Catalyst- and Solvent-Free Synthesis of Substituted Imidazo[1,2-a]pyridines

Significance

Reported is the rapid and convenient synthesis of imidazo[1,2-a]pyridines 3 via the condensation of 2-aminopyridines 1 with β-keto esters 2 under solvent-free conditions. Under thermal conditions, the products were obtained in 80-89% yield in under 35 minutes, except for one case (R^¹ = 4-Me-5-Br, R^² = Me, R^³ = Et) where a moderate 58% yield was obtained. Higher yields (85-95%) were obtained in under two minutes by performing the reaction under microwave irradiation on alumina support. Diversely substituted 2-aminopyridines and several β-keto esters were equally well tolerated in this process. A reasonable mechanism involving sequential condensation ­reactions is proposed without evidence.