Method of manufacture of 1,3-oxathiolane nucleosides
AssigneesGilead Sciences, Inc., Emory University
InventorsGeorge R. Painter, Dennis C. Liotta, Merrick R. Almond, Darryl G. Cleary, Jose D. Soria, Marcos Sznaidman
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Abstract
Processes for the preparation of 1,3-oxathiolane nucleosides are provided that include efficient methods for the preparation of the 1,3-oxathiolane ring and subsequent condensation of the 1,3-oxathiolane with a pyrimidine or purine base. Using the processes described herein, the compounds can be provided as isolated enantiomers.
Claims18
A process for preparing 2-[R1C(O)OCH2]-1,3-oxathiolanyl-5-one by directly reacting an acetal of the formula (R1O)2CHR wherein R is —(CH2—O—C(O)R1), and R1 is alkyl, aryl, heteroaryl, heterocyclic, alkaryl, alkylheteroaryl, or alkylheterocyclic, or aralkyl, with mercaptoacetic acid in an organic solvent, in the presence of a Lewis or protic acid.
A process for producing a 1,3-oxathiolane nucleoside comprising:
- (i) preparing a 5-halo-2-protected-oxymethyl-1,3-oxathiolane;
- and (ii) reacting the 5-halo-2-protected-oxymethyl-1,3-oxathiolane with a protected purine or pyrimidine base at a temperature below 25 degrees Celcius in the absence of a Lewis acid.
Dependencies are inferred from the claim text.