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 compound of formula (I) in free form or in pharmaceutically acceptable salt form which is 
       
         
           
           
               
               
           
         
       
     
     
         2 . A compound according to  claim 1  which is (R)-7-(2-(1-(4-butoxyphenyl)-2-methylpropan-2-ylamino)-1-hydroxyethyl)-5-hydroxybenzo[d]thiazol-2(3H)-one in free form. 
     
     
         3 . A compound according to  claim 1  which is (R)-7-(2-(1-(4-butoxyphenyl)-2-methylpropan-2-ylamino)-1-hydroxyethyl)-5-hydroxybenzo[d]thiazol-2(3H)-one in acetate salt form. 
     
     
         4 . A compound according to  claim 1  which is (R)-7-(2-(1-(4-butoxyphenyl)-2-methylpropan-2-ylamino)-1-hydroxyethyl)-5-hydroxybenzo[d]thiazol-2(3H)-one in glycolate salt form. 
     
     
         5 . A pharmaceutical composition comprising a therapeutically effective amount of a compound according to  claim 1  and one or more pharmaceutically acceptable carriers. 
     
     
         6 . A pharmaceutical composition according to  claim 5  wherein one of the pharmaceutically acceptable carriers is benzyl alcohol. 
     
     
         7 . A combination comprising a therapeutically effective amount of a compound according to  claim 1  and one or more therapeutically active co-agents. 
     
     
         8 . A process for the manufacture of a compound of formula (I) in free form or in pharmaceutically acceptable salt form 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. 
       
     
     
         9 . A process for the manufacture of a compound of formula (I) in free form or in pharmaceutically acceptable salt form according to  claim 8  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. 
       
     
     
         10 . A process for the manufacture of a compound of formula (I) in free form or in pharmaceutically acceptable salt form according to  claim 9  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. 
       
     
     
         11 . A process according to  claim 10  wherein the LG is chloro. 
     
     
         12 . A process according to  claim 11  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.