Patent EP-0115997-B1 (EP)
IPC: C07D235/30
Filed: 1984-02-01
Granted: 1987-07-22
Abstract: For the Contracting States : BE CH DE FR GB IT LI LU NL SE 1. Compounds with the formula (I) :   see diagramm : EP0115997,P26,F1   in which R1  represents a hydrogen atom or a   see diagramm : EP0115997,P26,F2   radical, R'1  being an alkyl radical containing from 1 to 5 carbon atoms or an aryl radical possibly substituted by a hydroxy radical, an alkyl radical containing from 1 to 5 carbon atoms, an alkoxy radical containing from 1 to 5 carbon atoms, a nitro radical or a halogen atom, n represents a whole number able to vary from 1 to 5, R2  represents a hydrogen atom, an alkyl radical containing from 1 to 5 carbon atoms, an aryl or arylalkyl radical containing from 6 to 15 carbon atoms, possibly substituted by an alkyl radical containing from 1 to 5 carbon atoms, an alkoxy radical containing from 1 to 5 carbon atoms, a hydroxyl radical, a halogen atom or a trifluoromethyl radical, R3  represents a heterocyclic radical chosen from the following radicals :- thiazolyl, 4,5-dihydrothiazolyl, pyridinyl, oxazolyl, isoxazolyl, imidazolyl, pyrimidyl, tetrazolyl, benzimidazolyl, benzothiazolyl or benzoxazolyl, possibly substituted by an alkyl radical containing from 1 to 5 carbon atoms or R3  represents a hydrogen atom, a phenyl radical possibly substituted by one or more radicals chosen from the group constituted by alkyl radicals containing from 1 to 5 carbon atoms, alkoxy radicals containing from 1 to 5 carbon atoms, a hydroxyl radical, a nitro radical, halogen atoms, a trifluoromethyl radical, a carboxymethyl radical, alkoxy carbonylmethyl radicals in which the alkoxy radical contains from 1 to 5 carbon atoms, aralkyloxy radicals containing from 7 to 15 carbon atoms and the radicals :   see diagramm : EP0115997,P27,F3   in which X and X', identical or different, represent a hydrogen atom or an alkyl radical containing from 1 to 5 carbon atoms, R3  however not being able to represent a phenyl radical, not substituted or substituted by one or more radicals chosen from the group constituted by alkyl radicals containing from 1 to 5 carbon atoms, alkoxy radicals containing from 1 to 5 carbon atoms, and halogen atoms, when R2  represents a hydrogen atom and when n is equal to 1 or 2, and R3  not being able to represent a phenyl radical substituted by a carboxymethyl radical when R2  represents a methyl radical and when n is equal to 1, as well as their addition salts with acids and bases. For the Contracting State : AT 1. Process for preparing compounds with the formula (I) :   see diagramm : EP0115997,P28,F1   in which R1  represents a hydrogen atom or a   see diagramm : EP0115997,P28,F2   radical, R'1  being an alkyl radical containing from 1 to 5 carbon atoms or an aryl radical possibly substituted by a hydroxy radical, an alkyl radical containing from 1 to 5 carbon atoms, an alkoxy radical containing from 1 to 5 carbon atoms, a nitro radical or a halogen atom, n represents a whole number able to vary from 1 to 5, R2  represents a hydrogen atom, an alkyl radical containing from 1 to 5 carbon atoms, an aryl or arylalkyl radical containing from 6 to 15 carbon atoms, possibly substituted by an alkyl radical containing from 1 to 5 carbon atoms, an alkoxy radical containing from 1 to 5 carbon atoms, a hydroxyl radical, a halogen atom or a trifluoromethyl radical, R3  represents a heterocyclic radical chosen from the following radicals :- thiazolyl, 4,5-dihydrothiazolyl, pyridinyl, oxazolyl, isoxazolyl, imidazolyl, pyrimidyl, tetrazolyl, benzimidazolyl, benzothiazolyl or benzoxazolyl, possibly substituted by an alkyl radical containing from 1 to 5 carbon atoms or R3  represents a hydrogen atom, a phenyl radical possibly substituted by one or more radicals chosen from the group constituted by alkyl radicals containing from 1 to 5 carbon atoms, alkoxy radicals containing from 1 to 5 carbon atoms, a hydroxyl radical, a nitro radical, halogen atoms, a trifluoromethyl radical, a carboxymethyl radical, alkoxy carbonylmethyl radicals in which the alkoxy radical contains from 1 to 5 carbon atoms, aralkyloxy radicals containing from 7 to 15 carbon atoms and the radicals :   see diagramm : EP0115997,P29,F3   in which X and X', identical or different, represent a hydrogen atom or an alkyl radical containing from 1 to 5 carbon atoms, R3  however not being able to represent a phenyl radical, not substituted or substituted by one or more radicals chosen from the group constituted by alkyl radicals containing from 1 to 5 carbon atoms, alkoxy radicals containing from 1 to 5 carbon atoms, and halogen atoms, when R2  represents a hydrogen atom and when n is equal to 1 or 2, and R3  not being able to represent a phenyl radical substituted by a carboxymethyl radical when R2  represents a methyl radical and when n is equal to 1, as well as their addition salts with acids and bases, characterized in that : - to prepare compounds with the formula (I) in which R1 , R2  and R3  have the previously given significance and in which n=1, as well as their addition salts with acids and bases, and acid with the formula (II) :   see diagramm : EP0115997,P29,F4   in which R'1  and R2  have the significances already indicated, or a functional derivative of this acid, is submitted to the action of a product with the formula (III) : H2 N-R3 in which R3  has the significance already indicated, so as to obtain a product with the formula (I) in which :   see diagramm : EP0115997,P29,F5   R'1  as well as R2  and R3  have the significances already indicated and in which n=1, which product with the formula (I), if necessary or desired, is saponified, so as to obtain a product with the formula (I) in which R1  represents a hydrogen atom, which products with the formula (I) are submitted, if desired, to the action of a base or an acid so as to form the corresponding salts ; - to prepare compounds with the formula (I) in which R1 , R2  and R3  have the previously given significance and in which n is a whole number varying from 1 to 5, as well as their addition salts with acids and bases, an acid with the formula (IV) :   see diagramm : EP0115997,P29,F6   in which X1  is a halogen atom and in which n and R2 have the significances given above, or a functional derivative of this acid, is submitted to the action of a product with the previous formula (III) (NH2 -R3 ), so as to obtain a product with the formula (V) :   see diagramm : EP0115997,P29,F7   in which X1 , n, R2  and R3  have the previosu significances, which is submitted to the action of the anion of a thioacid with the formula (VI) :   see diagramm : EP0115997,P30,F8   in which R'1  keeps its significance, so as to obtain a product with the formula (I) in which r1 = R'1   see diagramm : EP0115997,P30,F9   n represents a whole number able to vary from 1 to 5 and in which R'1 , R2  and R3  have the significances given above, which product with the formula (I), if necessary or desired, is saponified, so as to obtain a product with the formula (I) in which R1  represents a hydrogen atom, which products with the formula (I) are submitted, if desired, to the action of an acid or of a base so as to form the corresponding salts.