Sodium Carbonate → N-((1,2-dihydro-4,6-dimethyl-2-oxopyridin-3-yl)methyl)-1-isopropyl-3-methyl-6-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-indazole-4-carboxamide

Participants

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 (0.3 g, 0.69 mmol) in DMF (15 mL) was added 1-methyl-4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)piperazine (0.25 g, 0.82 mmol) followed by PdCl2(PPh3)2 (0.097 g, 0.13 mmol) and the mixture stirred 5 min. Sodium carbonate (0.184 g, 1.73 mmol) dissolved in water (2 mL) was added and the resulting reaction mixture was stirred at 110° C. for 4 h. The contents were then diluted with sodium bicarbonate solution and extracted with ethyl acetate (3×20 mL). The combined organic layers were washed with brine solution (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated to afford the crude product. The crude compound was purified by silica gel chromatography (eluent: 5% MeOH\DCM). The desired product was isolated as an off white solid with trace impurities. The impure compound was washed several times with cold water and triturated with hexane to afford the title compound as an off-white solid (80 mg, 22%). 1H NMR (DMSO-d6, 400 MHz): δ 1.447 (d, J=6.4 Hz, 6H), 2.112 (s, 3H), 2.235 (s, 6H), 2.411 (s, 7H), 3.551 (s, 4H), 4.363 (d, J=4.4 Hz, 2H), 4.991-5.054 (m, 1H), 5.870 (s, 1H), 6.942 (d, J=9.2 Hz, 1H), 7.321 (s, 1H), 7.880 (s, 1H), 7.99 (d, J=8.8 Hz, 1H), 8.403 (s, 1H), 8.569 (s, 1H), 11.483 (brs, 1H). LCMS (ES+) m/z: 528.29.

Provenance & Evidence