Zhejiang Cheng Yi Pharmaceutical Co., Ltd.

A method for the synthesis of the title compound [zafirlukast, N-[3-[[2-methoxy-4-[[[(2-methylphenyl)sulfonyl]amino]carbonyl]phenyl]methyl]-1-methyl-1H-indol-5-yl]carbamic cyclopentyl ester] is reported here.Methylation of 5-nitro-1H-indole provided 1-methyl-5-nitro-1H-indole.Alkylation with 4-(bromomethyl)-3-methoxybenzoic acid gave 3-methoxy-4-[(1-methyl-5-nitro-1H-indol-3-yl)methyl]benzoic acid.Sulfonamidation and reduction then gave 4-[(5-amino-1-methyl-1H-indol-3-yl)methyl]-3-methoxy-N-[(2-methylphenyl)sulfonyl]benzamide.A subsequent acylation delivered the target compound in 31.6% overall yield.The methylation, alkylation and reduction are key steps in this procedure.Product structures were determined by NMR, elemental anal., IR, MS.This improved procedure avoids the use of expensive reagents and the target compound was synthesized in a convenient way.The method is suitable for industrial manufacture

The compound 1-iodoethyl iso-Pr carbonate (2), prepared from 1-chloroethyl chloroformate in 43.7% yield was used to prepare cefpodoxime proxetil by esterification with cefpodoxime in 70% yield.