反应详情

温度

30 °C

Into a 50-mL round bottom flask, 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), 3-(((2-(diethylamino)ethyl)(methyl)amino)methyl)benzoic acid (74 mg, 0.28 mmol, 1.20 equiv), EDC.HCl (90 mg, 0.47 mmol, 2.01 equiv), and 4-dimethylaminopyridine (43 mg, 0.35 mmol, 1.51 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 sodium sulfate. The solids were filtered out. The resulting mixture was 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 58.5 mg (32%) of a yellow solid. 1H-NMR (300 MHz, CD3OD, ppm): δ 8.502-8.532(d, J=9.0 Hz, 1H), 8.277-8.286(m, 1H), 8.060(s, 1H), 7.851-7.966(m, 4H), 7.475-7.610(m, 5H), 6.949-6.958(m, 1H), 3.922(s, 2H), 3.450-3.485(m, 4H), 3.273-3.316(m, 2H), 3.035-3.108(m, 4H), 2.957-2.998(m, 2H), 2.449-2.475(m, 3H), 1.857-1.872(m, 4H), 1.666-1.683(m, 2H), 1.139-1.200(m, 6H). MS (ES, m/z): 676 [M+H]+.

1. customInto a 50-mL round bottom flask, was placed
2. washThe resulting mixture was washed with 3×10 mL of water and 1×10 mL of brine
3. dry with materialThe mixture was dried over sodium sulfate
4. filtrationThe solids were filtered out
5. concentrationThe resulting mixture was concentrated under vacuum
6. customThe crude product (150 mg) was purified by reverse phase HPLC
7. washeluting with a water/CH3CN gradient
8. additioncontaining 0.05% TFA