1-Hydroxybenzotriazole → HCID 178434421, compound

Participants

Reaction Steps

To 200 mg (0.57 mmol) of (1R,2R)-2-(5-cyano-6-(2-fluoro-4-hydroxyphenyl)-3-methyl-1H-pyrazolo[3,4-b]pyridine-4-yl)cyclopropane carboxylic acid diluted in 4 ml of anhydrous dimethylformamide are added, at 0° C., 121 mg (0.57 mmol) of tert-butyl 4-aminopiperidine-1-carboxylate, 76 mg (0.62 mmol) of N,N-dimethylpyridine-4-amine (DMAP), 110 mg (0.62 mmol of N,N-dimethyl-N-[(methylimino)methylene]propane-1,3-diamine hydrochloride (EDCI) and 84 mg (0.62 mmol) of 1H-benzo[d][1,2,3]triazole-1-ol (HOBT). The reaction mixture is stirred 20 h at room temperature. The solvent is concentrated, water is added and the product extracted several times with ethyl acetate. The organic phases are combined, dried over magnesium sulfate and concentrated. The residue is purified by chromatography on silica (cyclohexane/ethyl acetate eluent: 5:5 to 3:7) to give 158 mg of tert-butyl 4-((1R,2R)-2-(5-cyano-6-(2-fluoro-4-hydroxyphenyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropanecarboxamido)piperidine-1-carboxylate in the form of a white solid.

Provenance & Evidence