A convenient approach to the synthesis of new 4-amino substituted derivatives pyrido[2,3-d]pyrimidin-7-one

H. M. Zinchenko, L. V. Muzychka, Ye. V. Verves, O. B. Smolii

Abstract


This paper is devoted to development of a convenient approach to the synthesis of new pyrido[2,3-d]pyrimidin-7-one derivatives that contain alkylamino groups at position 4 of the heterocycle. The interaction of 4,6-dichloropyrimidine-5-carbaldehyde with (2-ethoxy-2-oxoethyl) triphenylphosphonium bromide in ethanol in the presence of triethylamine leads to formation of ethyl (2E)-3-(4,6-dichloropyrimidin-5-yl)acrylate. Heat treatment of 6-amino substituted pyrimidinylacrylate derivatives with sodium methylate leads to the intramolecular cyclization and replacement of the chlorine atom with the methoxy group forming 4-methoxypyrido[2,3-d]pyrimidin-7-ones. In order to introduce various nitrogen-containing substituents at position 4 of the heterocyclic system the aforementioned compounds were converted into 4-chloropyrido[2,3-d]pyrimidin-7-one derivatives using phosphorus oxychloride. The effective method has been developed for the synthesis of a series of amino substituted pyrido[2,3-d]pyrimidin-7-one by a direct reaction of ethyl (2E)-(4-chloro-6-aminopyrimidin-5-yl)acrylate with the secondary amines in the presence of triethylamine. Then ethyl acrylate formed was treated by heating with sodium methylate in methanol. Sulphur-containing derivatives of pyrido[2,3-d]pyrimidin-7-one were also synthesized. These derivatives were used to obtain pyrido[2,3-d]pyrimidin-7-ones containing the secondary amines at position 4 of the heterocyclic system. The structure of the compounds obtained has been proven using NMR-spectroscopy, mass-spectra and elemental analysis

Keywords


pyrido[2,3-d]pyrimidin-7-one; ethyl 3-(4,6-dichloropyrimidin-5-yl)acrylate; 4,6-dichloropyrimidine-5-carbaldehyde; cyclisation

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DOI: https://doi.org/10.24959/ophcj.16.906

Abbreviated key title: Ž. org. farm. hìm.

ISSN 2518-1548 (Online), ISSN 2308-8303 (Print)