Processes for intermediates for macrocyclic compounds

Abstract

The present invention is directed to novel macrocyclic compounds of formula (I) and their pharmaceutically acceptable salts, hydrates or solvates: wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , n 1 , m, p Z 1 , Z 2 , and Z 3 are as describe in the specification. The invention also relates to compounds of of formula (I) which are antagonists of the motilin receptor and are useful in the treatment of disorders associated with this receptor and with or with motility dysfunction.

1 - 39 . (canceled) 
     
     
         40 . A compound of formula (IV): 
       
         
           
           
               
               
           
         
         wherein R 1  is C 1 -C 4  alkyl; PG 5  is hydrogen or an amine protecting group; and PG 6  is hydrogen or a hydroxy protecting group. 
       
     
     
         41 . The compound of  claim 40 , wherein R 1  is methyl. 
     
     
         42 . The compound of  claim 40 , wherein PG 5  is hydrogen. 
     
     
         43 . The compound of  claim 40 , wherein PG 5  is a carbamate protecting group. 
     
     
         44 . The compound of  claim 40 , wherein PG 5  is selected from the group consisting of tert-butoxycarbonyl (Boc), benzyloxycarbonyl (Cbz), 9-fluorenylmethoxycarbonyl (Fmoc), α,α-dimethyl-3,5-dimethoxybenzyloxycarbonyl (Ddz) and allyloxycarbonyl (Alloc). 
     
     
         45 . The compound of  claim 40 , wherein PG 6  is hydrogen. 
     
     
         46 . The compound of  claim 40  represented by the following structures: 
       
         
           
           
               
               
           
         
         wherein PG 5  is hydrogen or an amine protecting group; and PG 6  is hydrogen or a hydroxy protecting group. 
       
     
     
         47 . The compound of  claim 44 , wherein PG 5  is α,α-dimethyl-3,5-dimethoxybenzyloxy-carbonyl (Ddz). 
     
     
         48 . The compound of  claim 46 , wherein PG 5  is α,α-dimethyl-3,5-dimethoxybenzyloxy-carbonyl (Ddz). 
     
     
         49 . The compound of  claim 47  represented by the following structures: 
       
         
           
           
               
               
           
         
       
     
     
         50 . The compound of  claim 44 , wherein PG 5  is tert-butoxycarbonyl (Boc). 
     
     
         51 . The compound of  claim 50  represented by the following structures: 
       
         
           
           
               
               
           
         
       
     
     
         52 . A process of using a compound of  claim 40  to make a compound of formula (I); 
       
         
           
           
               
               
           
         
         wherein R 1  is C 1 -C 4  alkyl. 
       
     
     
         53 . A process of using a compound of  claim 40  to make a compound of formula (G); 
       
         
           
           
               
               
           
         
         wherein R 1  is C 1 -C 4  alkyl and PG 1  is an amine protecting group.