2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 178501166, compound

Participants

Reaction Conditions

Reaction Steps

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).

Provenance & Evidence