[(1S,2R)-2-(aminomethyl)-2-(4-methylphenyl)cyclopropyl]methanol | 909396-90-3

• 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: [(1S,2R)-2-(aminomethyl)-2-(4-methylphenyl)cyclopropyl]methanol
• 英文别名: ((1S,2R)-2-(aminomethyl)-2-p-tolylcyclopropyl)methanol；((1S,2R)-2-(aminomethyl)-2-(p-tolyl)cyclopropyl)methanol
• CAS: 909396-90-3
• 化学式: C₁₂H₁₇NO
• 分子量: 191.273
• InChiKey: QKDYSFBCTMPWIV-NEPJUHHUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  46.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  [(1S,2R)-2-(aminomethyl)-2-(4-methylphenyl)cyclopropyl]methanol 在 氯化亚砜 作用下， 以 醋酸异丙酯 为溶剂， 生成 [(1R,2S)-2-(chloromethyl)-1-(4-methylphenyl)cyclopropyl]methanamine
  参考文献：
  名称：

  One-Pot Preparation of Cyclic Amines from Amino Alcohols

  摘要：

  DOI：

  10.15227/orgsyn.090.0251
• 作为产物：
  描述：

  对甲基苯乙腈 在 sodium hexamethyldisilazane 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 正己烷 为溶剂， 反应 8.0h， 生成 [(1S,2R)-2-(aminomethyl)-2-(4-methylphenyl)cyclopropyl]methanol
  参考文献：
  名称：

  Stereocontrolled Synthesis of Trisubstituted Cyclopropanes:  Expedient, Atom-Economical, Asymmetric Syntheses of (+)-Bicifadine and DOV21947

  摘要：

  An expedient, atom-economical, asymmetric synthesis of 1-aryl-3-azabicyclo[3.1.0]hexanes, including (+)-Bicifadine and DOV21947, in a single-stage through process without isolation of any intermediates has been developed. The key of this synthesis is the in-depth mechanistic understanding of the complicated epoxy nitrile coupling at each reaction stage. Therefore, the desired trisubstituted cyclopropane can be prepared in high ee and yield by controlling the reaction pathway through manipulating the nitrile anion aggregation state.

  DOI：

  10.1021/ol061650w

文献信息

• Chlorination/Cyclodehydration of Amino Alcohols with SOCl₂:  An Old Reaction Revisited
  作者：Feng Xu、Bryon Simmons、Robert A. Reamer、Edward Corley、Jerry Murry、David Tschaen

  DOI：10.1021/jo701877h

  日期：2008.1.1

  A simple, one-pot preparation of cyclic amines via efficient chlorination of amino alcohols with use of SOCl2 has been developed. This approach obviates the need for the classical N-protection/O-activation/cyclization/deprotection sequence commonly employed for this type of transformation. The reaction pathways and the general scope of this method have also been investigated.

  已经开发出一种简单的一锅法，通过使用SOCl 2对氨基醇进行有效氯化来制备环胺。该方法消除了通常用于这种类型的转化的经典的N-保护/ O-活化/环化/去保护序列的需要。还研究了该方法的反应途径和一般范围。
• Methods and compositions for production, formulation and use of 1-aryl-3-azabicyclo[3.1.0]hexanes
  申请人：Skolnick Phil

  公开号：US20060223875A1

  公开（公告）日：2006-10-05

  The invention provides novel 1-aryl-3-azabicyclo[3.1.0]hexanes that are active for modulating biogenic amine transport, along with compositions and methods for using these compounds to treat central nervous system disorders. Certain 1-aryl-3-azabicyclo[3.1.0]hexanes are provided that have at least one substituent on the aryl ring. In other embodiments 1-aryl-3-azabicyclo[3.1.0]hexanes are provided that have a substitution on the nitrogen at the ‘3’ position. In additional embodiments 1-aryl-3-azabicyclo[3.1.0]hexanes are provided which have one substitution on the aryl ring, as well as a substitution on the nitrogen at the ‘3’ position. The invention also provides novel methods of making aryl- and aza-substituted 1-aryl-3-azabicyclo[3.1.0]hexanes, including synthetic methods that form novel intermediate compounds of the invention for producing aryl- and aza-substituted 1-aryl-3-azabicyclo[3.1.0]hexanes.

  本发明提供了新型的1-芳基-3-氮杂双环[3.1.0]己烷，它们对生物胺转运的调节具有活性，以及使用这些化合物治疗中枢神经系统疾病的组合物和方法。提供了某些1-芳基-3-氮杂双环[3.1.0]己烷，其在芳基环上至少有一个取代基。在其他实施例中，提供了在“3”位的氮上有取代基的1-芳基-3-氮杂双环[3.1.0]己烷。在其他实施例中，提供了在芳基环上有一个取代基以及在“3”位的氮上有一个取代基的1-芳基-3-氮杂双环[3.1.0]己烷。本发明还提供了制备芳基和氮取代的1-芳基-3-氮杂双环[3.1.0]己烷的新方法，包括形成本发明的新中间化合物的合成方法，用于生产芳基和氮取代的1-芳基-3-氮杂双环[3.1.0]己烷。
• Methods and compositions for the treatment of neuropathies and related disorders
  申请人：Lippa S. Arnold

  公开号：US20070082939A1

  公开（公告）日：2007-04-12

  The present invention provides novel compositions and methods for treating symptoms associated with neuropathic disorders such as hyperalgesia, allodynia, and parasthesias, using a 1-aryl-3-azabicyclo[3.1.0] hexane. The invention further relates to the use of 1-aryl-3-azabicyclo[3.1.0] hexanes in pharmaceutical compositions and methods for treating neuropathic disorders and related symptoms in mammals. Patients amenable to treatment according to the invention include those suffering from diabetic neuropathies, post-herpetic neuralgia, trigeminal neuralgia, chronic lower back pain, sciatica, idiopathic and post-traumatic neuropathies, HIV-associated neuropathic pain, among many other neuropathic disorders and related symptoms.

  本发明提供了一种新型组合物和方法，用于治疗与神经病理性疾病相关的症状，如过度疼痛、触痛和感觉异常，使用1-芳基-3-氮杂双环[3.1.0]己烷。本发明还涉及在制药组合物中使用1-芳基-3-氮杂双环[3.1.0]己烷以及治疗哺乳动物神经病理性疾病和相关症状的方法。根据本发明可治疗的患者包括患有糖尿病神经病变、带状疱疹后遗神经痛、三叉神经痛、慢性腰痛、坐骨神经痛、特发性和创伤后神经病变、HIV相关神经病理性疼痛等许多神经病理性疾病和相关症状的患者。
• WO2006/96810
  申请人：——

  公开号：——

  公开（公告）日：——
• PROCESS FOR THE SYNTHESIS OF (+) AND (-)-1-ARYL-3-AZABICYCLO[3.1.0]HEXANES
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP2016053B1

  公开（公告）日：2010-11-10