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REACTION OF ETHYL 4-ARYL-6-BROMOMETHYL-2-OXO-1,2,3,4-TETRAHYDROPYRIMIDINE-5-CARBOXYLATES WITH N-METHYLMORPHOLINIUM 3-CYANO-1,4-DIHYDRO- AND 3-CYANO-1,4,5,6-TETRAHYDROPYRIDINE-2-THIOLATES

В. В. Доценко, И. А. Лебедева, С. Г. Кривоколыско, М. В. Повстяной, В. М. Повстяной, Е. О. Костырко
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Abstract


Alkylation of N-methylmorpholinium 4-Ar1-3-cyano-6-oxo-1,4,5,6-tetrahydropyridine-2-thiolates using ethyl 4-Ar-6-bromomethyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates (10% KOH, DMF) gives mixtures of diastereomers of ethyl 4-Ar-6-[(4-Ar1-3-cyano-1,4,5,6-tetrahydropyridin-2-ylthio)methyl]-1-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates in overall 30-58% yield. Under these conditions the N-methylmorpholinium 4-Ar1-5-(N-Ar2-carbamoyl)-3-cyano-6-methyl-1,4-dihydropyridine-2-thiolates undergo aromatization of the dihydropyridine ring to give ethyl 4-Ar-6-[4-Ar1-5-(N-Ar2-carbamoyl)-3-cyano-6-methylpyridin-2-ylthio)methyl]-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates (37-51%). In the absence of KOH, only the substituted pyridine-2(1H)-thione is formed as a product of oxidation of the dihydropyridine ring in the starting substrate. Some of the alkylation products obtained possess weak or moderate antibacterial activity towards the specific strains of Escherichia coli and Bacillus subtilis but are inactive towards Candida albicans and Staphylococcus aureus.

Authors: V. V. Dotsenko, I. A. Lebedeva, S. G. Krivokolysko, M. V. Povstyanoi, V. M. Povstyanoi, and E. O. Kostyrko.

English Translation in Chemistry of Heterocyclic Compounds, 2012, 48 (3), pp 462-469

http://link.springer.com/article/10.1007/s10593-012-1016-0


Keywords


Biginelli dihydropyrimidines; N-methylmorpholinium 1,4-dihydropyridine-2-thiolates; N-methylmorpholinium 1,4,5,6-tetrahydropyridine-2-thiolates; alkylation; biological activity; oxidation; Thorpe-Ziegler reaction

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