{"title":"One-Pot Three-Component Access to 2-Aminopyridine Derivatives","authors":"Ting Luo, Keyan Xue, Ruipeng Bao, Chengfei Tang, Xinhong Yu","doi":"10.1002/slct.202502547","DOIUrl":null,"url":null,"abstract":"<p>Derivatives of 2-aminopyridines are recognized for their significant biological activity and hold considerable pharmaceutical value. However, the synthetic methodologies available, particularly multi-component reactions (MCRs), for preparing substituted 2-aminopyridine derivatives remain relatively scarce, limiting structural diversity. Addressing this challenge, our study introduces an innovative one-pot, three-component cascade strategy. This approach capitalizes on the synergistic interplay between Knoevenagel condensation and nucleophilic aromatic substitution (S<sub>N</sub>Ar) reactions. Utilizing readily accessible starting materials—specifically 2-bromopyridine carboxaldehyde, ethyl cyanoacetate or cyanoacetamide, and diverse cyclic secondary amines—we efficiently assemble complex 2-aminopyridine scaffolds. The reaction proceeds smoothly in ethanol under reflux conditions at ambient pressure for a concise period of only 3 hours. This mild, eco-friendly, and highly efficient protocol achieves excellent yields of up to 94%. Its operational simplicity overcomes traditional synthesis limitations and significantly broadens the accessible substrate scope for these valuable compounds.</p>","PeriodicalId":146,"journal":{"name":"ChemistrySelect","volume":"10 28","pages":""},"PeriodicalIF":2.0000,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ChemistrySelect","FirstCategoryId":"92","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/slct.202502547","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
Derivatives of 2-aminopyridines are recognized for their significant biological activity and hold considerable pharmaceutical value. However, the synthetic methodologies available, particularly multi-component reactions (MCRs), for preparing substituted 2-aminopyridine derivatives remain relatively scarce, limiting structural diversity. Addressing this challenge, our study introduces an innovative one-pot, three-component cascade strategy. This approach capitalizes on the synergistic interplay between Knoevenagel condensation and nucleophilic aromatic substitution (SNAr) reactions. Utilizing readily accessible starting materials—specifically 2-bromopyridine carboxaldehyde, ethyl cyanoacetate or cyanoacetamide, and diverse cyclic secondary amines—we efficiently assemble complex 2-aminopyridine scaffolds. The reaction proceeds smoothly in ethanol under reflux conditions at ambient pressure for a concise period of only 3 hours. This mild, eco-friendly, and highly efficient protocol achieves excellent yields of up to 94%. Its operational simplicity overcomes traditional synthesis limitations and significantly broadens the accessible substrate scope for these valuable compounds.
期刊介绍:
ChemistrySelect is the latest journal from ChemPubSoc Europe and Wiley-VCH. It offers researchers a quality society-owned journal in which to publish their work in all areas of chemistry. Manuscripts are evaluated by active researchers to ensure they add meaningfully to the scientific literature, and those accepted are processed quickly to ensure rapid online publication.