4-Methylmorpholine → 6-bromo-1-(1-methylethyl)-N-[(6-methyl-2-oxo-1,2-dihydro-4,4'-bipyridin-3-yl)methyl]-1H-indazole-4-carboxamide

Participants

Reaction Steps

To a reaction vial were added 6-bromo-1-(1-methylethyl)-1H-indazole-4-carboxylic acid (90 mg, 0.318 mmol), 3-(aminomethyl)-6-methyl-4,4′-bipyridin-2(1H)-one (103 mg, 0.477 mmol), 1-hydroxy-7-azabenzotriazole (64.9 mg, 0.477 mmol), EDC (91 mg, 0.477 mmol) and DMSO (10 mL) followed by N-methylmorpholine (0.140 mL, 1.272 mmol) in one portion. The reaction contents were stirred at RT for 12 hr, after which time an additional 20 mg each of amine, EDC, and HOAt were added. After stirring for an additional 2 h, the reaction mixture was poured onto ice water (10 mL), stirred for 20 min, allowed to stand for 10 min, and filtered. The collected solid was rinsed with water (10 mL), and then purified by reverse phase HPLC (10-90% acetonitrile/water+0.1% TFA). The product fractions were treated with NaHCO3 (sat aq), extracted with EtOAc, and evaporated from water to afford the final product as a white solid (69 mg, 43%). 1H NMR (400 MHz, DMSO-d6) ppm 11.95 (s, 1H), 8.63-8.65 (d, 2H), 8.60 (s, 1H), 8.32 (s, 1H), 8.21 (s, 1H), 7.61 (s, 1H), 7.42 (d, 2H), 6.00 (s, 1H), 5.02 (m, 2H), 4.15 (s, 2H), 2.23 (s, 3H), 1.45 (d, 6H); MS(ES) [M+H]+ 481.8.

Provenance & Evidence