反应详情

温度

80 °C

A mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (950 mg, 3 mmol), (prepared as described for the starting material in Example 24), 2-bromo-4-bromomethylpyridine (765 mg, 3 mmol) and potassium carbonate (2.38 g 17 mmol) in DMF (10 ml) was heated at 80° C. for 2 hours. The mixture was allowed to cool, poured into water and extracted with ethyl acetate. The combined extracts were dried (MgSO4) and the solvent removed by evaporation and azeotroped with toluene. The residue was triturated with ethyl acetate/hexane and the solid product collected by filtration, washed with ethyl acetate/hexane and dried to give 7-((2-bromo-4-pyridyl)methoxy)-4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline (647 mg, 44%). m.p. 210-212° C. 1H NMR Spectrum: (DMSOd6) 3.98(s, 3H); 5.40(s, 2H); 7.25(s, 1H); 7.30(d, 1H); 7.50(s, 1H); 7.50(d, 1H); 7.55(m, 2H); 7.74(s, 1H); 7.86(s, 1H); 8.35(br s, 1H); 8.42(d, 1H); 9.56(s, 1H) MS-ESI: 489 [MH]30

1. custom(prepared
2. temperatureto cool
3. extractionextracted with ethyl acetate
4. dry with materialThe combined extracts were dried (MgSO4)
5. customthe solvent removed by evaporation
6. customazeotroped with toluene
7. customThe residue was triturated with ethyl acetate/hexane
8. filtrationthe solid product collected by filtration
9. washwashed with ethyl acetate/hexane
10. customdried