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

Authors

  • H. M. Zinchenko Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Ukraine
  • L. V. Muzychka Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Ukraine
  • Ye. V. Verves Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Ukraine
  • O. B. Smolii Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Ukraine

DOI:

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

Keywords:

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

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

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Published

2016-12-16

How to Cite

(1)
Zinchenko, H. M.; Muzychka, L. V.; Verves, Y. V.; Smolii, O. B. A Convenient Approach to the Synthesis of New 4-Amino Substituted Derivatives pyrido[2,3-d]pyrimidin-7-One. J. Org. Pharm. Chem. 2016, 14, 40-47.

Issue

Vol. 14 No. 4(56) (2016)

Section

Original Researches

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Copyright (c) 2016 National University of Pharmacy

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