ethyl 4-isocyanopiperidine-1-carboxylate | 1000698-78-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: ethyl 4-isocyanopiperidine-1-carboxylate
• CAS: 1000698-78-1
• 化学式: C₉H₁₄N₂O₂
• mdl: MFCD06200535
• 分子量: 182.222
• InChiKey: BQNABIARGPWQKO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.777
• 拓扑面积：
  33.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 4-isocyanopiperidine-1-carboxylate 、 5-(2-amino-5-chlorophenyl)-3-(2-furyl)-1H-1,2,4-triazole 在 Pd(opiv)2 、 氧气 作用下， 以 2-甲基四氢呋喃 为溶剂， 75.0 ℃ 、101.33 kPa 条件下， 反应 72.0h， 以43%的产率得到ethyl 4-((9-chloro-2-(furan-2-yl)-[1,2,4]triazolo[1,5-c]quinazolin-5-yl)amino)piperidine-1-carboxylate
  参考文献：
  名称：

  钯（II）催化异氰酸酯的好氧氧化插入合成偶氮[c]喹唑啉

  摘要：

  我们报告了使用空气作为化学计量氧化剂，钯（II）催化的异氰酸酯与各种（2-氨基苯基）唑类的好氧氧化偶联。通过这种新方法，获得了多种医学上有价值的氮杂[ c ]喹唑啉。

  DOI：

  10.1002/adsc.201301129
• 作为产物：
  描述：

  4-formylaminohexahydropyridine-1-carboxylic acid ethyl ester 在 N-甲基吗啉 、 三光气 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以1.52 g的产率得到ethyl 4-isocyanopiperidine-1-carboxylate
  参考文献：
  名称：

  钯催化好氧氧化异氰插入物可持续合成各种特权杂环

  摘要：

  O 2 in，H 2 O out：各种二胺和相关的双亲核试剂易于经历氧化异氰化物的插入，其中Pd（OAc）2（1 mol％）作为催化剂，O 2作为末端氧化剂，可得到多种与医学相关的N杂环。抗组胺药阿司咪唑和去甲阿司咪唑的正式合成证明了这种高度可持续性方法的实用性。

  DOI：

  10.1002/anie.201207410

文献信息

• Combining High‐Throughput Synthesis and High‐Throughput Protein Crystallography for Accelerated Hit Identification
  作者：Fandi Sutanto、Shabnam Shaabani、Rick Oerlemans、Deniz Eris、Pravin Patil、Mojgan Hadian、Meitian Wang、May Elizabeth Sharpe、Matthew R. Groves、Alexander Dömling

  DOI：10.1002/anie.202105584

  日期：2021.8.9

  mmol scale synthesis on 96-well format and on a high-throughput nanoscale format in a highly automated fashion. High-throughput PX of our libraries efficiently yielded potent covalent inhibitors of the main protease of the COVID-19 causing agent, SARS-CoV-2. Our results demonstrate, that the marriage of in situ HT synthesis of (covalent) libraires and HT PX has the potential to accelerate hit finding

  蛋白质晶体学 (PX) 广泛用于推动药物优化的高级阶段或通过片段浸泡发现药物化学起点。然而，PX 的最新进展可能会使其在早期药物发现中发挥更综合的作用。在这里，我们首次展示了高通量合成和高通量 PX 的相互作用。我们描述了一种实用的多组分反应方法，适用于以高度自动化的方式在 96 孔格式和高通量纳米级格式上进行毫摩尔级合成的不同结构单元的丙烯酰胺和丙烯酰胺和酯。我们文库的高通量 PX 有效地产生了 COVID-19 致病因子 SARS-CoV-2 的主要蛋白酶的有效共价抑制剂。我们的结果表明，（共价）库的原位 HT 合成和 HT PX 的结合有可能加速命中发现并为药物化学项目提供有意义的策略。
• Sustainable Three-Component Synthesis of Isothioureas from Isocyanides, Thiosulfonates, and Amines
  作者：Pieter Mampuys、Yanping Zhu、Tjøstil Vlaar、Eelco Ruijter、Romano V. A. Orru、Bert U. W. Maes

  DOI：10.1002/anie.201406717

  日期：2014.11.17

  Multiple applications of isothioureas as fine chemicals (or their precursors) are known, but a general sustainable method for their synthesis was hitherto unavailable. We report a novel general approach towards S‐alkyl and S‐aryl isothioureas through a copper(I)‐catalyzed three‐component reaction between amines, isocyanides, and thiosulfonates. The formal synthesis of a superpotent sweetener further

  异硫脲作为精细化学品（或其前体）的多种应用是已知的，但是迄今为止尚无通用的可持续合成方法。我们报告了一种通过胺，异氰化物和硫代磺酸盐之间的铜（I）催化的三组分反应对S-烷基和S-芳基异硫脲进行处理的新颖方法。高效甜味剂的形式合成进一步说明了我们方法的适用性。
• Novel benzimidazole derivatives
  申请人：Benson Martin Gregory

  公开号：US20080021027A1

  公开（公告）日：2008-01-24

  The invention is concerned with novel benzimidazole derivatives of formula (I) wherein R 1 to R 8 are as defined in the description and in the claims, as well as physiologically acceptable salts and esters thereof. These compounds bind to Farnesoid-X-receptors (FXR) and can be used to treat diseases which are modulated by FXR agonists such as diabetes and dyslipidemia.

  这项发明涉及公式（I）的新型苯并咪唑衍生物，其中R1至R8如描述和权利要求中所定义，以及其生理上可接受的盐和酯。这些化合物与法尼索酮-X-受体（FXR）结合，并可用于治疗由FXR激动剂调节的疾病，例如糖尿病和血脂异常。
• Palladium-Catalyzed Synthesis of 2-Aminobenzoxazinones by Aerobic Oxidative Coupling of Anthranilic Acids and Isocyanides
  作者：Tjøstil Vlaar、Romano V. A. Orru、Bert U. W. Maes、Eelco Ruijter

  DOI：10.1021/jo401924h

  日期：2013.10.18

  Isocyanides have emerged as valuable C-1 building blocks in palladium catalysis. Their potential has, however, mainly been exploited for the synthesis of amidines and amidine-containing heterocycles. To illustrate the broader applicability of isocyanides, we have recently developed a novel oxidative coupling of diamines and isocyanides furnishing valuable guanidine-containing heterocycles. We here report the extension of this protocol to the coupling of anthranilic acids and isocyanides leading to medicinally relevant 2-aminobenzoxazinones. This is a particularly challenging substrate class for this reaction due to the possibility of undesired decarboxylative pathways and the susceptibility of the products to nucleophilic attack. Therefore, this work underlines the generality and broad potential of the oxidative coupling of bisnucleophiles and isocyanides, facilitating the further implementation of this chemistry in library design.
• Modular Three-Component Synthesis of 4-Aminoquinolines via an Imidoylative Sonogashira/Cyclization Cascade
  作者：Jurriën W. Collet、Kelly Ackermans、Jeffrey Lambregts、Bert U.W. Maes、Romano V.A. Orru、Eelco Ruijter

  DOI：10.1021/acs.joc.7b02844

  日期：2018.1.19

  We developed a one-pot, two-stage synthetic route to substituted 4-aminoquinolines involving an imidoylative Sonogashira coupling followed by acid-mediated cyclization. This three-component reaction affords pharmaceutically valuable 4-aminoquinolines in a one-pot procedure from readily available starting materials. The reaction tolerates various substituents on the arene as well as the use of secondary and even primary isocyanides. Additionally, the wide tolerance for functionalized isocyanides allows for the one-pot synthesis of various substituted chloroquine analogues as well as other medicinally relevant products.