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

Participants

Reaction Conditions

Reaction Steps

4-Chloro-6-[(3R)-3-(1-methylethyl)-4-morpholinyl]-2-pyrimidinamine (350 mg, 1.36 mmol), (4-cyano-3-fluorophenyl)boronic acid (337 mg, 2.05 mmol, 1.5 equiv), tricyclohexylphosphine (57.3 mg, 0.20 mmol, 0.15 equiv), Pd2(dba)3 (94 mg, 0.10 mmol, 0.075 equiv) and K3PO4 (492 mg, 2.32 mmol, 1.7 equiv) were charged into a 30 mL microwave vial, followed by addition of 5 mL of 1,4-dioxane and 1.6 mL of water. The mixture was bubbled with argon for 10 minutes, followed by capping and heating in a oil bath at 100° C. for 20 hours. LCMS showed conversion complete. The mixture was filtered through celite and rinsed with EtOAc (40 mL). The filtrate was concentrated in vacuo. The residue was partitioned between EtOAc (50 mL) and brine (10 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 80% EtOAc in CHCl3 to afford the title compound (359 mg) as an off-white foam with a light yellow tint. LC-MS (ES) m/z=342 [M+H]+.

Provenance & Evidence