1,2-Dichloroethane → 6-bromo-N-((4-ethyl-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 (400 mg, 1.41 mmol) and 3-(aminomethyl)-4-ethyl-6-methyl-2(1H)-pyridinone.HCl (401 mg, 1.98 mmol) in DMSO (15 mL). 1-hydroxy-7-azabenzotriazole (308 mg, 2.26 mmol) was added and the resulting mixture was degassed with nitrogen for 10 minutes. N-methylmorpholine (0.64 ml, 5.79 mmol) and EDC (433 mg, 2.26 mmol) were added, the vessel was sealed, and the mixture was stirred at room temperature for 2 days. The mixture was poured onto 10 mL of ice-water and solids crashed out. 10% K2CO3 was added to adjust the pH˜8-9 and the contents were stirred for 10 min and then allowed to stand for another 10 min. Solids were filtered and air-dried. DMF along with some water were added and solids that precipitated were filtered. DCM was added and the contents purified by SiO2 chromatography (eluent: gradient 0 to 80:20:2 DCM/MeOH/NH4OH). The collected product was suspended in EtOAc along with some hexanes. Solids that precipitated were filtered and dried to afford the title compound as a white solid (504 mg, 82%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.54 (s, 1H) 8.63 (t, J=4.80 Hz, 1H) 8.37 (s, 1H) 8.20 (s, 1H) 7.70 (d, J=1.26 Hz, 1H) 5.93 (s, 1H) 5.06 (quin, J=6.57 Hz, 1H) 4.37 (s, 1H) 4.35 (s, 1H) 2.52-2.58 (m, 2H) 2.14 (s, 3H) 1.47 (s, 3H) 1.45 (s, 3H) 1.10 (t, J=7.58 Hz, 3H); LC-MS (ES) m/z=431.0/433.0

Provenance & Evidence