反应详情

Into a 50-mL round bottom flask, was placed a solution of 2-amino-5-chloro-N-(1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)benzamide 6d (150 mg, 0.39 mmol, 1.00 equiv) in dichloromethane (6 mL), and pyridine (93.6 mg, 1.18 mmol, 3.00 equiv). To this was added dropwise, a solution of 3-(methyl(2-morpholinoethyl)carbamoyl)benzoyl chloride 1f (147 mg, 0.47 mmol, 1.20 equiv) in dichloromethane (2 mL) over 10 min with stirring at 0° C. The resulting solution was stirred for 1 h at room temperature. The resulting solution was diluted with 2 mL of water, and adjusted to pH 8 with NH3.H2O (2 mol/L). The resulting solution was extracted with 2×5 mL of dichloromethane and the organic layers combined, dried over 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 67.2 mg (22%) of a white solid. 1H-NMR (300 MHz, DMSO, ppm): δ 11.67 (s, 1H), 11.54 (s, 1H), 9.62 (s, 1H), 8.68-8.67 (d, J=2.7 Hz, 1H), 8.71-8.38 (d, J=9.0 Hz, 1H), 8.16-8.02 (m, 5H), 7.79-7.65 (m, 5H), 6.968-6.960 (d, J=2.4 Hz, 1H), 4.01 (s, 2H), 3.84 (s, 2H), 3.42 (s, 6H), 3.18 (s, 2H), 2.98 (s, 3H). MS (ES, m/z): 655 [M+H]+.

1. customInto a 50-mL round bottom flask, was placed
2. additionTo this was added dropwise
3. extractionThe resulting solution was extracted with 2×5 mL of dichloromethane
4. dry with materialdried over sodium sulfate
5. concentrationconcentrated 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