反应详情

温度

80 °C

To a solution of tert-butyl (1S,3R)-3-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarbonyl)cyclopentylcarbamate (9.30 g, 18.1 mmol, Preparation #A.1) in 1,4-dioxane (100 mL) was added TEA (10.0 mL, 72.3 mmol) and SOCl2 (2.11 mL, 28.9 mmol). The mixture was heated at about 80° C. for about 1.5 h. The reaction mixture was cooled to ambient temperature, EtOAc and water (200 mL each) were added, and the layers were separated. The aqueous solution was extracted with EtOAc (2×100 mL) and the combined organic layers were washed with saturated aqueous NaHCO3 and brine (100 mL each). The organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by silica gel chromatography eluting with a gradient of 25-100% EtOAc in DCM to give tert-Butyl-(1S,3R)-3-(6-tosyl-6H-pyrrolo[2,3-e][1, 2, 4]triazolo[4,3-a]pyrazin-1-yl)cyclopentylcarbamate (7.65 g, 85%): LC/MS (Table 2, Method a) Rt=2.37 min; MS m/z: 497 (M+H)+.

1. temperatureThe reaction mixture was cooled to ambient temperature
2. customthe layers were separated
3. extractionThe aqueous solution was extracted with EtOAc (2×100 mL)
4. washthe combined organic layers were washed with saturated aqueous NaHCO3 and brine (100 mL each)
5. dry with materialThe organic extracts were dried over anhydrous Na2SO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe crude material was purified by silica gel chromatography
9. washeluting with a gradient of 25-100% EtOAc in DCM