反应详情

To a stirred solution of 4-chloro-2-(4-chloro-phenyl)-7-trifluoromethylquinazoline (52.0 g, 0.15 mol) in THF (400 mL) at 0° C. was added dropwise a solution of ethylamine (0.45 mol, 230 mL, 2 M in THF. The ice-bath was then removed and the reaction mixture was allowed to stir at room temperature for 1 h. The reaction mixture was concentrated under reduced pressure then partitioned between ethyl acetate (400 mL) and water (400 mL) removing any undissolved solid by vacuum filtration. The filtrate was concentrated to approximately 200 mL and the resultant precipitate was removed by vacuum filtration. The filtrate was again concentrated to approximately 100 mL volume and the resultant precipitate was removed by vacuum filtration. Finally the filtrate was cooled to 0° C. upon which [2-(4-chloro-phenyl)-7-trifluoromethyl-quinazolin-4-yl]ethylamine precipitated from solution. The precipitate (30 g) was isolated by vacuum filtration and dried under vacuum (10 mbar, 50° C.). A second amount of the precipitate of equal purity (19.6 g) was obtained following concentration of the filtrate to approximately 50 mL volume, cooling to 0° C., filtration and drying under vacuum. Combined yield=49.6 g, 93%; LC-MS: 2.9 min, 352 (M+); 1H NMR (DMSO-d6): δ 1.38 (t, 1 H, J=7 Hz), 3.77-3.85 (m, 2 H), 7.46 (d, 2 H, J=8.7 Hz), 7.64 (dd, 1 H, J=8.3, 1.8 Hz), 7.72-7.78 (br s, 1 H), 8.09 (s, 1 H), 8.17 (d, 1 H, J=8.3 Hz), 8.59 (d, 2 H, J=8.7 Hz).

1. customThe ice-bath was then removed
2. concentrationThe reaction mixture was concentrated under reduced pressure
3. customthen partitioned between ethyl acetate (400 mL) and water (400 mL)
4. customremoving any undissolved solid
5. filtrationby vacuum filtration
6. concentrationThe filtrate was concentrated to approximately 200 mL
7. customthe resultant precipitate was removed by vacuum filtration
8. concentrationThe filtrate was again concentrated to approximately 100 mL volume
9. customthe resultant precipitate was removed by vacuum filtration
10. temperatureFinally the filtrate was cooled to 0° C. upon which [2-(4-chloro-phenyl)-7-trifluoromethyl-quinazolin-4-yl]ethylamine
11. customprecipitated from solution