Antiviral compounds

Abstract

The invention is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

1 .- 46 . (canceled) 
     
     
         47 . A method of preparing compound 28: 
       
         
           
           
               
               
           
         
         or a salt thereof, comprising: 
         a) coupling compound III: 
       
       
         
           
           
               
               
           
         
         or a salt thereof, 
         with compound IV: 
       
       
         
           
           
               
               
           
         
         or a salt thereof, in presence of a base to provide compound A: 
       
       
         
           
           
               
               
           
         
         or a salt thereof, 
         b) contacting compound A or a salt thereof with an acid to provide compound B: 
       
       
         
           
           
               
               
           
         
         or a salt thereof, and 
         c) contacting compound B or a salt thereof with morpholine in presence of a reducing agent followed by hydrolysis to provide compound 28 or a salt thereof. 
       
     
     
         48 . The method of  claim 47 , wherein the base of step a) comprises cesium carbonate. 
     
     
         49 . The method of  claim 47 , wherein step a) comprises a temperature of about 65° C. 
     
     
         50 . The method of  claim 47 , wherein step a) further comprises a solvent. 
     
     
         51 . The method of  claim 50 , wherein the solvent comprises N-methyl-2-pyrrolidone. 
     
     
         52 . The method of  claim 47 , wherein the acid in step b) comprises hydrochloric acid. 
     
     
         53 . The method of  claim 47 , wherein the reducing agent in step c) comprises sodium triacetoxyborohydride. 
     
     
         54 . The method of  claim 47 , wherein the hydrolysis in step c) comprises a base. 
     
     
         55 . The method of  claim 54 , wherein the base comprises lithium hydroxide. 
     
     
         56 . A method of preparing compound III: 
       
         
           
           
               
               
           
         
         or a salt thereof, comprising: 
         a) coupling compound C: 
       
       
         
           
           
               
               
           
         
         
           or a salt thereof, 
           with compound D: 
         
       
       
         
           
           
               
               
           
         
         
           or a salt thereof, in presence of a base to provide compound E: 
         
       
       
         
           
           
               
               
           
         
         
           or a salt thereof; 
         
         b) deprotecting compound E to provide compound F: 
       
       
         
           
           
               
               
           
         
         or a salt thereof and 
         c) coupling compound F with compound I: 
       
       
         
           
           
               
               
           
         
         or a salt thereof, to provide compound III or a salt thereof. 
       
     
     
         57 . The method of  claim 56 , wherein the base in step a) comprises a mixture of [dimethylamino(triazolo[4,5-b]pyridin-3-yloxy)methylidene]-dimethylazanium hexafluorophosphate (HATU) and N,N-diisopropylethylamine. 
     
     
         58 . The method of  claim 56 , wherein step a) further comprises a solvent. 
     
     
         59 . The method of  claim 58 , wherein the solvent is a mixture of dimethyl formamide and dichloromethane. 
     
     
         60 . The method of  claim 56 , wherein step b) further comprises an acid. 
     
     
         61 . The method of  claim 60 , wherein the acid is hydrochloric acid. 
     
     
         62 . The method of  claim 56 , wherein step b) further comprises a solvent. 
     
     
         63 . The method of  claim 60 , wherein the solvent is dioxane. 
     
     
         64 . The method of  claim 56 , wherein step c) further comprises a solvent. 
     
     
         65 . The method of  claim 64 , wherein the solvent is ethyl acetate.