Highly efficient four-component synthesis of 4(3H)-quinazolinones: palladium-catalyzed carbonylative coupling reactions

Abstract

Given the importance of quinazolinones and carbonylative transformations, a palladium-catalyzed four-component carbonylative coupling system for the synthesis of diverse 4(3H)-quinazolinone in a concise and convergent fashion has been developed. Starting from 2-bromoanilines (1 mmol), trimethyl orthoformate (2 mmol), and amines (1.1 mmol), under 10 bar of CO, the desired products were isolated in good yields in the presence of Pd(OAc)2 (2 mol %), BuPAd2 (6 mol %) in 1,4-dioxane (2 mL) at 100 °C, using N,N-diisopropylethylamine (2 mmol) as the base. Notably, the process tolerates the presence of various reactive functional groups and is very selective for quinazolinones, and was used in the synthesis of the precursor to the bioactive dihydrorutaempine.

Keywords: heterocycles; multicomponent reactions; palladium; synthesis design; synthetic methods.