Reaction Steps
(3S,6R)-1-[6-Chloro-2-(methylamino)-4-pyrimidinyl]-N-cyclohexyl-6-methyl-3-piperidinecarboxamide (700 mg, 1.91 mmol), 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole (607 mg, 2.50 mmol, 1.3 equiv), Pd2(dba)3 (131 mg, 0.14 mmol, 0.075 equiv), tricyclohexylphosphine (80 mg, 0.287 mmol, 0.15 equiv), and K3PO4 (690 mg, 3.25 mmol, 1.7 equiv) were charged to a 30 mL microwave vial, followed by addition of 1,4-dioxane (12 mL) and water (4 mL). The mixture was bubbled with argon for 10 minutes, and heated at 100° C. for 20 hours. After cooling to room temperature, the mixture was filtered through celite, and the filtrate was concentrated in vacuo. The resulting residue was partitioned between EtOAc (50 mL) and brine (15 mL). The organic was dried over Na2SO4, filtered, and concentrated in vacuo. Purification was performed by silica gel column chromatography using a gradient elution of 1% A in CHCl3 to 75% A in CHCl3 (A was a mixture of 200/80/800 CH3OH/NH4OH/CHCl3). Trituration of the residue obtained from the chromatography in a mixture of MTBE (3 mL) and hexane (3 mL), followed by drying under vacuum at 65° C. for 24 hours afforded the title compound (496 mg) as solids. LC-MS (ES) m/z=448 [M+H]+. 1H NMR (400 MHz, CD3OD): δ 1.20-1.30 (m, 3H), 1.30 (d, J=6.8 Hz, 3H), 1.35-1.48 (m, 2H), 1.64-1.74 (m, 1H), 1.75-1.84 (m, 5H), 1.86-1.94 (m, 2H), 1.96-2.08 (m, 1H), 2.34-2.45 (m, 1H), 2.98 (s, 3H), 3.08-3.18 (m, 1H), 3.64-3.71 (m, 1H), 4.50-4.70 (bs, 1H), 4.75-4.95 (bs, 1H), 6.50 (s, 1H), 7.69 (dd, J=8.5, 1.1 Hz, 1H), 7.85 (d, J=8.6 Hz, 1H), 8.09 (s, 1H), 8.11 (s, 1H).
