KR830002786A - Process for preparing cephalosporin compound - Google Patents

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Description

Process for preparing cephalosporin compound

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Claims (23)

(a) D is a pyrimidine derivative of the formula (III) or a group of B defined below with the compound of formula (II) Reacting the pyrimidine derivative mixture with a pH range of 2.0 to 9.0 and a temperature of -20 ° to + 50 ° C. to produce a compound of formula (I) with the following definition, wherein D is not a pyridium or amino carbonyl (b) 7-amino-cephalosporinic acid of the formula (V) having the same definition as the following definition except for the ureido carboxylic acid or salt thereof or the active derivative thereof of the structural formula (IV) Reacting a derivative with a solvent at a temperature of -40 to + 40 ° C. to prepare a compound of formula (I) as defined below, wherein D excludes pyridinium or aminocarbonyl pyridinium groups, or (c) a compound of formula (VI), wherein E is hydrogen, is reacted with a compound of formula (IV) or pyridine or 4-amino carbonylpyridine in a solvent in the pH range 2 to 10 at a temperature of 0 to 100 ° C. Preparing a compound of formula (I) wherein S-Het, pyridinium or 4-aminocarbonyl pyridinium group and E is a hydrogen atom, or the ^{alkali-metal-ear} reacted again in the presence of methyl acrylate and methane -120 ° to about -10 (d) the structural formula M ⁺ OCH _3, which means that Y is a compound of the formula (Ⅰ) hydrogen M ⁺ an alkali metal The compound of formula (I) wherein Y is a methoxy group is prepared by reacting with a halogenating agent in an inert solvent at a temperature of ℃, and if necessary, the preparation of formula (I) or (I ′) wherein E is a protecting group that can be readily released in vitro and in From the compound, a free carboxylic acid of formula (I) or (I ') in which E is hydrogen is prepared and the compound of formula (I) or (I') in which E is hydrogen is To prepare a salt or ester, and when E is hydrogen, using their physiologically toxic salts and inorganic or organic bases to prepare the corresponding nontoxic salts of formula (Ia), or D is pyridinium Or amino car In the case of bonylpyridinium, a process for producing a novel cephalosporin of formula (I) or (I '), which comprises preparing a compound of formula (Ia). Wherein A is phenyl, 4-hydroxyphenyl, cyclohexyl, cyclohexane-1-yl, cyclohexa-1,4-dien-1-yl, 2 or 3-thienyl, 2 or 3-furyl group or 3 Is a phenyl group substituted with chlorine, hydroxy, or methoxy group at the 4 position (the substituents are the same or different from each other) Y is hydrogen or methoxy group D is hydrogen, hydroxy, acetoxy, aminocarbonyloxy, pyridinium, aminocarbonyl-pyridinium group, or S-Het group, wherein Het is 1-methyl-tetrazol-5-yl, tetrazole- 5-yl, 3-methyl-1,2,4-thiadiazol-5-yl, 1,2,4, -thiadiazol-5-yl, 2-methyl-1,3,4-thiadiazole -5-yl, 2-methylamino-1,3,4-thiadiazol-5-yl, 2-dimethyl amino-1,3,4-thiadiazol-5-yl, 2-formylimino-1 , 3,4-thiadiazol-5-yl, 2-acetylamino-1,3,4-thiadiazol-5-yl, 2-methyl-1,3,4-oxadiazol-5-yl, 1,2,3-triazol-4-yl, or 1,2,4-triazol-3-yl group, R is hydrogen, methyl, cyclopropyl, hydroxy, methoxy, ethoxy, R ₃ is a morpholino, thiomorpholino, thiomorpholino-S-oxide, thiomorpholino-S, S-dioxide group, Wherein R ₁ and R ₂ are the same or different and are hydrogen, an aliphatic branched or straight chain hydrocarbon containing 1 to 2 double or triple bonds and containing 1 to 6 carbon atoms, or 3 to 3 carbon atoms Cycloalkyl containing 6, alkyl group having 3 to 6 carbon atoms in the cycloalkyl moiety and substituted with a cycloalkyl group having 1 or 2 carbon atoms in the alkyl moiety. R ₁ and R ₂ together may form an alkylene chain having 2 to 7 carbon atoms to form a 3 to 8 ring heterocycle, R ₃ is a formyl, acetyl or ethyloxy-carbonyl group and Z is substituted by X A straight or branched alkylene group containing 1 to 4 carbon atoms or a cycloalkyl group containing 3 to 6 carbon atoms substituted with X, X is cyano, hydroxy, melcapto, amino, aminocarbonyl, aminosulfonyl, aminocarbonylamino, -C- -OR ₄ , -OCOR ₅ , -SR ₄ , -SOR ₄ -SO ₂ R ₄ R ₄ is a branched or straight chain alkyl group containing 1 to 3 carbon atoms, R ₅ is an alkyl group containing 1 to 3 carbon atoms or a hydrogen atom, or R ₄ and R ₅ together form a 3 to 6 ring heterocycle having a nitrogen atom at an arbitrary position; n is 0 or 1 R ₆ , R ₇ , R ₈ are the same or different from each other, hydrogen, halogen, amino, alkylamino, dialkylamino, hydroxy, alkoxy, formylamino, aliphatic acylamino, aminocarbonylamino, alkylamicarbonylamino , Dialkylaminocarbonylamino, nitro, alkylsulfonylamino, formyl, alkylcarbonyl, alcarbonyloxy, alkoxycarbonyl, alkoxycarbonyloxy, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, Aminocarboxyl, alkoxyaminocarboxyl, dialkylaminocarboxyl, alkoxycarbonylamino, cyano, melcapto, alkylmelcapto, alkylsulfinyl, alkylsulfonyl, aminosulfonyl, alkyl, dialkylaminosulfonyl, hydroxyl Phonyl or branched or straight chain alkyl. (Each alkyl group above contains 1 to 3 carbon atoms) R _P is hydrogen, alkyl containing 1 to 4 carbon atoms, alkoxy, amino, methylamino, dimethyl amino containing 1 to 3 carbon atoms E is a hydrogen or protecting group, which is an ester forming group that can be easily broken in vivo or in vitro, and can be easily removed by hydrolysis, hydrolysis or other treatments. B is a = NCO group or -NHCOCl, -NHCOBr or Active derivatives of -NH-COOH groups, such as M is a hydrogen atom or an alkali metal or alkaline earth metal. ※ Note: The disclosure is based on the initial application.