Methods for the preparation of ribosides

Abstract

Provided are methods of preparing compounds and pharmaceutical compositions for treating Filoviridae virus infections The compounds, compositions, and methods provided are particularly useful for the treatment of Marburg virus, Ebola virus and Cueva virus infections.

1 - 9 . (canceled) 
     
     
         10 . A method of preparing a compound of Formula (XI-a) 
       
         
           
           
               
               
           
         
         the method comprising:
 forming a reaction mixture with a cyanating agent, a Lewis Acid, a Bröenstedt acid, a solvent, and a compound of Formula (V-a) or (XI-b): 
 
       
       
         
           
           
               
               
           
         
         to prepare the compound of Formula (XI-a), 
         wherein 
         Bn is benzyl;
 each R b  is independently a hydroxy protecting group; 
 R 10  is H or awl trialkylsilyl group; and 
 the cyanating agent is TMSCN; 
 the Lewis Acid is TMSOTf; 
 the Bröenstedt acid is TFA; 
 the solvent is DCM; and 
 
         the hydroxy protecting group is benzyl. 
       
     
     
         11 . (canceled) 
     
     
         12 . The method of  claim 10 , wherein
 the compound of Formula (V-a) or Formula (V-b) are:   
       
         
           
           
               
               
           
         
       
     
     
         13 - 15 . (canceled) 
     
     
         16 . A method of preparing a compound of Formula (XI-b) 
       
         
           
           
               
               
           
         
         the method comprising:
 forming a reaction mixture with a Lewis Acid, a base, a solvent, a filtering agent, and a compound of Formula (XI-a): 
 
       
       
         
           
           
               
               
           
         
         to prepare the compound of Formula (XI-b) 
         wherein
 Bn is benzyl. 
 
       
     
     
         17 . The method of  claim 16 , wherein
 the Lewis Acid is BCl 3 ;   the base is Et 3 N;   the solvent is MeOH; and   the filtering agent is Celite®.   
     
     
         18 . (canceled) 
     
     
         19 . A method of preparing a compound of Formula (XI-c) 
       
         
           
           
               
               
           
         
         the method comprising:
 forming a reaction mixture with solvent, a reagent, an acid, and a compound of Formula (XI-b): 
 
       
       
         
           
           
               
               
           
         
         to prepare the compound of Formula (XI-b). 
       
     
     
         20 . The method of  claim 19  wherein
 the solvent is acetone; 
 the reagent is 2,2-dimethoxypropane; and 
 the acid is sulfuric acid. 
 
     
     
         21 - 42 . (canceled) 
     
     
         43 . The method of  claim 16 , wherein
 the Lewis Acid is BCl 3 ;   the base is Et 3 N;   the solvent is MeOH; and   the filtering agent is diatomaceous earth.