1,3,4-Oxadiazole derivatives and process for producing the same

Abstract

Oxadiazole derivatives represented by formula (I): (wherein R 1 represents a hydrogen atom or an amino-protective group; R 2 , R 3 , and R 4 each independently represents an alkyl group, a cycloalkyl group, a phenyl group which may be substituted, or a 3,4-methylenedioxyphenyl group, or R 3 and R 4 are taken together to represent a C 2-6 alkylene group), a process of producing the same, and a process for producing oxadiazole derivatives represented by formula (II): (wherein all symbols have the same meanings as described above) using the above derivative. According to the invention, the compound represented by formula (II) is produced through fewer steps in a high yield.

1 . A compound represented by formula (I):  
       
         
           
           
               
               
           
         
       
       (wherein R 1  represents a hydrogen atom or an amino-protective group; R 2 , R 3  and R 4  each independently represents 
 (1) a C 1-8  alkyl group,  
 (2) a C 3-7  cycloalkyl group,  
 (3) a phenyl group,  
 (4) a phenyl group substituted with one to three of a C 1-8  alkyl group, a C 1-8  alkoxy group, a halogen atom, a trifluoromethyl group, and a trifluoromethoxy group, or  
 (5) a 3,4-methylenedioxyphenyl group; or  
 (6) R 3  and R 4  are taken together to represent a C 2-6  alkylene group), a non-toxic salt thereof or a hydrate thereof.  
 
     
     
         2 . The compound according to  claim 1 , wherein R 1  represents a hydrogen atom in formula (I), said compound being represented by formula (I-1):  
       
         
           
           
               
               
           
         
       
       (wherein R 2 , R 3  and R 4  have the same meanings as in  claim 1) .  
     
     
         3 . The compound according to  claim 1 , wherein R 1  represents a benzyloxycarbonyl group, a t-butoxycarbonyl group or a trifluoroacetyl group in formula (I), said compound being represented by formula (I-2):  
       
         
           
           
               
               
           
         
       
       (wherein R 5  represents a benzyloxycarbonyl group, a t-butoxycarbonyl group or a trifluoroacetyl group; and R 2 , R 3  and R 4  have the same meanings as in  claim 1) .  
     
     
         4 . The compound according to  claim 1 , wherein R 2 , R 3  and R 4  each independently represents a C 1-8  alkyl group, a phenyl group or a 3,4-methylenedioxyphenyl group, or R 3  and R 4  are taken together to represent a C 2-5  alkylene group in formula (I).  
     
     
         5 . The compound according to  claim 4 , wherein R 2 , R 3  and R 4  each represents a methyl group; R 2  represents a methyl group, and R 3  and R 4  are taken together to represent an ethylene group; R 2  and R 3  each represents a methyl group, and R 4  represents a phenyl group; or R 2  and R 3  each represents a methyl group, and R 4  represents a 3,4-methylenedioxyphenyl group.  
     
     
         6 . The compound according to  claim 2 , which is 
 (1) 1-(2-t-butyl-1,3,4-oxadiazol-5-ylcarbonyl)-2-methylpropylamine, or    (2) 1-(2-(α,α-dimethylbenzyl)-1,3,4-oxadiazol-5-ylcarbonyl)-2-methylpropylamine.    
     
     
         7 . The compound according to  claim 3 , which is 
 (1) t-butyl N-(1-(2-t-butyl-1,3,4-oxadiazol-5-ylcarbonyl)-2-methylpropyl)carbamate, or    (2) t-butyl N-(1-(2-(α,α-dimethylbenzyl)-1,3,4-oxadiazol-5-ylcarbonyl)-2-methylpropyl)carbamate.    
     
     
         8 . A process for producing a compound represented by formula (I-2):  
       
         
           
           
               
               
           
         
       
       (wherein symbols in the formula have the same meanings as described below), comprising reacting a compound represented by formula (V):  
       
         
           
           
               
               
           
         
       
       (wherein R 5  has the same meaning as in  claim 3)  with a compound represented by formula (VI):  
       
         
           
           
               
               
           
         
       
       (wherein R 2 , R 3 , and R 4  have the same meanings as in  claim 1) .  
     
     
         9 . A process for producing a compound represented by formula (I-1)  
       
         
           
           
               
               
           
         
       
       (wherein symbols in the formula have the same meanings as described below), comprising subjecting a compound represented by formula (I-2):  
       
         
           
           
               
               
           
         
       
       (wherein R 2 , R 3 , R 4  and R 5  have the same meanings as in  claim 3)  to a deprotection reaction of the amino-protecting group.  
     
     
         10 . A process for producing a compound represented by formula (III):  
       
         
           
           
               
               
           
         
       
       (wherein R 2 , R 3 , R 4  and R 6  have the same meanings as described below) comprising subjecting a compound represented by formula (I-2):  
       
         
           
           
               
               
           
         
       
       (wherein R 2 , R 3 , R 4 , and R 5  have the same meanings as described in  claim 3)  to a deprotection reaction of the amino-protecting group, and subjecting the resulting compound represented by formula (I-1):  
       
         
           
           
               
               
           
         
       
       (wherein symbols in the formula have the same meanings as described above) to an amidation with a compound represented by formula (IV):  
       
         
           
           
               
               
           
         
       
       (wherein R 6  represents an amino-protecting group).  
     
     
         11 . A process for producing a compound represented by formula (II):  
       
         
           
           
               
               
           
         
       
       (wherein symbols in the formula have the same meanings as described below), comprising subjecting a compound represented by formula (I-2):  
       
         
           
           
               
               
           
         
       
       (wherein R 2 , R 3 , R 4 , and R 5  have the same meanings as in  claim 3)  to a deprotection reaction of the amino-protecting group, reacting the resulting compound represented by formula (I-1):  
       
         
           
           
               
               
           
         
       
       (wherein symbols in the formula have the same meanings as described above) with a compound represented by formula (IV), and subjecting the resulting compound represented by formula (III):  
       
         
           
           
               
               
           
         
       
       (wherein R 2 , R 3 , R 4   1  and R 6  have the same meanings as in  claim 10)  to a deprotection reaction of the amino-protecting group.