Synthesis of udp-glucose: n-acylsphingosine glucosyltransferase inhibitors

Abstract

Disclosed is a novel enantiomeric synthesis ceramide-like inhibitors of UDP-glucose: N-acylsphingosine glucosyltransferase. Also disclosed are novel intermediates formed during the synthesis.

1 - 23 : (canceled) 
     
     
         24 : A method of preparing a compound of formula (2) 
       
         
           
           
               
               
           
         
       
       said method comprising reacting a compound of formula (1) 
       
         
           
           
               
               
           
         
       
       with pyrrolidine, followed by hydrolysis. 
     
     
         25 : The method of  claim 24 , wherein the hydrolysis is carried out using methanol as solvent. 
     
     
         26 : The method of  claim 24 , wherein the compound of formula (1) is prepared by reacting (5S)-5-phenylmorpholin-2-one with 1,4-benzodioxan-6-carboxaldehyde. 
     
     
         27 : The method of  claim 26 , wherein (5S)-5-phenylmorpholin-2-one is prepared by reacting a compound of formula (i) 
       
         
           
           
               
               
           
         
       
       with a compound of formula (ii) 
       
         
           
           
               
               
           
         
       
     
     
         28 : The method of  claim 24 , further comprising reducing the compound of formula (2) to form a compound of formula (3) 
       
         
           
           
               
               
           
         
       
     
     
         29 : The method of  claim 28 , wherein the reduction is carried out using lithium aluminum hydride. 
     
     
         30 : A method of preparing a compound of formula (3) 
       
         
           
           
               
               
           
         
       
       said method comprising reducing a compound of formula (2) 
       
         
           
           
               
               
           
         
       
     
     
         31 : The method of  claim 30 , wherein the reduction is carried out using lithium aluminum hydride. 
     
     
         32 : The method of  claim 30 , wherein the compound of formula (2) is prepared by reacting a compound of formula (1) 
       
         
           
           
               
               
           
         
       
       with pyrrolidine, followed by hydrolysis. 
     
     
         33 : The method of  claim 32 , wherein the hydrolysis is carried out using methanol as solvent. 
     
     
         34 : The method of  claim 32 , wherein the compound of formula (1) is prepared by reacting (5S)-5-phenylmorpholin-2-one with 1,4-benzodioxan-6-carboxaldehyde. 
     
     
         35 : The method of  claim 34 , wherein (5S)-5-phenylmorpholin-2-one is prepared by reacting a compound of formula (i) 
       
         
           
           
               
               
           
         
       
       with a compound of formula (ii)