Process to ribofuranose sugar derivatives as intermediates to branched-chain nucleosides
View Patent ↗A novel process is provided for the preparation of ribofuranose sugar derivatives which are useful in the synthesis of branched-chain ribonucleoside inhibitors of HCV polymerase for the treatment of HCV infection. Also provided are useful intermediates obtained from the instant process.
1. A process for preparing a compound of structural formula I:
wherein R 1 is C 2-4 alkenyl, C 2-4 alkynyl, or C 1-6 alkyl unsubstituted or substituted with one to three substituents independently selected from fluorine, hydroxy, amino, mercapto, C 1-3 alkoxy, and C 1-3 alkylthio; and
R 2 is C 1-6 alkyl or aryl unsubstituted or substituted with one to three substituents independently selected from methoxy, methyl, and fluorine;
comprising the step of cleaving the R 3 protecting group in a compound of structural formula V:
wherein R 3 represents benzyl unsubstituted or substituted with one to three substituents independently selected from methyl, methoxy, halogen, and nitro;
by catalytic hydrogenolysis.
2. The process of claim 1 additionally comprising the step of producing a compound of structural formula V:
by treating a compound of structural formula IV:
wherein R 4 is hydrogen or formyl;
with base in an organic solvent.
3. The process of claim 2 additionally comprising the step of producing a compound of structural formula IV:
by oxidative cleavage of a compound of structural formula II:
4. The process of claim 3 additionally comprising the step of producing a compound of structural formula II:
by treating a compound of structural formula III:
with aqueous acid in an organic solvent.
5. The process of claim 1 wherein R 1 is methyl.
6. The process of claim 5 wherein R 3 is benzyl.
7. The process of claim 6 wherein R 2 is phenyl unsubstituted or substituted with one to three substituents independently selected from methoxy, methyl, and fluorine.
8. The process of claim 1 wherein R 1 is methyl, R 3 is benzyl, and R 2 is phenyl unsubstituted or substituted with one to three substituents independently selected from methoxy, methyl, and fluorine.
9. The process of claim 8 wherein R 2 is 4-methylphenyl.
10. The process of claim 2 wherein said base is diisopropylamine.
11. The process of claim 3 wherein said oxidative cleavage is carried out with periodic acid.
12. The process of claim 4 wherein said aqueous acid is aqueous tetrafluoroboric acid or aqueous perchloric acid.
13. A process for preparing a compound of structural formula I:
comprising the steps of:
(a) producing a compound of structural formula II:
wherein R 3 represents benzyl unsubstituted or substituted with one to three substituents independently selected from methyl, methoxy, halogen, and nitro; by treating a compound of structural formula III:
with aqueous acid in an organic solvent;
(b) producing a compound of structural formula IV:
wherein R 4 is hydrogen or formyl;
by oxidative cleavage of the compound of structural formula II;
(c) producing a compound of structural formula V:
by treating a compound of structural formula IV with base in an organic solvent; and
(d) cleaving the R 3 protecting group in a compound of structural formula V by catalytic hydrogenolysis.