(E)-3-(3-Pyridin-3-yl-phenyl)-acrylic acid ethyl ester | 158503-50-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (E)-3-(3-Pyridin-3-yl-phenyl)-acrylic acid ethyl ester
• CAS: 158503-50-5
• 化学式: C₁₆H₁₅NO₂
• 分子量: 253.301
• InChiKey: JLOLNKIQTMBMBI-UHFFFAOYSA-N

物化性质

• 沸点：
  425.7±33.0 °C(predicted)
• 密度：
  1.123±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.32
• 重原子数：
  19.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  39.19
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (E)-3-(3-Pyridin-3-yl-phenyl)-acrylic acid ethyl ester 在 草酰氯 、 二异丁基氢化铝 、 二甲基亚砜 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  Synthesis and Biological Activities of New HMG-CoA Synthase Inhibitors: 2-Oxetanones with a Side Chain Containing Biphenyl, Terphenyl or Phenylpyridine

  摘要：

  A series of 1233A analogs containing biphenylyl, terphenylyl or phenylpyridyl groups in their side chain were synthesized and tested for the inhibitory activities against 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase and inhibition for the cholesterol biosynthesis in the mouse liver. The compounds with an oxetane, cyclobutanone or gamma-butyrolactone ring as isosters of a 2-oxetanone ring were entirely inactive. Among sythetic analogs, anti-4-[3-[2-(5-isopropyl-2-pyridyl)-ethyl]-phenyl]ethyl]-3-hydroxymethyl-2-oxetanone (10b) was most active in vitro. The structure-activity relationships on the transformations of 2-oxetanone and its side chain were obtained.

  DOI：

  10.3987/com-94-6720
• 作为产物：
  描述：

  3-(3-(1,3-dioxolan-2-yl)phenyl)pyridine 在 盐酸 、 sodium hydride 作用下， 以 甲苯 为溶剂， 反应 0.67h， 生成 (E)-3-(3-Pyridin-3-yl-phenyl)-acrylic acid ethyl ester
  参考文献：
  名称：

  Synthesis and Biological Activities of New HMG-CoA Synthase Inhibitors: 2-Oxetanones with a Side Chain Containing Biphenyl, Terphenyl or Phenylpyridine

  摘要：

  A series of 1233A analogs containing biphenylyl, terphenylyl or phenylpyridyl groups in their side chain were synthesized and tested for the inhibitory activities against 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase and inhibition for the cholesterol biosynthesis in the mouse liver. The compounds with an oxetane, cyclobutanone or gamma-butyrolactone ring as isosters of a 2-oxetanone ring were entirely inactive. Among sythetic analogs, anti-4-[3-[2-(5-isopropyl-2-pyridyl)-ethyl]-phenyl]ethyl]-3-hydroxymethyl-2-oxetanone (10b) was most active in vitro. The structure-activity relationships on the transformations of 2-oxetanone and its side chain were obtained.

  DOI：

  10.3987/com-94-6720

文献信息

• Remote site-selective C–H activation directed by a catalytic bifunctional template
  作者：Zhipeng Zhang、Keita Tanaka、Jin-Quan Yu

  DOI：10.1038/nature21418

  日期：2017.3

  In chemical syntheses, the activation of carbon–hydrogen (C–H) bonds converts them directly into carbon–carbon or carbon–heteroatom bonds without requiring any prior functionalization. C–H activation can thus substantially reduce the number of steps involved in a synthesis. A single specific C–H bond in a substrate can be activated by using a ‘directing’ (usually a functional) group to obtain the desired

  在化学合成中，碳-氢 (C-H) 键的活化将它们直接转化为碳-碳或碳-杂原子键，无需任何事先的功能化。因此，C-H 活化可以大大减少合成中涉及的步骤数。可以通过使用“定向”（通常是官能团）基团来激活底物中的单个特定 C-H 键，从而选择性地获得所需的产物。由于所讨论的 C-H 键与导向基团的距离以及底物的形状，这种 C-H 活化反应的适用性会受到严重限制，但已经开发了几种方法来克服这些限制。在这样一种方法中，通过使用共价连接的 U 形模板，已经利用对官能团和底物 C-H 键之间的远端和几何关系的理解来实现元选择性 C-H 激活。然而，在没有合适的官能团来连接它的情况下，这个模板的化学计量安装是不可行的。在这里，我们报告了一种催化双功能腈模板的设计，该模板通过可逆配位而不是共价键结合杂环底物。与该模板协调的两个金属中心具有不同的作用：一个可逆地锚定催化剂附近的底物，另一个切割远程 C-H 键。使用这种策略，我们演示了远程、
• [EN] REMOTE HETEROARYL ALKENYLATION WITH CATALYTIC BIFUNCTIONAL TEMPLATE<br/>[FR] ALCÉNYLATION D'HÉTÉROARYLE À DISTANCE AVEC MODÈLE BIFONCTIONNEL CATALYTIQUE
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2018152107A1

  公开（公告）日：2018-08-23

  We report the design of a catalytic, bifunctional template that binds heterocyclic substrate via reversible coordination instead of covalent linkage, allowing remote site- selective C-H olefination of heterocycles. The two metal centers coordinated to this template play different roles; anchoring substrates to the proximity of catalyst and cleaving the remote C-H bonds respectively. Using this strategy, we demonstrate remote site-selective C-H olefination of heterocyclic substrates which do not have functional group handles for covalently attaching templates. For instance the olefination can be an alkenylation of a 3- phenylpyridine with an acrylate alkyl ester selective for the meta position of the phenyl group with respect to the pyridine, or can be an alkenylation of a quinoline with an acrylate alkyl ester selective for the 5-position of the quinoline.

  我们报告了一种设计良好的催化双功能模板，通过可逆配位而不是共价键合来结合杂环底物，从而实现对杂环的远程位选择性C-H烯化。与此模板配位的两个金属中心发挥不同的作用；将底物固定在催化剂附近并分别断裂远程的C-H键。利用这种策略，我们展示了对杂环底物的远程位选择性C-H烯化，这些底物没有适用于共价连接模板的官能团。例如，烯化可以是3-苯基吡啶与丙烯酸酯选择性烯化的一个示例，与吡啶相比，选择性作用于苯基的间位，或者可以是喹啉与丙烯酸酯选择性烯化的一个示例，选择性作用于喹啉的5位。
• Remote C−H Olefination of Heterocyclic Biaryls Enabled by Reversibly Bound Templates
  作者：Luo‐Yan Liu、Zhoulong Fan、Md Emdadul Hoque、Shaoqun Qian、Guangrong Meng、Nikita Chekshin、Keita Tanaka、Jennifer X. Qiao、Kap‐Sun Yeung、Jin‐Quan Yu

  DOI：10.1002/anie.202307581

  日期：2023.9.11

  Remote C−H functionalization of heterocyclic biaryls will be of great importance in synthesis and medicinal chemistry. Through adjusting the geometric relationship of the directing atom and target C−H bonds, two new catalytic templates have been developed to enable the functionalization of the more hindered ortho‐C−H bonds of heterobiaryls bearing directing heteroatom at the meta‐ or para‐positions, affording unprecedented site‐selectivity. The use of template chaperone also overcomes product inhibition and renders the directing templates catalytic. The utility of this protocol was demonstrated by olefination of heterocyclic biaryls with various substituents, overriding conventional steric and electronic effects. These ortho‐C−H olefinated heterobiaryls are sterically hindered and can often be challenging to prepare through aryl‐aryl coupling reactions.

  摘要杂环双芳基的远程 C-H 功能化在合成和药物化学中将具有重要意义。通过调整指导原子和目标 C-H 键的几何关系，我们开发出了两种新的催化模板，可以对在元或对位上带有指导杂原子的杂环双芳基中阻碍较大的正 C-H 键进行官能化，从而获得前所未有的位点选择性。模板伴侣的使用还克服了产物抑制作用，并使定向模板具有催化作用。通过对带有各种取代基的杂环双芳基进行烯化反应，证明了这一方案的实用性，克服了传统的立体和电子效应。这些正交-C-H 烯化杂环双芳基具有立体阻碍，通常很难通过芳基-芳基偶联反应制备。