1-Hydroxybenzotriazole → HCID 57920022, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of (S)-3-cyclohexyl-2-(2-oxo-4-m-tolyloxy-2,5-dihydro-pyrrol-1-yl)-propionic acid (150 mg, 0.4 mmol) in dichloromethane (10 mL) was gradually added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (250 mg, 1.3 mmol) and N,N-diisopropylethylamine (0.280 g, 2.17 mmol) at room temperature, under nitrogen. After 15 min, 1-hydroxybenzotriazole (200 mg, 1.3 mmol) and 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 67 mg, 0.4 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-m-tolyloxy-2,5-dihydro-pyrrol-1-yl)-propionamide (16 mg, 8%) as an off-white sticky solid: 1H NMR (400 MHz, CDCl3) δ ppm 0.84-1.06 (m, 2H), 1.15 (s, 6H), 1.17-1.30 (m, 3H), 1.58-1.93 (m, 8H), 2.35 (s, 3H), 3.00 (br. s., 1H), 3.94 (s, 2H), 4.07 (d, J=18.0 Hz, 1H), 4.30 (d, J=18.0 Hz, 1H), 4.83-4.94 (m, 1H), 4.97 (s, 1H), 6.67 (br. s., 1H), 6.91-6.99 (m, 2H), 7.06 (d, J=7.8 Hz, 1H), 7.26-7.32 (m, 2H), 8.96 (br. s., 1H).

Provenance & Evidence