The reaction of pyrazoles with 5-bromo enones furnished an unexpected series of stable N,O-aminals in a chemo- and regioselective and metal free reaction.

A simple and efficient procedure for the synthesis of ethyl 2-methylthio-and ethyl 2-benzylthio-6-methyl(aryl)-pyrimidine-4-carboxylates and their corresponding acid derivatives is reported. The products are obtained in good yields via the cyclocondensation reaction of ethyl 4-alkoxy-2-oxo-4-methyl(aryl)-but-3-enoates with 2-methylisothiourea sulfate or 2-benzylisothiourea hydrochloride, under mild, basic, aqueous conditions.

This study reports the chemo‐ and regioselective synthesis, at good yields, of (E)‐4‐(amino)‐1,1,1‐trifluoro‐5‐(4,5‐alkyl‐3‐(trifluoromethyl)‐1H‐pyrazol‐1‐yl)pent‐3‐en‐2‐ones (pyrazole‐enaminones), from the of N‐alkylation reaction of trifluoromethyl pyrazoles with 5‐bromo enaminones. The obtained compounds were tested as potential analgesics in a screening test involving mice. Three of these compounds significantly reduced the spontaneous nociception induced by the application of capsaicin, which is an algogenic substance. Compound 5 g presented satisfactory antinociceptive activity compared to celecoxib, a drug used as a positive control, without promoting locomotor changes in the mice. Moreover, molecular modeling simulations showed that compound 5 g interacts with the cyclooxygenase enzyme at the same binding site as celecoxib. Together, our data suggest that compound 5 g is a promising prototype for the development of new analgesic drugs.

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The 1,4-dicarbonyl scaffold ethyl 3-formyl-4,5-dihydrofuran-2-carboxylate was obtained through the rearrangement of the parent ethyl 2-(4,5-dihydrofuran-3-yl)-2-oxoacetate and applied to the synthesis of a series of 7-alkoxy-2,3-dihydrofuro[2,3-d]pyridazines. Twelve pyridazines­ were obtained in yields of up to 70%.

The regioselective synthesis of twenty novel [3-substituted 5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl][6-aryl-(2-methylthio)pyrimidin-4-yl]methanones from the cyclocondensation reactions of new 6-aryl-2-(methylthio)pyrimidine-4-carbohydrazides with 4-substituted 1,1,1-trifluorobut-3-en-2-ones is reported. Human acetylcholinesterase (HsAChE) and butyrylcholinesterase (HsBChE) inhibition tests were performed on selected products in order to explore the possible pharmacological applications of these compounds. Two compounds showed significant and selective inhibitory activity for BChE.

Three new series of compounds, 5-alkoxy-3-(trifluoromethyl)penta-2,4-dienenitriles, 5-(phenylthio)-3-(trifluoromethyl)penta-2,4-dienenitriles, and ethyl 4-alkoxy-2-(cyanomethylene)but-3-enoates, obtained from the olefination reaction of the respective enones with diethyl cyanomethylphosphonate via the Horner–Wadsworth–Emmons olefination are reported. All products were obtained as single regioisomers; however, the composition of the stereoisomers changed according to the enone substituents. A study based on 1H and 13C NMR chemical shifts, 1H–19F and 13C–19F NMR coupling constants, 1H NMR signal integrals, and HSQC, HMBC, and NOESY experiments was performed in order to assign the structure and percentage of each stereoisomer obtained.