Preparation of pyrido [2,3-b] pyrazine ring system via regioselective condensation reaction

László Kékesi, András Dancsó, Eszter Illyés, Sándor Boros, János Patób, Zoltán Greff, Gábor Németh, Rita Garamvölgyi, Ferenc Baska, L. Őrfi, G. Kéri

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The pyrido[2,3-b]pyrazine core structure can be found in several molecules that express biological activity. We have previously published a series of these compounds that showed erlotinib-resistant tumor inhibitor potential. The common way of their synthesis is the condensation of pyridinediamines and a-oxocarbonyl compounds. If the starting dioxo compound is unsymmetrical, two regioisomers can be formed, which can display significantly different biological activity. To study the regioselectivity of this reaction we chose a model reaction and examined the impact of the reaction temperature, the acidic or basic catalysis, the amount of starting materials or the usage of dehydrating agent on the outcome of the reaction. In summary, increased regio selectivity could be observed at low temperature in acidic solvents (e.g. acetic or trifluoroacetic acid). As a result, we were able to optimize the reaction conditions to increase the amount of the biologically more active isomer. The isomers were separated, characterized by their NMR spectra and HPLC retention values, and identified by single-crystal X-ray diffraction crystallography.

Original languageEnglish
Pages (from-to)651-656
Number of pages6
JournalLetters in Organic Chemistry
Volume11
Issue number9
Publication statusPublished - 2014

Fingerprint

Pyrazines
Condensation reactions
Bioactivity
Isomers
Trifluoroacetic Acid
Regioselectivity
Temperature
Crystallography
X Ray Crystallography
Catalysis
Acetic acid
X-Ray Diffraction
Acetic Acid
Tumors
Condensation
High Pressure Liquid Chromatography
Nuclear magnetic resonance
Single crystals
X ray diffraction
Molecules

Keywords

  • Acidic catalysis
  • Inhibitor
  • Pyrido[2 3-b]pyrazine
  • Regioselectivity
  • Thermal effect
  • X-ray crystal structure

ASJC Scopus subject areas

  • Organic Chemistry
  • Biochemistry

Cite this

Kékesi, L., Dancsó, A., Illyés, E., Boros, S., Patób, J., Greff, Z., ... Kéri, G. (2014). Preparation of pyrido [2,3-b] pyrazine ring system via regioselective condensation reaction. Letters in Organic Chemistry, 11(9), 651-656.

Preparation of pyrido [2,3-b] pyrazine ring system via regioselective condensation reaction. / Kékesi, László; Dancsó, András; Illyés, Eszter; Boros, Sándor; Patób, János; Greff, Zoltán; Németh, Gábor; Garamvölgyi, Rita; Baska, Ferenc; Őrfi, L.; Kéri, G.

In: Letters in Organic Chemistry, Vol. 11, No. 9, 2014, p. 651-656.

Research output: Contribution to journalArticle

Kékesi, L, Dancsó, A, Illyés, E, Boros, S, Patób, J, Greff, Z, Németh, G, Garamvölgyi, R, Baska, F, Őrfi, L & Kéri, G 2014, 'Preparation of pyrido [2,3-b] pyrazine ring system via regioselective condensation reaction', Letters in Organic Chemistry, vol. 11, no. 9, pp. 651-656.
Kékesi L, Dancsó A, Illyés E, Boros S, Patób J, Greff Z et al. Preparation of pyrido [2,3-b] pyrazine ring system via regioselective condensation reaction. Letters in Organic Chemistry. 2014;11(9):651-656.
Kékesi, László ; Dancsó, András ; Illyés, Eszter ; Boros, Sándor ; Patób, János ; Greff, Zoltán ; Németh, Gábor ; Garamvölgyi, Rita ; Baska, Ferenc ; Őrfi, L. ; Kéri, G. / Preparation of pyrido [2,3-b] pyrazine ring system via regioselective condensation reaction. In: Letters in Organic Chemistry. 2014 ; Vol. 11, No. 9. pp. 651-656.
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AU - Boros, Sándor

AU - Patób, János

AU - Greff, Zoltán

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