The IMDAV reaction between 3-(isoxazol-3-yl)allylamines and maleic anhydrides: an unusual approach to pyrrolo[3,4-c]pyridine derivatives, possessing anti-inflammatory activity†

Abstract

An unexpected cascade of N-acylation/intramolecular [4 + 2] cycloaddition/decarboxylation/isoxazole ring-opening reactions is observed in the course of the interaction between 3-(isoxazol-3-yl)allylamines and maleic or trifluoromethylmaleic anhydrides. This four-step sequence begins with the initial N-acylation of allylamines by the anhydride, followed by an intramolecular Diels–Alder reaction, which is accompanied by spontaneous decarboxylation, and ends with the opening of the isoxazole ring. As a result, an original approach to a pyrrolo[3,4-c]pyridine core was discovered. A test series of pyrrolo[3,4-c]pyridin-3-ones was investigated for anti-inflammatory activity and cytotoxicity, including the ability to inhibit NLRP3 inflammasome activation.