Modified fluorinated nucleoside analogues

Abstract

The disclosed invention provides compositions and methods of treating a Flaviviridae infection, including hepatitis C virus, West Nile Virus, yellow fever virus, and a rhinovirus infection in a host, including animals, and especially humans, using a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleosides, or a pharmaceutically acceptable salt or prodrug thereof.

1 - 129 . (canceled) 
     
     
         130 : A method of synthesizing a compound of formula 1-3: 
       
         
           
           
               
               
           
         
         comprising reacting a compound of formula 1-2: 
       
       
         
           
           
               
               
           
         
         with (diethylamino)sulfur trifluoride, wherein:
 R is lower alkyl, acyl, benzoyl, or mesyl; and 
 Pg is selected from among C(O)-alkyl, C(O)Ph, C(O)aryl, CH 3 , CH 2 -alkyl, CH 2 -alkenyl, CH 2 Ph, CH 2 -aryl, CH 2 O-alkyl, CH 2 O-aryl, SO 2 -alkyl, SO 2 -aryl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, or both Pg's may come together to form a 1,3-(1,1,3,3-tetraisopropyl-disiloxanylidene). 
 
       
     
     
         131 : The method of  claim 130 , wherein:
 R is methyl; and   Pg is CH 2 Ph.   
     
     
         132 : A method of synthesizing a compound of formula 2-5: 
       
         
           
           
               
               
           
         
         comprising reacting a compound of formula 2-4: 
       
       
         
           
           
               
               
           
         
         with (diethylamino)sulfur trifluoride, wherein:
 R 4  is NH 2 , NH-acyl, OH, O-acyl, or O-sulfonyl; and 
 PG is selected from among C(O)-alkyl, C(O)Ph, C(O)aryl, CH 3 , CH 2 -alkyl, CH 2 -alkenyl, CH 2 Ph, CH 2 -aryl, CH 2 O-alkyl, CH 2 O-aryl, SO 2 -alkyl, SO 2 -aryl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, or both Pg's may come together to form a 1,3-(1,1,3,3-tetraisopropyl-disiloxanylidene). 
 
       
     
     
         133 : The method of  claim 132  wherein:
 R 4  is NHBz; and 
 Pg is C(O)Ph.