Process for preparation of androgen receptor antagonist

Abstract

The present invention provides an isopropanol solvate of enzalutamide. The present invention also provides a process for the preparation of androgen receptor antagonist. In particular, the present invention provides a process for the preparation of enzalutamide or its pharmaceutically acceptable salts, hydrates, solvates, polymorphs or intermediates thereof.

We claim: 
     
         1 . A substantially pure enzalutamide having a purity of at least about 99% by area percentage of HPLC. 
     
     
         2 . The substantially pure enzalutamide according to  claim 1  which is substantially free from one or more impurities. 
     
     
         3 . The substantially pure enzalutamide according to  claim 2  wherein diketo-impurity-A, desflouro-impurity-B, impurity-C, impurity-D, impurity-E and impurity-F are each less than about 0.15% by area percentage of HPLC. 
     
     
         4 . Enzalutamide substantially free from diketo-impurity A. 
     
     
         5 . Enzalutamide substantially free from desfluoro-impurity-B. 
     
     
         6 . The enzalutamide according to  claim 4  prepared by a process comprising reacting a compound of Formula (IV), 
       
         
           
           
               
               
           
         
         with a compound of Formula (II), 
       
       
         
           
           
               
               
           
         
         optionally, in the presence of phenol to obtain the enzalutatnide substantially free from diketo-impurity-A. 
       
     
     
         7 . The process according to  claim 6  further comprising reacting a compound of Formula (VI), 
       
         
           
           
               
               
           
         
         with a compound of Formula (V), 
       
       
         
           
           
               
               
           
         
         wherein L is Cl, Br, I or a leaving group, 
         to obtain the compound of Formula (IV); and 
         optionally, purifying the compound of Formula (IV). 
       
     
     
         8 . A pharmaceutical composition comprising substantially pure enzalutamide having a purity of at least about 99% by area percentage of HPLC together with one or more of pharmaceutically acceptable carriers, excipients and diluents. 
     
     
         9 . The pharmaceutical composition comprising substantially pure enzalutamide according to  claim 8  which is substantially free from one or more impurities together with one or more of pharmaceutically acceptable carriers, excipients and diluents. 
     
     
         10 . A pharmaceutical composition comprising enzalutamide substantially free from diketo-impurity-A together with one or more of pharmaceutically acceptable carriers, excipients and diluents. 
     
     
         11 . The enzalutamide according to  claim 1  prepared by a process comprising reacting a compound of Formula (IV), 
       
         
           
           
               
               
           
         
         with a compound of Formula (II), 
       
       
         
           
           
               
               
           
         
         to obtain the enzalutamide of Formula (I).