反应详情

To a stirred solution of 339 (80 mg, 0.24 mmol) and 1-(4-fluorophenylcarbamoyl) cyclopropanecarboxylic acid (181, 111 mg, 0.50 mmol) in anhydrous DMF were added DIPEA (123 μL, 0.71 mmol) and HATU reagent (256 mg, 0.67 mmol). The reaction mixture was stirred at room temperature overnight under nitrogen, diluted with AcOEt, and successively washed with sat. NaHCO3, water, sat. NH4Cl, water and brine, and concentrated. The crude material was first purified by flash column chromatography (eluents 2% of NH4OH in methanol/CH2Cl2: 10/90) and precipitated in AcOEt (with traces of acetone)/hexanes to afford title compound 336 (75 mg, 58% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 10.32 (s, 1H), 10.04 (s, 1H), 8.65 (bs, 1H), 8.18 (d, J=5.5 Hz, 1H), 7.78 (dd, J=12.9, 2.2 Hz, 1H), 7.77 (d, J=1.8 Hz, 1H), 7.68 (d, J=1.2 Hz, 1H), 7.68-7.60 (m, 2H), 7.50 (s, 1H), 7.44 (dd, J=8.4, 1.8 Hz, 1H), 7.30 (t, J=8.9 Hz, 1H), 7.15 (t, J=9.0 Hz, 2H), 6.36 (dd, J=5.5, 1.6 Hz, 1H), 3.70 (s, 3H), 1.47 (s, 4H). MS (m/z): 545.0 (M+H)+.

1. washsuccessively washed with sat. NaHCO3, water, sat. NH4Cl, water and brine
2. concentrationconcentrated
3. customThe crude material was first purified by flash column chromatography (eluents 2% of NH4OH in methanol/CH2Cl2: 10/90)
4. customprecipitated in AcOEt (with traces of acetone)/hexanes