Synthesis and Antimicrobial Activity of N-5-Diaryl-7-Methyl-3-OXO-2,3-Dihydro-5H-[1,3]Thiazolo[3,2-a]Pyrimidine-6-Carboxamide Hydrochlorides

One of the most important problems in pharmaceutical chemistry is the design of highly effective and nontoxic drugs. The solution involves targeted synthesis and discovery of new biologically active compounds. In this respect, tetrahydropyrimidine-2(1H)-thiones, their derivatives, and condensed heterocycles based on them are some of the most promising classes of chemical compounds [1 – 7]. 5H-Thiazolo[3,2-a]pyrimidine derivatives are known to possess anti-inflammatory, antiparkinson, and antiherpes activity [8]. The synthesis of 5H-thiazolo[3,2-a]pyrimidines via the reaction of tetrahydropyrimidine-2(1H)-thione derivatives with -halocarboxylate esters was reported [9]. We investigated the reaction of N,6-diaryl-4-methyl-2thioxo-1,2,3,6-tetrahydropyrimidine-5-carboxamides with ethyl chloroacetate in order to prepare new heterocyclic compounds and study their antimicrobial activity. The reaction occurred upon storing the reagents at 120°C for 15-20 without a solvent and formed N,5-diaryl-7-methyl-3-oxo2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxamides (I-IX) (Scheme 1). Apparently, the first step involved nucleophilic substitution of the Cl atom in ethyl chloroacetate as a result of attack by the mercapto S atom formed via isomerization of the starting compound with subsequent intramolecular cyclization of the intermediate (i) (Scheme 2). Compounds I-IX were yellow crystalline compounds that were soluble in DMF and DMSO and with heating in HOAc and EtOH and insoluble in H 2 O, toluene, and benzene. IR spectra of the thiazolopyrimidine hydrochlorides had a characteristic high-frequency absorption band in the range 1752 – 1768 cm –1 that belonged to thiazoline carbonyl stretching vibrations and bands due to amide stretching vibrations (1648 – 1688) and a C=C bond (1600 – 1624). The high-frequency shift of the lactam carbonyl absorption band was apparently explained by protonation of the neighboring N atom. PMR spectra of I-IX showed resonances for aromatic protons and groups bonded to the aromatic ring in addition to resonances for 7-CH 3 protons at 1.80 – 2.28 ppm, a singlet for H-5 at 5.97 – 6.20, a singlet for the amide NH proton at 9.45 – 9.86, and doublets for methylene protons in the range 4.15 – 4.30. 13 C NMR spectra of IX included chemical shifts of C atoms that confirmed the proposed structure (see Experimental). Thus, the observed reaction allowed 5H-[1,3]thiazolo[3,2-a]pyrimidine hydrochlorides with the N-arylamide Pharmaceutical Chemistry Journal, Vol. 49, No. 8, November, 2015 (Russian Original Vol. 49, No. 8, August, 2015)