Process for preparing nucleoside prodrugs

Abstract

A process for preparing phosphoramidates of nucleosides where a desired enantiomer, having regard to the asymmetric chiral center of the phosphorus atom P, is provided in an enriched amount. The process comprises admixing a nucleoside with a phosphorochloridate in the presence of a catalyst comprising a metal salt selected from the group consisting of salts of Cu, Fe, La and Yb.

1 - 37 . (canceled) 
     
     
         38 . A method of treating cancer, wherein the method comprises administering to a human patient in need thereof a therapeutically effective amount of a composition comprising a compound of the formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein the ratio of the R P  diastereomer to the Se diastereomer is in the range from 1:20 to 0:100. 
       
     
     
         39 . The method of treatment of  claim 38 , wherein the composition further comprises a pharmaceutically acceptable carrier, diluent or excipient. 
     
     
         40 . The method of treatment of  claim 38 , wherein the cancer is breast cancer. 
     
     
         41 . The method of treatment of  claim 38 , wherein the cancer is colon cancer. 
     
     
         42 . The method of treatment of  claim 38 , wherein the cancer is prostate cancer. 
     
     
         43 . The method of treatment of  claim 38 , wherein the cancer is leukemia. 
     
     
         44 . The method of treatment of  claim 38 , wherein the composition is administered orally. 
     
     
         45 . The method of treatment of  claim 38 , wherein the composition is administered parenterally. 
     
     
         46 . The method of treatment of  claim 45 , wherein the composition is administered intravenously. 
     
     
         47 . The method of treatment of  claim 38 , wherein the composition is administered topically.