Methods of manufacturing benzoquinoline compounds

Abstract

The present invention relates to new methods of manufacturing benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), and intermediates thereof.

1 . A process of preparing a compound of Formula IV: 
       
         
           
           
               
               
           
         
       
       or a salt thereof, comprising:
 a step of reacting a compound of Formula II or a salt thereof with a compound of Formula III: 
 
       
         
           
           
               
               
           
         
         in the presence of a base; 
         wherein: 
         R 7 -R 12  and R 15  are independently selected from the group consisting of hydrogen and deuterium; and 
         Y 1  is selected from the group consisting of acetoxy, alkoxy, halogen, haloalkoxy, perhaloalkoxy, heteroalkoxy, and aryloxy, any of which may be optionally substituted.