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
Affiliations
Óscar Vázquez-Vera
Unidad Profesional Interdisciplinaria de Biotecnología, Instituto Politécnico Nacional, Av. Acueducto de Guadalupe S/N, Barr. La Laguna Ticomán, Gustavo A Madero C.P. 07340, Ciudad de México, Mexico
Daniel Segura-Olvera
Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, San Rafael Atlixco 186, Col. Vicentina, Iztapalapa C.P. 09340, Ciudad de México, Mexico
Mónica A. Rincón-Guevara
Departamento de Biotecnología, Universidad Autónoma Metropolitana-Iztapalapa, San Rafael Atlixco 186, Col. Vicentina, Iztapalapa C.P. 09340, Ciudad de México, Mexico
Atilano Gutiérrez-Carrillo
Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, San Rafael Atlixco 186, Col. Vicentina, Iztapalapa C.P. 09340, Ciudad de México, Mexico
Miguel A. García-Sánchez
Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, San Rafael Atlixco 186, Col. Vicentina, Iztapalapa C.P. 09340, Ciudad de México, Mexico
Ilich A. Ibarra
Laboratorio de Fisicoquímica y Reactividad de Superficies, Instituto de Investigaciones en Materiales, Universidad Nacional Autónoma de México, Circuito Exterior S/N, Ciudad Universitaria, Coyoacán C.P. 04510, Ciudad de México, Mexico
Leticia Lomas-Romero
Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, San Rafael Atlixco 186, Col. Vicentina, Iztapalapa C.P. 09340, Ciudad de México, Mexico
Alejandro Islas-Jácome
Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, San Rafael Atlixco 186, Col. Vicentina, Iztapalapa C.P. 09340, Ciudad de México, Mexico
Eduardo González-Zamora
Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, San Rafael Atlixco 186, Col. Vicentina, Iztapalapa C.P. 09340, Ciudad de México, Mexico
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.