((1R,2R,3S,4S)-3-carbamoyl-bicyclo[2.2.1]hept-5-en-2-yl)-carbamic acid tert-butyl ester | 871357-92-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ((1R,2R,3S,4S)-3-carbamoyl-bicyclo[2.2.1]hept-5-en-2-yl)-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[(1R,2R,3S,4S)-3-carbamoyl-2-bicyclo[2.2.1]hept-5-enyl]carbamate
• CAS: 871357-92-5
• 化学式: C₁₃H₂₀N₂O₃
• 分子量: 252.313
• InChiKey: DJGMHEFBXRYKPW-XFWSIPNHSA-N

物化性质

• 沸点：
  446.9±45.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  81.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ((1R,2R,3S,4S)-3-carbamoyl-bicyclo[2.2.1]hept-5-en-2-yl)-carbamic acid tert-butyl ester 在 碳酸氢钠 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 18.5h， 生成 (2-外,3-外)-3-(2,5-二氯嘧啶-4-基氨基)二环[2.2.1]庚-5-烯-2-甲酰胺
  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：

  (1S,2S,3R,4R)-3-((tert-butoxycarbonyl)amino)bicyclo[2.2.1]hept-5-ene-2-carboxylic acid 在 二碳酸二叔丁酯 、 碳酸氢铵 作用下， 以95%的产率得到((1R,2R,3S,4S)-3-carbamoyl-bicyclo[2.2.1]hept-5-en-2-yl)-carbamic acid tert-butyl ester
  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

• Stereoisomerically Enriched 3-Aminocarbonyl Bicycloheptene Pyrimidinediamine Compounds and their Uses
  申请人：Argade Ankush

  公开号：US20080051412A1

  公开（公告）日：2008-02-28

  The present invention provides stereoisomers and stereoisomeric mixtures of 3-aminocarbonyl-bicycloheptene-2,4-pyrimidinediamine compounds having antiproliferative activity, compositions comprising the compounds and methods of using the compounds to inhibit cellular proliferation and to treat proliferate diseases such as tumorigenic cancers.

  本发明提供了具有抗增殖活性的3-氨基羰基-双环庚烯-2,4-嘧啶二胺化合物的立体异构体和立体异构体混合物，包括含有该化合物的组合物和使用该化合物抑制细胞增殖和治疗增殖性疾病，如肿瘤性癌症的方法。
• FUSED BICYCLIC DERIVATIVES OF 2,4-DIAMINOPYRIMIDINE AS ALK AND c-MET INHIBITORS
  申请人：Ahmed Gulzar

  公开号：US20090221555A1

  公开（公告）日：2009-09-03

  The present invention provides a compound of formula I or II or a pharmaceutically acceptable salt form thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , A 1 , A 2 , A 3 , A 4 , and A 5 , are as defined herein. The compounds of formula I or II have ALK and/or c-Met inhibitory activity, and may be used to treat proliferative disorders.

  本发明提供公式I或II化合物或其药学上可接受的盐形式，其中R1、R2、R3、R4、R5、A1、A2、A3、A4和A5如本文所定义。公式I或II化合物具有ALK和/或c-Met抑制活性，可用于治疗增殖性疾病。
• Stereoisomerically Enriched 3-Aminocarbonyl Bicycloheptene Pyrimidinediamine Compounds And Their Uses
  申请人：Argade Ankush

  公开号：US20070179140A1

  公开（公告）日：2007-08-02

  The present invention provides stereoisomers and stereoisomeric mixtures of 3-aminocarbonyl-bicycloheptene-2,4-pyrimidinediamine compounds having antiproliferative activity, compositions comprising the compounds and methods of using the compounds to inhibit cellular proliferation and to treat proliferate diseases such as tumorigenic cancers.

  本发明提供了3-氨基甲酰基双环庚烯-2,4-嘧啶二胺化合物的立体异构体和立体异构体混合物，具有抗增殖活性，包括该化合物的组合物和使用该化合物抑制细胞增殖和治疗增殖性疾病，如肿瘤癌症的方法。
• Cycloalkyl Substituted Pyrimidinediamine Compounds And Their Uses
  申请人：Li Hui

  公开号：US20070299060A1

  公开（公告）日：2007-12-27

  The present disclosure provides 2,4-pyrimidinediamine compounds having antiproliferative activity, compositions comprising the compounds and methods of using the compounds to inhibit cellular proliferation and to treat proliferate diseases such as tumorigenic cancers.

  本公开提供具有抗增殖活性的2,4-嘧啶二胺化合物，包含该化合物的组合物以及使用该化合物抑制细胞增殖和治疗增殖性疾病，如肿瘤性癌症的方法。
• Fused Bicyclic Derivatives of 2,4-Diaminopyrimidine as ALK and c-MET Inhibitors
  申请人：Ahmed Gulzar

  公开号：US20120165519A1

  公开（公告）日：2012-06-28

  The present invention provides a compound of formula I or II or a pharmaceutically acceptable salt form thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , A 1 , A 2 , A 3 , A 4 , and A 5 , are as defined herein. The compounds of formula I or II have ALK and/or c-Met inhibitory activity, and may be used to treat proliferative disorders.

  本发明提供了式I或II的化合物或其药学上可接受的盐形式，其中R1、R2、R3、R4、R5、A1、A2、A3、A4和A5如本文所定义。式I或II的化合物具有ALK和/或c-Met抑制活性，并可用于治疗增生性疾病。