2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → ethyl rel-(1R,2S)-4-{1-[5-(3-{[4-(difluoromethyl)pyrimidin-2-yl]amino}-5-methylphenyl)pyrimidin-2-yl]ethenyl}-2-methylcyclohexanecarboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of ethyl rel-(1R,2S)-4-[1-(5-chloropyrimidin-2-yl)ethenyl]-2-methylcyclohexanecarboxylate (480 mg, 1.6 mmol), 4-(difluoromethyl)-N-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyrimidin-2-amine (570 mg, 1.6 mmol), tris(dibenzylideneacetone)-dipalladium(0) (140 mg, 0.16 mmol), XPhos (140 mg, 0.32 mmol) and potassium phosphate tribasic trihydrate (1.25 g, 4.8 mmol) in N,N-dimethylformamide (2 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 ethyl rel-(1R,2S)-4-{1-[5-(3-{[4-(difluoromethyl)pyrimidin-2-yl]amino}-5-methylphenyl)pyrimidin-2-yl]ethenyl}-2-methylcyclohexanecarboxylate. MS ESI calc'd for C28H32F2N5O2[M+G]+ 508. found 508. 1H NMR: (400 MHz, CD3OD) δ 9.02 (s, 2H), 8.64 (d, J=5.2 Hz, 1H), 8.01 (s, 1H), 7.60 (s, 1H), 7.21 (s, 1H), 7.04 (d, J=5.0 Hz, 1H), 6.58 (t, J=54.4 Hz, 1H), 6.36 (s, 1H), 5.52-5.49 (m, 1H), 4.16-4.10 (m, 2H), 2.44 (s, 3H), 1.94-1.59 (m, 7H), 1.25-1.24 (m, 5H), 1.03 (d, J=7.0 Hz, 3H).

Provenance & Evidence