Patent EP-0107622-B1 (EP)
IPC: C07D317/46
Filed: 1983-10-17
Granted: 1987-11-11
Abstract: 1. Claims (for the Contracting States : BE, CH, LI, DE, FR, GB, IT, LU, NL, SE) Compounds of the general formula I  see diagramm : EP0107622,P32,F1  in which R1 represents an alkyl, alkenyl or alkynyl radical that is unsubstituted or substituted by halogen having an atomic number of up to 35, lower alkoxy or by lower alkylthio and has, in total, that is to say including the substituents, a maximum of 12 carbon atoms, or represents a phenyl or naphthyl radical that is unsubstituted or substituted by lower alkyl, lower cycloalkyl, lower alkoxy, lower alkylthio, lower alkylsulphonyl, trifluoromethyl, hydroxy, lower alkanoyl, lower alkanoylamino, lower alkoxycarbonylamino and/or by lower alkylsulphonylamino, a monocyclic five-membered hetero ring of aromatic character having two nitrogen atoms or one nitrogen atom and/or one oxygen or sulphur atom in the ring or a six-membered hetero ring of aromatic character having one or two nitrogen atoms in the ring, or a bicyclic radical consisting of the said five- or six-membered hetero rings of aromatic character with a fused benzene ring, alk represents an alkylene, alkenylene or alkylidene radical having a maximum of 5 carbon atoms, n1 represents 0, 1 or 2 and n2 represents 0 or 1, R2 , R3 and R4 each represents, independently of the others, hydrogen, lower alkyl, lower alkoxy or halogen, and A represents the radical -O-R5 wherein R5 represents hydrogen or an alkyl radical having a maximum of 12 carbon atoms that is unsubstituted or is substituted by lower alkoxy or by halogen, 2- or 3-lower alkenyl, 2-lower alkynyl, phenyl-lower alkyl or cinnamyl, in which the phenyl radical may be substituted in the same manner as under R1 , or A represents the radical  see diagramm : EP0107622,P33,F1  in which either R6 and R7 each represents, independently of the other, hydrogen or lower alkyl, or R6 and R7 are bonded to one another and, together with the adjacent nitrogen atom, represent optionally lower alkyl-substituted tetra- to hexa-methyleneimino, 4-morpholinyl or 1H-tetrazol-1-yl, salts of compounds of the general formula I in which A represents OR5 wherein R5 represents hydrogen, with bases, and acid addition salts of compounds of the general formula I in which the radical R1 has a basic character, radicals designated "lower" having a maximum of 7 carbon atoms. 1. Claims (for the Contracting State AT) A process for the manufacture of compounds of the formula I  see diagramm : EP0107622,P36,F2  in which R1 represents an alkyl, alkenyl or alkynyl radical that is unsubstituted or substituted by halogen having an atomic number of up to 35, lower alkoxy or by lower alkylthio and has, in total, that is to say including the substituents, a maximum of 12 carbon atoms, or represents a phenyl or naphthyl radical that is unsubstituted or substituted by lower alkyl, lower cycloalkyl, lower alkoxy, lower alkylthio, lower alkylsulphonyl, trifluoromethyl, hydroxy, lower alkanoyl, lower alkanoylamino, lower alkoxycarbonylamino and/or by lower alkylsulphonylamino, a monocyclic five-membered hetero ring of aromatic character having two nitrogen atoms or one nitrogen atom and/or one oxygen or sulphur atom in the ring or a six-membered hetero ring of aromatic character having one or two nitrogen atoms in the ring, or a bicyclic radical consisting of the said five- or six-membered hetero rings of aromatic character with a fused benzene ring, alk represents an alkylene, alkenylene or alkylidene radical having a maximum of 5 carbon atoms, n1 represents 0, 1 or 2 and n2 represents 0 or 1, R2 , R3 and R4 each represents, independently of the others, hydrogen, lower alkyl, lower alkoxy or halogen, and A represents the radical -O-R5 wherein R5 represents hydrogen or an alkyl radical having a maximum of 12 carbon atoms that is unsubstituted or is substituted by lower alkoxy or by halogen, 2- or 3-lower alkenyl, 2-lower alkynyl, phenyl-lower alkyl or cinnamyl, in which the phenyl radical may be substituted in the same manner as under R1 , or A represents the radical  see diagramm : EP0107622,P36,F3  in which either R6 and R7 each represents, independently of the other, hydrogen or lower alkyl, or R6 and R7 are bonded to one another and, together with the adjacent nitrogen atom, represent optionally lower alkyl-substituted tetra- to hexa-methyleneimino, 4-morpholinyl or 1H-tetrazol-1-yl, salts of compounds of the general formula I in which A represents OR5 wherein R5 represents hydrogen with bases, and acid addition salts of compounds of the general formula I in which the radical R1 has a basic character, radicals designated "lower" having a maximum of 7 carbon atoms, characterised in that a) a compound of the general formula II  see diagramm : EP0107622,P37,F1  in which R1 , alk, n1 , n2 , R2 , R3 and R4 have the meanings given above, or a salt thereof, is reacted with a compound of the general formula III  see diagramm : EP0107622,P37,F2  in which Hal represents halogen and A has the meaning given above, or with a salt of such a compound in which A represents OR5 wherein R5 represents hydrogen, or b) in a compound of the general formula IV  see diagramm : EP0107622,P37,F3  in which A**b represents carboxy, lower alkoxycarbonyl or acetyl, and R1 , alk, n1 , n2 , R2 , R3 , R4 and A have the meanings given in claim 1, the radical A**b is replaced by hydrogen, or c) for the manufacture of a compound of the general formula I in which A has the meaning given above with the exception of a radical OR5 in which R5 represents hydrogen, and R1 , alk, n2 , R2 , R3 and R4 have the meanings given above and n1 represents 1 or 2, a compound of the general formula V  see diagramm : EP0107622,P37,F4  is reacted with a compound of the general formula VI R1 -(alk)n2 -S(O)n1-c -OH or with an anhydride thereof, in which A1 has the meaning given above for A with the exception of a radical OR5 in which R5 represents hydrogen, n1-c represents 1 or 2 and R2 , R3 and R4 , and R1 , alk and n2 have the meanings given above, or d) for the manufacture of a compound in which n2 is 1 or R1 is an aliphatic radical according to the definition and R1 or n2 , as the case may be, alk, n2 , R2 , R3 , R4 and A have the meanings given above, a compound of the general formula VII R1 -(alk)n2-d -Z**d in which Z**d represents a reactively esterified hydroxy group, especially halogen having an atomic number of at least 17, R1 has the meaning given above and n2 represents 1 or, if R2 is an aliphatic radical, may alternatively be 0, or a compound of the general formula VIII  see diagramm : EP0107622,P37,F5 in which Z**dd (cation) represents a monovalent anion or the normal equivalent of a polyvalent anion and R1 and n1 have the meanings given above, is reacted with a salt of a compound of the general formula IX  see diagramm : EP0107622,P38,F1  in which n1 , R2 , R3 , R4 and A have the meanings given in claim 1, or e) a metal compound, optionally formed in situ, of the general formula Xa or Xb R1 -(alk)n2 -M1  see diagramm : EP0107622,P38,F2  in which M1 represents a monovalent metal ion and M2 represents a divalent metal ion and R, alk and n2 have the meanings given above, is reacted with a compound of the general XIa or XIb  see diagramm : EP0107622,P38,F3   see diagramm : EP0107622,P38,F4  in which Hal represents halogen and n1 , R2 , R3 , R4 and A have the meanings given above, or f) for the manufacture of a compound of the general formula I in which A represents OR5 wherein R5 represents hydrogen, and R1 , alk, n1 , n2 , R2 , R3 and R4 have the meanings given above, or a salt of this compound : in a compound of the general formula XIII  see diagramm : EP0107622,P38,F5  in which A**f represents a group that can be converted into the carboxy group and R1 , alk, n1 , n2 , R2 , R3 and R4 have the meanings given above, the group A**f is converted into the carboxy group in free or salt form, or g) for the manufacture of a compound of the general formula I in which A has the meaning given above with the exception of a radical OR5 in which R5 represents hydrogen, and R1 , alk, n1 , n2 , R2 and R3 have the meanings given above : in a compound of the general formula XIV  see diagramm : EP0107622,P38,F6  in which A**g represents a radical that can be converted into a radical CO-A1 in which A1 has the meaning given above for A with the exception of a radical OR5 in which R5 represents hydrogen, and R1 , alk, n1 , n2 , R2 , R3 and R4 have the meanings given in claim 1, the radical A**g is converted into the radical -CO-A1 , and h) if desired, a compound of the general formula I in which n1 represents 0 or 1 is oxidised to form the corresponding compound in which n1 represents 1 or 2, or i) if desired, a compound of the general formula I in which n1 represents 2 or 1 is reduced to form the corresponding compound in which n1 represents 1 or 0, and/or, if desired, a resulting compound of the general formula I is converted in a different manner known per se into a different compound of the general formula I, and/or a compound of the general formula I obtained in the form of a racemate is separated into the optical antipodes, and/or a resulting compound of the general formula I in which A represents OR5 wherein R5 represents hydrogen is converted into a salt with a base, or such a compound is freed from a resulting salt, or a resulting compound of the general formula I of basic character is converted into an acid addition salt, or such a compound is freed from a resulting salt.