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

Participants

Reaction Steps

6-bromo-1-(1-methylethyl)-1H-indazole-4-carboxylic acid (237 mg, 0.84 mmol), 3-(aminomethyl)-4-cyclohexyl-6-methyl-2(1H)-pyridinone.TFA (378 mg, 1.13 mmol) and 1-hydroxy-7-azabenzotriazole (171 mg, 1.26 mmol) were stirred in 10 mL of DMSO for 10 min under nitrogen. N-methylmorpholine (0.37 ml, 3.35 mmol) was added along with EDC (241 mg, 1.26 mmol) and the mixture was stirred at rt overnight. An additional 0.2 eq of pyrdinone, HOAt, NMM and EDC were added and the contents were stirred at rt overnight. The reaction mixture was then poured onto ice-water. A solution of 10% K2CO3 in water was added to afford a pH˜8-9 solution. The reaction mixture was stirred at rt for 30 min and then allowed to stand at rt for 30 min. Precipitated solids were filtered and air-dried. The collected solid was treated with EtOAc (not soluble) and hexanes, and then concentrated in vacuo. To the isolated solid was then added DMF followed by heating and sonication. Water was added and beige solids crashed out. The precipitated solids were filtered, washed with water, air-dried, and dried in vacuum oven for 2 hours. The title compound was collected as a solid (308 mg, 74%). 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); LCMS: 485.2/487.2 (Br pattern).

Provenance & Evidence