Patent EP-0104671-A2 (EP)
Inventor: HEYMES RENE
IPC: C07D501/34
Filed: 1981-02-13
Abstract: 1. Claims for Contracting States : BE CH DE GB IT LI LU NL SE Products of general formula (I') :  see diagramm : EP0104671,P40,F2 syn isomers in which R, A, X', R'a, n have the following significances either A] R represents, either a linear or branched alkyl, alkenyl, alkynyl or cycloalkyl radical having at most 6 carbon atoms, or an acetyl, propionyl, butyryl, valeryl, hexanoyl, acryloyl, crotonyl, benzoyl or carbamoyl radical, each of these radicals being optionally substituted by one or more radicals chosen from the following radicals ; carboxy optionally salified or esterified, methoxy, carboxyl, ethoxy carbonyl, carbamoyl, amino dimethylcarbamoyl, methylamino, dimethylamino, halogen, methoxy, ethoxy, propyloxy, methylthio, phenyl ethylthio, tetrazolyl, phenylthio, tetrazolylthio or thiadiazolylthio optionally substituted by methyl, or R represents a methoxycarbonyl or ethoxycarbonyl radical, A represents a hydrogen atom, an equivalent of an alkali metal, of an alkaline earth metal, of magnesium, of ammonium or of an aminated organic base, or A represents the remainder of an easily cleavable ester group, R'a represents an alkyl radical optionally interrupted by a heteroatom, linear or branched alkenyl or alkynyl radical having at most 6 carbon atoms, or a benzyl or phenylethyl radical optionally substituted by a carboxy, amino or dimethylaminoethyl radical, n is equal to 0, 1 or 2, X' represents a sulphur atom optionally oxidised in the form of the sulphoxide or sulphone, or an oxygen atom, it being understood that R does not represent an alkenyl or alkynyl radical having at most 6 carbon atoms or a linear or branched alkyl radical having at most 6 carbon atoms optionally substituted by one or more radicals chosen from the following, carboxy optionally salified or esterified, alkoxycarbonyl, amino, alkylamino, dialkylamino or heterocyclic aryl, when the radical -X'-R'a represents an alkoxy, alkylthio or alkenylthio radical ; or B] n is equal to 0, A represents a hydrogen atom and either R represents a -CH2 -CH2 -NH2 , -CH2 CO2 H or -C(CH3 )2 CO2 H radical, X' represents a sulphur or oxygen atom and R'a represents a methyl or ethyl radical or R represents a  see diagramm : EP0104671,P41,F1  radical, X' represents an oxygen or sulphur atom and R'a represents a methyl radical as well as the salts of products of formula (I') with mineral or organic acids. 1. Claims for Contracting State : AT Preparation process for products of general formula (I')  see diagramm : EP0104671,P45,F1  syn isomers in which R, A, X', R'a, n have the following significances either A] R represents, either a linear or branched alkyl radical, an alkenyl, alkynyl or cycloalkyl radical having at most 6 carbon atoms, carbamoyl each of these radicals being optionally substituted by one or more of the following radicals, carboxy optionally salified or esterified, methoxy carboxyl, ethoxy carbonyl, carbamoyl, amino-dimethylcarbamoyl, methylamino, dimethylamino, halogen, methoxy, ethoxy, propyloxy, methylthio, phenyl ethylthio, tetrazolyl, phenylthio, tetrazolylthio or thiadiazolylthio optionally substituted by methyl, or R represents a methoxycarbonyl or ethoxycarbonyl radical, A represents a hydrogen atom, an equivalent of an alkali metal, of an alkaline earth metal, of magnesium, of ammonium or of an aminated organic base, or A represents the remainder of an easily cleavable ester group, R'a represents an alkyl radical optionally interrupted by a heteroatom, linear or branched alkenyl or alkynyl radical having at most 6 carbon atoms, or a benzyl or phenylethyl radical optionally substituted by a carboxy, amino or dimethylaminoethyl radical, n is equal to 0, 1 or 2, X' represents a sulphur atom optionally oxidised in the form of the sulphoxide or sulphone, or an oxygen atom, it being understood that R does not represent an alkenyl or alkynyl radical having at most 6 carbon atoms or a linear or branched alkyl radical having at most 6 carbon atoms optionally substituted by one or more of the following carboxy optionally salified or esterified, alkoxycarbonyl, amino, alkylamino, dialkylamino or heterocyclic aryl, when the -X'-R'a radical represents an alkoxy, alkylthio or alkenylthio radical ; or B] n is equal to 0, A represents a hydrogen atom and either R represents a CH2 -CH2 -NH2 , -CH2 CO2 H or -C(CH3 )2 CO2 H radical, X' represents a sulphur or oxygen atom and R'a represents a methyl or ethyl radical or R represents a  see diagramm : EP0104671,P45,F2  radical, X' represents an oxygen or sulphur atom and R'a represents a methyl radical as well as the salts of products of formula (I') with mineral or organic acids characterised in that a product of formula (II)  see diagramm : EP0104671,P46,F1  in which n, X' and R'a have the significance indicated previously and A' represents a hydrogen atom or the remainder of an easily cleavable ester group, is treated by a product of formula (III) :  see diagramm : EP0104671,P46,F2  or a functional derivative of this acid, formula (III) in which R1 represents a hydrogen atom or a protector group of the amino radical and either R' represents a linear or branched alkyl radical, an alkenyl, alkynyl or cycloalkyl radical having at most 6 carbon atoms, or R' represents one of the following radicals, acetyl, propionyl, butyryl, valeryl, hexanoyl, acryloyl, crotonoyl, benzoyl, carbamoyl or alkoxycarbonyl, each of these radicals being optionally substituted, to obtain a product of formula (IV) :  see diagramm : EP0104671,P46,F3  in which R1 , R', A', R'a, X' and n have the previous significance, which product, if desired, in the case where n is equal to 0 and X' represents a sulphur or oxygen atom, is treated with an oxidation agent, to obtain a product of formula (IV) in which n is equal to 1 or 2 and X' represents a sulphur atom oxidised in the form of the sulphoxide or sulphone or an oxygen atom and, which product of formula IV, if necessary or if desired, is subjected to one or more of the following reactions, in any order : a) detachment by hydrolysis, hydrogenolysis or by the action of thiourea of all or part of the ester groups or the protector groups of the amino radical or radicals, b) esterification or salification of the carboxylic radical or radicals by a base, c) salification of the amino radical or radicals by an acid.