1-Hydroxybenzotriazole → HCID 24966090, compound

Participants

Reaction Conditions

Reaction Steps

Triethylamine (0.21 mL) was added to a solution of 3-(tert-butoxycarbonyl)-1-cyclopropyl-4-ethoxy-1H-indole-6-carboxylic acid (177 mg), 6-(1H-pyrazol-4-yl)spiro[chroman-2,4′-piperidin]-4-one hydrochloride (156 mg), WSC hydrochloride (106 mg) and HOBT (85 mg) in DMF (4 mL) and the mixture was stirred at 90° C. for 1 hour. After cooling to room temperature, the mixture was diluted with ethyl acetate, then washed with water, 1N hydrochloric acid solution, aqueous saturated sodium bicarbonate and saturated saline in this order, and dried over sodium sulfate. The solution was filtered, concentrated, and purified through silica gel column chromatography (chloroform/methanol) to give the methyl ester of the title compound as a colorless amorphous substance. TFA (3 ml) was added to the solution of this ester in chloroform (10 ml) at room temperature and stirred for 3 h. The solvent was evaporated and the residue was crystallized from a mixed solvent of methanol and ether to give title compound as a colorless solid. 1H-NMR (400 MHz, DMSO-d6) δ: 8.03 (2H, s), 7.94 (1H, s), 7.87 (1H, d, J=2.4 Hz), 7.83 (1H, dd, J=8.5, 2.4 Hz), 7.33 (1H, d, J=1.0 Hz), 7.10 (1H, d, J=8.5 Hz), 6.79 (1H, d, J=1.0 Hz), 4.31-4.19 (1H, br m), 4.21 (2H, q, J=7.0 Hz), 3.85-3.21 (4H, br m), 2.89 (2H, s), 2.11-1.70 (4H, br m), 1.39 (3H, t, J=7.0 Hz), 1.10-1.00 (4H, m); MS [M+H]+=555.

Provenance & Evidence