Synthesis of 6‐[[(hydroxyimino)phenyl]methyl]‐1‐[(1‐methylethyl)sulfonyl]‐1H‐imidazo[4,5‐b]pyridin‐2‐amine. An aza analogue of enviroxime

Abstract

Abstract6‐[[(Hydroxyimino)phenyl]methyl]‐1‐[(1‐methylethyl)sulfonyl]‐1H‐imidazo[4,5‐b]pyridin‐2‐amine (1), an aza analogue of enviroxime, was synthesized in eight steps from 6‐hydroxynicotinic acid (2). Acid 2 was nitrated, chlorinated with phosphorus pentachloride, and subjected to Friedel‐Crafts aroylation to give 6‐chloro‐5‐nitro‐3‐pyridyl phenyl ketone (5). Amination of 5 was followed by reduction of the nitro group and condensation with ethoxycarbonylisothiocyanate to give 6‐benzyl‐2‐ethoxycarbonylamino‐1H‐imidazo[4,5‐d]pyridine (8). The ethoxycarbonyl moiety of 8 was cleaved, N‐1 was isopropylsulfonylated, and the carbonyl moiety was condensed with hydroxylamine to give 1. Compound 1 was inactive against rhinovirus 1B and poliovirus type 1.