反应详情

温度

70 °C

To a solution of 4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)bicyclo[2.2.2]-octan-1-amine (0.20 g, 0.46 mmol, Example #9, Step F) in MeCN (5 mL) was added 1-(3,3-difluoroazetidin-1-ylsulfonyl)-3-methyl-1H-imidazol-3-ium trifluoromethanesulfonate (0.19 g, 0.50 mmol). The reaction mixture was heated to about 70° C. for about 24 h. The solvent was removed under reduced pressure. The residue was partitioned between EtOAc (30 mL) and water (10 mL). The layers were separated and the organic layer was washed with water (10 mL) and brine (2×10 mL), dried over anhydrous MgSO4, filtered, and the solvent was removed under reduced pressure. The crude material was purified by flash chromatography on silica gel eluting with a gradient of 0-10% MeOH in DCM to give 3,3-difluoro-N-(4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)bicyclo[2.2.2]octan-1-yl)azetidine-1-sulfonamide (0.119 g, 38%): LC/MS (Table 1, Method a) Rt=2.32 min; MS m/z 592 (M+H)+.

1. customThe solvent was removed under reduced pressure
2. customThe residue was partitioned between EtOAc (30 mL) and water (10 mL)
3. customThe layers were separated
4. washthe organic layer was washed with water (10 mL) and brine (2×10 mL)
5. dry with materialdried over anhydrous MgSO4
6. filtrationfiltered
7. customthe solvent was removed under reduced pressure
8. customThe crude material was purified by flash chromatography on silica gel eluting with a gradient of 0-10% MeOH in DCM