Microwave-Assisted, Rapid Synthesis of Benzimidazole based Potential Anticancer Agent Methyl 1-benzyl-2-(4-fluoro-3-nitrophenyl)-1Hbenzo[ d]imidazole-5-carboxylate (TJ08) via T3P Mediated Cyclization

Abstract

A novel microwave assisted protocol for the rapid synthesis of methyl 1-benzyl-2-(4-fluoro-3- nitrophenyl)-1H-benzo[d]imidazole-5-carboxylate (TJ08) with potent antileukemic activity has been developed with excellent yields in 31 min of reaction time over 5 steps, whereas the conventional heating method required around 17 h. In this method, n-propanephosphonic acid anhydride (T3P) was used as a coupling reagent for amidation, during this reaction the in situ generated byproduct n-propylphosphonic acid subsequently catalyzes the cyclization reaction to form benzimidazole ring and hence this novel protocol affords to synthesize the novel benzimidazole derivatives expeditiously to develop new druggable compounds.