Synthesis and N-alkylation of diethyl 4,7-dihydroazolo[1,5-a]pyrimidin-5,6-dicarboxylates

M. O. Kolosov, M. J. K. Al-Ogaili, O. G. Kulyk, V. D. Orlov

Abstract


It has been shown that the ternary condensation of oxaloacetic ester (diethyl 2-oxosuccinate), aromatic aldehydes and 3-amino-1,2,4-triazole or 5-aminotetrazole in dimethylformamide results in formation of the corresponding diethyl 7-aryl-4,7-dihydroazolo[1,5-a]pyrimidin-5,6-dicarboxylates. By 1H NMR spectroscopy (according to the data of the chemical shifts of C(2)H-protons for the corresponding N(4)H- and N(4)-methylderivatives of 7-phenyl-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-5,6-dicarboxylate) it has been found that alkylation of 4,7-dihydro[1,2,4]azolo[1,5-a]pyrimidin-5,6-dicarboxylates in the acetonitrile–saturated water alkali system leads selectively to formation of N(4)-alkyl derivatives. Both the starting compounds obtained and their N(4)-methylsubstituted analogues together with relative diethyl 4-aryl-3,4-dihydropyrimidin-2(1H)-on-5,6-dicarboxylates, 6-unsubstituted 4-aryl-3,4-dihydropyrimidin-2(1H)-on-5-dicarboxylates and the derivatives of 6-COR-7-aryl-4,7-dihydro[1,2,4] triazolo[1,5-a]pyrimidines are the promising objects for studying benzyl C(7)-functionalization of 4,7-dihydroazolo 1,5-a]pyrimidines, as well as of reactions associated with the presence of double C=C-bonds activated by two electron withdrawing groups. Obtaining of the key N(4)H- and N(4)Me-derivatives of 7-phenyl-4,7-dihydro[1,2,4] triazolo- and tetrazolo[1,5-a]pyrimidin-5,6-dicarboxylates also opens the way to the research of biological properties of the compounds of this class. It is noteworthy that being a three-component one the reaction studied, without any doubts, are appropriate for the synthesis of the derivatives of 7-aryl-4,7-dihydro[1,2,4]triazolo- and tetrazolo[1,5-a]pyrimidines containing two electron withdrawing substituents in positions 5 and 6.


Keywords


ternary condensation; diethyl 4,7-dihydroazolo[1,5-a]pyrimidin-5,6-dicarboxylates; Biginelli reaction; alkylation; C-functionalization; benzyl position

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References


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DOI: https://doi.org/10.24959/ophcj.15.846

Abbreviated key title: Ž. org. farm. hìm.

ISSN 2518-1548 (Online), ISSN 2308-8303 (Print)