Synthesis of 2-Amino-quinazolin-4(3H)-ones Using 2-Bromo-N-phenylbenzamide and Cyanamide Ullmann Cross-Coupling.

Abstract

Herein, an approach for synthesizing 2-amino-3-substituted quinoline-4(3H)-ones and N-phenylbenzamide derivatives was developed. A series of quinoline-4(3H)-ones were synthesized through Ullmann cross-coupling under air conditions using inexpensive, readily available cyanamide with 2-bromo-N-phenylbenzamide as the starting material, copper iodide as the catalyst, and potassium tert-butoxide as the base in dimethyl sulfoxide. Noteworthy aspects of this method include its cost-effectiveness, the accessibility of raw materials, wide substrate applicability, ligand-free, open-air conditions, and simple operating procedures. Furthermore, investigations under similar reaction conditions further show that substituting water, alcohols, phenols, amines, or mercaptans for cyanamide as the nucleophilic reagent can be used to prepare 2-functionalized N-phenylbenzamides.