Patent EP-0051819-A2 (EP)
Inventor: SHINMA NOBUO
IPC: C07D317/54
Filed: 1981-10-29
Abstract: 1. Claims for the Contracting States : BE, CH, DE, FR, GB, IT, LI, LU, NL, SE Compounds of the formula  see diagramm : EP0051819,P24,F1 wherein X represents oxygen, sulphur or hydroxyimino ; Y represents methylene or imino ; R**1 represents hydroxy, phosphonooxy, glycosyloxy, acylated glycosyloxy, acyloxy or lower-alkoxy-carbonyloxy ; R**2 represents lower-alkoxy, lower-alkenyloxy or lower-alkylthio ; R**3 represents lower-alkoxy ; R**4 represents lower-alkyl, p-lower-alkoxybenzoyl or substituted or unsubstituted phenyl, benzyl, pyridylmethyl, furfuryl, tetrahydrofurfuryl, thienyl, tetrahydrothenyl, pyrrolylmethyl, pyrrolinylmethyl or pyrrolidinylmethyl, with the proviso that Y is not methylene when R**4 is alkyl, phenyl, substituted phenyl, benzyl or p-hydroxy-benzyl and with the further proviso that R**2 and R**3 are different from one another when R**4 is p-methoxybenzyl and Y is methylene, and pharmaceutically usable salts thereof. 1. Claims for the Contracting State : AT A process for the manufacture of compounds of the formula  see diagramm : EP0051819,P26,F2  wherein X represents oxygen, sulphur or hydroxyimino ; Y represents methylene or imino ; R**1 represents hydroxy, phosphonooxy, glycosyloxy, acylated glycosyloxy, acyloxy or lower-alkoxy-carbonyloxy ; R**2 represents lower-alkoxy, lower-alkenyloxy or lower-alkylthio ; R**3 represents lower-alkoxy ; R**4 represents lower alkyl, p-lower-alkoxybenzoyl or substituted or unsubstituted phenyl, benzyl, pyridylmethyl, furfuryl, tetrahydrofurfuryl, thienyl, tetrahydrothenyl, pyrrolylmethyl, pyrrolinylmethyl or pyrrolidinylmethyl, with the proviso that Y is not methylene when R**4 is alkyl, phenyl, substituted phenyl, benzyl or p-hydroxybenzyl and with the further proviso that R**2 and R**3 are different from one another when R**4 is p-methoxybenzyl and Y is methylene, and pharmaceutically usable salts thereof, characterized by a) hydrogenating a compound of the formula  see diagramm : EP0051819,P26,F3  wherein X, R**1 , R**2 , R**3 and R**4 are as in formula I, in the presence of a catalyst in a solvent, or b) reacting a reactive derivative of a carboxylic acid of the formula  see diagramm : EP0051819,P26,F4  wherein R**2 and R**3 are as in formula I and R**1' is a protected hydroxy group, with a compound of the formula R**4 -NH2 wherein R**4 is as in formula I, and then removing the protecting group of the hydroxy group, or c) reacting an acetophenone of the formula  see diagramm : EP0051819,P27,F1  wherein R**1 , R**2 and R**3 are as in formula I, with iodine in a tertiary amine and reacting the salt obtained with an amine of formula IV above, or d) rearranging an ester of the formula  see diagramm : EP0051819,P27,F2  wherein R**2 , R**3 and R**4 are as in formula I, in the presence of a base in a solvent, or e) reacting a ketone of the formula  see diagramm : EP0051819,P27,F3  wherein R**2 , R**3 and R**4 are as in formula I, with a hydroxylamine salt in a solvent, or f) reacting a carbonyl compound of the formula  see diagramm : EP0051819,P27,F4  wherein Y, R**2 , R**3 and R**4 are as in formula I, with phosphorus pentasulphide in the presence of a base in a solvent, or g) reacting a phenol of the formula  see diagramm : EP0051819,P28,F1  wherein Y, R**2 , R**3 and R**4 are as in formula I and X' is oxygen or sulphur, with an acylating agent in the presence of a base, or h) reacting a phenol of formula IX above with phosphorus oxychloride or dibenzyl phosphorochloridate in the presence of a base in a solvent and hydrolyzing or hydrogenolyzing the reaction product and, if desired, converting a compound obtained into a salt, or i) reacting a phenol of formula IX above with a glycosyl halide or an acylated glycosyl halide in the presence of a catalyst in a solvent and, if desired, thereafter removing the acyl groups.