反应详情

温度

100 °C

Xantphos (93 mg, 0.161 mmol), palladium(II) acetate (24.2 mg, 0.108 mmol), and cesium carbonate (350 mg, 1.08 mmol) were added to a degassed solution of 2-chloro-4-(trifluoromethyl)pyrimidine (103 mg, 0.565 mmol), 1-{6-[3-amino-5-(morpholin-4-yl)phenyl]pyridin-2-yl}cyclobutanol (175 mg, 0.538 mmol) in dioxane (45.3 mL) and the reaction mixture was heated to 100° C. for 2 hours and then for 5 hours at 115° C. Then, the reaction mixture was cooled to room temperature, diluted with water, extracted with ethyl acetate, washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by silica gel chromatography (ethyl acetate:hexanes) to afford 1-{6-[3-(morpholin-4-yl)-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl]pyridin-2-yl}cyclobutanol as an off-white solid. MS APCI calc'd for C24H25F3N5O2 [M+H]+ 472. found 472. 1H NMR (NMR Hz 400 MHz, Acetone-d6): δ 9.26 (s, 1H), 8.82 (d, J=4.8 Hz, 1H), 8.16 (s, 1H), 7.90 (t, J=7.8 Hz, 1H), 7.84-7.77 (m, 2H), 7.66 (d, J=7.8 Hz, 1H), 7.53 (s, 1H), 7.23 (d, J=4.9 Hz, 1H), 3.86 (t, J=4.4 Hz, 4H), 3.30 (t, J=4.4 Hz, 4H), 2.74-2.63 (m, 2H), 2.43 (m, 2H), 2.04 (m, 2H).

1. temperatureThen, the reaction mixture was cooled to room temperature
2. extractionextracted with ethyl acetate
3. washwashed with brine
4. dry with materialdried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe crude product was purified by silica gel chromatography (ethyl acetate:hexanes)