4-(E)-4-(dimethylamino)-1-(4-fluorophenyl)but-1-enyl-3-(hydroxymethyl)benzonitrile | 1370643-23-4

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(E)-4-(dimethylamino)-1-(4-fluorophenyl)but-1-enyl-3-(hydroxymethyl)benzonitrile
• 英文别名: 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-buten-1-yl]-3-(hydroxymethyl)-benzonitrile (Citalopram Olefinic Impurity)；4-[(E)-4-(dimethylamino)-1-(4-fluorophenyl)but-1-enyl]-3-(hydroxymethyl)benzonitrile
• CAS: 1370643-23-4
• 化学式: C₂₀H₂₁FN₂O
• 分子量: 324.398
• InChiKey: IAICSOQOSARWDY-RMOCHZDMSA-N

物化性质

• 沸点：
  504.9±50.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  47.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  西酞普兰 、 4-(E)-4-(dimethylamino)-1-(4-fluorophenyl)but-1-enyl-3-(hydroxymethyl)benzonitrile 在 甲基磺酰氯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以45%的产率得到西酞普兰烯二聚体氯化物
  参考文献：
  名称：

  Process Development of Citalopram/Escitalopram Oxalate: Isolation and Synthesis of Novel Impurities

  摘要：

  During process optimization of Escitalopram oxalate novel impurities, 6 and 7 were observed, which were isolated and characterized, and the proposed structure was confirmed by chemical synthesis. Investigation of the cause of impurities formation improved the yield and purity of the drug product during the bulk API synthesis.

  DOI：

  10.1021/op300039c
• 作为产物：
  描述：

  在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以16.5%的产率得到4-(E)-4-(dimethylamino)-1-(4-fluorophenyl)but-1-enyl-3-(hydroxymethyl)benzonitrile
  参考文献：
  名称：

  Process Development of Citalopram/Escitalopram Oxalate: Isolation and Synthesis of Novel Impurities

  摘要：

  During process optimization of Escitalopram oxalate novel impurities, 6 and 7 were observed, which were isolated and characterized, and the proposed structure was confirmed by chemical synthesis. Investigation of the cause of impurities formation improved the yield and purity of the drug product during the bulk API synthesis.

  DOI：

  10.1021/op300039c

文献信息

• Crystalline composition containing escitalopram
  申请人：Jensen B. Kim

  公开号：US20050196453A1

  公开（公告）日：2005-09-08

  The present invention discloses crystalline particles of escitalopram oxalate which either have a broad particle size distribution or comprise at least 0.01% (w/w) of Z-4-(4-dimethylamino-1-(4-fluorophenyl)-but-1-enyl)-3-hydroxymethyl-benzonitrile, said particles being suitable for use in direct compression. Furthermore, the invention discloses a novel pharmaceutical unit dosage form containing such crystalline particles of escitalopram oxalate as well as methods for manufacture of such crystalline particles of escitalopram oxalate Finally, the invention provides a method for reduction of the amount of hydroxyl containing impurities in a solution of citalopram or escitalopram.

  本发明公开氧化艾司西酞普兰结晶颗粒，其具有广泛的颗粒大小分布或含有至少0.01%（w/w）的Z-4-(4-二甲基氨基-1-(4-氟苯基)-丁-1-烯基)-3-羟甲基-苯甲腈，这些颗粒适用于直接压缩。此外，该发明还公开了一种含有这种氧化艾司西酞普兰结晶颗粒的新型药物单剂量形式，以及制造这种结晶颗粒的方法。最后，该发明提供了一种减少西酞普兰或氧化艾司西酞普兰溶液中含有羟基杂质量的方法。
• CRYSTALLINE BASE OF ESCITALOPRAM AND ORODISPERSIBLE TABLETS COMPRISING ESCITALOPRAM BASE
  申请人：Dancer Robert

  公开号：US20080161584A1

  公开（公告）日：2008-07-03

  The present invention relates to the crystalline base of the well known antidepressant drug escitalopram, S-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzo-furancarbonitrile, formulations of said base, a process for the preparation of purified salts of escitalopram, such as the oxalate, using the base, the salts obtained by said process and formulations containing such salts, and a process for the preparation of purified escitalopram free base or salts of escitalopram, such as the oxalate, using the hydrobromide, the salts obtained by said process and formulations containing such salts. Finally the present invention relates to an orodispersible tablet having a hardness of at least 22 N and an oral-disintegration time of less than 120 s and comprising an active pharmaceutical ingredient adsorbed onto a water soluble filler wherein the active pharmaceutical ingredient has a melting point in the range of 40-100° C., as well as a method for making such an orodispersible tablet.

  本发明涉及已知抗抑郁药物艾司西酞普兰的晶体基础物，即S-1-[3-(二甲氨基)丙基]-1-(4-氟苯基)-1,3-二氢-5-异苯并呋喃-2-碳腈，该基础物的制剂，使用基础物制备纯化艾司西酞普兰盐（如草酸盐）的过程，通过该过程获得的盐以及含有这种盐的制剂，以及使用羟溴酸盐制备纯化艾司西酞普兰游离基或艾司西酞普兰盐（如草酸盐）的过程，通过该过程获得的盐以及含有这种盐的制剂。最后，本发明涉及一种口崩片，其硬度至少为22 N，口腔分解时间小于120 s，包括吸附在水溶性填充剂上的活性药物成分，其中活性药物成分的熔点在40-100℃的范围内，并且制备这种口崩片的方法。
• CRYSTALLINE COMPOSITION CONTAINING ESCITALOPRAM OXALATE
  申请人：H. LUNDBECK A/S

  公开号：EP1732514A1

  公开（公告）日：2006-12-20
• CRYSTALLINE BASE OF ESCITALOPRAM AND ORODISPERSIBLE TABLETS COMPRISING ESCITALOPRAM BASE
  申请人：H. Lundbeck A/S

  公开号：EP1896439B1

  公开（公告）日：2011-02-02
• US7420068B2
  申请人：——

  公开号：US7420068B2

  公开（公告）日：2008-09-02