New straightforward synthesis of 2-amino-6-methyl-5-(pyridin-4-ylsulfanyl)-3H-quinazolin-4-one

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.