Fluorinated heterocyclic compounds and methods of synthesis

Abstract

Compositions of the present invention comprise fluorinated heterocyclic compounds, including monofluoroflosequinan and difluoroflosequinan. The methods of the present invention comprise the synthesis of monofluoroflosequinan and difluoroflosequinan.

1 . A composition comprising 7-fluoro-3-fluoromethylsulfinyl-1-methyl-4-quinolone.  
   
   
       2 . A composition comprising monofluoroflosequinan, said monofluoroflosequinan having the structure:  
     
       
         
         
             
             
         
       
     
   
   
       3 . A method, comprising: 
 a) providing: 
 i) 7-fluoro-3-fluoromethylthio-1-methyl-4-quinolone and ii) m-chloroperbenzoic acid (MCPBA); and  
   b) reacting said 7-fluoro-3-fluoromethylthio-1-methyl-4-quinolone and m-chloroperbenzoic acid in a solvent under conditions such that 7-fluoro-3-fluoromethylsulfinyl-1-methyl-4-quinolone is produced.    
   
   
       4 . The method of  claim 3 , wherein said solvent is dichloromethane (DCM).  
   
   
       5 . A method, comprising 
 a) providing: 
 i) 7-fluoro- 1-methyl-3-methylsulfinyl-4-quinolone (flosequinan), and ii) (diethylamino)sulfur trifluoride (DAST); and  
   b) reacting said 7-fluoro-1-methyl-3-methylsulfinyl-4-quinolone (flosequinan), and (diethylamino)sulfur trifluoride in a solvent under conditions such that 7-fluoro-3-fluoromethylthio-1-methyl-4-quinolone is produced.    
   
   
       6 . The method of  claim 5 , wherein said solvent is dichloromethane (DCM).  
   
   
       7 . The method of  claim 5 , wherein said providing step a) additionally provides iii) a catalyst and said reacting step b) occurs in the presence of said catalyst.  
   
   
       8 . The method of  claim 7 , wherein said catalyst is antimony chloride (SbCl 3 ).  
   
   
       9 . A composition comprising 3-difluoromethylsulfinyl-7-fluoro-1-methyl-4-quinolone.  
   
   
       10 . A composition comprising difluoroflosequinan, said difluoroflosequinan having the structure:  
     
       
         
         
             
             
         
       
     
   
   
       11 . A method, comprising: 
 a) providing: 
 i) 7-fluoro-3-fluoromethylthio- 1-methyl-4-quinolone,  
 ii) SELECTFLUOR and iii) triethylamine and  
   b) reacting said 7-fluoro-3-fluoromethylthio-1-methyl-4-quinolone, SELECTFLUOR and triethylamine in a solvent under conditions such that 3-difluoromethylthio-7-fluoro-1-methyl-4-quinolone is produced; and    c) further reacting said 3-difluoromethylthio-7-fluoro-1-methyl-4-quinolone with m-chloroperbenzoic acid (MCPBA) in a solvent under conditions such that 3-difluoromethylsulfinyl-7-fluoro-1-methyl-4-quinolone is produced.    
   
   
       12 . The method of  claim 11 , wherein said solvent in step b) is acetonitrile.  
   
   
       13 . The method of  claim 11 , wherein said solvent in step c) is dichloromethane (DCM).