2-Benzyliden-1-azabicyclo[2.2.2]octan-3-on | 52455-72-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 奎宁环
• 英文名称: 2-Benzyliden-1-azabicyclo[2.2.2]octan-3-on
• 英文别名: (E)-2-Benzyliden-3-chinuclidinon；2-benzylidenequinuclidin-3-one；2-Benzyliden-3-quinuclidinon；(2E)-2-benzylidene-1-azabicyclo[2.2.2]octan-3-one
• CAS: 52455-72-8
• 化学式: C₁₄H₁₅NO
• 分子量: 213.279
• InChiKey: RBGFDYWXBIXLSF-JLHYYAGUSA-N

物化性质

• 沸点：
  388.2±32.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-Benzyliden-1-azabicyclo[2.2.2]octan-3-on 在 sodium tetrahydroborate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 0.5h， 以1.89 g的产率得到2-Benzylidene-1-azabicyclo[2.2.2]octan-3-ol
  参考文献：
  名称：

  Identification of a Series of 3-(Benzyloxy)-1-azabicyclo[2.2.2]octane Human NK1 Antagonists

  摘要：

  The synthesis and in vitro and in vivo evaluation of a series of 3-(benzyloxy)-1-azabicyclo[2.2.2]octane NK1 antagonists are described. While a number of 3,5-disubstituted benzyl ethers afford high affinity, the 3,5-bis(trifluoromethyl)benzyl was found to combine high in vitro affinity with good oral activity. Detailed structure-activity relationship studies in conjunction with data from molecular modeling and mutagenesis work have allowed the construction of a model of the pharmacophore. Specific interactions that have been identified include an interaction between His-197 and one of the rings of the benzhydryl, a Lipophilic pocket containing His-265 that the benzyl ether occupies, and a possible hydrogen bond between Gln-165 and the oxygen of the benzyl ether.

  DOI：

  10.1021/jm00024a007
• 作为产物：
  描述：

  3-奎宁环酮盐酸盐 在 四苯硼钠 作用下， 以 溶剂黄146 为溶剂， 生成 2-Benzyliden-1-azabicyclo[2.2.2]octan-3-on
  参考文献：
  名称：

  Mutual Z-/E-isomerization of ferrocenylmethylene- and arylidene-substituted carbo- and heterocycles

  摘要：

  DOI：

  10.1016/s0022-328x(98)00383-0

文献信息

• [EN] PROCESS FOR THE SYNTHESIS OF 2-BENZHYDRYL-3 QUINUCLIDINONE<br/>[FR] PROCÉDÉ DE SYNTHÈSE DE 2-BENZHYDRYL-3 QUINUCLIDINONE
  申请人：PROCOS SPA

  公开号：WO2019086434A1

  公开（公告）日：2019-05-09

  The present invention discloses a process for the preparation of 2-benzhydryl-3-quinuclidinone (1). (I). The process of the invention allows to obtain the intermediate 2-benzhydryl-3-quinuclidinone (1) by reaction of 2-benzylidene-3-quinuclidinone (2) with the Grignard reagent phenylmagnesium halide, in particular chloride or bromide, in the presence of catalytic amounts of copper (I) salts. Taking advantage of the high efficiency of the catalytic system of the copper (I) salts, 2-benzhydryl-3-quinuclidinone (1) is obtained in higher yields than those of the known processes. Advantageously, since the amounts of copper (I) salts are catalytic, the latter can easily be removed from the reaction mixture, and the process is carried out in the presence of solvents less toxic and expensive than those used in the state of the art.

  本发明揭示了一种制备2-苯基二苯基甲基-3-喹啉酮（1）的方法。该发明的方法允许通过2-苯甲烯基-3-喹啉酮（2）与格氏试剂苯基镁卤化物（特别是氯化物或溴化物）在铜（I）盐的催化下反应，从而获得中间体2-苯基二苯基甲基-3-喹啉酮（1）。利用铜（I）盐催化系统的高效性，比已知方法的产率更高地得到2-苯基二苯基甲基-3-喹啉酮（1）。优点在于，由于铜（I）盐的用量是催化剂，后者可以轻松地从反应混合物中去除，并且该过程在使用比现有技术中使用的溶剂更少毒性和昂贵的溶剂的情况下进行。
• Tyrosine kinase inhibitors
  申请人：Rigel Pharmaceuticals, Inc.

  公开号：US10851093B2

  公开（公告）日：2020-12-01

  Disclosed are imidazole compounds, as well as pharmaceutical compositions and methods of use thereof. One embodiment is a compound having the structure and pharmaceutically acceptable salts, prodrugs and N-oxides thereof (and solvates and hydrates thereof), wherein R1, X, Y1, Y2, Y3 and Z are as described herein. In certain embodiments, a compound disclosed herein inhibits a cellular TAM receptor, and can be used to treat disease mediated by or involving the TAM receptor family.

  所公开的是咪唑类化合物及其药物组合物和使用方法。其中一种化合物具有如下结构 及其药学上可接受的盐、原药和 N-氧化物（及其溶解物和水合物），其中 R1、X、Y1、Y2、Y3 和 Z 如本文所述。在某些实施方案中，本文公开的化合物可抑制细胞TAM受体，并可用于治疗由TAM受体家族介导或涉及TAM受体家族的疾病。
• Process for the synthesis of 2-benzhydryl-3 quinuclidinone
  申请人：Procos S.P.A.

  公开号：US11286254B2

  公开（公告）日：2022-03-29

  The present invention discloses a process for the preparation of 2-benzhydryl-3-quinuclidinone (1). (I). The process of the invention allows to obtain the intermediate 2-benzhydryl-3-quinuclidinone (1) by reaction of 2-benzylidene-3-quinuclidinone (2) with the Grignard reagent phenyl-magnesium halide, in particular chloride or bromide, in the presence of catalytic amounts of copper (I) salts. Taking advantage of the high efficiency of the catalytic system of the copper (I) salts, 2-benzhydryl-3-quinuclidinone (1) is obtained in higher yields than those of the known processes. Advantageously, since the amounts of copper (I) salts are catalytic, the latter can easily be removed from the reaction mixture, and the process is carried out in the presence of solvents less toxic and expensive than those used in the state of the art.

  本发明公开了一种制备2-双苯甲基-3-喹诺里西啶酮(1)的方法。(I)。本发明的方法允许通过将2-苯甲酰基-3-喹诺里西啶酮(2)与格氏试剂苯基镁卤化物反应，特别是在铜(I)盐催化量的存在下，获得中间体2-双苯甲基-3-喹诺里西啶酮(1)。利用铜(I)盐催化系统的高效性，可获得比已知方法更高的产率的2-双苯甲基-3-喹诺里西啶酮(1)。而且，由于铜(I)盐的使用量是催化量，它们可以很容易地从反应混合物中去除，并且该过程在毒性较低、成本较低的溶剂存在下进行，与现有技术中使用的溶剂相比。
• GORBYLEVA, O. I.;FILIPENKO, T. YA.;MIXLINA, E. E.;TURCHIN, K. F.;SHEJNKER+, XIMIYA GETEROTSIKL. SOEDIN., 1982, N 6, 793-797
  作者：GORBYLEVA, O. I.、FILIPENKO, T. YA.、MIXLINA, E. E.、TURCHIN, K. F.、SHEJNKER+

  DOI：——

  日期：——
• PROCESS FOR THE SYNTHESIS OF 2-BENZHYDRYL-3 QUINUCLIDINONE
  申请人：Procos S.p.A.

  公开号：EP3704116A1

  公开（公告）日：2020-09-09

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