反应详情

温度

2.5 °C

A mixture of 5-azacytosine (5.0 g, 44.6 mol), HMDS (6.3 mL, 29.8 mol), and TMSC1 (6 mL, 47.3 mmol) in acetonitrile (78 mL) was heated to reflux for 20 hours under an inert atmosphere. TMS-triflate (9 mL, 50 mmol) and 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose (14.2 g, 44.6 mmol were added directly to the silylated 5-azacytosine in acetonitrile. The addition was performed at ambient temperature and under an inert atmosphere. The reaction mixture was maintained under stirring for 20 hours, then poured over a pre-cooled (0-5° C.) sodium bicarbonate solution (10%, 500 mL). The resulting mixture was extracted with dichloromethane (3×75 mL). The combined organic extract was washed with cooled (0-5° C.) 10% sodium bicarbonate (2×25 mL) and brine (2×25 mL), then dried over magnesium sulfate (10.0 g), filtered, and the filtrate concentrated in vacuum to dryness. The off-white foam dissolved in methanol (120 mL) was treated with a solution of 25% sodium methoxide in methanol (1.0 g, 4.62 mmol). Soon a white solid started to separate. The suspension was stirred at ambient temperature for 15 hours, then the solid was filtered off, washed with methanol (3×5 mL) and anhydrous ether (2×5 mL), then dried in vacuum. The crude 5-azacytidine (4.5 g, 41.3%) was further purified from DMSO and methanol (for details see Example 4).

1. temperaturewas heated
2. temperatureto reflux for 20 hours under an inert atmosphere
3. additionThe addition
4. customwas performed at ambient temperature and under an inert atmosphere
5. temperatureThe reaction mixture was maintained
6. additionpoured over
7. extractionThe resulting mixture was extracted with dichloromethane (3×75 mL)
8. extractionThe combined organic extract
9. washwas washed
10. dry with materialdried over magnesium sulfate (10.0 g)
11. filtrationfiltered
12. concentrationthe filtrate concentrated in vacuum to dryness
13. dissolutionThe off-white foam dissolved in methanol (120 mL)
14. customto separate
15. stirringThe suspension was stirred at ambient temperature for 15 hours
16. filtrationthe solid was filtered off
17. washwashed with methanol (3×5 mL) and anhydrous ether (2×5 mL)
18. customdried in vacuum
19. customThe crude 5-azacytidine (4.5 g, 41.3%) was further purified from DMSO and methanol (for details see Example 4)