反应详情

温度

80 °C

To a stirring mixture of 4-(trifluoromethoxy)benzene-1-sulfonyl chloride (0.060 g, 0.23 mmol) and 3-methyl-1-(quinolin-5-yl)-1H-pyrazol-5-amine (prepared from Example 4 step b, 0.050 g, 0.22 mmol) in pyridine (1.0 mL) was heated at 80° C. for 1 h. After cooling to room temperature, dichloromethane was added to the reaction mixture and washed with 1 M aqueous sodium hydrogen sulfate (1 mL). The aqueous layer was further extracted with dichloromethane (2×5 mL), and the combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The crude residue was purified by flash chromatography (SiO2, 2-10% methanol in dichloromethane) and purification by reverse phase HPLC(C18 column, acetonitrile-H2O with 0.1% TFA as eluent) to give the title compound as a white solid (0.010 g, 0.022 mmol, 10%). 1H NMR (400 MHz, CDCl3) δ 8.75 (d, J=4.0 Hz, 1H), 8.01 (d, J=8.8 Hz, 1H), 7.71 (s, 1H), 7.69 (s, 1H), 7.56 (t, J=8.4 Hz, 1H), 7.49 (d, J=8.4 Hz, 1H), 7.21-7.17 (m, 4H), 6.12 (s, 1H), 2.34 (s, 3H); MS: (ES) m/z calculated for C20H16F3N4O3S [M+H]+ 449.1. found 449.7.

1. temperatureAfter cooling to room temperature
2. washwashed with 1 M aqueous sodium hydrogen sulfate (1 mL)
3. extractionThe aqueous layer was further extracted with dichloromethane (2×5 mL)
4. dry with materialthe combined organic layers were dried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe crude residue was purified by flash chromatography (SiO2, 2-10% methanol in dichloromethane) and purification by reverse phase HPLC(C18 column, acetonitrile-H2O with 0.1% TFA as eluent)