反应详情

温度

100 °C

4.0M HCl in Dioxane (4.0 ml) was added to a suspension of tert-butyl 4-[(4-chloro-7-methoxyquinazolin-6-yl)oxy]piperidine-1-carboxylate (2.62 g) and 3-chloro-2-fluoroaniline (1.08 g) in iso-propanol (50 ml). The reaction mixture was stirred and heated at 100° C. for 2 hours. The yellow precipitate was filtered hot and washed with iso-propanol followed by diethylether and dried under vacuum to give 6-(piperidin-4-yloxy)-4-(3-chloro-2-fluoroanilino)-7-methoxyquinazoline as a di-hydrochloride salt (2.38 g); 1H NMR Spectrum: (DMSO d6) 1.84–1.99 (m, 2H), 2.22–2.33 (m, 2H), 3.12–3.33 (m, 4H), 4.00 (s, 3H), 5.08 (m, 1H), 7.34 (t, 1H), 7.40 (s, 1H), 7.50 (t, 1H), 7.62 (t, 1H), 8.80 (s, 1H), 8.84–8.94 (m, 2H), 8.99–9.11 (m, 1H); Mass Spectrum: (M+H)+ 403.

1. filtrationThe yellow precipitate was filtered hot
2. washwashed with iso-propanol
3. customdried under vacuum