Synthesis of bicyclic pyrimido[2,1-b][1, 3]thiazines based on 3,4-dihydropyrimidine-(1H)-2-thiones

Abstract

Keywords: 3,4-dihydropyrimidine(1H)-2-thiones, pyrimidino[2,1-b][1,3]thiazines, 3-bromopropionyl chloride, intramolecular heterocyclization, X-ray crystallographic analysis.Today an enormous number of derivatives of 3,4-dihydropyrimidin-2-ones(2-thiones) with various aromatic and heterocyclic functional substituents have been synthesized by the Biginelli reaction, numerous methods including microwave and solvent-free methods have been developed for their production, and highly effective catalysts leading to a significant increase in the yields and reduction of the time for the condensation have been found [1][2][3][4][5][6][7]. Many researches on the synthesis and subsequent modification of derivatives of 3,4-dihydropyrimidin(1H)-2-ones have continued in many countries with developed pharmaceutical industry; this is due to the fact that they display of a wide range of pharmacological activity -antihypertensive, antibacterial, antiviral, antitumor, etc. [8-10], making further searches in the 3,4-dihydro-pyrimidin-2-one-(2-thione) series extremely promising.In [11] we proposed a convenient method for the synthesis of new derivatives of bicyclic 3,5-dihydro-2H-thiazolo[3,2-a]pyrimidines from 3,4-dihydropyrimidine-2-thiones, established their stereochemical structure, and studied the conditions for cyclization with various haloacetyl reagents [12]. In an attempt to produce bicyclic thiazine derivatives based on 4-aryl-substituted 3,4-dihydropyrimidine-2-thiones the acylation of 4-arylsubstituted 3,4-dihydropyrimidine-2-thiones 1a-c with 3-bromopropionyl chlorides according to the Scheme was realized. (Compounds 1a-c are shown in a thiol tautomer form.) Acylation was conducted in solution of anhydrous DMF in the presence of a twofold excess of potassium carbonate with the reaction mixture heated from 25 to 120°C for 6-10 h. Here, as expected, the heterocyclization products 2a-c in the form of slightly yellowish crystalline substances were isolated. The most

Chemistry of 1,3-thiazin-4-ones and their derivatives, 1995 - mid-2018

“…207 3-Bromopropanoyl chloride 374 with K 2 CO 3 in DMF at 120 °C has similarly been used to yield pyrimidines 376 (Scheme 113). 208…”