反应详情

温度

60 °C

3-Methoxy-1H-pyrazolo[3,4-b]pyridin-5-amine (50 mg, 0.305 mmol) in N,N-dimethylformamide (3.0 mL) was sequentially treated with 2,6-dichloro-3-(propylsulfonamido)benzoic acid (356 mg, 1.14 mmol), EDCI (117 mg, 0.609 mmol), and HOBt (82.3 mg, 0.609 mmol) and heated to 60° C. After 72 hours, the reaction mixture was allowed to cool to ambient temperature. The mixture was diluted with ethyl acetate, washed with water (4×), sodium bicarbonate (2×), and brine (1×), dried over sodium sulfate, and concentrated. The crude product was applied directly to a silica gel column and eluted with a gradient (30% to 100%) of ethyl acetate-hexanes to provide 2,6-dichloro-N-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-(propylsulfonamido)benzamide (67.8 mg, 0.0524 mmol, 35.4% yield) as a solid. 1H NMR (400 MHz, d6-DMSO) δ 12.63-12.59 (s, 1H), 11.04-11.00 (s, 1H), 9.83-9.79 (s, 1H), 8.59-8.570 (d, 1H), 8.47-8.45 (d, 1H), 7.60-7.57 (m, 2H), 4.03-4.01 (s, 3H), 3.21-3.13 (m, 2H), 1.83-1.73 (m, 2H), 1.02-0.97 (t, 3H); MS (APCI-neg) m/z=456.1 (M−H).

1. temperatureto cool to ambient temperature
2. washwashed with water (4×), sodium bicarbonate (2×), and brine (1×)
3. dry with materialdried over sodium sulfate
4. concentrationconcentrated
5. washeluted with a gradient (30% to 100%) of ethyl acetate-hexanes