反応 #47303
ord-7f225a565afc41c383a5ef8209ebb6f8
反応方程式
反応物
試薬
反応条件
後処理
- 1洗浄washed with saturated ammonium chloride, water
- 2乾燥a saturated sodium chloride solution and dried over sodium sulfate
- 3濃縮The organic layer was concentrated
- 4その他the crude product was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 12 g, 20% to 70% ethyl acetate/hexanes)
実験手順
A solution of (S)-3-cyclohexyl-2-[2-oxo-4-(2-trifluoromethyl-phenoxy)-2,5-dihydro-pyrrol-1-yl]-propionic acid (prepared as in Example 32, 307 mg, 0.77 mmol) in N,N-dimethylformamide (4 mL) was treated with 1-(2-methoxy-ethyl)-1H-pyrazol-3-ylamine (prepared in U.S. Pat. Appl. US2008021032 Example 72, 130 mg, 0.92 mmol), benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (663 mg, 1.5 mmol) and N,N-diisopropylethylamine (193 mg, 1.5 mmol). The reaction mixture was stirred for 4 h at 25° C., under nitrogen. The reaction mixture was diluted with ethyl acetate, washed with saturated ammonium chloride, water, a saturated sodium chloride solution and dried over sodium sulfate. The organic layer was concentrated, and the crude product was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 12 g, 20% to 70% ethyl acetate/hexanes) to afford (S)-3-cyclohexyl-N-[1-(2-methoxy-ethyl)-1H-pyrazol-3-yl]-2-[2-oxo-4-(2-trifluoromethyl-phenoxy)-2,5-dihydro-pyrrol-1-yl]-propionamide. This material was dissolved in dichloromethane (4 mL) and treated with hydrogen chloride in diethyl ether (1 M, 2 mL). Solvents were evaporated and the residue was triturated with diethyl ether. The solid was filtered to give (S)-3-cyclohexyl-N-[1-(2-methoxy-ethyl)-1H-pyrazol-3-yl]-2-[2-oxo-4-(2-trifluoromethyl-phenoxy)-2,5-dihydro-pyrrol-1-yl]-propionamide hydrochloride (133 mg, 31%) as a light yellow solid: LR-ES-MS m/z calculated for C26H23F3N4O4 [M]+ 520, observed [M+H]+ 521; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.68-1.40 (m, 6H) 1.40-1.83 (m, 7H) 3.19 (s, 3H) 3.62 (t, J=5.2 Hz, 2H) 4.12 (t, J=5.2 Hz, 2H) 4.16 (d, J=18.7 Hz, 1H) 4.57 (d, J=18.7 Hz, 1H) 4.88 (dd, J=10.6, 5.4 Hz, 1H) 4.94 (s, 1H) 6.39 (d, J=2.1 Hz, 1H) 7.51 (t, J=7.2 Hz, 1H) 7.55 (d, J=2.1 Hz, 1H) 7.64 (d, J=7.8 Hz, 1H) 7.73-7.90 (m, 2H) 10.75 (s, 1H).