Indoline derivative and process for producing the same

Abstract

The present invention provides novel synthetic intermediates for the production of indoline derivatives, which exhibit excellent ACAT inhibitory activity, and processes for the preparation thereof.

1 . A synthetic intermediate of general formula (I)  
     
       
         
         
             
             
         
       
     
     wherein R 1  represents a protective group for the amino group, R 2  and R 3  are the same or different and each represents a lower alkyl group; a salt or an amide derivative thereof.  
   
   
       2 . (canceled)  
   
   
       3 . A process for the preparation of a synthetic intermediate of general formula (I)  
     
       
         
         
             
             
         
       
     
     wherein R 1  represents a protective group for the amino group, R 2  and R 3  are the same or different and each represents a lower alkyl group; or a salt thereof, which process comprises the reaction of a compound of general formula (IV)  
     
       
         
         
             
             
         
       
     
     wherein R 1 , R 2  and R 3  have the same meanings as given above; with a compound of general formula (V)  
     
       
         
         
             
             
         
       
     
     or a salt thereof.  
   
   
       4 . A process for the preparation of a synthetic intermediate of general formula (VI′)  
     
       
         
         
             
             
         
       
     
     wherein R 1  represents a protective group for the amino group, R 2  and R 3  are the same or different and each represents a lower alkyl group; or a salt thereof, which process comprises the reduction of the hydroxyl group of a compound of general formula (I)  
     
       
         
         
             
             
         
       
     
     wherein R 1 , R 2  and R 3  have the same meanings as given above; or a salt thereof by phosphorous acid and an alkali metal iodide.  
   
   
       5 . A process for preparation according to  claim 4  wherein the reduction is carried out in an organic acid.  
   
   
       6 . A process for the preparation of a synthetic intermediate of general formula (II)  
     
       
         
         
             
             
         
       
     
     wherein R 1  represents a protective group for the amino group, R 2  and R 3  are the same or different and each represents a lower alkyl group, R 4  represents a hydrogen atom or a protective group for the carboxyl group; or a salt thereof, which process comprises the nitration of a compound of general formula (VI)  
     
       
         
         
             
             
         
       
     
     wherein R 1 , R 2 , R 3  and R 4  have the same meanings as given above; or a salt thereof.  
   
   
       7 . A process for the preparation of a synthetic intermediate of general formula (VII)  
     
       
         
         
             
             
         
       
     
     wherein R 1  represents a protective group for the amino group, R 2  and R 3  are the same or different and each represents a lower alkyl group, R 4  represents a hydrogen atom or a protective group for the carboxyl group; or a salt thereof, which process comprises the reduction of a compound of general formula (II)  
     
       
         
         
             
             
         
       
     
     wherein R 1 , R 2 , R 3  and R 4  have the same meanings as given above; or a salt thereof.  
   
   
       8 . A process for the preparation of a synthetic intermediate of general formula (VIII)  
     
       
         
         
             
             
         
       
     
     wherein R 1  represents a protective group for the amino group, R 2  and R 3  are the same or different and each represents a lower alkyl group, R 4  represents a hydrogen atom or a protective group for the carboxyl group; or a salt thereof, which process comprises the pivaloylation of a compound of general formula (VII)  
     
       
         
         
             
             
         
       
     
     wherein R 1 , R 2 , R 3  and R 4  have the same meanings as given above; or a salt thereof.  
   
   
       9 . A process for the preparation of a synthetic intermediate of general formula (III)  
     
       
         
         
             
             
         
       
     
     wherein R 2  and R 3  are the same or different and each represents a lower alkyl group, R 4  represents a hydrogen atom or a protective group for the carboxyl group, nOc represents an octyl group; or a salt thereof, which process comprises the octylation of a compound of general formula (IX)  
     
       
         
         
             
             
         
       
     
     wherein R 2 , R 3  and R 4  have the same meanings as given above; or a salt thereof.  
   
   
       10 . A process for preparation according to  claim 9  wherein said process is carried out using xylene as a solvent.  
   
   
       11 . A process for preparation according to  claim 9  wherein said process is carried out using butyl acetate as a solvent.  
   
   
       12 . A process for preparation according to  claim 8  wherein said process is carried out using diisopropylethylamine as a base.  
   
   
       13 . A process for preparation according to  claim 9  wherein said process is carried out using diisopropylethylamine as a base.  
   
   
       14 . A process for preparation according to  claim 10  wherein said process is carried out using diisopropylethylamine as a base.  
   
   
       15 . A process for preparation according to  claim 11  wherein said process is carried out using diisopropylethylamine as a base.