1-Hydroxybenzotriazole → 6-bromo-N-((1,2-dihydro-4,6-dimethyl-2-oxopyridin-3-yl)methyl)-1-isopropyl-3-methyl-1H-indazole-4-carboxamide

関与物質

反応手順

To a stirred solution of 6-bromo-1-isopropyl-3-methyl-1H-indazole-4-carboxylic acid, 1 (6.5 g, 21.88 mmol) in DCM (250 mL) was added EDC.HCl (5.01 g, 26.23 mmol), HOBt (3.545 g, 26.20 mmol) followed by diisopropyl ethyl amine (14.11 g, 109.37 mmol) and stirred at room temperature for 15 min. To the resulting mixture, 3-(amino methyl)-4,6-dimethylpyridin-2(1H)-one (3.32 g, 21.84 mmol) followed by DMAP (catalytic amount) was added and the reaction mixture was stirred at room temperature for 5 h. The reaction mixture was diluted with DCM (300 mL) and washed with 1N HCl solution (250 mL), saturated NaHCO3 solution (250 mL) and brine solution. The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was triturated with diethyl ether (100 mL), filtered, and dried to afford 6-bromo-N-((1,2-dihydro-4,6-dimethyl-2-oxopyridin-3-yl)methyl)-1-isopropyl-3-methyl-1H-indazole-4-carboxamide as an off white solid (5.5 g, 58%). 1H NMR (DMSO-d6, 400 MHz): δ 1.412 (d, J=6.4 Hz, 6H), 2.112 (s, 3H), 2.215 (s, 3H), 2.383 (s, 3H), 4.319 (d, J=5.2 Hz, 2H), 4.907-4.972 (m, 1H), 5.864 (s, 1H), 7.129 (d, J=1.2 Hz, 1H), 8.011 (d, J=1.2 Hz, 1H), 8.473 (t, J=5 Hz, 1H), 11.479 (brs, 1H). LCMS (ES+): 431.02 [M+H].

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