反应详情

温度

90 °C

A mixture of methyl trans-4-{(5-chloropyrimidin-2-yl)[(methylsulfonyl)oxy]methyl}cyclohexanecarboxylate (48 mg, 0.13 mmol), 4-(difluoromethyl)-N-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyrimidin-2-amine (48 mg, 0.13 mmol), tris(dibenzylideneacetone)-dipalladium(0) (6.1 mg, 0.006 mmol), XPhos (6.2 mg, 0.012 mmol), and potassium phosphate tribasic trihydrate (0.11 g, 0.4 mmol) in 1,4-dioxane/water (2 mL/0.5 mL) was stirred at 90° C. under a nitrogen atmosphere for 12 hours. After cooling to 20° C., 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-{[5-(3-{[4-(difluoromethyl)pyrimidin-2-yl]amino}-5-methylphenyl)pyrimidin-2-yl][(methylsulfonyl)oxy]methyl}cyclohexanecarboxylate. MS ESI calc'd. for C26H30F2N5O5S[M+H]+ 562. found 562. 1H NMR: (400 MHz, CD3OD) δ 9.12 (s, 2H), 8.66 (d, J=4.8 Hz, 1H), 8.05 (s, 1H), 7.65 (s, 1H), 7.26 (s, 1H), 7.06 (d, J=4.8 Hz, 1H), 6.61 (t, J=54.4 Hz, 1H), 5.47 (d, J=7.0 Hz, 1H), 3.66 (s, 3H), 3.08 (s, 3H), 2.46 (s, 3H), 2.34 (s, 1H), 2.10-2.00 (m, 4H), 1.52-1.31 (m, 5H).

1. temperatureAfter cooling to 20° C.
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)