Process for preparing heterocyclic derivatives

Abstract

The present invention relates to a novel process, useful for preparing key intermediates of formula (I) in the synthesis of various compounds, among them compounds which are potent and specific antagonists of D3 receptors, in which X may be Nitrogen or Sulfur; Het means aryl or heteroaryl; each of which may be substituted by 1 to 4 groups J selected from: halogen, C1-C6 alkyl C1-C6 alkoxy, halo C1-C6 alkyl C2-C6 alkenyl, C2-C6 alkynyl, halo C1-C6 alkoxy, —C(O)R 1 , nitro, hydroxy, —NR 2 R 3 , cyano or a group Z; R 1 is a C1-C4 alkyl —OR 3 or —NR 3 R 4 ; R 2 is hydrogen or C1-C6 alkyl; R 3 is hydrogen or C1-C6 alkyl; R is H, C1-C6 alkyl aryl, benzyl; each of which may be substituted by 1 to 4 groups J; according to the following Scheme 1: in which step a means a reaction in basic conditions of compounds (IIA) with 3-thiosemicarbazide derivatives, followed by a treatment with an inorganic base and n-propane phosphonic cyclic anhydride and final pH adjustment with inorganic acids to give compounds of formula (II).

1 . Process for preparing thiazole or triazole derivatives of formula (I) 
       
         
           
           
               
               
           
         
         in which 
         X may be Nitrogen or Sulfur; 
         Het means aryl or heteroaryl; each of which may be substituted by 1 to 4 groups J selected from:
 halogen, C1-C6 alkyl C1-C6 alkoxy, halo C1-C6 alkyl C2-C6 alkenyl, C2-C6 alkynyl, halo C1-C6 alkoxy, —C(O)R 1 , nitro, hydroxy, —NR 2 R 3 , cyano or a group Z; 
 
         R 1  is a C1-C4 alkyl —OR 3  or —NR 3 R 4 ; 
         R 2  is hydrogen or C1-C6 alkyl; 
         R 3  is hydrogen or C1-C6 alkyl; 
         R is H, C1-C6 alkyl aryl, benzyl; each of which may be substituted by 1 to 4 groups J; 
         according to the following Scheme 1: 
       
       
         
           
           
               
               
           
         
         in which 
         step a means a reaction in basic conditions of compounds (IIA) with 3-thiosemicarbazide derivatives, followed by a treatment with an inorganic base and n-propane phosphonic cyclic anhydride and finally pH adjustment with inorganic acids to give compounds of formula (II).