反应详情

34.7 mL of BSTFA are added to a suspension of 6.3 g of azacytosine in 126 mL of acetonitrile. The mixture is brought to 50° C. and it is stirred for 90 minutes. 7 mL titanium tetrachloride and then a solution of 16.7 g of 1,2,3,5-tetra-O-acetyl-D-ribofuranose in 33 mL of acetonitrile are added to the limpid solution, in about ten minutes. Stirring is maintained for 120 minutes, it is cooled to room temperature and it is slowly poured onto a mixture constituted by 500 ml of dichloromethane and 330 mL of water into which 9.5 g of sodium bicarbonate had been previously dissolved. Stirring is carried out for 15 minutes and the pH is adjusted to pH=4.5 using 30% sodium hydroxide in water. It is filtered on earth filter, the mixture is left to settle and phases are separated. The aqueous phase is washed twice using 125 ml of dichloromethane for each washing. The organic phases which are anhydrified by treating them with anhydrous calcium chloride are combined. Concentration is carried out at low pressure until a viscous residue is obtained. The residue is recovered with 250 mL of methanol, it is concentrated once again at low pressure until a viscous residue is obtained. 250 mL of methanol are added, it is heated to 50° C. and 15 mL of a 10% solution of sodium methylate in methanol are added. It is stirred for 1 hour, it is cooled to room temperature, it is stirred to complete precipitation and the solid is filtered by washing it on the filter with methanol. 4.7 g of azacitidine with HPLC purity (UV 254 nm) of 97.2% are obtained after drying at low pressure.

1. customis brought to 50° C.
2. stirringStirring
3. temperatureis maintained for 120 minutes
4. additionit is slowly poured onto a mixture
5. dissolutionhad been previously dissolved
6. stirringStirring
7. waitis carried out for 15 minutes
8. filtrationIt is filtered on earth
9. filtrationfilter
10. waitthe mixture is left
11. customphases are separated
12. washThe aqueous phase is washed twice
13. additionby treating them with anhydrous calcium chloride
14. concentrationConcentration
15. customis obtained
16. customThe residue is recovered with 250 mL of methanol, it
17. concentrationis concentrated once again at low pressure until a viscous residue
18. customis obtained
19. temperatureit is heated to 50° C.
20. stirringIt is stirred for 1 hour
21. temperatureit is cooled to room temperature
22. stirringit is stirred to complete precipitation
23. filtrationthe solid is filtered
24. washby washing it on the
25. filtrationfilter with methanol