To a 20-mL screw-cap vial was added 4-bromo-2-fluoro-6-hydroxybenzonitrile (500 mg, 2.315 mmol), bis-pinacolato diboron (705 mg, 2.78 mmol), potassium acetate (568 mg, 5.79 mmol), PdCl2(dppf).CH2Cl2 adduct (95 mg, 0.116 mmol), and 1,4-dioxane (8 mL). The vial was capped and stirred for 4 h at 100° C. on a stirrer hot-plate. The reaction mixture was allowed to cool, then was diluted with ethyl acetate (50 mL) and washed with water (20 mL). The organic layer was dried over Na2SO4 and concentrated. The residue was added to a 20 mL microwave vial and 4-chloro-N-methyl-6-[(3R)-3-methyl-4-morpholinyl]-2-pyrimidinamine (0.279 g, 1.15 mmol), PdCl2(dppf).CH2Cl2 adduct (0.047 g, 0.058 mmol), K2CO3 (2 M, 1.725 mL, 3.45 mmol), and 1,4-dioxane (6 mL) were added. The resulting mixture was heated at 140° C. for 10 minutes in a microwave reactor. The organic layer was separated and the aqueous was diluted with water (10 mL), neutralized with 0.1 N HCl (pH paper), then extracted with EtOAc (3×50 mL). The organics were combined, and then dried over Na2SO4. The dried solution was concentrated, then purified by flash chromatography 0-10% CH3OH in CH2Cl2 (24 g column, dry-loaded) to afford the title compound (0.37 g) as a brown solid. LC-MS (ES) m/z=344 [M+H]+.
