Pyridine Synthesis via Directed Aziridination of Phenols in Continuous Flow

连续流中苯酚直接氮丙啶化合成吡啶

• 批准号: 9402418
• 负责人: Evan Styduhar
• 金额: $ 0.18万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9402418
• 关键词: Acetates; Address; Amination; Amines; Anti-Inflammatory Agents; Anti-inflammatory; Applications Grants; Chemicals; Complex Mixtures; Development; Evaluation; Event; Generations; Goals; Human; Human Biology; Lead; Libraries; Life; Malignant Neoplasms; Methodology; Methods; Modernization; Natural Product Drug; Omeprazole; Pathway interactions; Pattern; Pharmaceutical Preparations; Phase; Phenols; Preparation; Prevalence; Process; Reaction; Reagent; Research; Route; Site; Solvents; Source; Structure; Techniques; Technology; Therapeutic; abiraterone; base; crizotinib; flexibility; innovation; nitrene; pyridine; scaffold

Project Summary/Abstract The pyridine heterocycle is a privileged motif that appears in countless natural products, drugs, and materials. As the most prevalent heterocyclic aromatic ring in chemical therapeutics, the pyridine motif is featured in a plethora of blockbuster drugs such as Xalkori, Prilosec, and Zytiga. Due to the enormous prevalence of pyridines in human life, new and innovative methodologies to access this motif remain highly sought after. Numerous preparative methods require specialized starting materials and also necessitate strictly defined substitution patterns, which limit structural diversity. Conversely, transforming readily available and inexpensive precursors, that have all substitution intact, directly to the pyridine scaffold would constitute a simple, flexible, and powerful means to access these frameworks. The proposed research aims to develop a directed aziridination methodology in a continuous flow reactor that would allow access to pyridines from readily available phenol starting materials. This transformation has been historically challenging because of the nonregioselective aziridination of the arene ring with nitrene sources, which leads to complex mixtures of products. This powerful new strategy will rely on a directed aziridination to provide regioselectivity in the event. Continuous flow techniques will prove critical to this key transformation in order to avoid various undesired reaction pathways by means that are unparalleled in standard batch synthesis. Finally, a ring contraction process would then furnish libraries of highly valued pyridines in a multi-step, one-flow approach.

项目总结/摘要 吡啶杂环是一种特殊的基序，出现在无数的天然产物、药物和药物中。 材料.作为化学治疗中最普遍的杂环芳环，吡啶基序是 在大量的重磅炸弹药物中，如Xalkori，Prilosec和Zytiga。特别巨大 由于吡啶类化合物在人类生活中的普遍存在，因此获得该基序的新的和创新的方法仍然非常重要。 追捧许多制备方法需要专门的起始材料，并且还需要严格的 定义的替代模式，限制了结构多样性。相反，转换现成的和 具有完整的所有取代基的廉价前体直接连接到吡啶骨架上将构成一种 简单、灵活、强大的方法来访问这些框架。这项研究旨在开发一种 在连续流动反应器中的定向氮杂环丙烷化方法， 容易获得的苯酚原料。这种转变在历史上一直具有挑战性，因为 芳烃环与氮烯源的非区域选择性氮杂环丙烷化，这导致以下物质的复杂混合物： 产品.这种强大的新策略将依赖于定向氮丙啶化，以提供事件中的区域选择性。 连续流技术将被证明是关键的这一关键转变，以避免各种不希望的 通过在标准分批合成中无与伦比的手段实现反应途径。最后，环收缩 然后，该工艺将以多步骤、单流程的方法提供高价值的吡啶文库。