Synthesis of 5-Azacytidine

Abstract

The present invention provides a method for the preparation of 5-azacytidine, wherein 5-azacytidine is represented by the structure: The method involves the silylation of 5-azacytosine, followed by the coupling of silylated 5-azacytosine to a protected β-D-ribofuranose derivative. The coupling reaction is catalyzed by trimethylsilyl trifluoromethanesulfonate (TMS-Triflate).

1 - 30 . (canceled)  
     
     
         31 . A method of preparing 5-azacytidine comprising the steps of: 
 a) reacting 5-azacytidine with at least one silylating reagent to yield silylated 5-azacytidine;    b) adding directly to the reaction mixture of a), a non-metallic Lewis acid catalyst and protected β-D-ribofuranose; and    c) deprotecting and desilylating the product of step b).    
     
     
         32 . The method of  claim 31  wherein each said silylating reagent is a trimethylsilyl (TMS) reagent.  
     
     
         33 . The method of  claim 31  wherein each said silylating reagent is selected from the group consisting of hexamethyldisilizane (HMDS) and chlorotrimethylsilane (TMSCl).  
     
     
         34 . The method of  claim 31  wherein the silylation reaction step in a) is carried out in the presence of ammonium sulfate.  
     
     
         35 . The method of  claim 31  wherein the silylation reaction step in a) is carried out in the presence of a dry organic solvent.  
     
     
         36 . The method of  claim 35  wherein said dry organic solvent is a polar solvent.  
     
     
         37 . The method of  claim 36  wherein said polar solvent is acetonitrile.  
     
     
         38 . The method of  claim 31  wherein said protected ribofuranose is selected from the group consisting of:  
       
         
           
           
               
               
           
         
       
     
     
         39 . The method of  claim 31  further comprising: 
 d) recrystallizing the product from step c).    
     
     
         40 . The method of  claim 39  wherein step e) comprises: 
 i) dissolving the product form step c) in dimethylsulfoxide;    ii) adding methanol to the solution of i); and    iii) isolating the recrystallized product.