Benzothiazolone compound

Abstract

The present invention provides a compound of formula (I) in free form or in pharmaceutically acceptable salt form a method for manufacturing the compound of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and pharmaceutical compositions.

1 . A process for the manufacture of a compound of formula (I) in free form or in pharmaceutically acceptable salt form which is 
       
         
           
           
               
               
           
         
         which includes the steps of:
 a. the reaction of a compound of formula (IIa) in free form or in pharmaceutically acceptable salt form 
 
       
       
         
           
           
               
               
           
         
         
           
             in which R a  and R b  are protecting groups with 2-(4-butoxy-phenyl)-1,1-dimethyl-ethylamine; 
           
           b. the cleavage of any protecting groups still present; 
           c. the recovery of the so obtainable compound of formula (I) in free form or in pharmaceutically acceptable salt form. 
         
       
     
     
         2 . A process for the manufacture of a compound of formula (I) in free form or in pharmaceutically acceptable salt form according to  claim 1  in which compound (IIa) is obtained by the reaction of a compound of formula (IIIa) in free form or in pharmaceutically acceptable salt form 
       
         
           
           
               
               
           
         
         in which in which R a  and R b  are protecting groups and LG is a leaving group with a base and optionally a phase transfer catalyst. 
       
     
     
         3 . A process for the manufacture of a compound of formula (I) in free form or in pharmaceutically acceptable salt form according to  claim 2  in which compound (IIIa) is obtained by the stereoselective reduction of a compound of formula (IVa-2) in free form or in pharmaceutically acceptable salt form 
       
         
           
           
               
               
           
         
         in which R a  and R b  are protecting groups and LG is a leaving group. 
       
     
     
         4 . A process according to  claim 3  wherein the LG is chloro. 
     
     
         5 . A process according to  claim 4  in which compound (IVa′-2) in free form or in pharmaceutically acceptable salt form 
       
         
           
           
               
               
           
         
         is obtained by the reaction of a compound of formula (Va) in free form or in pharmaceutically acceptable salt form 
       
       
         
           
           
               
               
           
         
         in which R a  and R b  are protecting groups and Hal is a halogen with 2-chloro-N-methoxy-N-methyl-acetamide in the presence of a strong base.