4-Methylmorpholine → 3-Bromo-N-[(1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl]-1-(4-methylphenyl)-1H-indazole-6-carboxamide

Participants

Reaction Conditions

Reaction Steps

3-Bromo-1-(4-methylphenyl)-1H-indazole-6-carboxylic acid (233.7 mg, 0.389 mmol, with 4 equivalents of sodium chloride), (1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethanamine bis-hydrochloride (94.2 mg, 0.471 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (156.1 mg, 0.814 mmol), 1-hydroxy-7-azabenzotriazole (28.9 mg, 0.212 mmol), and N-methylmorpholine (0.171 mL, 1.554 mmol) were dissolved in N,N-dimethylformamide (3.800 mL) at 25° C. The reaction mixture was heated to 50° C. and allowed to stir for 10 min. The reaction was stopped, quenched by addition of water (ca 0.5 mL) and trifluoroacetic acid (ca 0.5 mL). The reaction mixture purified directly by preparative HPLC (Reverse phase (C-18)), eluting with acetonitrile/water+0.1% trifluoroacetic acid. The product fractions were concentrated under reduced pressure. The residue was taken up in ethyl acetate (15 mL), washed with sodium bicarbonate (2×20 mL) and saturated aqueous sodium chloride (1×15 mL), dried (sodium sulfate), filtered, and the solvent evaporated under reduced pressure to give the title compound (153.9 mg, 0.350 mmol, 90% yield) as a tan solid. HRMS: [M+1]=440.0730.

Provenance & Evidence