(1R,2R)-N1,N2-bis(4-chloro-8-methoxyquinolin-2-yl)cyclohexane-1,2-diamine | 1370730-92-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (1R,2R)-N1,N2-bis(4-chloro-8-methoxyquinolin-2-yl)cyclohexane-1,2-diamine
• 英文别名: (1R,2R)-1-N,2-N-bis(4-chloro-8-methoxyquinolin-2-yl)cyclohexane-1,2-diamine
• CAS: 1370730-92-9
• 化学式: C₂₆H₂₆Cl₂N₄O₂
• 分子量: 497.424
• InChiKey: GCXNUJDHAWKQJP-WOJBJXKFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  68.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  四氢吡咯 、 (1R,2R)-N1,N2-bis(4-chloro-8-methoxyquinolin-2-yl)cyclohexane-1,2-diamine 反应 17.0h， 以62%的产率得到(1R,2R)-N₁,N₂-bis(8-methoxy-4-(pyrrolidin-1-yl)quinolin-2-yl)cyclohexane-1,2-diamine
  参考文献：
  名称：

  The hydrophobically-tagged MDM2–p53 interaction inhibitor Nutlin-3a-HT is more potent against tumor cells than Nutlin-3a

  摘要：

  疏水标记的MDM2-p53相互作用抑制剂Nutlin-3a-HT在p53重新激活时降低MDM2水平，对肿瘤细胞的作用比Nutlin-3a更强。

  DOI：

  10.1039/c9cc07795b
• 作为产物：
  描述：

  邻甲氧基苯胺 在 potassium tert-butylate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 、 三氯氧磷 作用下， 以 甲苯 为溶剂， 反应 10.1h， 生成 (1R,2R)-N1,N2-bis(4-chloro-8-methoxyquinolin-2-yl)cyclohexane-1,2-diamine
  参考文献：
  名称：

  The hydrophobically-tagged MDM2–p53 interaction inhibitor Nutlin-3a-HT is more potent against tumor cells than Nutlin-3a

  摘要：

  疏水标记的MDM2-p53相互作用抑制剂Nutlin-3a-HT在p53重新激活时降低MDM2水平，对肿瘤细胞的作用比Nutlin-3a更强。

  DOI：

  10.1039/c9cc07795b

文献信息

• STEREOSELECTIVE METHODS, CATALYSTS AND INTERMEDIATES FOR THE SYNTHESIS OF (-)-NUTLIN-3 AND RELATED COMPOUNDS
  申请人：Johnston Jeffrey N.

  公开号：US20120088915A1

  公开（公告）日：2012-04-12

  The present invention provides methods and intermediates are provided for the preparation of (−)-Nutlin-3. Methods and intermediates are also provided for the enantioselective addition of aryl nitromethanes to aldimines. Bis(amidine) catalysts for the use in these and other reactions are also provided.

  本发明提供了用于制备(−)-Nutlin-3的方法和中间体。还提供了用于对芳基硝基甲烷与醛亚胺进行对映选择性加成的方法和中间体。此外，还提供了用于这些及其他反应中使用的双(胺基)催化剂。
• Development of an Intermittent-Flow Enantioselective Aza-Henry Reaction Using an Arylnitromethane and Homogeneous Brønsted Acid–Base Catalyst with Recycle
  作者：Sergey V. Tsukanov、Martin D. Johnson、Scott A. May、Morgan Rosemeyer、Michael A. Watkins、Stanley P. Kolis、Matthew H. Yates、Jeffrey N. Johnston

  DOI：10.1021/acs.oprd.5b00245

  日期：2016.2.19

  continuous stirred tank reactor (CSTR). A significant benefit of this strategy was the integration of an organocatalytic enantioselective reaction with straightforward product separation, including recycle of the catalyst, resulting in increased intensity of the process by maintaining high catalyst concentration in the reactor. A continuous campaign confirmed that these conditions could effectively provide high

  使用均相的布朗斯台德酸碱催化剂在芳基硝基甲烷和Boc保护的芳基醛亚胺之间进行立体选择性aza-Henry反应，从批处理形式转换为自动间歇流动过程。这项工作证明了具有产品结晶和试剂缓慢添加的新型间歇流装置的优点，这不适用于标准连续设备：活塞流管反应器（PFR）或连续搅拌釜反应器（CSTR）。该策略的显着优点是有机催化对映选择性反应与直接的产物分离（包括催化剂的循环）相结合，通过保持反应器中的高催化剂浓度而提高了工艺强度。
• Preparation of (−)-Nutlin-3 Using Enantioselective Organocatalysis at Decagram Scale
  作者：Tyler A. Davis、Anna E. Vilgelm、Ann Richmond、Jeffrey N. Johnston

  DOI：10.1021/jo401321a

  日期：2013.11.1

  Chiral nonracemic cis-4,5-bis(aryl)imidazolines have emerged as a powerful platform for the development of cancer chemotherapeutics, stimulated by the Hoffmann-La Roche discovery that Nutlin-3 can restore apoptosis in cells with wild-type p53. The lack of efficient methods for the enantioselective synthesis of cis-imidazolines, however, has limited their more general use. Our disclosure of the first enantioselective synthesis of (-)-Nutlin-3 provided a basis to prepare larger amounts of this tool used widely in cancer biology. Key to the decagram-scale synthesis described here was the discovery of a novel bis(amidine) organocatalyst that provides high enantioselectivity at warmer reaction temperature (-20 degrees C) and low catalyst loadings. Further refinements to the procedure led to the synthesis of (-)-Nutlin-3 in a 17 g batch and elimination of all but three chromatographic purifications.
• US8889863B2
  申请人：——

  公开号：US8889863B2

  公开（公告）日：2014-11-18