Patent EP-0017238-B1 (EP)
IPC: C07D501/57
Filed: 1980-04-03
Granted: 1983-03-16
Abstract: 1. Claims for the Contracting States : BE, CH, DE, FR, GB, IT, LI, NL Cephem compounds of the general formula I  see diagramm : EP0017238,P11,F1  wherein n is 0 or 1, R**1 is hydrogen or alkoxy having 1 to 4 carbon atoms and R**2 is azido or a radical -SR**3 , in which R**3 is a five-membered heterocycle with 1 to 4 nitrogen atoms and optionally one sulfur atom, a five-membered heterocycle with 1 to 2 nitrogen atoms and one oxygen atom or a six-membered heterocycle with 1 to 3 nitrogen atoms and optionally one sulfur atom, wherein these heterocycles may also carry a fused benzene nucleus or may be substituted by alkyl with 1 to 4 carbon atoms by trifluormethyl, by carboxymethyl, by hydroxy, by amino, by alkyl-amino with 1 to 4 carbon atoms in the alkyl part, by dialkyl-amino with 1 to 4 carbon atoms in each alkyl part, by phenyl or by a five- or six-membered heterocycle which may contain 1 to 2 nitrogen atoms and optionally also one sulfur or oxygen atom, alkyl with 1 to 4 carbon atoms or aliphatic acyl with 1 to 4 carbon atoms, and in which the methoximino group is in the syn-position, and pharmacologically acceptable salts and esters thereof. 1. Claims for the Contracting State : AT Process for the manufacture of cephem compounds of the general formula I  see diagramm : EP0017238,P11,F2  wherein n is 0 or 1, R**1 is hydrogen or alkoxy having 1 to 4 carbon atoms and R**2 is azido or a radical -SR**3 , in which R**3 is a five-membered heterocycle with 1 to 4 nitrogen atoms and optionally one sulfur atom, a five-membered heterocycle with 1 to 2 nitrogen atoms and one oxygen atom or a six-membered heterocycle with 1 to 3 nitrogen atoms and optionally one sulfur atom, wherein these heterocycles may also carry a fused benzene nucleus or may be substituted by alkyl with 1 to 4 carbon atoms by trifluormethyl, by carboxymethyl, by hydroxy, by amino, by alkyl-amino with 1 to 4 carbon atoms in the alkyl part, by dialkyl-amino with 1 to 4 carbon atoms in each alkyl part, by phenyl or by a five- or six-membered heterocycle which may contain 1 to 2 nitrogen atoms and optionally also one sulfur or oxygen atom, alkyl with 1 to 4 carbon atoms or aliphatic acyl with 1 to 4 carbon atoms, and in which the methoximino group is in the syn-position, and pharmacologically acceptable salts and esters thereof, which comprises a) reacting cephem compounds of the general formula II  see diagramm : EP0017238,P11,F5  wherein R**1 and n are as defined above, in the presence of a solvent and a base, with an azide or with compounds of the formula HSR**3 , in which R**3 is as defined above or, b) reacting cephem compounds of the general formula III in the form of their salts or esters  see diagramm : EP0017238,P12,F1 wherein n, R**1 and R**2 are as defined above, with reactive derivatives of 2-(1,3-thiazol-4-yl)-2-syn-methoximinoacetic acid and, if desired, in the compounds obtained according to a) or b) alpha) converting a salt obtained into the free carboxylic acid and optionally further esterifying the latter or beta) converting a salt obtained directly into an ester or gamma) saponifying an ester obtained and optionally converting the carboxylic acid obtained into a salt or delta) subsequently oxidizing a compound of the formula I wherein n is zero or subsequently reducing a compound of the formula I in which n is 1 and, if desired, further converting the resulting cephem compounds obtained according to steps alpha, beta or gamma.