Methods for isolating crystalline Form I of 5-azacytidine
View Patent ↗The invention includes methods for isolating crystalline Form I of 5-azacytidine substantially free of other forms, wherein 5-azacytidine is represented by the formula: The invention also includes pharmaceutical compositions comprising Form I of 5-azacytidine.
1. A method for isolating crystalline Form I of 5-azacytidine substantially free of other forms, the method comprising:
recrystallizing 5-azacytidine from a solvent mixture comprising at least one primary solvent and at least one co-solvent selected from the group consisting of C 2 -C 5 alcohols, aliphatic ketones, and alkyl cyanides, by cooling said solvent mixture from a temperature selected to allow said 5-azacytidine to dissolve completely to about ambient temperature; and
isolating the recrystallized 5-azacytidine.
2. The method of claim 1 wherein said primary solvent is a polar solvent.
3. The method of claim 2 wherein said polar solvent is a polar aprotic solvent.
4. The method of claim 3 wherein said polar aprotic solvent is selected from the group consisting of dimethylsulfoxide, dimethylformamide, dimethylacetamide, and N-methylpyrrolidinone.
5. The method of claim 4 wherein said polar aprotic solvent is dimethylsulfoxide.
6. The method of claim 1 wherein said co-solvent is acetonitrile.
7. The method of claim 1 wherein said co-solvent is ethanol.
8. The method of claim 1 wherein said co-solvent is methylethyl ketone.
9. The method of claim 1 wherein said co-solvent is 2-propanol (isopropyl alcohol).
10. The method of claim 1 wherein said co-solvent is 1-propanol.
11. A method for isolating crystalline Form I of 5-azacytidine substantially free of other forms, the method comprising:
recrystallizing 5-azacytidine from a solvent mixture comprising at least one primary solvent and at least one co-solvent selected from the group consisting of C 3 -C 5 alcohols and alkyl cyanides by cooling said solution from a temperature selected to allow said 5-azacytidine to dissolve completely to about −20° C.; and
isolating the recrystallized 5-azacytidine.
12. The method of claim 11 wherein said primary solvent is a polar solvent.
13. The method of claim 12 wherein said polar solvent is a polar aprotic solvent.
14. The method of claim 13 wherein said polar aprotic solvent is selected from the group consisting of dimethylsulfoxide, dimethylformamide, dimethylacetamide, and N-methylpyrrolidinone.
15. The method of claim 14 wherein said polar aprotic solvent is dimethylsulfoxide.
16. The method of claim 11 wherein said co-solvent is acetonitrile.
17. The method of claim 11 wherein said co-solvent is 2-propanol (isopropyl alcohol).
18. The method of claim 11 wherein said co-solvent is 1-propanol.