Synthesis of new thiazolopyrimidines proceeding from 4-aryl-substituted 3,4-dihydropyrimidine-2(1H)-thiones

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S _MeOH O Et3N Recently a number of publications grew considerably in the field of the chemistry of 4-aryl-3,4-dihydropyrimidin-2-ones and 4-aryl-3,4-dihydropyrimidine-2thione obtained by the three-component Biginelli condensation. It is not only due to their preparative accessibility but also to their wide range of pharmacological action (analgesic, antibacterial, antihypertension etc.) [1– 3]. The presence of several reactive nucleophilic centers also attracts attention to, e.g., 4-aryl-3,4-dihydropyrimidine-2-thiones for it makes possible carry out both versatile monoand dialkylation and acetylation [4, 5] and also very promising cyclizations. For instance, a method was described of a cyclization of 4-phenyl-3,4dihydropyrimidine-2(1H)-thione into 3,5-dihydro-2Hthiazolo[3,2-a]pyrimidine by boiling in DMF with chloroacetic acid [6]. Aiming to preparation from 4-aryl-substituted 3,4dihydropyrimidine-2(1H)-thiones of new 3,5-dihydro-2Hthiazolo[3,2-a]pyrimidines derivatives we developed a new preparatively more accessible method consisting in the boiling of toluene solutions of 4-aryl-substituted 3,4-dihydropyrimidine-2(1H)-thiones with a slight excess of methyl chloroacetate in the presence of triethylamine. It was expected that the reaction would stop at the formation of one of intermediate products of Sor N-alkylation whose formation depended on the solvents and acceptors used affecting apparently the process of thione-thiol transition [5]. However in 86–90% yield the target cyclization products IIa–IId were isolated. The formation of 3,5-dihydro-2H-thiazolo[3,2-a]pyrimidines IIa–IId was proved by the lack in the IR spectra of the absorption bands of amino groups and also the absence in the 1H NMR spectra of the signals of ester methoxy group and of N3H protons observed in the initial compounds and in their monoalkylated products as doublets in the region 9.2 ppm. The methylene protons CH2 of the thiazole ring turned out to be nonequivalent and thus appeared as a doublet of doublets with a coupling constant of 17.7 Hz.