Traitement en cours

Veuillez attendre...

Paramétrages

Paramétrages

Aller à Demande

1. WO2007099082 - NOUVEAU PROCÉDÉ PERMETTANT DE PRÉPARER DES FORMES I ET II POLYMORPHIQUES DE STAVUDINE

Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

[ EN ]

CLAIMS
1. A process for the preparation of stavudine form I or II which comprises reacting 5'-acetate-2',3'-diacetyl-5-methyluridine with catalytic amounts of sodium methoxide.
2. A process according to claim 1, characterized by the use of 0.2÷0.01 moles, preferably 0.05÷0.01 moles of sodium methoxide/mole of 5 '-acetate-2',3 '-diacetyl-5-methyluridine.
3. A process according to claim 2, characterized by the use of about 0.02 moles of sodium methoxide/mole of 5 '-acetate-2',3 '-diacetyl-5-methyluridine.
4. A process according to any of the above claims, characterized in that the reaction of 5 '-acetate-2',3 '-diacetyl-5-methyluridine with sodium methoxide is performed in a C1-C4 alcohol.
5. A process according to claim 4, characterized in that said alcohol is methanol.
6. A process according to claims 4 to 5, characterized in that said reaction is performed at the reflux temperature of the alcohol.
7. A process according to claim 6, characterized in that said reaction is performed at 40÷65°C, preferably at 50÷65°C, more preferably at 500C.
8. A process according to any of the above claims, characterized in that the reaction mixture is heated for 3÷10 hours, preferably 5÷8 hours.
9. A for the preparation of stavudine form I according to any of the above claims, characterized in that the product obtained by reacting 5 '-acetate-2',3 '-diacetyl-5-methyluridine with sodium methoxide is suspended in isopropanol and the thus-obtained suspension is heated to reflux.
10. A process according to claim 9, characterized in that the suspension is heated to reflux for at least 2 hours, preferably for 2÷15 hours, more preferably for 2÷4 hours.
11. A process according to claims 9-10, characterized in that the heated suspension is cooled to 0÷30°C, preferably to 15÷25°C.
12. A process according to claim 11, characterized in that isopropanol is added to the cooled suspension.
13. A process according to claim 12, characterized in that the cooled suspension is stirred and subsequently filtered at 0÷30°C, preferably at 15÷25°C.
14. A process according to claims 9-13, characterized in that the product obtained by reacting 5'-acetate-2',3'-diacetyl-5-methyluridine with sodium methoxide is stavudine form II or a mixture of stavudine forms I and II.
15. A process according to claims 9-14, characterized in that the product obtained by reacting 5'-acetate-2',3'-diacetyl-5-methyluridine with sodium methoxide is neither isolated nor purified before being suspended in isopropanol.

16. A process for the isolation of stavudine form I according to claims 1-8, characterized in that the product obtained by reacting 5'-acetate-2',3'-diacetyl-5-methyluridine with sodium methoxide is suspended in isopropanol under stirring.