反应详情

温度

90 °C

A mixture of 4-(chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (3.28 g, 10 mmol), (prepared as described for the starting material in Example 2), 1-bromo-3-tetrahydropyranyloxypropane (2.5 g, 11 mmol) and potassium carbonate (5.0 g, 36 mmol) in DMF (50 ml) was stirred and heated at 90° C. for 3 hours. The reaction mixture was allowed to cool, was diluted with water (500 ml) and extracted with ethyl acetate (3×100 ml). The extracts were combined, washed with water (×3), and then brine, and dried (MgSO4). The solvent was removed by evaporation and the residue was purified by column chromatography eluting with ethyl acetate. The purified product was recrystallized from ethyl acetatethexane to give 4-(chloro-2-fluoroanilino)-6-methoxy-7-tetrshydropyran-2-yloxypropoxy)quinazoline (2.25 g, 49%).

1. custom(prepared
2. temperatureto cool
3. extractionextracted with ethyl acetate (3×100 ml)
4. washwashed with water (×3)
5. dry with materialbrine, and dried (MgSO4)
6. customThe solvent was removed by evaporation
7. customthe residue was purified by column chromatography
8. washeluting with ethyl acetate
9. customThe purified product was recrystallized from ethyl acetatethexane