dehydromequitazine | 151129-13-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻嗪类
• 英文名称: dehydromequitazine
• 英文别名: Mequitazine Impurity 4；10-(1-azabicyclo[2.2.2]oct-2-en-3-ylmethyl)phenothiazine
• CAS: 151129-13-4
• 化学式: C₂₀H₂₀N₂S
• 分子量: 320.458
• InChiKey: ZJKGVIZUGFYBCS-UHFFFAOYSA-N

物化性质

• 熔点：
  149 °C
• 沸点：
  490.5±25.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  31.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  dehydromequitazine 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 24.0h， 以91%的产率得到美喹他嗪
  参考文献：
  名称：

  Expedient Synthesis of Mequitazine an Antihistaminic Drug by Palladium Catalyzed Allylic Alkylation of Sodium Phenothiazinate

  摘要：

  报告了一种简短而直接的抗组胺药物美克替嗪的合成方法，该方法基于在温和条件下，采用钯催化的烯丙基烷基化反应，将1-氮杂双环[2.2.2]辛-2-烯-3-基乙酸甲酯与苯噻嗪钠进行反应。

  DOI：

  10.1248/cpb.57.1300
• 作为产物：
  描述：

  吩噻嗪 、 1-aza-bicyclo[2.2.2]oct-2-en-3-ylmethyl acetate 在 sodium hydride 、 四(三苯基膦)钯 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 反应 3.42h， 以92%的产率得到dehydromequitazine
  参考文献：
  名称：

  Expedient Synthesis of Mequitazine an Antihistaminic Drug by Palladium Catalyzed Allylic Alkylation of Sodium Phenothiazinate

  摘要：

  报告了一种简短而直接的抗组胺药物美克替嗪的合成方法，该方法基于在温和条件下，采用钯催化的烯丙基烷基化反应，将1-氮杂双环[2.2.2]辛-2-烯-3-基乙酸甲酯与苯噻嗪钠进行反应。

  DOI：

  10.1248/cpb.57.1300

文献信息

• NOVEL QUINUCLIDINE DERIVATIVE USEFUL IN THE PREPARATION OF MEQUITAZINE
  申请人：Mioskowski Charles

  公开号：US20100105897A1

  公开（公告）日：2010-04-29

  The invention relates to a 1-aza-bicyclo[2.2.2]oct-2-en-3-ylmethyl acetate of the formula (I), wherein said compound is useful as a synthesis intermediate for the production of mequitazine.

  该发明涉及一种式(I)的1-aza-bicyclo[2.2.2]辛-2-烯-3-甲基醋酸酯，该化合物可用作生产美喹嗪的合成中间体。
• NEW QUINUCLIDINE DERIVATIVE USEFUL IN THE PREPARATION OF MEQUITAZINE
  申请人：MIOSKOWSKI Charles

  公开号：US20120088917A1

  公开（公告）日：2012-04-12

  The invention relates to a 1-aza-bicyclo [2.2.2] oct-2-en-3-ylmethyl acetate of the formula (I), wherein said compound is useful as a synthesis intermediate for the production of mequitazine.

  本发明涉及一种式为(I)的1-aza-bicyclo [2.2.2] oct-2-en-3-ylmethyl乙酸酯，其中该化合物可用作合成中间体，用于生产美可替嗪。
• Process for the preparation of a highly pure phenothiazine compound
  申请人：SUMIKA FINE CHEMICALS Co., Ltd.

  公开号：EP1074552A2

  公开（公告）日：2001-02-07

  According to the method of the present invention, an alkali metal compound, dimethyl sulfoxide, trimethyloxosulfonium halide and 3-quinuclidinone are added in a specific order to give the following compound [II]. This compound is, without treatment or isolation, directly reacted with an alkali metal salt of phenothiazine to give the following compound [III], from which the following compound [I] is obtained. During the production of compound [I], a by-produced acidic gas is removed and water is added to ensure industrial, safe and efficient production of compound [I] at a constantly high yield. Inasmuch as the present invention enables production of the following highly pure compound [A] by eliminating hydrogen halide of compound [I] in glyme in the presence of at least one kind of a base selected from potassium hydroxide and potassium alkoxide, compound [A] having a high purity of not less than 85 mol% can be provided.

  根据本发明的方法，按特定顺序加入碱金属化合物、二甲基亚砜、三羟甲基锍卤化物和 3-奎宁环酮，得到下列化合物[II]。该化合物不经处理或分离，直接与吩噻嗪的碱金属盐反应，得到以下化合物[III]，并由此得到以下化合物[I]。在生产化合物[I]的过程中，要除去副产的酸性气体，并加入水，以确保工业化、安全和高效地生产化合物[I]，并保持较高的产率。由于本发明可以在至少一种从氢氧化钾和氧化钾中选出的碱存在下，通过在甘汞中消除化合物[I]的卤化氢来生产下列高纯度化合物[A]，因此可以提供纯度不低于 85 摩尔%的高纯度化合物[A]。
• Short and Straightforward Enantioselective Synthesis of Both Enantiomers of Mequitazine through Iridium-Catalyzed Asymmetric Hydrogenation of a Nonfunctionalized Cyclic Enamine
  作者：Philippe Maillos、Virginie Ratovelomanana-Vidal、Sébastien Gauthier、Laurent Larquetoux、Marc Nicolas、Tahar Ayad

  DOI：10.1055/s-0033-1341274

  日期：——

  A short and straightforward asymmetric synthesis of both enantiomers of the antihistaminic drug mequitazine is reported. This atom-economical and attractive method features an iridium-catalyzed asymmetric hydrogenation of a nonfunctionalized cyclic enamine as a key step to install the C-3-stereogenic center. After a full investigation of the effects of catalyst precursors, ligands, solvents, temperature, and hydrogen pressure, mequitazine (1) is obtained in good yield (up to 80%) and with acceptable enantiomeric excesses up to 47%.
• NOUVEAU DÉRIVE DE LA QUINUCLIDINE UTILE DANS LA PRÉPARATION DE LA MEQUITAZINE
  申请人：Pierre Fabre Medicament

  公开号：EP2109609B1

  公开（公告）日：2013-06-12