反应详情

In a hydrogenation flask, ethanol (300 ml) was added to 10% palladium on carbon (9.9 g, 0.2 wt. equivalents, 50% wet), followed by 5-(azidomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine (49.62 g, 151 mmol, 1 equivalent, e.g. which can be as prepared in Intermediate 6) in ethanol (900 ml). The mixture was hydrogenated overnight at room temperature and room pressure (using the Wright valve); during which the flask was vented and refilled once. The catalyst was removed by filtration and the filtrate was evaporated to give a grey solid. The residue was purified by column chromatography, using a relatively small amount of silica (1500 ml of 9385 silica), eluting initially with 5% methanol in dichloromethane (to elute some fast-moving impurities), followed by 10% and finally 15% methanol in dichloromethane to give the title compound as an almost white solid (41.25 g). LCMS m/z 304 [MH+]; TRET=1.65 and 1.69 min (split peak). NMR (d6-DMSO) showed a trace of methanol present in the product.

1. additionrefilled once
2. customThe catalyst was removed by filtration
3. customthe filtrate was evaporated
4. customto give a grey solid
5. customThe residue was purified by column chromatography
6. washeluting initially with 5% methanol in dichloromethane (
7. washto elute some fast-moving impurities),