Selective synthesis of fluorinated benzyl- or phenylpyrimidines from the heterocyclisation of α-trifluoroacetylarylpropanenitriles

Some 5-benzyl-6-trifluoromethyl-2,4-diaminopyrimidines analogous to trimethoprim and 6-aryl-5-trifluoroethyl-2,4-diaminopyrimidines analogous to pyrimethamine were prepared from the same synthons, trifluoromethylated β-ketonitriles. The heterocyclisation between enol ether of β-ketonitrile and guanidine leading to these compounds was studied.These fluorinated novel compounds were tested for their in vitro activity against Toxoplasma gondii, a widespread apicomplexan protozoa responsible for congenital toxoplasmosis and cerebral toxoplasmosis in immunocompromised patients.