反应详情

2-Bromoethyl ether (1.57 ml, 12 mmol) was added to a mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (1 g, 3.1 mmol), (prepared as described for the starting material in Example 2), and potassium carbonate (1.73 g, 12 mmol) in DMF (10 ml). The mixture was stirred for 18 hours at ambient temperature and was partitioned between ethyl acetate and water. The organic layer was separated, washed with water and then brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by column chromatography on silica eluting with methylene chloride/acetonitrile/methanol (60/38/2). The purified product was triturated with ether, collected by filtration, washed with ether and dried under vacuum to give 7-(2-(2-bromoethoxy)ethoxy)-4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline (763 mg, 52%).

1. custom(prepared
2. customwas partitioned between ethyl acetate and water
3. customThe organic layer was separated
4. washwashed with water
5. dry with materialbrine, dried (MgSO4)
6. customthe solvent removed by evaporation
7. customThe residue was purified by column chromatography on silica eluting with methylene chloride/acetonitrile/methanol (60/38/2)
8. customThe purified product was triturated with ether
9. filtrationcollected by filtration
10. washwashed with ether
11. customdried under vacuum