One-pot synthesis of quinazolin-4(3H)-ones and fused quinazolinones by a palladium-catalyzed domino process

Abstract

An efficient one-pot synthesis of quinazolin-4(3H)-ones, benzoimidazo[2,1-b]quinazolin-12(6H)-ones and imidazo[2,1-b]quinazolin-5(1H)-ones via a palladium-catalyzed domino process has been developed. The Pd-catalyzed reactions of 2-azidobenzamides 1 with isocyanides 2 produced quinazolin-4(3H)-ones 4 at room temperature by a domino Pd-catalyzed cross-coupling/carbodiimide-mediated cyclization. However, as 2-azido-N-(2-bromophenyl)benzamides 1 were used under heating condition in the presence of Cs2CO3, the benzoimidazo[2,1-b]quinazolin-12(6H)-ones 5 were directly obtained by twice Pd-catalyzed domino cyclization. A domino reogioselective 5-exo-dig intramolecular cyclization reaction of alkynyl-containing azides 6 with isocyanides 2 generated imidazo[2,1-b]quinazolin-5(1H)-ones 9 in 74–93% yields in the presence of catalyst Pd(PPh3)4 and K2CO3.