1,2-Dichloroethane → 6-bromo-N-((4-cyclohexyl-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-isopropyl-1H-indazole-4-carboxamide

Participants

Reaction Steps

In a 25 mL sealable tube under nitrogen were combined 6-bromo-1-(1-methylethyl)-1H-indazole-4-carboxylic acid (237 mg, 0.84 mmol) and 3-(aminomethyl)-4-cyclohexyl-6-methyl-2(1H)-pyridinone.TFA (434 mg, 1.3 mmol) in DMSO (10 mL). 1-hydroxy-7-azabenzotriazole (194 mg, 1.42 mmol) was added and the resulting mixture was degassed with nitrogen for 10 minutes. N-methylmorpholine (0.39 mL, 3.52 mmol) and EDC (273 mg, 1.42 mmol) were added, the vessel was sealed, and the mixture was stirred at room temperature for 2 days. The mixture was poured into 10 mL of ice-water and beige solids crashed out. K2CO3 (10%) was added to adjust the pH˜8-9 and the mixture stirred for 30 min and let stand for another 30 min. Solids were filtered off and air-dried. DMF was added, it was heated and sonicated and some water was added. Solids that precipitated were filtered, washed with water and dried to afford the title compound (307 mg, 73%) as a light beige solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.53 (s, 1H) 8.63 (t, J=4.80 Hz, 1H) 8.37 (s, 1H) 8.20 (s, 1H) 7.68 (d, J=1.26 Hz, 1H) 6.01 (s, 1H) 5.05 (dt, J=13.14, 6.57 Hz, 1H) 4.43 (d, J=4.80 Hz, 2H) 2.84 (t, J=11.24 Hz, 1H) 2.15 (s, 3H) 1.70 (d, J=13.39 Hz, 2H) 1.60 (d, J=12.13 Hz, 3H) 1.47 (s, 3H) 1.45 (s, 3H) 1.42 (br. s., 1H) 1.17-1.39 (m, 4H). MS (ES) [M+H]+ 485.2, 487.2.

Provenance & Evidence