PROCEDIMIENTO PARA LA PREPARACION DE 7-ACILAMIDO-7-ALCOXICEFALOSPORINAS

摘要

1445743 Production of 7-amino and 7- acylamino-7-alkoxy cephalosporins ELI LILLY & CO 3 Oct 1973 [16 Oct 1972] 46093/73 Heading C2C Compounds of the formula wherein R‹ represents a primary C 1-4 alkyl group or -CD 3 ; R1 represents an acetoxy, carbamoyloxy,α- methoxy - p - hydroxycinnamoyloxy, propionyloxy, benzoyloxy, methoxy, methylthio, 1 - methyl - 1,2,3,4- tetrazol - 5 - ylthio, or 5 - methyl - 1,3,4- thiadiazol - 2 - ylthio radical; R2A represents hydrogen or R2; and R2 represents C 1-6 alkyl, 2,2,2 - trichloroethyl, 2 - iodoethyl, tert - C 5-7 - alkenyl, tert - C 5-7 - alkynyl, benzyl, nitrobenzyl, tetrahydropyranyl, succinimidomethyl, phthalimidomethyl, methoxybenzyl, dimethoxybenzyl, cyanomethyl, nitrophenyl, dinitrophenyl, 2,4,6 - trinitrophenyl, bis-(pmethoxyphenyl)methyl, triphenylmethyl, diphenylmethyl, benzyloxymethyl, C 3-6 - alkanoyloxymethyl, or phenacyl, are obtained by reacting an imino halide of the formula wherein X represents chlorine or bromine, R2B is the same as R2, C 2-4 -alkanoyl or a radical of the formula wherein each R3 independently represents C 1-4 alkyl or halogen, provided that at least one R3 represents C 1-4 alkyl; and R4 represents an acylamino group wherein the acyl group is C 1-4 alkanoyl, benzoyl, naphthoyl, C 2-5 -alkoxycarbonyl, C 6-7 - cycloalkoxy - carbonyl, phenoxycarbonyl, benzyloxycarbonyl, naphthyloxycarbonyl, one of the said groups substituted with from one to three groups selected from halogen, nitro, C 1-4 -alkoxy, cyano, and in the case of benzoyl, naphthoyl, benzyloxy, and naphthyloxy, by C 1-4 -alkyl, or phthaloyl, with an alcohol of the formula under essentially non-aqueous conditions. Those compounds wherein R‹ represents-CD 3 are claimed to be novel. The products may subsequently be reacted, optionally in situ, with a compound of one of the formulae or wherein X represents halogen and R5 represents C 1-8 alkanoyl, azidoacetyl, cyanoacetyl, haloacetyl, Ar-CH 2 -CO- where Ar denotes phenyl, thienyl, furyl, pyrrolyl, or phenyl substituted with from one to three substituents selected from halogen, trifluoromethyl, protected amino, protected hydroxy, C 1-3 alkyl, C 1-3 alkoxy, cyano and nitro, wherein Ar1 represents phenyl, pyridyl, or substituted phenyl as defined above, and Y is oxygen or sulphur, Ar-CH(B)-CO- wherein Ar is as defined above and B is protected amino, protected hydroxy, protected carboxy,-CN or - N 3 , 2-(3-sydnone)acetyl or 2-(1H-tetrazol-1- yl)acetyl. The starting materials of Formula (II) are preferably prepared in situ by the reaction of a compound of the formula with PCl 5 or other acid halide. The products may be de-esterified where necessary and protecting groups may be removed by conventional means. The free acids of those products which have been reacylated possess antibacterial properties. Reference has been directed by the Comptroller to Specifications 1,348,984 and 1,348,987.