A series of new [1,2,4]triazolo[4,3-a]pyrimidine derivatives was prepared using a one-pot three-component synthesis from 5-amino-1-phenyl-1H-1,2,4-triazoles, aromatic aldehydes and ethyl acetoacetate. The compound structures were confirmed by IR, ¹H-NMR, ¹³C-NMR, HRMS and X-ray analyses. The biological activity of these compounds as antitumor agents was evaluated. Their antitumor activities against cancer cell lines (MDA-MB-231 and MCF-7) were tested by the MTT in vitro method. Among them, compounds 4c and 4j displayed the best antitumor activity with IC₅₀ values of 17.83 μM and 19.73 μM against MDA-MB-231 and MCF-7 cell lines, respectively, compared to the Cisplatin reference.

Fluoromethylated imidazo[1,2-a]pyrimidines and benzimidazo[1,2-a]pyrimidines were synthesized through Michael addition/intramolecular cyclization reaction by condensation of 2-amino imidazole derivatives with ethyl 4,4,4-trifluorobut-2-ynoate and using C–O bond activation. The synthons thus obtained can be functionalized by forming new chemical bonds, including C–C, C–N and C–S, to provide easy access to a wide range of novel trifluoromethylated imidazo[1,2-a]pyrimidines and benzimidazo[1,2-a]pyrimidines in good to excellent yields. Preliminary biological evaluation revealed a number of derivatives displaying micromolar IC₅₀ values against monoamine oxidase B and butyrylcholinesterase, two important targets in the field of neurodegenerative disorders.

A convenient and efficient synthetic route to C3-arylated 7-trifluoromethylpyrazolo[1,5-a]pyrimidin-5-one derivatives has been reported starting from 3-bromo-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-5-one through a Suzuki–Miyaura cross-coupling reaction. The arylation (heteroarylation) strategy can be performed using a wide variety of aryl and heteroaryl boronic acids and requiring a tandem catalyst XPhosPdG2/XPhos to avoid the debromination reaction. These optimized conditions were successfully extended to the synthesis of 7-, 8- and 9-arylated pyrimido[1,2-b]indazol-2-ones from their corresponding brominated starting materials. Furthermore, the second C-5 arylation of C3-arylated pyrazolo[1,5-a]pyrimidin-5-ones was achieved under standard Suzuki–Miyaura cross-coupling conditions, after activating the C–O bond of the lactam function with PyBroP, giving access to a small library of 3,5-diarylated 7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidines in good to excellent yields. The interest of this approach has been highlighted by the synthesis of a known anti-inflammatory agent. Additionally, a preliminary biological evaluation has revealed that a number of derivatives display micromolar IC₅₀ values against monoamine oxidase B, an important target in the field of neurodegenerative disorders.