Process for the preparation of thiazolidinedione derivatives

Abstract

A process for preparing a compound of formula (I) or a tautomeric form thereof or a pharmaceutically acceptable salt thereof, wherein: A 1 represents a substituted or unsubstituted aromatic heterocyclyl group; R 1 represents a hydrogen atom, an alkyl group, an acyl group, an aralkyl group, wherein the aryl moiety may be substituted or unsubstituted, or a substituted or unsubstituted aryl group; A 2 represents a benzene ring having in total up to five substituents; and n represents an integer in the range of from 2 to 6, which process comprises catalytically reducing a compound of formula (II): wherein A 1 , R 1 , A 2 and n are as defined in relation to formula (I), characterized in that the reduction reaction is carried out using a hydrogen pressure above 20 psi; and thereafter if required forming a pharmaceutically acceptable salt and/or a pharmaceutically acceptable solvate of the compound of formula (I).

1 . A process for preparing a compound of formula (I):  
       
         
           
           
               
               
           
         
       
       or a tautomeric form thereof or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, wherein: 
 A 1  represents a substituted or unsubstituted aromatic heterocyclyl group;  
 R 1  represents a hydrogen atom, an alkyl group, an acyl group, an aralkyl group, wherein the aryl moiety may be substituted or unsubstituted, or a substituted or unsubstituted aryl group;  
 A 2  represents a benzene ring having in total up to five substituents; and  
 n represents an integer in the range of from 2 to 6,  
 which process comprises catalytically reducing a compound of formula (II):  
                     
 wherein A 1 , R 1 , A 2  and n are as defined in relation to formula (1), characterised in that the reduction reaction is carried out using a hydrogen pressure above 20 psi; and thereafter if required forming a pharmaceutically acceptable salt and/or a pharmaceutically acceptable solvate of the compound of formula (I).  
 
     
     
         2 . A process according to  claim 1 , wherein the reaction is carried out using a hydrogen pressure in the range of from 50 to 1500 psi, 60 to 1500 psi, 75 to 1500 psi, 70 to 1000 psi or 200 to 1500 psi.  
     
     
         3 . A process according to  claim 1  or  claim 2 , wherein the reaction hydrogen pressure is in the range of from 70 to 1000 psi.  
     
     
         4 . A process according to any one of  claims 1  to  3 , wherein the reaction hydrogen pressure is 70, 75, 80, 500 or 1000 psi.  
     
     
         5 . A process according to any one of  claims 1  to  4 , wherein the hydrogenation catalyst is a 10% palladium-on-carbon catalyst.  
     
     
         6 . A process according to any one of  claims 1  to  5 , wherein the catalyst loading is 5 to 100%, (% w/w of catalyst to substrate).  
     
     
         7 . A process according to any one of  claims 1  to  6 , wherein the reaction solvent is acetic acid, aqueous acetic acid, an alkanol, an alkanol admixed with an aqueous mineral acid, tetrahydrofuran or tetrahydrofuran admixed with an aqueous mineral.  
     
     
         8 . A process according to  claim 7 , wherein the reaction solvent is acetic acid.  
     
     
         9 . A process according to any one of  claims 1  to  8 , wherein the reaction temperature is in the range of from 80° C. to 115° C.  
     
     
         10 . A process according to any one of  claims 1  to  9 , wherein the compound of formula (II) is 5-{4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzylidene}-2,4-thiazolidinedione, or a tautomeric form thereof or a salt thereof, or a solvate thereof, and the compound of formula (I) is 5-{4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl}-2,4-thiazolidinedione, or a tautomeric form thereof or a salt thereof, or a solvate thereof.