Trifluoromethylated β-enamino diketones undergo type 1,2-addition leading to regioselective synthesis of trifluoromethylated azoles containing an azomethine group.

An alternative highly regioselective synthetic method for the preparation of 3,5-disubstituted 4-formyl-N-arylpyrazoles in a one-pot procedure is reported. The methodology developed was based on the regiochemical control of the cyclocondensation reaction of β-enamino diketones with arylhydrazines. Structural modifications in the β-enamino diketone system allied to the Lewis acid carbonyl activator BF were strategically employed for this control. Also a one-pot method for the preparation of 3,5-disubstituted 4-hydroxymethyl-N-arylpyrazole derivatives from the β-enamino diketone and arylhydrazine substrates is described.

An efficient one-pot method is described for the highly regioselective synthesis of α-ketoamide N-arylpyrazoles from secondary β-enamino diketones. For this, the key intermediate, 4-acyl 3,5-dihydroxypyrrolone, was generated in situ and underwent bimolecular nucleophilic substitution at C-5 by arylhydrazine, with subsequent heterocyclization at the carbonyl carbon of the acyl group. This strategy allowed for regiochemical control of α-ketoamide N-arylpyrazoles from β-enamino diketones and arylhydrazines.

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In this article, a series of 29 new pyrimidine N‐acylhydrazone hybrids were synthesized and evaluated in vitro against Leishmania amazonensis and Trypanosoma cruzi protozoa that cause the neglected diseases cutaneous leishmaniasis and Chagas disease, respectively. Eight of the target compounds showed significant antiprotozoal activities with IC50 values in 4.3–33.6 μM range. The more active compound 4f exhibited selectivity index greater than 15 and drug‐like properties based on Lipinski's rule.