Efficient Syntheses of Ethyl 2-Methylthio- and Ethyl 2-Benzylthio-6-methyl(aryl)pyrimidine-4-carboxylates and Their Carboxylic Acid Derivatives

Abstract

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.

Regioselective Synthesis of Pyrazolyl-pyrimidine Hybrids of Pharmacological Interest

“…Pyrimidine 1 was obtained by a previously reported method. 13 Flash chromatography was performed using silica gel (230-400 mesh). The melting points were determined on a MqAPF-302, Digital Melting Point Apparatus, Micro Chemistry Equip.…”

“…Scheme 2 shows the full synthetic strategy adopted in this study, which is a continuation of the study recently published by our research group, in which a series of ethyl 6-aryl-2-(methylthio)-pyrimidine-4-carboxylates 1 were prepared. 13 In the present study, compounds 1 were converted into the new hydrazides 3-6 by reacting hydrazine hydrochloride with the ester 1. Subsequent reaction of hydrazide 3-6 with 4-alkoxy-1,1,1-trifluorobut-3-en-2-ones 7 furnished the final products, (4,5-dihydropyrazol-1yl)(pyrimidin-4-yl)methanones 8-11 in very good yields.…”

Synthesis of Penta-2,4-dienenitriles by the Horner–Wadsworth–Emmons Olefination of Enones

“…This study began with the preparation of the enones with the general structure VI, which were obtained in accordance with our previously developed method, 27 and enones VIII, which were also obtained in accordance with our previously reported methods. 28 The enones of general structure VII were prepared by the reaction of alkoxy-substituted enones VI with benzenethiol in dichloromethane and in the presence of boron trifluoride-diethyl ether complex, following similar procedures reported by Martins and co-workers 29 for the synthesis of 1,1,1-trihalo-4-(phenylseleno)alk-3-en-2-ones. For the compounds of structure VII, only compounds 2a and 2h were known; however, compound 2a was synthesized previously by the acylation of a vinyl sulfide, 30 whereas compound 2h was obtained by the reaction of enone 1h with benzenethiol catalyzed by hydrated indium trichloride.…”

Synthesis of a New Polyfunctionalised Pyrimidine-4-carboxylate and Its Application for the Construction of a Series of Pyrimidine Derivatives

“…One of the most used methods is the classical cyclocondensation reaction of 1,3-dicarbonyl compounds with 1,3-dinucleophiles, such as amidine, guanidine, or thiourea derivatives, known as Pinner synthesis. 5 The cyclocondensation of enoates, 6,7 enaminones, 8 and unsymmetrical enamino diketones [9][10][11] with 1,3-nucleophilic systems have also been used in the synthesis of the pyrimidine ring.…”

“…Pyrimidine carboxylate derivatives have been reported as important building blocks for the synthesis of pyrimidine carboxylic acids, pyrimidine carbohydrazides, pyrimidine carboxamides, 7 and fused pyrimidines. 10 More specifically, 5-substituted acyl pyrimidine-4-carboxylates have a large synthetic potential due to the 1,4-dieletrophilic system.…”