Reaction Steps
To a stirred solution of 6-bromo-N-((1,2-dihydro-4,6-dimethyl-2-oxopyridin-3-yl)methyl)-1-isopropyl-3-methyl-1H-indazole-4-carboxamide (300 mg, 0.696 mmol) in DMF (30 mL) was added 6-(dimethylamino)pyridin-3-yl-3-boronic acid, 1 (127 mg, 0.765 mmol) followed by sodium carbonate (184.4 mg, 1.74 mmol) dissolved in water (3 mL) and degassed with argon for 1 h. Then PdCl2(PPh3)2 (48.8 mg, 0.069 mmol) was added and again degassed with argon for 15 min and stirred at 110° C. for 4 h. The reaction mixture was filtered through Celite pad and washed with ethyl acetate (50 mL). The filtrate was diluted with water and extracted with ethyl acetate (4×90 mL). The combined organic layers were separated and washed with cold water (2×50 mL), brine solution (50 mL), dried over anhydrous Na2SO4, filtered, and concentrated to afford the crude product (450 mg). The crude compound was purified by silica gel chromatography (eluent: 5% MeOH: DCM) to afford 100 mg of desired product which was triturated with hexane and the solid was filtered and dried to afford the title compound as an off white solid (100 mg, 30%). 1H NMR (DMSO-d6, 400 MHz): δ 1.559 (d, J=6.8 Hz, 6H), 2.102 (s, 3H), 2.403 (s, 3H), 2.539 (s, 3H), 3.125 (s, 6H), 4.616 (s, 2H), 4.754-4.820 (m, 1H), 5.893 (s, 1H), 6.557 (d, J=8.8 Hz, 1H), 7.313 (s, 1H), 7.401 (d, J=5.2 Hz, 1H), 7.448 (s, 1H), 7.707 (d, J=8.8 Hz, 1H), 8.438 (s, 1H), 11.502 (brs, 1H). 1H NMR (D2O Ex in DMSO, 400 MHz): δ 1.559 (d, J=6.8 Hz, 6H), 2.115 (s, 3H), 2.408 (s, 3H), 2.538 (s, 3H), 3.124 (s, 6H), 4.616 (s, 2H), 4.754-4.820 (m, 1H), 5.899 (s, 1H), 6.557 (d, J=8.8 Hz, 1H), 7.318 (s, 1H), 7.450 (s, 1H), 7.718 (d, J=8.8 Hz, 1H), 8.438 (s, 1H). LCMS (ES+): 473.19.
