反应详情

温度

50 °C

To a solution of 1-(5-fluoropyridin-2-yl)-3-phenyl-1H-pyrazole-4-carboxylic acid (0.10 g, 0.22 mmol) in DMF (1 mL) were added (1R)-1-[1-oxido-6-(trifluoromethyl)pyridin-3-yl]ethanamine (63.5 mg, 0.26 mmol), EDC (73.2 mg, 0.38 mmol), HOAT (14.8 mg, 0.11 mmol) and triethylamine (0.12 mL, 0.87 mmol). The mixture was stirred at 50° C. After 3 h, the mixture was filtered. The filtrate was purified by reverse phase chromatography (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% ammonium hydroxide) and gave the title compound (92 mg). The mixture was converted to hydrochloride salt using HCl (4.0 M in dioxane). HRMS 472.1410 (M+1). 1H NMR (500 MHz, DMSO): 9.25 (s, 1H); 8.89 (d, J=7.2 Hz, 1H); 8.60 (d, J=2.8 Hz, 1H); 8.54 (s, 1H); 8.09 (dd, J=9.0, 3.9 Hz, 1H); 8.02 (td, J=8.5, 2.9 Hz, 1H); 7.94 (d, J=8.4 Hz, 1H); 7.79-7.76 (m, 2H); 7.54 (d, J=8.4 Hz, 1H); 7.40 (t, J=3.1 Hz, 3H); 5.13-5.06 (m, 1H); 1.48 (d, J=7.1 Hz, 3H).

1. filtrationthe mixture was filtered
2. customThe filtrate was purified by reverse phase chromatography (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% ammonium hydroxide)