反应详情

A suspension of 4-(3-chloro-2-fluoroanilino)-6-[1-(chloroacetyl)piperidin-4-yloxy]-7-methoxyquinazoline (0.15 g) (starting material for Example 17) and sodium iodide (0.02 g) in morpholine (5 ml) was stirred at ambient temperature for 16 hours. The mixture was evaporated under vacuum and the residue dissolved in methylene chloride/methanol. This was adsorbed onto silica and purified by column chromatography on silica eluting with increasingly polar mixtures of methylene chloride/methanol (100/0 to 90/10). The fractions containing the title product were combined and evaporated under vacuum. The residue was triturated with diethylether, filtered and dried under vacuum to give the title product as a beige crystalline solid (0.105 g); 1H NMR Spectrum: (DMSO d6 and CD3COOD) 1.57-1.80 (m, 2H), 1.91-2.12 (m, 2H), 2.40-2.51 (m, 4H), 3.14-3.48 (m, 4H), 3.52-3.61 (m, 4H), 3.81-3.90 (m, 2H), 3.94 (s, 3H), 4.76 (m, 1H), 7.20-7.30 (m, 2H), 7.42-7.54 (m, 2H), 7.85 (s, 1H), 8.36 (s, 1H); Mass Spectrum: (M+H)+ 530.

1. customThe mixture was evaporated under vacuum
2. dissolutionthe residue dissolved in methylene chloride/methanol
3. custompurified by column chromatography on silica eluting
4. temperaturewith increasingly polar mixtures of methylene chloride/methanol (100/0 to 90/10)
5. additionThe fractions containing the title product
6. customevaporated under vacuum
7. customThe residue was triturated with diethylether
8. filtrationfiltered
9. customdried under vacuum