Facile synthetic approaches for new series of pyrazole-4-carbonitrile derivatives

Abstract

Aldol condensation of 3-acetyl-1-(4-fluorophenyl)-5-phenyl-1H-pyrazole-4-carbonitrile with benzaldehyde afforded 1-(4-fluorophenyl)-5-phenyl-3-((E)-3-phenylacryloyl)-1H-pyrazole-4-carbonitrile, which in turn reacted with a series of 1,2- and 1,3-binucleophiles to afford new substituted pyrazoles, pyrimidines, and condensed azolopyrimidine derivatives attached to pyrazole scaffold at position 3. Moreover, multicomponent condensation reactions (MCRs) were used as an alternative method, and 1H–13C heteronuclear single quantum coherence (HSQC) in addition to heteronuclear multiple-bond correlation (HMBC) spectra were used for full confirmation of a selected example of these compounds. The reactivity of 1-(4-fluorophenyl)-5-phenyl-3-((E)-3-phenylacryloyl)-1H-pyrazole-4-carbonitrile towards active methylene derivatives, including malononitrile and ethyl cyanoacetate, was explored and afforded 2-amino-6-(4-cyano-1-(4-fluorophenyl)-5-phenyl-1H-pyrazol-3-yl)-4-phenylpyridine-3-carbonitrile and ethyl 6-(4-cyano-1-(4-fluorophenyl)-5-phenyl-1H-pyrazol-3-yl)-1,2-dihydro-2-oxo-4-phenylpyridine-3-carboxylate, respectively.