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

• Published in: Molecules (Basel, Switzerland) Vol. 23; no. 8; p. 2029
• Main Authors: Vázquez-Vera, Óscar, Segura-Olvera, Daniel, Rincón-Guevara, Mónica A, Gutiérrez-Carrillo, Atilano, García-Sánchez, Miguel A, Ibarra, Ilich A, Lomas-Romero, Leticia, Islas-Jácome, Alejandro, González-Zamora, Eduardo
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14-08-2018; MDPI
• Subjects: Adducts; Aromatic compounds; aromatization; aza-Diels-Alder cycloadditions; Bacteria; benzo[f][1,7]naphthyridines; cascade processes; Collaboration; Combinatorial Chemistry Techniques; Cyclization; Cycloaddition; Cycloaddition Reaction; Cytotoxicity; Dehydration; Diels-Alder reactions; Glycerol; microwave assisted synthesis; Microwaves; Molecular Structure; multicomponent reactions; Naphthyridines - chemical synthesis; Naphthyridines - chemistry; one-pot procedures; Oxidation; Pharmaceutical sciences; Prostate; Reagents; Substitutes; Sulfur; multicomponent reactions; aromatization; benzo[f][1,7]naphthyridines; one-pot procedures; aza-Diels-Alder cycloadditions; microwave assisted synthesis; cascade processes
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules23082029

A series of eight new 5-aryl-benzo[
][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[
][1,7]naphthyridine is the core of various bioactive products. It is relevant to emphasize that the synthesis or isolation of benzo[
][1,7]naphthyridines containing a substituted aromatic ring in the C-5 position, has not been published before.