反应详情

To a solution of 1-(4-fluorophenyl)-5-isopropylpyrazol-4-amine (0.03 g, 0.14 mmol) in DMF (1.0 mL) was added 2-[4-chloro-5-methyl-3-(trifluoromethyl)pyrazol-1-yl]propanoic acid (0.035 g, 0.14 mmol), followed by diisopropylethylamine (0.042 g, 0.32 mmol) and HATU (0.057 g, 0.15 mmol). After stirring at room temperature for 1 h, the reaction was diluted with water and the aqueous layer was extracted with ethyl acetate (2×5 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. The resulting crude product was purified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent) to give the title compound as a white solid (0.020 g, 0.044 mmol, 32%). 1H NMR (400 MHz, CDCl3) δ 8.18 (s, 1H), 8.02 (s, 1H), 7.34-7.24 (m, 2H), 7.21-7.11 (m, 2H), 5.05 (q, J=7.2 Hz, 1H), 3.03-2.91 (m, 1H), 2.38 (s, 3H), 1.90 (d, J=7.2 Hz, 3H), 1.25 (dd, J=13.9, 7.1 Hz, 3H), 1.08 (d, J=7.2 Hz, 3H); MS: (ES) m/z calculated for C20H20ClF4N5O [M+H]+ 458.1, found 457.9.

1. extractionthe aqueous layer was extracted with ethyl acetate (2×5 mL)
2. washThe combined organic layers were washed with brine
3. dry with materialdried (Na2SO4)
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe resulting crude product was purified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent)