反应详情

温度

30 °C

Into a 5-mL vial, was placed a solution of 2-amino-5-(piperidin-1-yl)-N-(1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)benzamide 8d (100 mg, 0.23 mmol, 1.00 equiv) in dichloromethane (5 mL), 4-(((2-(diethylamino)ethyl)(methyl)amino)methyl)benzoic acid (74 mg, 0.28 mmol, 1.20 equiv), EDC.HCl (90 mg, 0.47 mmol, 2.00 equiv), and 4-dimethylaminopyridine (43 mg, 0.35 mmol, 1.50 equiv). The resulting solution was stirred overnight at 30° C. in an oil bath. The reaction progress was monitored by LCMS. The resulting mixture was washed with 3×10 mL of water and 1×10 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product (150 mg) was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 57.8 mg (31%) of a light yellow solid. 1H-NMR (300 MHz, CD3OD, ppm): δ 8.684 (d, J=9 Hz, 1H), 8.392-8.400 (m, 1H), 8.179 (s, 1H), 8.047-8.075 (m, 3H), 7.991-7.999 (m, 1H), 7.589-7.727 (m, 5H), 7.078-7.087 (m, 1H), 4.007 (s, 2H), 3.556-3.615 (m, 4H), 3.393-3.436 (m, 2H), 3.171-3.263 (m, 4H), 3.052-3.095 (m, 2H), 2.538-2.560 (m, 3H), 1.998 (m, 4H), 1.788-1.804 (m, 2H), 1.286-1.334 (m, 6H). MS (ES, m/z): 676 [M+H]+.

1. washThe resulting mixture was washed with 3×10 mL of water and 1×10 mL of brine
2. dry with materialThe mixture was dried over anhydrous sodium sulfate
3. concentrationconcentrated under vacuum
4. customThe crude product (150 mg) was purified by reverse phase HPLC
5. washeluting with a water/CH3CN gradient
6. additioncontaining 0.05% TFA