2,2-difluoro-3-carbamoyl ribose sulfonate compounds and process for the preparation of beta nucleosides
AssigneeEli Lilly and Company
InventorMarvin E. Wildfeuer
Life of this patent
Estimating the term…
Abstract
This invention provides novel 1-alkylsulfonyl-2,2-difluoro-3-carbamoyl ribose intermediates and intermediate nucleosides derived therefrom. The compounds are particularly useful in the preparation of 2'-deoxy-2',2'-difluoro-beta-cytidine and other beta anomer nucleosides which are antiviral and anticancer agents.
Claims21
An intermediate of the formula ##STR27## wherein R is a hydroxy protecting group, R.sub.1 and R.sub.2 are each selected from the group consisting of hydrogen, unsubstituted and substituted C.sub.1 -C.sub.8 alkyl, and unsubstituted and substituted phenyl, and R.sub.3 is C.sub.1 -C.sub.8 alkyl.
An intermediate of the formula:
- ##STR28## wherein R is a hydroxy protecting group and R.sub.1 and R.sub.2 are each selected from the group consisting of hydrogen, unsubstituted and substituted C.sub.1 -C.sub.8 alkyl, and unsubstituted and substituted phenyl.
An intermediate of the formula:
- ##STR29## wherein R is a hydroxy protecting group and R.sub.1 and R.sub.2 are each selected from the group consisting of hydrogen, unsubstituted and substituted C.sub.1 -C.sub.8 alkyl, and unsubstituted and substituted phenyl.
A process for the preparation of a beta nucleoside of the formula:
- ##STR30## where B is a protected pyrimidine nucleobase residue, which comprises:
- reacting an intermediate of the formula:
- ##STR31## with a protected pyrimidine nucleobase B-H in the presence of a Lewis acid in a non-reactive solvent at a temperature between about 80.degree. and 120.degree. C., wherein R is a hydroxy protecting group, R.sub.1 and R.sub.2 are each selected from the group consisting of hydrogen, unsubstituted and substituted C.sub.1 -C.sub.8 alkyl, and unsubstituted and substituted phenyl, and R.sub.3 is C.sub.1 -C.sub.8 alkyl.
An intermediate of the formula ##STR32## wherein R is a hydroxy protecting group, R.sub.1 and R.sub.2 are each selected from the group consisting of hydrogen, unsubstituted and substituted C.sub.1 -C.sub.8 alkyl, and unsubstituted and substituted phenyl, and B is selected from the group consisting of a protected and an unprotected pyrimidine nucleobase.
Dependencies are inferred from the claim text.