2-(2-((trimethylsilyl)ethynyl)phenyl)acetonitrile | 1226571-52-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(2-((trimethylsilyl)ethynyl)phenyl)acetonitrile
• 英文别名: 2-Trimethylsilylethynyl phenylacetonitrile, AldrichCPR；2-[2-(2-trimethylsilylethynyl)phenyl]acetonitrile
• CAS: 1226571-52-3
• 化学式: C₁₃H₁₅NSi
• 分子量: 213.354
• InChiKey: IOIIANDDAOLUBY-UHFFFAOYSA-N

物化性质

• 沸点：
  301.4±34.0 °C(Predicted)
• 密度：
  0.98±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.98
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  23.8
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-(2-((trimethylsilyl)ethynyl)phenyl)acetonitrile 在 甲醇 、 copper(l) iodide 、 sodium tetrachloropalladate(II) 、 lithium hydroxide monohydrate 、 potassium carbonate 、 2-二叔丁基膦-1-苯基吲哚 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 4.0h， 生成 3-(5-((2-(cyanomethyl)phenyl)ethynyl)thiophen-2-yl)propanoic acid
  参考文献：
  名称：

  Discovery of Potent and Orally Bioavailable GPR40 Full Agonists Bearing Thiophen-2-ylpropanoic Acid Scaffold

  摘要：

  The free fatty acid receptor GPR40 is predominantly expressed in pancreatic beta-cells and enhances insulin secretion in a glucose dependent manner. Therefore, GPR40 agonists are possible novel insulin secretagogues with reduced or no risk of hypoglycemia for the treatment of type 2 diabetes mellitus (T2DM). Chemically and structurally diverse GPR40 agonists with high safety are pursued for the clinical development of GPR40-based pharmacotherapeutics. Herein we report our design and discovery of a new chemotype of GPR40 agonists free of the typical phenylpropanoic acid scaffold. The thiophen-2-ylpropanoic acid containing GPR40 modulators functioned as full agonists with high-efficacy response (E-max) and reduced lipophilicity. Significantly, the lead compound in this series, (R)-7k, exhibited more potent in vitro glucose-stimulated insulin secretion and in vivo glucose-lowering effects (10 mg/kg, po) than the GPR40 partial agonist TAK-875, which was once in phase III clinical trials, and high selectivity over the relevant receptors GPR120 and PPAR gamma.

  DOI：

  10.1021/acs.jmedchem.6b01357
• 作为产物：
  描述：

  2-溴溴苄 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三乙胺 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 17.33h， 生成 2-(2-((trimethylsilyl)ethynyl)phenyl)acetonitrile
  参考文献：
  名称：

  Gold-Catalyzed 1,2-Oxoarylations of Nitriles with Pyridine-Derived Oxides

  摘要：

  AbstractWe report the first success in the gold‐catalyzed oxoarylations of nitriles with pyridine‐derived N‐oxides using gold carbenes as initiators. These oxoarylations were also achieved satisfactorily in intermolecular three‐component oxidations, including diverse alkenyldiazo esters, nitriles, and pyridine‐based oxides.

  DOI：

  10.1002/anie.201403015

文献信息

• Nickel-Catalyzed C(sp³)–H Functionalization of Benzyl Nitriles: Direct Michael Addition to Terminal Vinyl Ketones
  作者：Ninghui Zhang、Chunli Zhang、Xiaoping Hu、Xin Xie、Yuanhong Liu

  DOI：10.1021/acs.orglett.1c02074

  日期：2021.8.6

  An efficient nickel(0)-catalyzed addition of benzyl nitriles to terminal vinyl ketones via C(sp3)–H functionalization has been developed. The reaction provides a novel and efficient protocol for the synthesis of α-functionalized benzyl nitriles with a wide range of structural diversity under mild reaction conditions while obviating the use of a strong base. The work might be potentially useful toward

  已经开发出一种通过 C(sp 3 )-H 官能化将苄基腈有效地在镍 (0) 催化下加成到末端乙烯基酮上的方法。该反应为在温和的反应条件下合成具有广泛结构多样性的 α-官能化苄腈提供了一种新颖有效的方案，同时避免了使用强碱。这项工作可能有助于开发使用手性氮配体的对映选择性变体。
• Palladium(II)-Catalyzed Cascade Reactions of Ene–Ynes Tethered to Cyano/Aldehyde: Access to Naphtho[1,2-<i>b</i>]furans and Benzo[<i>g</i>]indoles
  作者：Moumita Jash、Sukanya De、Subhendu Pramanik、Chinmay Chowdhury

  DOI：10.1021/acs.joc.9b00861

  日期：2019.7.19

  cyano/aldehyde group is described. It involves successive hetero- and benz-annulations in one pot via trans-oxo/aminopalladation onto alkyne, followed by 1,2-addition to cyano/aldehyde, providing a convenient synthesis of both naphtho[1,2-b]furans and benzo[g]indoles. The reaction constitutes a fast intramolecular assembly through several carbon–carbon and carbon–heteroatom bond formations taking place

  描述了一种有效的钯（II）催化带有氰基/醛基的烯炔基的级联反应。它涉及在一个锅中通过反式-羰基/氨基palpalation到炔烃上的连续异环和苯环，然后将1，2-加成到氰基/醛中，从而方便地合成萘并[1,2- b ]呋喃和苯并[ g ]吲哚。该反应通过一个罐中发生的数个碳-碳和碳-杂原子键构成了一种快速的分子内组装。该反应操作简单，与一系列官能团相容并且本质上是原子经济的。
• One-Pot Procedure for the Synthesis of Unsymmetrical Diarylalkynes
  作者：René Severin、Jessica Reimer、Sven Doye

  DOI：10.1021/jo100460v

  日期：2010.5.21

  Unsymmetrical diarylalkynes are accessible by a one-pot procedure from two different aryl halides and (trimethylsilyl)acetylene. The three-component coupling is initialized by a Pd/Cu-catalyzed Sonogashira coupling of an aryl halide with (trimethylsilyl)acetylene. After subsequent desilylation Ilk; formed aryl(trimethylsilyl)acetylene with aqueous potassium hydroxide, a second Sono-gashira coupling with an aryl iodide that does not require any additional Pd/Cu-catalyst gives access to an unsymmetrical diarylalkyne.
• Synthesis of <i>ortho</i>-Diamino-Functionalized 1-Arylnaphthalenes through Nickel-Catalyzed Cyclization of Ynamide-Benzylnitriles with Organoboronic Acids
  作者：Xiaoping Hu、Peizhuo Lv、Ninghui Zhang、Yuanhong Liu

  DOI：10.1021/acs.orglett.1c02957

  日期：2021.10.15
• Discovery of Potent and Orally Bioavailable GPR40 Full Agonists Bearing Thiophen-2-ylpropanoic Acid Scaffold
  作者：He Li、Qi Huang、Cheng Chen、Bin Xu、He-Yao Wang、Ya-Qiu Long

  DOI：10.1021/acs.jmedchem.6b01357

  日期：2017.4.13

  The free fatty acid receptor GPR40 is predominantly expressed in pancreatic beta-cells and enhances insulin secretion in a glucose dependent manner. Therefore, GPR40 agonists are possible novel insulin secretagogues with reduced or no risk of hypoglycemia for the treatment of type 2 diabetes mellitus (T2DM). Chemically and structurally diverse GPR40 agonists with high safety are pursued for the clinical development of GPR40-based pharmacotherapeutics. Herein we report our design and discovery of a new chemotype of GPR40 agonists free of the typical phenylpropanoic acid scaffold. The thiophen-2-ylpropanoic acid containing GPR40 modulators functioned as full agonists with high-efficacy response (E-max) and reduced lipophilicity. Significantly, the lead compound in this series, (R)-7k, exhibited more potent in vitro glucose-stimulated insulin secretion and in vivo glucose-lowering effects (10 mg/kg, po) than the GPR40 partial agonist TAK-875, which was once in phase III clinical trials, and high selectivity over the relevant receptors GPR120 and PPAR gamma.