Selective Synthesis of Fluorinated Benzyl‐ or Phenylpyrimidines from the Heterocyclization of α‐Trifluoroacetylarylpropanenitriles.

Abstract

Selective Synthesis of Fluorinated Benzyl-or Phenylpyrimidines from the Heterocyclization of α-Trifluoroacetylarylpropanenitriles. -The new method allows the preparation of fluorinated phenyl-or benzylpyrimidines, analogues of trimethoprim and pyrimethamine, simply by varying the nature of the solvent. For example, heterocyclization of enol ethers (III) with guanidine (IV) in methanol provides the phenylpyrimidines (V) whereas the same reaction carried out in acetonitrile affords benzylpyrimidines (VII). The synthetic approach to phenylpyrimidine (XII) is adopted from a previously reported method. Concerning the bioactivity of pyrimidines (Vb) and (XI) on T. gondii, they reveal activity comparable to that of trimethoprim but they are less active than pyrimethamine. -(BERBER*, H.; MIRAND, C.; DEROUIN, F.; J.