反应详情

温度

25 °C

To a yellow suspension of 2-(5-methoxy-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (443 mg, 1.01 mmol) in dioxane (14 mL) and water (4 mL) at 0° C. was added sulfamic acid (590 mg, 6.07 mmol, Eq: 6.00), followed by drop-wise addition of a solution of sodium chlorite (149 mg, 1.32 mmol) and KH2PO4 (1.65 g, 12.1 mmol2.00) in water (4.5 mL) via dropping funnel over 15 min. The ice bath was removed and the light yellow suspension was stirred at 25° C. for 18 h. LCMS indicated reaction about 50% complete, THF (10 mL) added to the yellow suspension then addition at 25° C. of more reagents: sulfamic acid (590 mg, 6.07 mmol, Eq: 6.00) solid, followed by a dropwise addition of a solution of sodium chlorite (149 mg, 1.32 mmol) and KH2PO4 (1.65 g, 12.1 mmo12.00) in 10 mL of water and stirring continued at 25° C. for 4 h. Mixture diluted with water (50 mL) and extracted with dichloromethane (3×40 mL). The combined organic layers were dried (MgSO4), added some charcoal heated to reflux, after cooling down to 25° C., filtered over a celite pad and evaporated. Light yellow solid residue was dissolved in dichloromethane/MeOH and dichloromethane evaporated to promote solid formation, solid separated by filtration, rinsed with MeOH and hexanes and dried to give 2-(5-methoxy-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (238 mg, 525 μmol, 51.8%). MS (M+H)+=454 (>90% purity); 1H NMR (CDCl3) δ: 9.38 (s, 1H), 8.38 (s, 1H), 7.92 (d, J=2.6 Hz, 1H), 7.41 (d, J=9.1 Hz, 1H), 7.19 (dd, J=9.3, 2.5 Hz, 1H), 5.79 (s, 2H), 4.21 (s, 3H), 3.99 (s, 3H), 3.60-3.73 (m, 2H), 0.93-1.06 (m, 2H), 0.00 (s, 9H).

1. customover 15 min
2. customThe ice bath was removed
3. customreaction about 50% complete
4. additionaddition at 25° C. of more reagents
5. stirringstirring
6. waitcontinued at 25° C. for 4 h
7. extractionextracted with dichloromethane (3×40 mL)
8. dry with materialThe combined organic layers were dried (MgSO4)
9. additionadded some charcoal
10. temperatureheated
11. temperatureto reflux
12. temperatureafter cooling down to 25° C.
13. filtrationfiltered over a celite pad
14. customevaporated
15. dissolutionLight yellow solid residue was dissolved in dichloromethane/MeOH
16. customdichloromethane evaporated
17. customseparated by filtration
18. washrinsed with MeOH and hexanes
19. customdried