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Synthesis of CF3-Substituted 5-Functionalized Hexahydro- and Tetrahydropyrimidin-2-ones
Published: 30 October 2012 by MDPI in The 16th International Electronic Conference on Synthetic Organic Chemistry session General Organic Synthesis
Abstract: 5-Functionalized hexahydro- and 1,2,3,4-tetrahydropyrimidin-2-ones are currently the focus of considerable interest due to their multifaceted pharmacological profiles. During the last two decades, remarkable progress has been achieved in the development of synthetic approaches to these heterocycles. However, some of them particularly those containing pharmacophoric trifluoromethyl group remained practically unknown. Here we report a general and convenient synthesis of CF3-substituted 5-functionalized hexahydro- and tetrahydropyrimidin-2-ones. The synthesis started with preparation of readily available N-(1-tosylethyl)urea and N-[(1-acetoxy-2,2,2-trifluoro)ethyl]urea. The prepared ureidoalkylating reagents were treated with sodium enolates of such CH-acids as acetyl acetone, ethyl acetoacetate, and ethyl trifluoroacetoacetate to give either the products of substitution of the tosyl or acetoxy groups, CF3-containing oxoalkylureas, or their cyclic isomers, 4-hydroxyhexahydropyrimidin-2-ones in high yields and diastereoselectivity. The obtained products were converted into the corresponding CF3-substituted 5-acyl-1,2,3,4-tetrahydropyrimidin-2-ones using acid-catalyzed dehydration.
Keywords: 1,2,3,4-Tetrahydropyrimidin-2-ones, Ureidoalkylation, trifluoromethylsubstituted compounds