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, 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 (I), 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).

1 - 10 . (canceled)  
     
     
         11 . A process for preparing a compound selected from 5-{4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl}-2,4-thiazolidinedione, or a tautomeric form thereof, or a pharmaceutical acceptable salt thereof or a pharmaceutically acceptable solvate thereof, comprising 
 catalytically reducing 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, at a temperature above 70° C. using a hydrogen pressure above 20 psi, and    thereafter optionally forming a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate of 5-{4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl}-2,4-thiazolidinedione, or a tautomeric form thereof.    
     
     
         12 . The process according to  claim 11 , wherein the hydrogen pressure is in the range of from 50 to 1500 psi.  
     
     
         13 . The process according to  claim 11 , wherein the hydrogen pressure is in the range of from 70 to 1000 psi.  
     
     
         14 . The process according to  claim 11 , wherein the hydrogen pressure is in the range of from 70 to 80 psi.  
     
     
         15 . The process according to  claim 11 , wherein the catalyst is a palladium catalyst.  
     
     
         16 . The process according to  claim 15 , wherein the catalyst comprises a palladium-on-carbon catalyst.  
     
     
         17 . The process according to  claim 15 , wherein the catalyst comprises a 5-10% palladium-on-carbon catalyst.  
     
     
         18 . The process according to  claim 15 , wherein the catalyst loading is 10 to 50 wt/wt %.  
     
     
         19 . The process according to  claim 15 , wherein the catalyst loading is 25 to 50 wt/wt %.  
     
     
         20 . The process according to  claim 11 , wherein the reduction is conducted at a temperature in the range of from 80° to 115° C.  
     
     
         21 . The process according to  claim 11 , wherein 5-{4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzylidene}-2,4-thiazolidinedione, or a tautomeric form thereof is catalytically reduced.  
     
     
         22 . The process according to  claim 11 , wherein a salt of 5-{4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzylidene}-2,4-thiazolidinedione, or a tautomeric form thereof is catalytically reduced.  
     
     
         23 . The process according to  claim 22 , wherein a mineral acid salt of 5-{4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzylidene}-2,4-thiazolidinedione, or a tautomeric form thereof is catalytically reduced.  
     
     
         24 . The process according to  claim 23 , wherein the mineral acid is hydrobromic acid, hydrochloric acid, or sulphuric acid.  
     
     
         25 . The process according to  claim 22 , wherein an organic acid salt of 5-{4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzylidene}-2,4-thiazolidinedione, or a tautomeric form thereof is catalytically reduced.  
     
     
         26 . The process according to  claim 25 , wherein the organic acid is methanesulphonic acid or tartaric acid.