1-Hydroxybenzotriazole → HCID 57920074, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of (S)-3-cyclohexyl-2-[2-oxo-4-(3-trifluoromethyl-phenoxy)-2,5-dihydro-pyrrol-1-yl]-propionic acid (180 mg, 0.5 mmol) in dichloromethane (10 mL) was gradually added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (259 mg, 1.2 mmol) and N,N-diisopropylethylamine (292 mg, 2.3 mmol) at room temperature, under nitrogen. After 15 min, 1-hydroxybenzotriazole (208 mg, 1.41 mol) and 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 70 mg, 0.5 mmol) were added to the reaction mixture. The reaction mixture was then stirred at 23° C. for 48 h. The reaction mixture was diluted with ethyl acetate and washed with a saturated aqueous ammonium chloride solution followed by a saturated aqueous sodium bicarbonate solution. The organic layer was then washed with a saturated aqueous sodium chloride solution, separated, dried over sodium sulfate and concentrated in vacuo to afford the crude product, which was purified by flash column chromatography (silica gel (100-200 mesh)) which afforded (S)-3-cyclohexyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-[2-oxo-4-(3-trifluoromethyl-phenoxy)-2,5-dihydro-pyrrol-1-yl]-propionamide (45 mg, 19%) as an off-white sticky solid: 1H NMR (400 MHz, CDCl3) δ ppm 0.78-1.04 (m, 2H), 1.13 (br. s., 6H), 1.15-1.31 (m, 3H), 1.56-1.93 (m, 8H), 2.66 (br. s., 1H), 3.92 (br. s., 2H), 4.10 (d, J=18.1 Hz, 1H), 4.40 (d, J=18.1 Hz, 1H), 4.94 (br. s., 1H), 5.00 (br. s., 1H), 6.64 (br. s., 1H), 7.27 (br. s., 1H), 7.39 (br. s., 1H), 7.45 (br. s., 1H), 7.54 (br. s., 2H), 9.02 (br. s., 1H).

Provenance & Evidence