Eglė Arbačiauskienė

Sonogashira Coupling Offers a New Synthetic Route to Thieno[2,3-c]pyrazoles

Abstract 1,3-Disubstituted-5-chloro-4-iodopyrazoles are selectively coupled with phenylacetylene under typical Sonogashira reaction conditions [PdCl2(PPh3)2, CuI, Et3N, dimethylformamide (DMF)] to obtain the corresponding 5-chloro-4-(phenylethynyl)pyrazoles in good yield. The latter are smoothly cyclized with Na2S in DMF into the corresponding thieno[2,3-c]pyrazoles. Detailed spectroscopic investigations (1H, 13C, and 15N NMR, mass, and infrared) of all compounds are reported.

(2E)-3-(3-Methoxy-1-phenyl-1H-pyrazol-4-yl)-2-propenal

The palladium-catalyzed reaction of 4-bromo-3-methoxy-1-phenyl-1H-pyrazole with acrolein diethyl acetal gives the title compound in good yield. Detailed spectroscopic data (1H NMR, 13C NMR, 15N NMR, IR, MS) are presented.

4-Bromo-3-methoxy-1-phenyl-1H-pyrazole

Abstract: The title compound was prepared by treatment of 4-bromo-1-phenyl-1 H -pyrazol-3-ol with sodium hydride/methyl iodide in good yield. Detailed spectroscopic data ( 1 H NMR, 13 C NMR, 15 N NMR, IR, MS) are presented. Keywords: pyrazole; 1 H -pyrazol-3-ol; methylation; NMR Bromo(hetero)arenes are valuable starting materials for further functionalization, for instance via metalation reactions (halogen-metal exchange) [1] or transition-metal-catalyzed cross coupling reactions [2–4]. With an OH- or OR function in ortho -position to the bromo atom, such (hetero)arenes can be considered as potential precursors for condensed systems involving a ring-oxygen atom (condensed furans, pyranes) [5]. However, for some of the above mentioned functionalization reactions, free hydroxy groups are unfavourable, for instance in metalation reactions [6] or in Suzuki-type cross couplings [7]. In such cases, the OH group has to be masked. In this regard, a possible option is to transform the OH into the very stable OMe group. The O–Me bond then can be cleaved in the course of the cyclization reaction into the

On the Tautomerism of N-Substituted Pyrazolones: 1,2-Dihydro-3H-pyrazol-3-ones versus 1H-Pyrazol-3-ols

The tautomerism of 1-phenyl-1,2-dihydro-3H-pyrazol-3-one was investigated. An X-ray crystal structure analysis exhibits dimers of 1-phenyl-1H-pyrazol-3-ol units. Comparison of NMR (nuclear magnetic resonance) spectra in liquid state (1H, 13C, 15N) with those of “fixed” derivatives, as well as with the corresponding solid state NMR spectra reveal this compound to exist predominantly as 1H-pyrazol-3-ol molecule pairs in nonpolar solvents like CDCl3 or C6D6, whereas in DMSO-d6 the corresponding monomers are at hand. Moreover, the NMR data of different related 1H-pyrazol-3-ol derivatives are presented.

Synthesis and anti-mitotic activity of 2,4- or 2,6-disubstituted- and 2,4,6-trisubstituted-2H-pyrazolo[4,3-c]pyridines

An efficient synthetic route for the synthesis of 2H-pyrazolo[4,3-c]pyridines, primarily varying by the substituents at the 2-, 4- and 6-positions, is described here. A Sonogashira-type cross-coupling reaction was employed to yield 3-alkynyl-1H-pyrazole-4-carbaldehydes, ethanones and propanones from the corresponding 1H-pyrazol-3-yl trifluoromethanesulfonates. Subsequent treatment of the coupling products with dry ammonia afforded a versatile library of 2H-pyrazolo[4,3-c]pyridines, which were then evaluated for their cytotoxicity against K562 and MCF-7 cancer cell lines. The most potent of these compounds displayed low micromolar GI50 values in both cell lines. Active compounds induced dose-dependent cell-cycle arrest in mitosis, as shown by flow cytometric analysis of DNA content and phosphorylation of histone H3 at serine-10. Moreover, biochemical assays revealed increased activities of caspases-3/7 in treated cells, specific fragmentation of PARP-1, and phosphorylation of Bcl-2, collectively confirming apoptosis as the mechanism of cell death.