Activated 2-methylidene-1,3-thiazolidin-4-ones in a promising approach to the synthesis of polyfunctional thiazolo[3,2-c]pyrimidines

A preparatively convenient and efficient synthetic route to new 5H-[1,3]thiazolo[3,2-c]pyrimidine derivatives is described which involves the cyclocondensation of acyl or alkoxycarbonyl alpha-functionalized 2-methylidene-1,3-thiazolidin-4-ones with 1-chlorobenzyl isocyanates. The optimal reaction conditions, viz., heating reagents in toluene in the absence of an organic base, afford the target products in 48-74% yields. Some tert-butyl 2-(4-oxo-1,3-thiazolidin-2-ylidene)ethanoates produce, along with the desired tert-butyl [1,3] thiazolo[3,2-c]pyrimidine-8-carboxylates, the corresponding 8-carboxylic acids in 18-21% yields. A reliable structural determination of all the synthesized compounds has been performed by elemental analysis and a number of spectroscopic methods (H-1 and C-13 NMR, HPLC/MS, and FT-IR) as well as by X-ray diffraction analysis.