Brønsted acid-mediated cyclization-dehydrosulfonylation/reduction sequences: An easy access to pyrazinoisoquinolines and pyridopyrazines

Abstract

An efficient and alternative synthetic approach has been developed to prepare various N-(arylethyl)piperazine-2,6-diones from 4-benzenesulfonyliminodiacetic acid and primary amines using carbonyldiimidazole in the presence of a catalytic amount of DMAP at ambient temperature. Piperazine-2,6-diones are successfully transformed to pharmaceutically useful pyridopyrazines or pyrazinoisoquinolines and ene-diamides via an imide carbonyl group activation strategy using a Brønsted acid. Subsequent dehydrosulfonylation reactions of the ene-diamides, in a one pot manner, smoothly transformed them to substituted pyrazinones. A concise synthesis of praziquantel (1) has also been achieved through this method.