反应详情

温度

25 °C

In a round bottom flask under argon was placed 3-bicyclo[2.2.1]hept-7-yl-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-propionic acid (32 mg, 0.085 mmol) in dichloromethane (5 mL). To this mixture was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (16 μL, 0.094 mmol) and 1-hydoxybenzotriazole (12 mg, 0.089 mmol) and stirred at 25° C. for 2 h. After this time, 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared as in US20080021032, Example 80, 16 mg, 0.102 mmol) was added and stirred for 16 h at 25° C. The reaction was diluted with dichloromethane (10 mL) and washed with a 1N aqueous hydrochloric acid solution (10 mL), water (10 mL), a saturated aqueous sodium bicarbonate solution (10 mL), dried over magnesium sulfate and concentrated in vacuo. Purification by AnaLogix IntelliFlash flash chromatography (4 g column, 20% ethyl acetate/hexanes to 80% ethyl acetate/hexanes) afforded 3-bicyclo[2.2.1]hept-7-yl-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-propionamide (27 mg, 61%) as yellow foam: HR-ES-MS m/z calculated for C27H33N4O4Cl [M+H]+ 513.2263, observed 513.2263; 1H NMR (300 MHz, CDCl3) δ ppm 1.15 (s, 6H), 1.15-1.31 (m, 4H), 1.43-1.59 (m, 3H), 1.65 (d, J=8.5 Hz, 2H), 1.70-1.87 (m, 1H), 1.90-2.09 (m, 3H), 2.80 (br. s., 1H), 3.93 (s, 2H), 4.16 (d, J=18.1 Hz, 1H), 4.32 (d, J=18.1 Hz, 1H), 4.76 (t, J=7.7 Hz, 1H), 4.89 (s, 1H), 6.70 (s, 1H), 7.17-7.25 (m, 1H), 7.27-7.37 (m, 3H), 7.48 (d, J=8.2 Hz, 1H), 8.74 (br. s., 1H).

1. customIn a round bottom flask under argon was placed
2. stirringstirred for 16 h at 25° C
3. washwashed with a 1N aqueous hydrochloric acid solution (10 mL), water (10 mL)
4. dry with materiala saturated aqueous sodium bicarbonate solution (10 mL), dried over magnesium sulfate
5. concentrationconcentrated in vacuo
6. customPurification by AnaLogix IntelliFlash flash chromatography (4 g column, 20% ethyl acetate/hexanes to 80% ethyl acetate/hexanes)