tert-butyl 4-cyano-4,4-diphenylbutanoate | 931409-69-7

• 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: tert-butyl 4-cyano-4,4-diphenylbutanoate
• CAS: 931409-69-7
• 化学式: C₂₁H₂₃NO₂
• 分子量: 321.419
• InChiKey: DZDLTKILBXLUBQ-UHFFFAOYSA-N

物化性质

• 沸点：
  466.2±45.0 °C(Predicted)
• 密度：
  1.076±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  50.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-cyano-4,4-diphenylbutanoate 在 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 36.0h， 生成 5-oxo-5-[(3R)-3-phenoxypyrrolidin-1-yl]-2,2-diphenylpentanenitrile
  参考文献：
  名称：

  Inhalation by Design: Novel Tertiary Amine Muscarinic M₃ Receptor Antagonists with Slow Off-Rate Binding Kinetics for Inhaled Once-Daily Treatment of Chronic Obstructive Pulmonary Disease

  摘要：

  A novel tertiary amine series of potent muscarinic M-3 receptor antagonists are described that exhibit potential as inhaled long-acting bronchodilators for the treatment of chronic obstructive pulmonary disease. Geminal dimethyl functionality present in this series of compounds confers very long dissociative half-life (slow off-rate) from the M-3 receptor that mediates very long-lasting smooth muscle relaxation in guinea pig tracheal strips. Optimization of pharmacokinetic properties was achieved by combining rapid oxidative clearance with targeted introduction of a phenolic moiety to secure rapid glucuronidation. Together, these attributes minimize systemic exposure following inhalation, mitigate potential drug-drug interactions, and reduce systemically mediated adverse events. Compound 47 (PP-3635659) is identified as a Phase II clinical candidate from this series with in vivo duration of action studies confirming its potential for once-daily use in humans.

  DOI：

  10.1021/jm200884j
• 作为产物：
  描述：

  丙烯酸叔丁酯 、 二苯乙腈 在 氢氧化钾 作用下， 以 甲醇 、 叔丁醇 为溶剂， 反应 23.5h， 以90%的产率得到tert-butyl 4-cyano-4,4-diphenylbutanoate
  参考文献：
  名称：

  WO2007/34325

  摘要：

  公开号：

文献信息

• Carboxamide derivatives as muscarinic receptor antagonists
  申请人：Glossop Alan Paul

  公开号：US20070105831A1

  公开（公告）日：2007-05-10

  The invention relates to compounds of formula processes and intermediates for their preparation, their use as muscarinic antagonists and pharmaceutical composition containing them.

  本发明涉及具有下列公式的化合物、其制备方法和中间体，以及包含它们的抗胆碱能药物组合物。
• Carboxamide Derivatives As Muscarinic Receptor Antagonists
  申请人：Glossop Paul Alan

  公开号：US20100029720A1

  公开（公告）日：2010-02-04

  The invention relates to compounds of formula processes and intermediates for their preparation, their use as muscarinic antagonists and pharmaceutical composition containing them.

  本发明涉及具有以下式的化合物，以及制备它们的过程和中间体，它们作为毒蕈碱受体拮抗剂的用途和包含它们的制药组合物。
• Development of a Scaleable Synthesis of a Geminal Dimethyl Tertiary Amine as an Inhaled Muscarinic Antagonist for the Treatment of COPD
  作者：Barry R. Dillon、Dannielle F. Roberts、David A. Entwistle、Paul A. Glossop、Craig J. Knight、Daniel A. Laity、Kim James、Celine F. Praquin、Ross S. Strang、Christine A. L. Watson

  DOI：10.1021/op200233r

  日期：2012.2.17

  An efficient and scalable process for the synthesis of muscarinic antagonist, PF-3635659 1, is described, illustrating redesign of an analogue-targeted synthesis which contained a scale-limiting rhodium-activated C H amination step. The final route includes a reproducible modified Bouveault reaction which has not previously been reported on a substrate of this complexity, or on such a scale with over 5 kg of the requisite gem-dimethylamine prepared via this methodology.
• US7772223B2
  申请人：——

  公开号：US7772223B2

  公开（公告）日：2010-08-10