Catalyst‐Free One‐Pot Multi‐Component Synthesis of 2‐Substituted Quinazolin‐4‐carboxamides from 2‐Aminophenyl‐2‐oxoacetamides, Aldehydes, and Ammonium Acetate

Herein, we report a simple and straightforward catalyst‐free one‐pot multi‐component synthesis of quinazolin‐4‐carboxamides using 2‐(2‐aminophenyl)‐N,N‐dialkyl‐2‐oxoacetamide, aldehydes and ammonium acetate. As compared to the conventional approached for quinazolin‐4‐carboxamides synthesis, this transformation demonstrates very good reactivity by tolerating a large number of functional groups, and proceeds with good to moderate yields under mild conditions. Notably, the synthesized 6‐bromoquinazolin‐4‐carboxamide was subjected to Suzuki‐Miyaura cross‐coupling and Buchwald‐Hartwig C−N bond forming reactions providing a straightforward method to obtain structurally diverse and valuable quinazoline scaffolds. Furthermore, the reaction could be easily scaled up to gram scale. With this novel one‐pot method using variety of aldehydes and 2‐aminophenyl‐2‐oxoacetamides, twenty eight novel quinazoline analogues were obtained in moderate to good yields. And it was applicable to a variety of quinazoline derivatives when 6‐bromoquinazolin‐4‐carboxamide was subjected to Suzuki‐Miyaura cross‐coupling and Buchwald‐Hartwig C−N bond forming reactions. Novel and facile one‐pot method in this work could be worth while applying to the synthesis of therapeutically valuable quinazoline derivatives.