1,1-二甲基-2-苯并革-3-基)苯基]乙烯]- | 1040351-42-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噁庚英
• 中文名称: 1,1-二甲基-2-苯并革-3-基)苯基]乙烯]-
• 中文别名: 孟鲁司特醚杂质；孟鲁司特醚
• 英文名称: (E)-2-(3-(1,1-dimethyl-1,3,4,5-tetrahydrobenzo[c]oxepin-3-yl)styryl)-7-chloroquinoline
• 英文别名: 7-chloro-2-[(E)-2-[3-(1,1-dimethyl-4,5-dihydro-3H-2-benzoxepin-3-yl)phenyl]ethenyl]quinoline
• CAS: 1040351-42-5；168214-67-3
• 化学式: C₂₉H₂₆ClNO
• 分子量: 439.985
• InChiKey: LOMMSDDMLICVMB-XNTDXEJSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  32
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  22.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2-[2-[(3S)-3-[3-[(E)-2-(7-氯-2-喹啉基)乙烯基]苯基]-3-[(甲烷磺酰基)氧基]丙基]苯基]-2-丙醇 在 chromatography under protic conditions 作用下， 生成 2-(2-((E)-3-(3-((E)-2-(7-Chloroquinolin-2-yl)vinyl)phenyl)allyl)phenyl)propan-2-ol 、 1,1-二甲基-2-苯并革-3-基)苯基]乙烯]-
  参考文献：
  名称：

  Kinetic Analysis and Subambient Temperature Chromatography of an Active Ester

  摘要：

  The inherent instability of active esters provides a chromatographic challenge. A normal phase HPLC gradient was developed using nonprotic solvents and a diol stationary phase to determine the impurity profile of a mesylate which, under protic conditions, undergoes intramolecular ring closure to a cyclic ether. On-column cyclization of the analyte was found to be extensive at room temperature but insignificant at -30 degrees C. The on-column reaction rate was determined as a function of column temperature, and an Arrhenius activation energy was calculated.

  DOI：

  10.1021/ac00109a059

文献信息

• [EN] PROCESS FOR THE PREPARATION OF MONTELUKAST SODIUM<br/>[FR] PROCÉDÉ POUR LA PRÉPARATION DE MONTÉLUKAST SODIQUE
  申请人：RICHTER GEDEON NYRT

  公开号：WO2012020271A1

  公开（公告）日：2012-02-16

  The present invention relates to a process for the synthesis of Montelukast sodium of formula I the chemical name of which is [(R)-(E)]-1-[[[1-[3-[2-(7-chloro-2- quinolinyl)ethenyl]phenyl] -3 - [2-( 1 -hydroxy- 1 -methylethyl)phenyl]propyl] thio]methyl] - -cyclopropaneacetic acid sodium salt. The present invention further provides compounds of general formulae V, VI, VIb and VIII as new intermediates.

  本发明涉及一种用于合成Montelukast钠的过程，其化学名称为[(R)-(E)]-1-[[[1-[3-[2-(7-氯-2-喹啉基)乙烯基]苯基]-3-[2-(1-羟基-1-甲基乙基)苯基]丙基]硫基]甲基]- -环丙烷乙酸钠盐的化学式I。本发明还提供了通式V、VI、VIb和VIII的新中间体化合物。
• PROCESS FOR PREPARING MONTELUKAST SODIUM CONTAINING CONTROLLED LEVELS OF IMPURITIES
  申请人：Brand Michael

  公开号：US20080188664A1

  公开（公告）日：2008-08-07

  The present invention is directed to a process of preparing montelukast or a salt thereof with minimal amounts of impurities, such as a dehydration impurity (compound (VI)) or a cyclic ether impurity (compound (VIII)).

  本发明涉及一种制备蒙特卢卡斯特或其盐的方法，该方法可在最小量的杂质存在下进行，例如脱水杂质（化合物（VI））或环醚杂质（化合物（VIII））。
• Process for the purification of montelukast
  申请人：ESTEVE QUIMICA, S.A.

  公开号：EP1886997A1

  公开（公告）日：2008-02-13

  It relates to a process for the purification of Montelukast, or pharmaceutically salts thereof, or solvates thereof, including stereoisomers or mixture thereof which comprises carrying out a specific set of selective solvent extractions of Montelukast or its impurities in a mixture of an organic solvent and water at specific ranges of pH and temperature which depend on the type of impurities to remove. In particular, it comprises at least one wash of an aqueous phase containing crude Montelukast in salt form with an organic solvent, at a pH comprised between 12.0 and 13.5; and optionally one or more washes of the resulting aqueous phase with an organic solvent at a pH comprised between 8.5 and 10.0. Montelukast is recovered by acidification at a pH comprised between 4.5 and 8.0 and solvent extraction, and is isolated either as acid or in salt form.

  这涉及一种用于纯化蒙特鲁卡斯特或其药用盐或溶剂结晶体的过程，包括立体异构体或其混合物，其包括在特定范围的pH和温度下，在有机溶剂和水的混合物中进行特定的选择性溶剂萃取蒙特鲁卡斯特或其杂质的一套步骤，这取决于要去除的杂质类型。具体而言，它包括至少用一个有机溶剂对含有盐形式的粗蒙特鲁卡斯特的水相进行洗涤，其pH值介于12.0和13.5之间；并且可选地，用一个或多个有机溶剂对结果水相进行洗涤，其pH值介于8.5和10.0之间。蒙特鲁卡斯特通过在pH值介于4.5和8.0之间的酸化和溶剂萃取中回收，并以酸或盐形式隔离。
• METHOD FOR THE PREPARATION OF MONTELUKAST
  申请人：Halama Ales

  公开号：US20100174083A1

  公开（公告）日：2010-07-08

  A method of preparation of Montelukast of formula (I) by reaction of the compound of formula (III) and a compound of formula (IX), characterized in that the reaction is carried out in the presence of a base, an inert solvent and a component increasing selectivity of the process, especially of a polyether of general formula (XIII), wherein R stands for hydrogen or an alkyl and the value of n varies from 1 to 40, polyethyleneglycol of general formula (XIV), wherein n=1 to 40 or a crown-ether of formulae (XV), (XVI) or (XVII).

  根据公式（I）的蒙特卢卡斯特制备方法，通过化合物公式（III）和化合物公式（IX）的反应制备，其特征在于在碱、惰性溶剂和增加过程选择性的组分（特别是一般公式（XIII）的聚醚）的存在下进行反应，其中R代表氢或烷基，n值在1到40之间变化，一般公式（XIV）的聚乙二醇，其中n=1到40，或公式（XV）、（XVI）或（XVII）的冠醚。
• PROCESS FOR PREPARATION OF MONTELUKAST SODIUM
  申请人：Laurus Labs Private Limited

  公开号：US20150299127A1

  公开（公告）日：2015-10-22

  Disclosed is a process for the preparation of montelukast sodium. The process comprises a) reacting 2-(2-(3(S)-(3-(2-(7-chloro-2-quinolinyl)-ethenyl)phenyl)-3-hydroxypropyl)phenyl)-2-propanol with methane sulfonyl chloride and coupling the resultant mesylate compound with 1-(mercaptomethyl)cyclopropane acetic acid in presence of a base and free alkali source followed by saltification with an amine in a single step reaction and b) converting the montelukast amine salt to montelukast sodium salt.

  本发明揭示了一种制备蒙特卢卡斯钠的方法。该方法包括a)将2-(2-(3(S)-(3-(2-(7-氯-2-喹啉基)-乙烯基)苯基)-3-羟基丙基)苯基)-2-丙醇与甲烷磺酰氯反应，并在碱和自由碱源存在下将产生的甲磺酸酯化合物与1-(巯基甲基)环丙基乙酸偶联，然后在单步反应中与胺盐酸化合成盐，并b)将蒙特卢卡斯胺盐转化为蒙特卢卡斯钠盐。