反应详情

To a bright yellow slurry of 5-(2,6-difluorophenyl)-3-(6-(5,6-dihydropyridin-1(2H)-yl)pyrazin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (0.225 g, 0.475 mmol) and NMO (aldrich) (0.083 g, 0.713 mmol) in 3 mL acetone and 1 mL water was added osmium tetroxide 4% solution in water (aldrich) (0.151 mL, 0.024 mmol). The reaction was sealed and stirred rapidly over the weekend. The heterogeneous reaction was refreshed with NMO (aldrich) (0.083 g, 0.713 mmol) and osmium tetroxide 4% solution in water (aldrich) (0.151 mL, 0.024 mmol) and stirred rapidly for 36 h. The heterogeneous reaction was refreshed with NMO (aldrich) (0.083 g, 0.713 mmol) and osmium tetroxide 4% solution in water (Aldrich) (0.151 mL, 0.024 mmol) and stirred rapidly 48 h. The reaction was treated with 2 mL sat'd aqueous NaHSO3, and partitioned between water and DCM. The aqueous layer was extracted with DCM 4 times, and the combined organics were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The material was treated with 10% MeOH in DCM and adsorbed onto 2 g silica gel, then purified by silica gel chromatography (40 g column) using 0-75% 90/10 DCM/MeOH in DCM. The product-containing fractions were concentrated to afford racemic cis-1-(6-(5-(2,6-difluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yl)piperidine-3,4-diol (0.10 g, 0.197 mmol, 41.5% yield) as a yellow solid: MS (ESI, pos. ion) m/z: 508 (M+1).

1. customThe reaction was sealed
2. customThe heterogeneous reaction
3. stirringstirred rapidly for 36 h
4. customThe heterogeneous reaction
5. stirringstirred rapidly 48 h
6. additionThe reaction was treated with 2 mL
7. custompartitioned between water and DCM
8. extractionThe aqueous layer was extracted with DCM 4 times
9. dry with materialthe combined organics were dried over anhydrous Na2SO4
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. additionThe material was treated with 10% MeOH in DCM
13. custompurified by silica gel chromatography (40 g column)
14. concentrationThe product-containing fractions were concentrated