New Straightforward Synthesis of2‐Amino‐6‐methyl‐5‐(pyridin‐4‐ylsulfanyl)‐3H‐quinazolin‐4‐one

Abstract

The synthesis of 2‐amino‐6‐methyl‐5‐(pyridin‐4‐ylsulfanyl)‐3H‐quinazolin‐4‐one (1) was studied via three different synthetic routes starting from 4‐bromo‐5‐methylisatin. The best route was established, which is a straightforward route via 2‐guanidino‐5‐bromo‐6‐methyl‐quinazolin‐4‐one (6) as the key intermediate and a one‐pot synthesis by treatment of compound 6 with 4‐mercaptopyridine and KOH via the Ullmann reaction. When removing the amidino group from 2‐guanyl of compound 6 under strong alkaline conditions, surprisingly we found that 4‐mercaptopyridine could prevent the bromo group on a quinazoline ring from substitution by a hydroxyl group. Furthermore we found that 4‐mercaptopyridine analogues such as hydroxypyridinones also play a role of protecting agent in such a reaction system.

Keywords:

• bromo group
• 4‐mercaptopyridine
• protecting agent
• quinazolin‐4‐one
• synthesis

Acknowledgment

This work was partially supported by grants from the Guangdong Provincial Natural Science Foundation (No. 994078) and Foundation of Jinan University. We are grateful to Kai‐Bei Yu of Chengdu Institute of Organic Chemistry for performing the X‐ray crystallographic analysis and Zhongshan University Analyses Center for NMR, MS, and elemental analyses.