Microwave-assisted Cu(i)-catalyzed one-pot tandem synthesis of pyridoimidazole-fused quinolines as new antimycobacterial agents: DFT and ESI-HRMS study

Abstract

In this study, an improved microwave irradiation protocol was developed for synthesizing pyrido[2′,1′:2,3]imidazo[4,5-c]quinoline from 2-(2-bromophenyl)imidazo[1,2-a]pyridine and various benzaldehydes using copper iodide as a catalyst. This protocol also employed benzyl alcohols and methyl arenes in addition to benzaldehyde. The proposed mechanism was supported by DFT and ESI-HRMS studies. Tandem oxidative addition, reductive amination, and intramolecular cyclization under microwave conditions result in the formation of new C–N and C–C bonds, respectively. Among the synthesized derivatives, compounds 3k, 3o, 3u, and 3w exhibited antimycobacterial activity against M. tuberculosis H37Rv ATCC 27294. An in silico ADMET profile was also performed to assess the active compound's safety and efficacy.