反应详情

温度

65 °C

A stirred solution containing 2-amino-4,6-dichloropyrimidine (17.74 g, 0.11 mol) and 4-{[2-(trifluoromethyl)pyridin-4-yl]oxy}aniline (Intermediate 2U) in water (400 mL), isopropanol (100 mL) and concentrated hydrochloric acid (5 mL) was heated at 65° C. for 18 h. The reaction was cooled to 0° C. and the yellow-tan solid was collected by suction filtration and washed with water. The filtered product was dissolved in hot N,N-dimethylformamide (90° C.) and triethylamine was slowly added until the solution was slightly basic (pH˜8). The solution was then cooled to rt, added to vigorously stirred ice water (1.2 L), and stirring was continued for 1 h. The tan solids were collected by suction filtration and washed sequentially with water, isopropanol, diethyl ether and finally hexane. The material was dried by air suction to afford a light tan solid, 28.8 g (77%). 1H NMR (DMSO-d6) δ ppm 9.46 (s, 1H), 8.59 (d, 1H, J=5.6 Hz), 7.81 (d, 2H, J=9.0), 7.37 (d, 1H, J=2.4 Hz), 7.17 (d, 2H, J=9.0 Hz), 7.11 (dd, 1H, J=2.6, 5.6 Hz), 6.78 (s, 2H), 6.00 (s, 1H).

1. temperatureThe reaction was cooled to 0° C.
2. filtrationthe yellow-tan solid was collected by suction filtration
3. washwashed with water
4. dissolutionThe filtered product was dissolved in hot N,N-dimethylformamide (90° C.)
5. additiontriethylamine was slowly added until the solution
6. temperatureThe solution was then cooled to rt
7. additionadded to vigorously stirred ice water (1.2 L)
8. filtrationThe tan solids were collected by suction filtration
9. washwashed sequentially with water, isopropanol, diethyl ether and finally hexane
10. customThe material was dried by air suction
11. customto afford a light tan solid, 28.8 g (77%)