One-Pot Three-Component Access to 2-Aminopyridine Derivatives

IF 2 4区 化学 Q3 CHEMISTRY, MULTIDISCIPLINARY
Ting Luo, Keyan Xue, Ruipeng Bao, Chengfei Tang, Xinhong Yu
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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.

Abstract Image

一锅三组分法获得2-氨基吡啶衍生物
2-氨基吡啶衍生物因其显著的生物活性和相当大的药用价值而被公认。然而,可用的合成方法,特别是多组分反应(mcr),制备取代的2-氨基吡啶衍生物仍然相对缺乏,限制了结构的多样性。为了应对这一挑战,我们的研究引入了一种创新的一锅三组分级联策略。这种方法利用了Knoevenagel缩合和亲核芳香取代(SNAr)反应之间的协同作用。利用易于获得的起始材料-特别是2-溴吡啶甲醛,氰乙酸乙酯或氰乙酰胺,以及各种环仲胺-我们有效地组装复杂的2-氨基吡啶支架。在乙醇回流条件下,在环境压力下,反应顺利进行,时间仅为3小时。这种温和、环保、高效的方法可实现高达94%的收率。其操作简单,克服了传统合成的局限性,大大拓宽了这些有价值化合物的可及底物范围。
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来源期刊
ChemistrySelect
ChemistrySelect Chemistry-General Chemistry
CiteScore
3.30
自引率
4.80%
发文量
1809
审稿时长
1.6 months
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.
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