Molecules (Aug 2018)

Synthesis of New 5-Aryl-benzo[f][1,7]naphthyridines via a Cascade Process (Ugi-3CR/Intramolecular Aza-Diels-Alder Cycloaddition)/Aromatization

  • Óscar Vázquez-Vera,
  • Daniel Segura-Olvera,
  • Mónica A. Rincón-Guevara,
  • Atilano Gutiérrez-Carrillo,
  • Miguel A. García-Sánchez,
  • Ilich A. Ibarra,
  • Leticia Lomas-Romero,
  • Alejandro Islas-Jácome,
  • Eduardo González-Zamora

DOI
https://doi.org/10.3390/molecules23082029
Journal volume & issue
Vol. 23, no. 8
p. 2029

Abstract

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A series of eight new 5-aryl-benzo[f][1,7]naphthyridines were synthesized in 17 to 64% overall yields via an improved MW-assisted cascade-like one pot process (Ugi–three component reaction/intramolecular aza-Diels-Alder cycloaddition) coupled to an aromatization process from tri-functional dienophile-containing ester-anilines, substituted benzaldehydes and the chain-ring tautomerizable 2-isocyano-1-morpholino-3-phenylpropan-1-one as starting reagents, under mild conditions. The doubly activated dienophile and the aza-diene functionalities of the eight new Ugi-adducts were exploited to perform an in situ aza-Diels-Alder cycloaddition/aromatization (dehydration/oxidation) process, toward the complex polysubstituted 5-aryl-polyheterocycles, which could be taken as starting point for further SAR studies because the benzo[f][1,7]naphthyridine is the core of various bioactive products. It is relevant to emphasize that the synthesis or isolation of benzo[f][1,7]naphthyridines containing a substituted aromatic ring in the C-5 position, has not been published before.

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