((1S,2S)-2-(4-chlorophenyl)cyclopropyl)methanol | 388631-88-7

• 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: ((1S,2S)-2-(4-chlorophenyl)cyclopropyl)methanol
• 英文别名: [trans-2-(4-Chlorophenyl)cyclopropyl]methanol；[(1S,2S)-2-(4-chlorophenyl)cyclopropyl]methanol
• CAS: 388631-88-7
• 化学式: C₁₀H₁₁ClO
• 分子量: 182.65
• InChiKey: RHLUDCBNPQCUQK-PSASIEDQSA-N

物化性质

• 沸点：
  287.9±23.0 °C(Predicted)
• 密度：
  1.234±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  ((1S,2S)-2-(4-chlorophenyl)cyclopropyl)methanol 在 伯吉斯试剂 、 sodium hydride 、 一水合肼 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 、 mineral oil 为溶剂， 反应 38.5h， 生成 7-(((1S,2S)-2-(4-chlorophenyl)cyclopropyl)methoxy)-3-(cyclopropylmethyl)-8-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine
  参考文献：
  名称：

  Triazolopyridine ethers as potent, orally active mGlu2 positive allosteric modulators for treating schizophrenia

  摘要：

  Triazolopyridine ethers with mGlu(2) positive allosteric modulator (PAM) activity are disclosed. The synthesis, in vitro activity, and metabolic stability data for a series of analogs is provided. The effort resulted in the discovery of a potent, selective, and brain penetrant lead molecule BMT-133218 ((+)-7m). After oral administration at 10 mg/kg, BMT-133218 demonstrated full reversal of PCP-stimulated locomotor activity and prevented MK-801-induced working memory deficits in separate mouse models. Also, reversal of impairments in executive function were observed in rat set-shifting studies at 3 and 10 mg/kg (p.o.). Extensive plasma protein binding as the result of high lipophilicity likely limited activity at lower doses. Optimized triazolopyridine ethers offer utility as mG1u(2) PAMs for the treatment of schizophrenia and merit further preclinical investigation. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.11.018
• 作为产物：
  描述：

  (2E)-3-(4-氯苯基)丙烯酰氯 在 lithium aluminium tetrahydride 、 palladium diacetate 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 ((1S,2S)-2-(4-chlorophenyl)cyclopropyl)methanol
  参考文献：
  名称：

  Triazolopyridine ethers as potent, orally active mGlu2 positive allosteric modulators for treating schizophrenia

  摘要：

  Triazolopyridine ethers with mGlu(2) positive allosteric modulator (PAM) activity are disclosed. The synthesis, in vitro activity, and metabolic stability data for a series of analogs is provided. The effort resulted in the discovery of a potent, selective, and brain penetrant lead molecule BMT-133218 ((+)-7m). After oral administration at 10 mg/kg, BMT-133218 demonstrated full reversal of PCP-stimulated locomotor activity and prevented MK-801-induced working memory deficits in separate mouse models. Also, reversal of impairments in executive function were observed in rat set-shifting studies at 3 and 10 mg/kg (p.o.). Extensive plasma protein binding as the result of high lipophilicity likely limited activity at lower doses. Optimized triazolopyridine ethers offer utility as mG1u(2) PAMs for the treatment of schizophrenia and merit further preclinical investigation. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.11.018

文献信息

• Catalytic Asymmetric Cyclopropanation of Allylic Alcohols with Titanium-TADDOLate:  Scope of the Cyclopropanation Reaction
  作者：André B. Charette、Carmela Molinaro、Christian Brochu

  DOI：10.1021/ja0108382

  日期：2001.12.1

  titanium-TADDOLate complex was effective at catalyzing the cyclopropanation reaction of allylic alcohols in the presence 1 equiv of bis(iodomethyl)zinc. After initial optimization of the catalyst structure, excellent yields and enantiomeric ratios were obtained for 3-aryl- or 3-heteroaryl-substituted allylic alcohols (up to 97:3). Alkyl-substituted allylic alcohols gave modest yields and enantiomeric ratios (up

  在 1 当量的双（碘甲基）锌存在下，亚化学计量的钛-TADDOLate 络合物可有效催化烯丙醇的环丙烷化反应。在对催化剂结构进行初步优化后，3-芳基-或3-杂芳基-取代的烯丙醇（高达97:3）获得了优异的产率和对映体比率。烷基取代的烯丙醇的产率和对映体比例适中（高达 87:13），但与其他亚化学计量手性配体观察到的相比，这些更有利。本文介绍了该反应的完整合成范围。
• Highly Enantioselective Intermolecular Cyclopropanation Catalyzed by Dirhodium(II) Tetrakis[3(<i>S</i>)-phthalimido-2-piperidinonate]: Solvent Dependency of the Enantioselection
  作者：Shinji Kitagaki、Hideo Matsuda、Nobuhide Watanabe、Shun-ichi Hashimoto

  DOI：10.1055/s-1997-994

  日期：1997.10

  The enantioselectivity in cyclopropanations catalyzed by dirhodium(II) tetrakis[3(S)-phthalimido-2-piperidinonate] has been found to be substantially improved by employing ether as the rarely used solvent. Cyclopropanations of styrenes or 1,1-disubstituted alkenes with 2,4-dimethyl-3-pentyl diazoacetate in ether are promoted by this catalyst to afford the corresponding cyclopropane products in the highest levels of enantioselectivity (up to 98% ee) reported to date for the dirhodium(II)-catalyzed intermolecular cyclopropanation reactions.

  由二铑(II)四[3(S)-邻苯二甲酰胺-2-哌啶酸酯]催化的环丙烷化反应中的对映选择性已被发现通过使用作为罕见溶剂的醚显著改善。该催化剂促进了苯乙烯或1,1-二取代烯烃与2,4-二甲基-3-戊基二氮酰乙酸酯在醚中进行的环丙烷化反应，产生了相应的环丙烷产品，报告的对映选择性达到最高水平（高达98% ee），这是迄今为止二铑(II)催化的分子间环丙烷化反应中所取得的最高记录。
• A Chiral Bis(oxazoline) Ligand Embedded into Polysiloxane Gel: Application to a Reusable Copper Catalyst for Asymmetric Cyclopropanation
  作者：Yukihiro Motoyama、Takashi Nishikata、Hideo Nagashima

  DOI：10.1002/asia.201000527

  日期：2011.1.3

  “Box”ed in: A novel polysiloxane gel encapsulated CuII/bis(oxazoline) (CuII/Box) species was synthesized and used as a recyclable catalyst in the asymmetric cyclopropanation of alkenes with L‐menthyl diazoacetate.

  在“框” ED：一种新颖的聚硅氧烷凝胶包封的Cu II /双（恶唑啉）（铜II /箱）物种合成并用作与烯烃的不对称环丙烷可回收催化剂大号-薄荷基重氮基。
• Highly Efficient Asymmetric Simmons-Smith Cyclopropanation Promoted by Chiral Heteroorganic Aziridinyl Ligands
  作者：Michał Rachwalski、Sylwia Kaczmarczyk、Stanisław Leśniak、Piotr Kiełbasiński

  DOI：10.1002/cctc.201300883

  日期：2014.3

  Enantiomerically pure heteroorganic catalysts, bearing a hydroxy moiety, a stereogenic sulfinyl group, and a chiral aziridine moiety, have proved highly efficient in the asymmetric Simmons–Smith cyclopropanation of allylic alcohols, which generates the desired products in high yields (up to 95 %) and with ee values up to 94 %. The effect of the stereogenic centers at the sulfinyl sulfur atom and in

  具有羟基部分，立体亚砜基和手性氮丙啶部分的对映体纯杂有机催化剂在烯丙醇的不对称Simmons-Smith环丙烷化中被证明是高效的，从而以高收率（高达95％）生成所需的产物且ee值高达94％。讨论了亚砜基硫原子和氮丙啶部分的立体中心对标题反应的立体化学过程的影响。
• TRIAZOLOPYRIDINE ETHER DERIVATIVES AND THEIR USE IN NEUROLOGICAL AND PYSCHIATRIC DISORDERS
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20160237081A1

  公开（公告）日：2016-08-18

  The disclosure generally relates to compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds modulate the mGluR2 receptor and may be useful for the treatment of various disorders of the central nervous system.

  本公开涉及公式I的化合物，包括它们的盐，以及使用这些化合物的组合物和方法。这些化合物调节mGluR2受体，可能有助于治疗各种中枢神经系统的疾病。