Potassium Phosphate, Tribasic → 2,6-Difluoro-4-{2-(methylamino)-6-[(3R)-3-(1-methylethyl)-4-morpholinyl]-4-pyrimidinyl}benzonitrile

Participants

Reaction Conditions

Reaction Steps

4-Chloro-N-methyl-6-[(3R)-3-(1-methylethyl)-4-morpholinyl]-2-pyrimidinamine (1.70 g, 6.28 mmol), (4-cyano-3,5-difluorophenyl)boronic acid (1.72 g, 9.42 mmol, 1.5 equiv), tricyclohexylphosphine (0.264 g, 0.94 mmol, 0.15 equiv), Pd2(dba)3 (0.431 g, 0.47 mmol, 0.075 equiv), and K3PO4 (2.27 g, 10.67 mmol, 1.7 equiv) were charged into a 250 mL RB flask, followed by addition of 1,4-dioxane (30 mL) and water (10 mL). The mixture was degassed and back flushed with argon (5×). The mixture was heated in an oil bath at 100° C. for 20 hours. LCMS showed complete conversion. The mixture was filtered through celite and rinsed with EtOAc (150 mL). The filtrate was concentrated in vacuo. The residue was partitioned between EtOAc (150 mL) and brine (40 mL). The organic was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography using gradient elution of 1% EtOAc in CHCl3 to 100% EtOAc, to afford the title compound (1.64 g) as a yellow foam. LC-MS (ES) m/z=374 [M+H]+.

Provenance & Evidence