A. Fesenko, A. Shutalev
Sep 5, 2013
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Influential Citations
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Journal
Chemistry of Heterocyclic Compounds
Abstract
Pyrido[4,3-d]pyrimidines are of current interest due to their multifaceted pharmacological profiles. For example, they manifest remarkable inhibitory properties against epidermal growth factor receptor tyrosine kinase [1] and dihydrofolate reductase [2]. A significant number of methods for the preparation of pyrido[4,3-d]pyrimidines have been reported so far in the literature (for reviews, see [3, 4]). However, these methods do not include intramolecular aza-Wittig reaction, which is widely used today for nitrogen heterocycle ring construction (for reviews, see [5, 6]). Herein, we describe our preliminary results on the preparation of previously unknown hexahydropyrido[4,3-d]pyrimidin-2-ones using the Staudinger–aza-Wittig reaction of 5-acyl-4-(2-azidoethyl)-3,4-dihydropyrimidin-2(1H)-ones mediated by PPh3. Readily available N-(3-azido-1-tosylpropyl)urea (1) was used as a starting material. This compound was prepared by three-component condensation of 3-azidopropanal, p-toluenesulfinic acid, and urea in water [7]. The reaction of urea 1 with the Na-enolate of acetylacetone (2a) in MeCN afforded hydroxypyrimidine 4a [7], which was dehydrated in the presence of TsOH (EtOH, reflux, 1 h) to give tetrahydropyrimidine 5a in 77% yield.