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

G.S. Jagadeesha1,, N.R. Thimmegowda1,*,, K. Mantelingu2,, D.S. Prasanna3, and K.S. Rangappa4,

1Department of Chemistry, Government S.K.S.J. Technological Institute (Affiliated to Visvesvaraya Technological University, Karnataka), K.R. Circle, Bangalore-560001, India

2Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysuru-570006, India

3Department of Applied Sciences, Visvesvaraya Technological University, Center for Postgraduate Studies, Bengaluru Region, Muddenahalli, Chikkaballapur District-562101, India

4Institution of Excellence, University of Mysore, Mysore-570006, India

*Corresponding author: E-mail: nrthimmegowda@gmail.com

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.

Keywords

Benzimidazole derivative, T3P, Anticancer agent, Antileukemic activity.

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