exo-3-azatricyclo[4.2.1.0^2,5]non-7-en-4-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: exo-3-azatricyclo[4.2.1.0^2,5]non-7-en-4-one
• 英文别名: (+/-)-3-aza-tricyclo[4.2.1.0^2,5]non-7-en-4-one；(1S,2S,5R,6R)-3-azatricyclo[4.2.1.02,5]non-7-en-4-one
• 化学式: C₈H₉NO
• 分子量: 135.166
• InChiKey: WBZQHVKGKQXWMW-WNJXEPBRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  exo-3-azatricyclo[4.2.1.0^2,5]non-7-en-4-one 在 4-二甲氨基吡啶 作用下， 以 四氢呋喃 、 甲基叔丁基醚 、 水 为溶剂， 反应 162.0h， 生成 (1R,2R,3S,4S)-3-((tert-butoxycarbonyl)amino)bicyclo[2.2.1]hept-5-ene-2-carboxylic acid
  参考文献：
  名称：

  Development and Scale-Up of an Optimized Route to the ALK Inhibitor CEP-28122

  摘要：

  Evolution of the process strategies to prepare CEP-28122, an anaplastic lymphoma kinase (ALK) inhibitor, is presented. The initial medicinal chemistry route, used for the preparation of key supplies for biological screening, is reviewed. In addition, the process research and development of the final optimized process for manufacture of preclinical and clinical supplies is discussed. Details regarding a blocking group strategy for selective nitration; discovery of a one-pot transfer hydrogenation to effect a reductive amination, nitro group reduction, and dehalogenation; an enzymatic resolution of a critical intermediate; and the discovery of a novel, stable, in situ generated mixed mesylate hydrochloride salt of the API are disclosed.

  DOI：

  10.1021/op200313v
• 作为产物：
  描述：

  4-Oxo-3-aza-exo-tricyclo<4.2.1.0>non-7-en-3-sulfonylchlorid 在 碳酸氢钠 、 sodium carbonate 、 sodium sulfite 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 1.25h， 以8.89 kg的产率得到exo-3-azatricyclo[4.2.1.0^2,5]non-7-en-4-one
  参考文献：
  名称：

  Development and Scale-Up of an Optimized Route to the ALK Inhibitor CEP-28122

  摘要：

  Evolution of the process strategies to prepare CEP-28122, an anaplastic lymphoma kinase (ALK) inhibitor, is presented. The initial medicinal chemistry route, used for the preparation of key supplies for biological screening, is reviewed. In addition, the process research and development of the final optimized process for manufacture of preclinical and clinical supplies is discussed. Details regarding a blocking group strategy for selective nitration; discovery of a one-pot transfer hydrogenation to effect a reductive amination, nitro group reduction, and dehalogenation; an enzymatic resolution of a critical intermediate; and the discovery of a novel, stable, in situ generated mixed mesylate hydrochloride salt of the API are disclosed.

  DOI：

  10.1021/op200313v

文献信息

• [EN] PROCESS FOR MAKING BETA 3 AGONISTS AND INTERMEDIATES<br/>[FR] PROCÉDÉ DE PRÉPARATION D'AGONISTES BÊTA 3 ET D'INTERMÉDIAIRES ASSOCIÉS
  申请人：MERCK SHARP & DOHME

  公开号：WO2013062881A1

  公开（公告）日：2013-05-02

  The present invention is directed to processes for preparing beta 3 agonists of Formula (I) and Formula (II) and their intermediates. The beta 3 agonists are useful in the treatment of certain disorders, including overactive bladder, urinary incontinence, and urinary urgency.

  本发明涉及制备β3激动剂的方法，其化学式为(I)和(II)，以及它们的中间体。这些β3激动剂在治疗某些疾病方面很有用，包括膀胱过度活跃、尿失禁和尿急。
• [1,2,4]THIADIAZINE 1,1-DIOXIDE COMPOUNDS
  申请人：Ruebsam Frank

  公开号：US20090306057A1

  公开（公告）日：2009-12-10

  The invention is directed to [1,2,4]thiadiazine 1,1-dioxide compounds and pharmaceutical compositions containing such compounds that are useful in treating infections by hepatitis C virus.

  这项发明涉及[1,2,4]噻二嗪1,1-二氧化物化合物和含有这种化合物的药物组合物，可用于治疗丙型肝炎病毒感染。
• Stereocontrolled One-Step Synthesis of Difunctionalised Cispentacin Derivatives through Ring-Opening Metathesis of Norbornene β-Amino Acids
  作者：Loránd Kiss、Márton Kardos、Enikő Forró、Ferenc Fülöp

  DOI：10.1002/ejoc.201403493

  日期：2015.2

  Through the ring-opening metathesis of norbornene or oxanorbornene β-amino acids with ethylene in the presence of certain Ru catalysts, a facile and convenient stereocontrolled one-step method was devised for the preparation of divinylated cispentacins and oxacyclic cispentacin stereoisomers with four chiral centres. The products are interesting scaffolds for peptide chemistry and for the synthesis of novel

  通过在某些Ru催化剂存在下降冰片烯或氧杂降冰片烯β-氨基酸与乙烯的开环复分解反应，设计了一种简便的立体控制一步法制备具有四个手性中心的二乙烯基顺喷素和氧杂环戊烯酸立体异构体。这些产品是用于肽化学和通过烯键转换合成新型功能化材料的有趣支架。开环复分解不影响起始分子的手性中心，因此它们的立体化学是保守的，并决定了产物中手性中心的构型。
• Enantiomeric discrimination of cyclic β-amino acids using (18-crown-6)-2,3,11,12-tetracarboxylic acid as a chiral NMR solvating agent
  作者：Cora D. Chisholm、Ferenc Fülöp、Eniko Forró、Thomas J. Wenzel

  DOI：10.1016/j.tetasy.2010.07.031

  日期：2010.9

  (18-Crown-6)-2,3,11,12-tetracarboxylic acid is an excellent chiral NMR solvating agent for cyclic β-amino acids with cyclopentane, cyclohexane, cycloheptane, cyclopentene, cyclohexene, bicyclo[2.2.1]heptane, and bicyclo[2.2.1]heptene rings. The crown ether was added to the neutral β-amino acids in methanol-d4. A neutralization reaction between the crown ether and β-amino acid forms the ammonium ion needed for

  （18-Crown-6）-2,3,11,12-四羧酸是一种出色的手性NMR溶剂，用于环β-氨基酸与环戊烷，环己烷，环庚烷，环戊烯，环己烯，双环[2.2.1]庚烷，和双环[2.2.1]庚烯环。将冠醚加入到甲醇-d 4中的中性β-氨基酸中。冠醚和β-氨基酸之间的中和反应形成有利缔合所需的铵离子。在所研究的每种底物上均观察到两个氢原子α与β-氨基酸的胺和羧酸部分的对映体区别。对于相似结构的底物，某些氢原子的对映异构顺序的变化趋势与绝对构型相关。
• Selective Transformation of Norbornadiene into Functionalized Azaheterocycles and β‐Amino Esters with Stereo‐ and Regiocontrol
  作者：Anas Semghouli、Zsanett Benke、Attila M. Remete、Tamás T. Novák、Santos Fustero、Loránd Kiss

  DOI：10.1002/asia.202100956

  日期：2021.12

  An efficient stereocontrolled and selective synthesis of some functionalized azaheterocycles has been achieved from readily available norbornene β-amino acids or norbornene β-lactams by ring-opening/ring-closing metathesis protocols.

  通过开环/闭环复分解方案，已从现成的降冰片烯 β-氨基酸或降冰片烯 β-内酰胺中实现了一些功能化氮杂杂环的有效立体控制和选择性合成。