Reaction Steps
(3S,6R)-1-[6-Chloro-2-(methylamino)-4-pyrimidinyl]-N-cyclohexyl-6-methyl-3-piperidinecarboxamide (440 mg, 1.20 mmol), 3-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole (466 mg, 1.80 mmol, 1.5 equiv), tricyclohexylphosphine (50 mg, 0.18 mmol, 0.15 equiv), Pd2(dba)3 (83 mg, 0.09 mmol, 0.075 equiv) and K3PO4 (434 mg, 2.04 mmol, 1.7 equiv) were charged to a 30 mL microwave vial, followed by addition of 1,4-dioxane (4.5 mL) and water (1.5 mL). The mixture was bubbled with argon for 10 minutes, followed by capping and heating at 100° C. for 20 hours. The mixture was filtered through celite, and rinsed with EtOAc (50 mL). The filtrate was concentrated in vacuo, and the residue was partitioned between EtOAc (50 mL) and brine (20 mL). The organic was dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography using a gradient elution with 1% EtOAc in CHCl3 to 100% EtOAc. This purified material was combined with purified product from a duplicate run. The combined residue was triturated in a mixture of CHCl3 (1 mL) and hexane (6 mL). Drying under vacuum at 65° C. for 20 hours afforded the title compound (194 mg) as a beige solid. LC-MS (ES) m/z=462 [M+H]+. 1H NMR (400 MHz, CD3OD): δ 1.20-1.34 (m, 3H), 1.30 (d, J=6.8 Hz, 3H), 1.35-1.45 (m, 2H), 1.64-1.71 (m, 1H), 1.73-1.83 (m, 5H), 1.85-1.95 (m, 2H), 1.95-2.07 (m, 1H), 2.35-2.45 (m, 1H), 2.59 (s, 3H), 2.98 (s, 3H), 3.07-3.17 (m, 1H), 3.63-3.73 (m, 1H), 4.45-4.65 (bs, 1H), 6.48 (s, 1H), 7.66 (dd, J=8.5, 1.1 Hz, 1H), 7.78 (d, J=8.6 Hz, 1H), 8.02 (s, 1H).
