Reactivity and regioselectivity in the acylation of 2,4-diaminoquinazolines

Abstract

2-(2-Aminophenyl)quinazoline-4-amines were selectively acylated at the phenylamino group by anhydrides, isocyanates or acyl chlorides, at room temperature. A similar selectivity was obtained in the reaction with ethoxymethylene derivatives and orthoesters. Acylation of the exocyclic imino substituent in the quinazolino-quinazoline tetracyclic structure also occurred under mild conditions with acetic anhydride and isocyanates. Hydrolysis to release the aniline substituent was performed with concd HCl (1 equiv at 60 °C) and with 3 M NaOH (3 equiv, rt), leading to the formylated derivative or cleaving the acyl group in the heterocyclic amine.