反应详情

温度

110 °C

A mixture of methyl trans-4-[1-(5-chloropyrimidin-2-yl)ethenyl]cyclohexanecarboxylate (8 mg, 0.028 mmol), 4-(difluoromethyl)-N-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyrimidin-2-amine (10.3 mg, 0.028 mmol), tris(dibenzylideneacetone)-dipalladium(0) (1.3 mg, 1.42 μmol), XPhos (1.36 mg, 2.85 μmol) and potassium phosphate tribasic (18 mg, 0.085 mmol) in 1,4-dioxane (2 mL) and water (0.5 mL) was stirred at 110° C. under a nitrogen atmosphere for 3 hours. After cooling to room temperature, the mixture was diluted with brine and extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (ethyl acetate/petroleum ether) to afford methyl trans-4-{1-[5-(3-{[4-(difluoromethyl)pyrimidin-2-yl]amino}-5-methylphenyl)pyrimidin-2-yl]ethenyl}cyclohexanecarboxylate. MS ESI calc'd for C26H28F2N5O2 [M+H]+ 480. found 480. 1H NMR: (400 MHz, CDCl3) δ 8.94 (s, 2H), 8.72 (d, J=4.8 Hz, 1H), 8.62 (d, J=5.2 Hz, 1H), 7.88 (s, 1H), 7.37 (s, 1H), 7.13-7.11 (m, 1H), 7.04-7.03 (m, 1H), 6.43 (s, 1H), 5.48 (s, 1H), 3.69 (s, 3H), 3.09-3.06 (m, 1H), 2.46 (s, 3H), 2.05-2.02 (m, 3H), 1.69-1.62 (m, 3H), 1.39-1.33 (m, 3H).

1. temperatureAfter cooling to room temperature
2. extractionextracted with ethyl acetate
3. dry with materialThe combined organic layers were dried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customThe residue was purified by chromatography on silica gel (ethyl acetate/petroleum ether)