Purine derivatives for the treatment of viral infections

Abstract

The present invention relates to purine derivatives, processes for their preparation, pharmaceutical compositions, and their use in treating viral infections.

1 - 5 . (canceled) 
     
     
         6 . A process of making a compound having the following structure: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
       
       wherein the process comprises: contacting a first reactant having the following structure: 
       
         
           
           
               
               
           
         
         with a second reactant having the following structure: 
       
       
         
           
           
               
               
           
         
         in the presence of a base selected from the group consisting of EtONa and NH3 to provide the compound; 
       
       wherein:
 R 1 , R 2 , and R 3  are independently selected from the group consisting of H, hydroxyl, C 1-6  alkyl, C 1-4  alkoxy, trifluoromethyl, C 3-6  cycloalkyl, phenyl, halogen, hydroxyl-C 1-4  alkyl, C 1-4 -alkoxy-C 1-4 -alkyl-, or C 1-4  alkyl-diethoxyphosphoryl. 
 
     
     
         7 . The process of  claim 6 , wherein the first reactant, the second reactant, and the base are combined in a solvent selected from the group consisting of methanol and ethanol. 
     
     
         8 . The process of  claim 6 , wherein the second reactant has the following structure: 
       
         
           
           
               
               
           
         
       
     
     
         9 . The process according to  claim 6 , wherein the compound has a structure selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         10 . A process of making a compound having the following structure: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
       
       wherein the process comprises: contacting a first reactant having the following structure: 
       
         
           
           
               
               
           
         
         with a second reactant having the following structure: 
       
       
         
           
           
               
               
           
         
       
       wherein:
 X is N or C; and 
 HetAr is imidazolyl, pyrimidyl, pyrrolyl, pyrazolyl, furyl, oxazolyl, oxadiazolyl, isoxazolyl, pyrazinyl and thiazolyl, each of which is optionally substituted by one or more substituents independently selected from hydroxyl, C 1-6  alkyl, C 1-4  alkoxy, trifluoromethyl, C 3-6  cycloalkyl, phenyl, halogen, hydroxyl-C 1-4  alkyl, C 1-4 -alkoxy-C 1-4 -alkyl-, and C 1-4  alkyl-diethoxyphosphoryl. 
 
     
     
         11 . The process according to  claim 10 , wherein the second reactant is pyrazole optionally substituted by one or more substituents independently selected from hydroxyl, C 1-6  alkyl, C 1-4  alkoxy, trifluoromethyl, C 3-6  cycloalkyl, phenyl, halogen, hydroxyl-C 1-4  alkyl, C 1-4 -alkoxy-C 1-4 -alkyl-, and C 1-4  alkyl-diethoxyphosphoryl. 
     
     
         12 . The process according to  claim 10 , wherein the compound is selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         13 . A process of making a compound of formula (I): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
       
       wherein the process comprises: contacting a reactant having the following structure: 
       
         
           
           
               
               
           
         
         with iron and acetic acid 
       
       wherein:
 R 1  is pyrazole; 
 R 2  is selected from the group consisting of pyridine and imidazopyridine, wherein pyridine is optionally substituted one or two times with methyl or methoxy; and 
 Y is C 1-4  alkylene. 
 
     
     
         14 . The process according to  claim 13 , wherein the compound of formula (I) has a structure selected from the group consisting of: