Ammonium Chloride-Promoted Four-Component Synthesis of Pyrrolo[3,4-b]pyridin-5-one

A novel multicomponent synthesis of 5-aminooxazole starting from simple and readily available inputs is described. Thus, simply heating a methanol solution of an aldehyde 3, an amine 4, and an α-isocyanoacetamide 5 provided the 5-aminooxazole (1) in good to excellent yield. The reaction of 1 with α,β-unsaturated acyl chloride 13 lead to the formation of pyrrolo[3,4-b]pyridin-5-one (2) in a single operation. A triple domino sequence, acylation/IMDA/retro-Michael cycloreversion, is involved in this new scaffold-generating reaction. After the observation that ammonium chloride can significantly accelerate the oxazole formation in toluene, a one-pot four-component synthesis of 2 is developed.