Reaction Steps
To a stirred solution of (S)-2-[4-(3-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-3-cyclohexyl-propionic acid (200 mg, 0.6 mmol) in dichloromethane (10 mL) was gradually added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (115 mg, 0.6 mmol) and N,N-diisopropylethylamine (213 mg, 1.7 mmol) at room temperature, under nitrogen. After 15 min,, 1-hydroxybenzotriazole (0.092 g, 0.625 mmol) and 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 85 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)-2-[4-(3-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-3-cyclohexyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-propionamide (0.075 g, 27%) as a white solid: 1H NMR (400 MHz, CDCl3) δ ppm 0.84-1.11 (m, 2H), 1.16 (s, 3H), 1.19-1.35 (m, 3H), 1.27 (s, 3H), 1.60-1.98 (m, 8H), 3.39 (br. s., 1H), 3.95 (s, 2H), 4.09 (d, J=18.0 Hz, 1H), 4.28 (d, J=18.0 Hz, 1H), 4.89 (dd, J=9.2, 6.5 Hz, 1H), 5.03 (s, 1H), 6.69 (d, J=2.2 Hz, 1H), 7.09 (dd, J=8.2, 1.8 Hz, 1H), 7.21 (t, J=1.8 Hz, 1H), 7.27 (m, 1H), 7.30 (d, J=2.2 Hz, 1H), 7.36 (t, J=8.2 Hz, 1H), 8.49 (br. s., 1H).
