An exceptionally mild synthetic strategy using cascade reaction for 3,4‐dihydronaphthyridinones having aliphatic substituent on amide nitrogen

• Published in: ChemistrySelect (Weinheim) 2019-01, Vol.4 (2), p.709-712
• Main Authors: Tazawa, Aoi, Ishizawa, Kohei, Ando, Junki, Watanabe, Masayuki, Azumaya, Isao, Hikawa, Hidemasa, Tanaka, Minoru
• Format: Article
• Language: English
• Subjects: coupling; dihydronaphthyridinone; intramolecular cyclization; reductive amination; X-ray crystal analysis
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.201802104

A facile synthetic procedure for 3,4‐dihydronaphthyridinone derivatives is described. This synthetic route involves the cascade reaction of methyl nicotinate having an ethoxyvinyl group with various amines. The desired cyclization products were obtained using pyridylacetaldehyde formation and subsequent reductive amination/cyclization with amines. For the preparation of vinyl ether derivatives, we employed the coupling reaction, and the method would be applicable to various related substrates. Furthermore, all the reactions to N‐alkyl products proceeded rapidly at ambient temperature in good yields using simple and safe protocols. This strategy allows the generation of dihydronaphthyridinone derivatives containing various amines. 3,4‐Dihydronaphthyridinone derivatives could be synthesized by pyridylacetaldehyde formation and subsequent reductive amination/cyclization with various amines. The reaction conditions of both steps were very mild and the desired cyclization products were obtained in good yields.