Synthesis of renin inhibitors involving a cycloaddition reaction

Abstract

The invention related to a novel process, novel process steps and novel intermediates useful in the synthesis of pharmaceutically active compounds, especially renin inhibitors, such as Aliskiren. Inter alia, the invention relates to a process for the manufacture of a compound of the formula III, wherein R, R 1 , and R′ are as defined in the specification, or a salt thereof, and a compound of formula IV wherein R, R 1 , R 2 and R′ are as defined in the specification, and processes of manufacturing these.

1 . A process for the manufacture of a compound of the formula XXIII, 
       
         
           
           
               
               
           
         
         wherein R is alkyl and R 1  is alkoxyalkyl or a salt thereof, comprising one or more of the following steps either individually or in any combination: 
         the manufacture of a compound of the formula (III) or a salt thereof, 
       
       
         
           
           
               
               
           
         
         the manufacture of a compound of the formula IV or a salt thereof, 
       
       
         
           
           
               
               
           
         
         the manufacture of a compound of the formula VI or a salt thereof, 
       
       
         
           
           
               
               
           
         
         the manufacture of a compound of the formula VII or a salt thereof, 
       
       
         
           
           
               
               
           
         
         the manufacture of a compound of the formula VIII or a salt thereof, and 
       
       
         
           
           
               
               
           
         
         the manufacture of a compound of the formula IX or a salt thereof. 
       
       
         
           
           
               
               
           
         
       
     
     
         2 . The process according to  claim 1  comprising the steps of:
 the manufacture of a compound of the formula III or a salt thereof, and/or 
 the manufacture of a compound of the formula IV or a salt thereof. 
 
     
     
         3 . The process according to  claim 1  comprising the steps of
 the manufacture of a compound of the formula IV or a salt thereof, and/or 
 the manufacture of a compound of the formula VII or a salt thereof. 
 
     
     
         4 . A process for the manufacture of a compound of the formula XXIII, 
       
         
           
           
               
               
           
         
         wherein R and R 1  are as defined in  claim 1   
         or a salt thereof, comprising one or more of the following steps either individually or in any combination: 
         the manufacture of a compound of the formula III or a salt thereof, 
         the manufacture of a compound of the formula IV or a salt thereof, 
         the manufacture of a compound of the formula VI or a salt thereof, and 
         the manufacture of a compound of the formula XII or a salt thereof. 
       
     
     
         5 . A process for the manufacture or a compound of the formula XXIII, 
       
         
           
           
               
               
           
         
         wherein R and R 1  are as defined in  claim 1  or a salt thereof, comprising one or more of the following steps either individually or in any combination: 
         the manufacture of a compound of the formula III or a salt thereof, 
         the manufacture of a compound of the formula IV or a salt thereof, 
         the manufacture of a compound of the formula VII or a salt thereof, and 
         the manufacture of a compound of the formula XIII or a salt thereof.