Synthesis of Disubstituted 3-Phenylimidazo[1,2-a]pyridines via a 2-Aminopyridine/CBrCl3 α-Bromination Shuttle

Abstract

A versatile protocol for the synthesis of disubstituted 3-phenylimidazo[1,2-a]pyridines by coupling 2-aminopyridine with phenylacetophenones, phenylacetones, or β-tetralone has been developed. Isolated yields of up to 97% were obtained at 80 °C within 5 h. The 2-aminopyridine/CBrCl₃ system acts as an α-bromination shuttle by transferring Br from CBrCl₃ to the α-carbon of the carbonyl moiety. This triggers a series of steps with double C-N/C-N bond formation to the final product. The distinct advantages of this protocol include the use of commercially available inexpensive substrates, simplicity of a metal-free one-pot synthesis, and ease of scale-up to multigram quantities.