反应 #47532
ord-bcc4e793129b4ed78cb846e529dcf35e
反应方程式
反应物
试剂
反应条件
后处理
- 1其他at room temperature
- 2洗涤washed with a saturated aqueous ammonium chloride solution
- 3洗涤The organic layer was then washed with a saturated aqueous sodium chloride solution
- 4其他separated
- 5干燥dried over sodium sulfate
- 6浓缩concentrated in vacuo
- 7其他to afford the crude product, which
- 8其他was purified by flash column chromatography (silica gel (100-200 mesh)) which
实验过程
To a stirred solution of (S)-3-cyclohexyl-2-[4-(2,3-dimethyl-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-propionic acid (240 mg, 0.7 mmol) in dichloromethane (10 mL) was gradually added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (390 mg, 2.0 mmol) and N,N-diisopropylethylamine (440 mg, 3.4 mmol) at room temperature, under nitrogen. After 15 min,, 1-hydroxybenzotriazole (310 mg, 2.1 mmol) and 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 106 mg, 0.7 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-2-[4-(2,3-dimethyl-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-propionamide (105 mg, 32%) as an off-white solid: 1H NMR (400 MHz, CDCl3) δ ppm 0.82-1.08 (m, 2H), 1.14 (br. s., 6H), 1.17-1.30 (m, 3H), 1.57-1.98 (m, 8H), 2.09 (s, 3H), 2.29 (s, 3H), 3.92 (s, 2H), 4.08 (d, J=18.0 Hz, 1H), 4.28 (d, J=18.0 Hz, 1H), 4.75 (br. s., 2H), 4.78 (br. s., 1H), 4.87 (t, J=7.6 Hz, 1H), 6.67 (d, J=2.0 Hz, 1H), 6.93 (d, J=7.8 Hz, 1H), 7.02-7.14 (m, 2H), 7.28 (d, J=2.0 Hz, 1H).