IE38194L - 7-amino-7-alkoxycephalosporins - Google Patents

Abstract

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 ; R<SP>1</SP> 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; R<SP>2A</SP> represents hydrogen or R<SP>2</SP>; and R<SP>2</SP> 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, R<SP>2B</SP> is the same as R<SP>2</SP>, C 2-4 -alkanoyl or a radical of the formula wherein each R<SP>3</SP> independently represents C 1-4 alkyl or halogen, provided that at least one R<SP>3</SP> represents C 1-4 alkyl; and R<SP>4</SP> 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 R<SP>5</SP> 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 Ar<SP>1</SP> 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. [GB1445743A]