反应详情

温度

80 °C

4-[(3-Chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl trifluoromethanesulfonate, (described in Example 1 preparation of starting materials), (3 g, 6.64 mmol) was dissolved in dimethylformamide (21 ml) and n-butyl vinyl ether (4.3 ml, 33.2 mmol), triethylamine (2.3 ml, 16.6 mmol), 1,3-bis(diphenylphosphino)propane (438 mg, 1.06 mmol) and palladium acetate (223 mg, 1 mmol) added. The mixture was heated at 80° C. for 2 hours, allowed to cool and stirred at room temperature over night. 2M aqueous hydrochloric acid (24 ml) was added and the mixture stirred for 0.5 hours. The mixture was basified with saturated aqueous sodium hydrogen carbonate and extracted with ethyl acetate. The organic extracts were washed with brine, dried over magnesium sulfate and concentrated under reduced pressure. The resulting solid was suspended in methanol and filtered to give 1-{4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}ethanone (1.7 g, 74%) as a pale yellow solid; 1H NMR (spectrum): (DMSO d6) 2.62 (s, 3H); 4.02 (s, 3H); 7.27 (m, 2H); 7.49 (t, 2H); 8.48 (s, 1H); 8.72 (s, 1H); 10.19 (s, 1H). Mass Spectrum: (M+H)+ 346.

1. temperatureto cool
2. stirringthe mixture stirred for 0.5 hours
3. extractionextracted with ethyl acetate
4. washThe organic extracts were washed with brine
5. dry with materialdried over magnesium sulfate
6. concentrationconcentrated under reduced pressure
7. filtrationfiltered