反应详情

4-Chloro-5-fluoroquinazoline (6.76 g) was dissolved in iso-propanol (200 ml) and 4-amino-2-methylphenol (5.00 g) was added. The mixture was heated under reflux for 2 hours, causing a yellow solid to precipitate. The mixture was cooled to ambient temperature and the solid was collected by filtration. The solid was dissolved in a boiling mixture of methanol (500 ml) and water (100 ml) to give a brown solution. With vigorous stirring, the solution was basified with aqueous ammonia (0.880, 10 ml), causing a light brown solid to precipitate. The mixture was concentrated in vacuo to such a volume that all of the methanol had been removed, leaving the product as a suspension in aqueous solution. The suspension was cooled; the solid was collected by filtration, triturated with ethyl acetate and dried over P2O5 in a vacuum oven to give 2-methyl-4-[(5-fluoroquinazolin-4-yl)amino]phenol as a light brown solid (8.18 g, 82%); NMR spectrum (DMSO-d6) 3.30 (s, 3H), 6.78 (d, 1H), 7.28 (m, 2H), 7.38 (dd, 1H), 7.57 (d, 1H), 7.78 (m, 1H), 8.43 (s, 1H), 8.88 (d, 1H), 9.22 (s, 1H); Mass spectrum MH+ 270.

1. temperatureThe mixture was heated
2. temperatureunder reflux for 2 hours
3. customto precipitate
4. filtrationthe solid was collected by filtration
5. dissolutionThe solid was dissolved in a boiling mixture of methanol (500 ml) and water (100 ml)
6. customto give a brown solution
7. customto precipitate
8. concentrationThe mixture was concentrated in vacuo to such a volume that all of the methanol
9. customhad been removed
10. customleaving the product as a suspension in aqueous solution
11. temperatureThe suspension was cooled
12. filtrationthe solid was collected by filtration
13. customtriturated with ethyl acetate
14. dry with materialdried over P2O5 in a vacuum oven