging from 0 to 4;
X is NR4;
R1 is H or CH3;
R1a is H;
R2 is CH3, CH2CH3, Cl, Br or I;
each R3 is independently selected from F, Cl, Br, cyano, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy and C1-C2 haloalkoxy; and
R4 is H.

13. A compound of claim 12 wherein:
Q2 is U-44 or U-45;
R1 is H;
R2 is CH3; and
each R3 is independently selected from F, Cl, Br, cyano and methoxy.