Lacosamide intermediate compound, preparation method thereof and use thereof

Abstract

A new compound is provided, which is used for preparing lacosamide. A novel method for preparing lacosamide is also provided. During the reaction, iodomethane and silver oxide that are cost expensive are not used, nor a Pd-c catalyst is used, so the production cost is low, the raw materials and accessory materials are cheap and easily available, and the process is simple, so that industrial production is easy to realize; and moreover, the yield is high, and good economic efficiency can be achieved.

1 . A compound represented by Formula (I): 
       
         
           
           
               
               
           
         
         wherein R1 is benzyloxycarbonyl, 9-fluorenemethoxycarbonyl, 2-biphenylyl-2-propoxycarbonyl, phthalimidyl, p-tosyl, trifluoroacetyl, formyl, acetyl, benzoyl, benzyl, allyl, dialkyl phosphoryl, tert-butoxycarbonyl, or a C 1 -C 20  aliphatic alkoxycarbonyl; R2 is hydrogen, hydroxyl, a C 1 -C 20  aliphatic hydrocarbyl or an aromatic hydrocarbyl; and when R2 is methyl, R1 is not acetyl, benzyloxycarbonyl, or tert-butoxycarbonyl; and when R2 is hydrogen, R1 is not benzyloxycarbonyl. 
       
     
     
         2 . The compound according to  claim 1 , wherein the structural formula is shown in Formula (I-1): 
       
         
           
           
               
               
           
         
         wherein R1 is 9-fluorenemethoxycarbonyl, 2-biphenylyl-2-propoxycarbonyl, phthalimidyl, p-tosyl, trifluoroacetyl, formyl, acetyl, benzoyl, benzyl, allyl, dialkyl phosphoryl, tert-butoxycarbonyl, or a C 1 -C 20  aliphatic alkoxycarbonyl. 
       
     
     
         3 . The compound according to  claim 1 , wherein the structural formula is shown in Formula (I-2): 
       
         
           
           
               
               
           
         
         wherein R1 is benzyloxycarbonyl, 9-fluorenemethoxycarbonyl, 2-biphenylyl-2-propoxycarbonyl, phthalimidyl, p-tosyl, trifluoroacetyl, formyl, acetyl, benzoyl, benzyl, allyl, dialkyl phosphoryl, tert-butoxycarbonyl, or a C 1 -C 20  aliphatic alkoxycarbonyl; R2 is a C 1 -C 20  aliphatic hydrocarbyl; and when R2 is methyl, R1 is not acetyl, benzyloxycarbonyl, or tert-butoxycarbonyl. 
       
     
     
         4 . The compound according to  claim 1 , specifically being (R)—N-benzyl-2-(ethoxycarbonylamino)-3-hydroxypropionamide or (R)—N-benzyl-2-(ethoxycarbonylamino)-3-methoxypropionamide. 
     
     
         5 . A method for preparing the compound according to  claim 2 , wherein a compound represented by Formula (II) and a compound represented by R1-R3 are used: 
       
         
           
           
               
               
           
         
         wherein R1 is defined as in  claims 2 ; and R3 is a halogen. 
       
     
     
         6 . A method for preparing the compound according to  claim 3 , comprising a step of an alkylation reaction of a compound represented by Formula (I-1) and 
       
         
           
           
               
               
           
         
         wherein R1 is benzyloxycarbonyl, 9-fluorenemethoxycarbonyl, 2-biphenylyl-2-propoxycarbonyl, phthalimidyl, p-tosyl, trifluoroacetyl, formyl, acetyl, benzoyl, benzyl, allyl, dialkyl phosphoryl, tert-butoxycarbonyl, or a C 1 -C 20  aliphatic alkoxycarbonyl; R2 is a C 1 -C 20  aliphatic hydrocarbyl; and when R2 is methyl, R1 is not acetyl, benzyloxycarbonyl, or tert-butoxycarbonyl. 
       
     
     
         7 . The preparation method according to  claim 6 , wherein an alkylating agent for the alkylation reaction is dimethyl sulfate. 
     
     
         8 . A method for preparing lacosamide, comprising:
 Step 1: deprotecting the compound according to  claim 1 , to obtain a compound represented by Formula (V):   
       
         
           
           
               
               
           
         
         wherein R1 and R2 are as defined in  claim 1 ; 
         Step 2: reacting the compound of Formula (V) with acetyl chloride, to prepare lacosamide. 
       
     
     
         9 . The preparation method according to  claim 8 , wherein the deprotection reaction is performed in the presence of trifluoroacetic acid or an inorganic acid with hydrochloric acid being preferred or an inorganic base with potassium hydroxide or sodium hydroxide being preferred. 
     
     
         10 . A method for preparing (R)-2-amino-N-benzyl-3-hydroxypropionamide, comprising:
 condensating (R)-2-(tert-butoxyamino)-3-hydroxylpropionic acid and benzylamine to obtain (R)—N-benzyl-2-(tert-butoxycarbonylamino)-3-hydroxypropionamide, and deprotecting (R)—N-benzyl-2-(tert-butoxycarbonylamino)-3-hydroxypropionamide to obtain (R)-2-amino-N-benzyl-3-hydroxypropionamide.   
     
     
         11 . The preparation method according to  claim 10 , wherein the deprotection reaction is performed in the presence of trifluoroacetic acid or an inorganic acid with hydrochloric acid being preferred or an inorganic base with potassium hydroxide or sodium hydroxide being preferred.