(R)-(3-benzyl-3-methyl-2,3-dihydrobenzofuran-6-yl)(piperidin-1-yl)methanone | 1196995-96-6

• 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: (R)-(3-benzyl-3-methyl-2,3-dihydrobenzofuran-6-yl)(piperidin-1-yl)methanone
• 英文别名: [(3R)-3-benzyl-3-methyl-2H-1-benzofuran-6-yl]-piperidin-1-ylmethanone
• CAS: 1196995-96-6
• 化学式: C₂₂H₂₅NO₂
• 分子量: 335.446
• InChiKey: ZEMCXAZYSOBAGF-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  3-羟基-4-碘苯甲酸 在 草酰氯 、 四丁基氯化铵 、 palladium diacetate 、 potassium carbonate 、 二甲基亚砜 、 三乙胺 、 N,N-二异丙基乙胺 、 氯甲酸甲酯 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 sodium hydroxide 、 肼 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 丁酮 、 二乙二醇 为溶剂， 反应 105.34h， 生成 (R)-(3-benzyl-3-methyl-2,3-dihydrobenzofuran-6-yl)(piperidin-1-yl)methanone
  参考文献：
  名称：

  A synthetic approach for (S)-(3-benzyl-3-methyl-2,3-dihydro-benzofuran-6-yl)-piperidin-1-yl-methanone, a selective CB2 receptor agonist

  摘要：

  (S)-(3-Benzyl-3-methyl-2,3-dihydro-benzofuran-6-yl)-piperidin-1-yl-methanone, a selective CB2 receptor agonist, was obtained from 3-hydroxy-4-iodo benzoic acid in nine steps with 97.4% ee and 3.4% total yield, which involved palladium catalyzed tandem intramolecular Heck/Suzuki cross coupling reaction, chemical resolution with (+)-norephedrine and Wolf-Kishner reaction as the key steps. (S)-(3-Benzyl-3-methyl-2,3-dihydro-benzofuran-6-yl)-piperidin-1-yl-methanone will be evaluated in vivo studies and this approach will be applied in the optimization process of CB2 receptor agonist. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2012.04.076

文献信息

• Ruthenium(II)‐Catalyzed Asymmetric Inert C−H Bond Activation Assisted by a Chiral Transient Directing Group
  作者：Guozhu Li、Qinzhe Liu、Laxmaiah Vasamsetty、Weicong Guo、Jun Wang

  DOI：10.1002/anie.201913733

  日期：2020.2.24

  A ruthenium(II)-catalyzed asymmetric intramolecular hydroarylation assisted by a chiral transient directing group has been developed. A series of 2,3-dihydrobenzofurans bearing chiral all-carbon quaternary stereocenters have been prepared in remarkably high yields (up to 98 %) and enantioselectivities (up to >99 % ee). By this methodology, a novel asymmetric total synthesis of CB2 receptor agonist

  已经开发了由手性瞬态导向基团辅助的钌（II）催化的不对称分子内氢芳基化反应。制备了一系列带有手性全碳四元立体中心的2，3-二氢苯并呋喃，具有很高的收率（高达98％）和对映选择性（高达> 99％ee）。通过这种方法，已经成功地开发了新颖的不对称的CB2受体激动剂MDA7的全合成。
• Palladium-Catalyzed Enantioselective Reductive Heck Reactions: Convenient Access to 3,3-Disubstituted 2,3-Dihydrobenzofuran
  作者：Zhan-Ming Zhang、Bing Xu、Yanyan Qian、Lizuo Wu、Yuanqi Wu、Lujia Zhou、Yu Liu、Junliang Zhang

  DOI：10.1002/anie.201806372

  日期：2018.8.6

  intramolecular hydroarylation of allyl aryl ethers was realized by palladium‐catalyzed reductive heck reactions utilizing a new chiral sulfinamide phosphine ligand (N‐Me‐XuPhos). N‐Me‐XuPhos can be easily prepared on gram scale from readily available starting materials in a one‐pot synthesis approach. A series of optically active 2,3‐dihydrobenzofurans bearing a quaternary stereocenter were obtained in good

  烯丙基芳基醚的高对映选择性分子内氢芳基化反应的第一个例子是通过使用新的手性亚磺酰胺膦配体（N- Me - XuPhos）进行钯催化的还原性heck反应而实现的。N- Me - XuPhos可以通过一锅合成方法轻松地从容易获得的起始原料中以克为单位制备。以良好的收率和优异的对映选择性获得了一系列带有季立体中心的旋光2,3-二氢苯并呋喃。该反应的实用性已在CB2受体激动剂的直接合成中得到验证。此外，将氘有效地掺入了产品中。
• Neuroprotective CB2 receptor agonists
  申请人：THE CLEVELAND CLINIC FOUNDATION

  公开号：US10835521B2

  公开（公告）日：2020-11-17

  A method of treating or preventing a neuroinflammatory and/or neurodegenerative disease in a subject by administering a pharmaceutically effective amount of a CB2 receptor agonist is described. The CB2 receptor agonist can be a compound according to formula I (structurally represented) or a pharmaceutically acceptable salt thereof, with R1 and R2 functional groups as defined herein. Administration of the CB2 receptor agonist activates CB2 receptors in the microglia, and can restore synaptic plasticity, cognition, and memory in subjects having elevated levels of amyloid-13 peptide in the brain.

  本文描述了一种通过施用药学有效量的 CB2 受体激动剂来治疗或预防受试者的神经炎症和/或神经退行性疾病的方法。CB2 受体激动剂可以是根据式 I（结构表示）的化合物或其药学上可接受的盐，其 R1 和 R2 官能团如本文所定义。施用 CB2 受体激动剂可激活小胶质细胞中的 CB2 受体，并可恢复大脑中淀粉样蛋白-13 肽水平升高的受试者的突触可塑性、认知和记忆。
• NEUROPROTECTIVE CB2 RECEPTOR AGONISTS
  申请人：THE CLEVELAND CLINIC FOUNDATION

  公开号：US20160193201A1

  公开（公告）日：2016-07-07

  A method of treating or preventing a neuroinflammatory and/or neurodegenerative disease in a subject by administering a pharmaceutically effective amount of a CB2 receptor agonist is described. The CB2 receptor agonist can be a compound according to formula I (structurally represented) or a pharmaceutically acceptable salt thereof, with R1 and R2 functional groups as defined herein. Administration of the CB2 receptor agonist activates CB2 receptors in the microglia, and can restore synaptic plasticity, cognition, and memory in subjects having elevated levels of amyloid-13 peptide in the brain.
• [EN] NEUROPROTECTIVE CB2 RECEPTOR AGONISTS<br/>[FR] AGONISTES NEUROPROTECTEURS DES RÉCEPTEURS CB2
  申请人：CLEVELAND CLINIC FOUNDATION

  公开号：WO2014011949A2

  公开（公告）日：2014-01-16

  A method of treating or preventing a neuroinflammatory and/or neurodegenerative disease in a subject by administering a pharmaceutically effective amount of a CB2 receptor agonist is described. The CB2 receptor agonist can be a compound according to formula I or a pharmaceutically acceptable salt thereof, with R1 and R2 as defined herein. Administration of the CB2 receptor agonist activates CB2 receptors in the microglia, and can restore syntaptic plasticity, cognition, and memory in subjects having elevated levels of amyloid-ß peptide in the brain.