Antiviral compounds

Abstract

The disclosure 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 .- 38 . (canceled) 
     
     
         39 . A compound of formula (B): 
       
         
           
           
               
               
           
         
       
     
     
         40 . A compound of formula (A): 
       
         
           
           
               
               
           
         
       
     
     
         41 . A method of making a compound of formula (A): 
       
         
           
           
               
               
           
         
         comprising brominating a compound of formula (B): 
       
       
         
           
           
               
               
           
         
         under conditions sufficient to form a compound of formula (A). 
       
     
     
         42 . The method of  claim 41 , wherein brominating a compound of formula (B) comprises contacting compound of formula (B) with pyridinium tribromide. 
     
     
         43 . A method of making a compound of formula (B): 
       
         
           
           
               
               
           
         
         comprising contacting a compound of formula (F): 
       
       
         
           
           
               
               
           
         
         with trifluoroacetic acid under conditions sufficient to form a compound of formula (B). 
       
     
     
         44 . A method of making a compound of formula (F): 
       
         
           
           
               
               
           
         
         comprising contacting a compound of formula (G): 
       
       
         
           
           
               
               
           
         
         with ethynyltrimethylsilane under conditions sufficient to form a compound of formula (F). 
       
     
     
         45 . A method of making a compound of formula (A): 
       
         
           
           
               
               
           
         
         comprising brominating a compound of formula (C): 
       
       
         
           
           
               
               
           
         
         under conditions sufficient to form a compound of formula (D): 
       
       
         
           
           
               
               
           
         
         and contacting a compound of formula (D) with (2,2,6,6-tetramethylpiperidin-1-yl)-oxyl and bleach under conditions sufficient to form a compound of formula (A). 
       
     
     
         46 . The method of  claim 45 , wherein brominating a compound of formula (C) comprises contacting compound of formula (C) with pyridinium tribromide. 
     
     
         47 . A method of making a compound of formula (A): 
       
         
           
           
               
               
           
         
         comprising brominating a compound of formula (E): 
       
       
         
           
           
               
               
           
         
         under conditions sufficient to form a compound of formula (A). 
       
     
     
         48 . The method of  claim 47 , wherein brominating a compound of formula (E) comprises contacting compound of formula (E) with pyridinium tribromide. 
     
     
         49 . A method of making a compound of formula (H): 
       
         
           
           
               
               
           
         
         comprising contacting a compound of formula (I): 
       
       
         
           
           
               
               
           
         
         with a compound of formula (J): 
       
       
         
           
           
               
               
           
         
         under conditions sufficient to form a compound of formula (H); 
         wherein PG is a protecting group. 
       
     
     
         50 . A method of making a compound of formula (H-a): 
       
         
           
           
               
               
           
         
         comprising contacting a compound of formula (I-a): 
       
       
         
           
           
               
               
           
         
         with a compound of formula (J): 
       
       
         
           
           
               
               
           
         
         under conditions sufficient to form a compound of formula (H-a). 
       
     
     
         51 . A method of making a compound of formula (K): 
       
         
           
           
               
               
           
         
         comprising cyclizing a compound of formula (H): 
       
       
         
           
           
               
               
           
         
         under conditions sufficient to form a compound of formula (K); 
         wherein PG is a protecting group. 
       
     
     
         52 . The method of  claim 51 , wherein cyclizing a compound of formula (H) comprises contacting a compound of formula (H) with an amine or amine salt. 
     
     
         53 . The method of  claim 52 , wherein the amine salt is ammonium acetate. 
     
     
         54 . A method of making a compound of formula (K-a): 
       
         
           
           
               
               
           
         
         comprising cyclizing a compound of formula (H-a): 
       
       
         
           
           
               
               
           
         
         under conditions sufficient to form a compound of formula (K-a). 
       
     
     
         55 . The method of  claim 54  wherein cyclizing a compound of formula (H-a) comprises contacting a compound of formula (H-a) with an amine or amine salt. 
     
     
         56 . The method of  claim 55 , wherein the amine salt is ammonium acetate. 
     
     
         57 . A method of making a compound of formula (M): 
       
         
           
           
               
               
           
         
         comprising contacting a compound of formula (M) with acid under conditions sufficient to form a compound of formula (N): 
       
       
         
           
           
               
               
           
         
       
     
     
         58 . The method of  claim 57 , further comprising contacting a compound of formula (N) with a compound of formula (O): 
       
         
           
           
               
               
           
         
         under conditions sufficient to form a compound of formula (L): 
       
       
         
           
           
               
               
           
         
       
     
     
         59 . A method of making a compound of formula (L): 
       
         
           
           
               
               
           
         
         comprising contacting a compound of formula (M): 
       
       
         
           
           
               
               
           
         
         with acid under conditions sufficient to form a material, 
         and contacting the material with a compound of formula (O): 
       
       
         
           
           
               
               
           
         
         under conditions sufficient to form a compound of formula (L); 
         wherein PG is a protecting group. 
       
     
     
         60 . A method of making a compound of formula (L): 
       
         
           
           
               
               
           
         
         comprising contacting a compound of formula (M-a): 
       
       
         
           
           
               
               
           
         
         with acid under conditions sufficient to form a material; 
         and contacting the material with a compound of formula (O): 
       
       
         
           
           
               
               
           
         
         under conditions sufficient to form a compound of formula (L).