反应详情

温度

40 °C

NaH (0.188 g, 4.70 mmol) in DMF (5 mL) was added dropwise to 1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-ol (1.00 g, 3.92 mmol, prepared as described in WO 2007/103308) in DMF (10 mL). The reaction mixture was then warmed to 40° C. and stirred for 30 minutes. After cooling to room temperature, 1,1,1-trifluoro-N-phenyl-N-(trifluoromethylsulfonyl)methanesulfonamide (1.68 g, 4.70 mmol) was added and stirred at room temperature for 1 hour. Then tert-butyl piperazine-1-carboxylate (1.61 g, 8.62 mmol) was added. The mixture was warmed to 80° C. and stirred for 3 hours. The reaction was then cooled to room temperature, and a saturated solution of NH4Cl (30 mL) was added. The mixture was extracted with ethyl acetate (2×30 mL) and dried over sodium sulfate. After removal of solvent, the resulting residue was purified by column chromatography (hexane:ethyl acetate, 5:1) to give tert-butyl 4-(1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (1.64 g, 99% yield) as a solid. MS APCI (+) m/z 424.1 detected. 1H NMR (400 Hz, DMSO-d6) δ 8.24 (s, 1H), 8.13 (d, J=5.2 Hz, 1H), 7.18 (d, J=8.4 Hz, 2H), 6.84 (d, J=8.4 Hz, 2H), 6.42 (d, J=5.2 Hz, 1H), 5.49 (s, 2H), 3.69 (s, 3H), 3.64 (m, 4H), 3.53 (m, 4H).

1. temperatureAfter cooling to room temperature
2. stirringstirred at room temperature for 1 hour
3. temperatureThe mixture was warmed to 80° C.
4. stirringstirred for 3 hours
5. temperatureThe reaction was then cooled to room temperature
6. extractionThe mixture was extracted with ethyl acetate (2×30 mL)
7. dry with materialdried over sodium sulfate
8. customAfter removal of solvent
9. customthe resulting residue was purified by column chromatography (hexane:ethyl acetate, 5:1)