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

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].

1. additionwas added
2. stirringthe reaction mixture was stirred at room temperature for 5 h
3. washwashed with 1N HCl solution (250 mL), saturated NaHCO3 solution (250 mL) and brine solution
4. dry with materialThe organic layer was dried over anhydrous Na2SO4
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe residue was triturated with diethyl ether (100 mL)
8. filtrationfiltered
9. customdried

ORD record

ord-b235fd55c9f14442a928a3e1f23c7dfa

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08846935B2