Reaction Steps
(3S,6R)-1-[6-Chloro-2-(methylamino)-4-pyrimidinyl]-6-methyl-N-(phenylmethyl)-3-piperidinecarboxamide (600 mg, 1.61 mmol), 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole (509 mg, 2.09 mmol, 1.3 equiv), Pd2(dba)3 (110 mg, 0.12 mmol, 0.075 equiv), tricyclohexylphosphine (68 mg, 0.24 mmol, 0.15 equiv), and K3PO4 (579 mg, 2.73 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 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 gradient elution of 1% A to 70% A in CHCl3 (A was a mixture of 200/80/800 CH3OH/NH4OH/CHCl3). Trituration of the residue collected from the chromatography in a mixture of CHCl3 (2 mL), MTBE (3 mL) hexane (6 mL), followed by drying under vacuum at 65° C. for 20 hours gave the title compound (526 mg) as a pale yellowish solid. LC-MS (ES) m/z=456 [M+H]+. 1H NMR (400 MHz, CD3OD): δ 1.31 (d, J=7.1 Hz, 3H), 1.75-1.90 (m, 3H), 1.99-2.10 (m, 1H), 2.45-2.55 (m, 1H), 2.97 (s, 3H), 3.10-3.19 (m, 1H), 4.42 (s, 2H), 4.50-4.60 (bs, 1H), 4.75-4.85 (bs, 1H), 6.50 (s, 1H), 7.24-7.38 (m, 5H), 7.69 (dd, J=8.5, 1.1 Hz, 1H), 7.84 (d, J=8.6 Hz, 1H), 8.09 (s, 1H), 8.10 (s, 1H).
