Preparation of nucleosides ribofuranosyl pyrimidines

摘要

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.;

主权项

1. 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.