Pot‐, Atom‐ and Step‐Economic (PASE) Multicomponent Approach to the 5‐(Dialkylphosphonate)‐Substituted 2,4‐Diamino‐5H‐chromeno[2,3‐b]pyridine Scaffold

• Published in: European journal of organic chemistry 2019-07, Vol.2019 (26), p.4171-4178
• Main Authors: Elinson, Michail N., Vereshchagin, Anatoly N., Anisina, Yuliya E., Fakhrutdinov, Artem N., Goloveshkin, Alexander S., Egorov, Mikhail P.
• Format: Article
• Language: English
• Subjects: Multicomponent reactions; Phosphonates; Reaction mechanisms; Synthesis design
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201900240

A new multicomponent reaction is reported: the one‐pot transformation of salicylaldehydes, 2‐aminoprop‐1‐ene‐1,1,3‐tricarbonitrile (malononitrile dimer), and trialkylphosphites results in the efficient formation of (2,4‐diamino‐3‐cyano‐5H‐chromeno[2,3‐b]pyridin‐5‐yl)phosphonates. The scope of this one‐pot reaction was investigated. The isolation of substituted phosphonates is very easy. The optimized reaction conditions and a mechanistic rationale for the complex multicomponent transformation are presented. This facile PASE approach offers a powerful tool for the selective formation of new types of functionalized 5‐P‐substituted 2,4‐diamino‐5H‐chromeno[2,3‐b]pyridine scaffolds containing the phosphonate fragment, which are promising compounds for various biomedical applications, among them the treatment of human inflammatory diseases and cancer therapy. The multicomponent reaction of salicylaldehydes, 2‐aminoprop‐1‐ene‐1,1,3‐tricarbonitrile, and trialkylphosphites leads to dialkyl (2,4‐diamino‐3‐cyano‐5H‐chromeno[2,3‐b]pyridin‐5‐yl)phosphonates, promising compounds in biomedical applications. This is a new pot‐, atom‐, and step‐economic (PASE) approach to the 5‐(dialkylphosphonate) substituted 2,4‐diamino‐5H‐chromeno[2,3‐b]pyridine scaffold.