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US 8,912,321 B2Granted
Preparation of nucleosides ribofuranosyl pyrimidines
AssigneeGilead Pharmasset LLC
InventorsSteven D. Axt, Keshab Sarma, Justin Vitale, Jiang Zhu, Bruce Ross, Suguna Rachakonda, Quingwu Jin, Byoung-Kwon Chun
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Abstract
The present process provides an improved method for the preparation of 4-amino-1-((2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-hydroxymethyl-3-methyl-tetrahydrofuran-2-yl)-1H-pyrimidin-2-one of the formula (IV) which is a potent inhibitor of Hepatitis C Virus (HCV) NS5B polymerase.
Claims7
A process for the preparation of 4-amino-1-((2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-hydroxymethyl-3-methyl-tetrahydro-furan-2-yl)-1H-pyrimidin-2-one of formula IV
- comprising
- a) transforming a compound of formula II
- wherein R is aryl or alkyl
- into a compound of formula III
- wherein R is aryl or alkyl,
- wherein the transformation comprises a reduction in the presence of a reducing agent and a subsequent chlorination in the presence of a chlorinating agent;
- b) converting the compound of formula III into a compound of formula I
- wherein R is aryl or alkyl and Bz is benzoyl,
- wherein the conversion comprises reacting the compound of formula III with O-trimethyl silyl-N4-benzoylcytosine in the presence of a Lewis acid;
- and
- c) hydrolyzing the compound of formula I to afford the 4-amino-1-((2R,3R,4R,5 5R)-3-fluoro-4-hydroxy-5-hydroxymethyl-3-methyl-tetrahydro-furan-2-yl)-1H-pyrimidin-2-one of formula IV,
- wherein the hydrolysis is performed in the presence of a base.
9 more elements
Dependencies are inferred from the claim text.