Process for preparing n-methyl-4-benzylcarbamidopyridinium chloride

Abstract

The present application relates to a new salt of N-methyl-4-benzylcarbami-dopyridine, a process for its preparation, a pharmaceutical composition comprising this compound and its use for the treatment or prevention of viral diseases.

1 . A process for the preparation of N-methyl-4-benzylcarbamidopyridinium chloride comprising the following step: quaterisation of the pyridinium ring atom of isonicotinic acid benzylamide with chloromethane according to the following reaction scheme 
       
         
           
           
               
               
           
         
       
     
     
         2 . The process according to  claim 1  wherein a solvent selected from the group consisting of 2-propanol, aqueous ethanol and acetonitrile is used. 
     
     
         3 . The process of  claim 1  wherein the process is carried out at a temperature in the range of 50-120° C. and under pressure. 
     
     
         4 . The process according to  claim 2  wherein the reaction is carried out in acetonitrile with heating and permanent passing of chloromethane gas through the reaction mixture without any pressure application. 
     
     
         5 . The process of  claim 1  wherein the reaction time is in the range from 1-20 h. 
     
     
         6 . The process according to  claim 1  wherein the molar ratio between isonicotinic acid benzylamide and chloromethane is in the range of 1-1.5. 
     
     
         7 . The process according to  claim 2  wherein the solvent is ethanol 96%, wherein the reaction is carried out at a pressure in the range of 0.1-1 MPa (1-10 bar) and wherein the molar ratio between isonicotinic acid benzylamide and chloromethane is in the range of 1-1.5. 
     
     
         8 . The process according to  claim 1 , further comprising the step of recrystallisation of the raw product from ethanol 96%. 
     
     
         9 - 17 . (canceled) 
     
     
         18 . The process of  claim 1  wherein the N-methyl-4-benzylcarbamidopyridinium chloride comprises impurities in the range of less than 0.5%. 
     
     
         19 . The process of  claim 1  wherein the N-methyl-4-benzylcarbamidopyridinium chloride comprises impurities in the range of less than 0.05%. 
     
     
         20 . The process of  claim 1  wherein the N-methyl-4-benzylcarbamidopyridinium has a melting temperature in the range of 198° C. to 203° C.