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

A novel multicomponent synthesis of 5-aminooxazoles starting from simple and readily available inputs is described. Thus, simply heating a methanol soln. of an aldehyde, an amine, and an alpha -isocyanoacetamide provided 5-aminooxazoles, e.g., I, in good to excellent yield. The reaction of the 5-aminooxazoles with ClCOCH:CHCOOEt led to the formation of pyrrolo[3,4-b]pyridin-5-ones, e.g., II, 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 the pyrrolo[3,4-b]pyridin-5-ones is developed. [on SciFinder (R)]