1-(4-氟苯基)-1-(3-二甲基氨基丙基)-5-氯二氢异苯并呋喃 | 64169-45-5

• 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
• 中文名称: 1-(4-氟苯基)-1-(3-二甲基氨基丙基)-5-氯二氢异苯并呋喃
• 中文别名: 艾司西酞普兰杂质 5-氯 (F)
• 英文名称: Lu 10-134-C
• 英文别名: 5-chloro-1-(3-dimethylaminopropyl)-1-(4-fluorophenyl)-phthalan；1-(4'-fluorophenyl)-1-(3-dimethylaminopropyl)-5-chlorophthalane；1-(4'-fluorophenyl)-1-(3-dimethylaminopropyl)-5-chlorophtalane；1-(4-Fluorophenyl)-1-(3-dimethylaminopropyl)-5-chlorophthalane；3-[5-chloro-1-(4-fluorophenyl)-3H-2-benzofuran-1-yl]-N,N-dimethylpropan-1-amine
• CAS: 64169-45-5
• 化学式: C₁₉H₂₁ClFNO
• 分子量: 333.833
• InChiKey: COAPWBUTTSOWLG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  sodium cyanide 、 1-(4-氟苯基)-1-(3-二甲基氨基丙基)-5-氯二氢异苯并呋喃 在 锌 三苯基膦 、 nickel dichloride 作用下， 以 乙腈 为溶剂， 反应 16.17h， 生成 西酞普兰
  参考文献：
  名称：

  [EN] PROCESS FOR THE PREPARATION OF 1-(3-DIMETHYLAMINOPROPYL) -1-(4-FLUOROPHENYL) -1,3-DIHYDROISOBENZOFURAN -5-CARBONITRILE
  [FR] PROCEDE POUR LA PREPARATION DE 1-(3-DIMETHYLAMINOPROPYL)-1-(4-FLUOROPHENYL)-1,3-DIHYDROISOBENZOFURANE-5-CARBONITRILE

  摘要：

  本发明涉及一种用于制备西酞普兰的新型工艺，包括对式II的邻苯二酮化合物进行卤代作用，其中R是一个适合改变为CN的基团，以得到式III的酸卤化合物，其中R如上定义，X是卤素，然后通过两个连续反应与适当的有机金属卤化物或有机硼烷或通过与有机金属4-氟苯基卤化物或4-氟苯基硼烷反应后进行还原和烷基化，以及将R交换为氰基以得到西酞普兰。反应的顺序可以根据使用的起始化合物等因素进行变化。

  公开号：

  WO2004011450A1

文献信息

• Method for the preparation of citalopram
  申请人：H. Lundbeck A/S

  公开号：US20020061925A1

  公开（公告）日：2002-05-23

  Method for the preparation of citalopram comprising reaction of a compound of Formula (IV) 1 wherein R is Cl or Br with a cyanide source in the presence of a nickel catalyst and isolation of the corresponding 5-cyano compound, i.e. citalopram.

  制备西酞普兰的方法包括在存在镍催化剂的情况下，将化合物IV的R为Cl或Br的化合物与氰化物源反应，并分离出相应的5-氰基化合物，即西酞普兰。
• Process for preparing citalopram
  申请人：——

  公开号：US20030144534A1

  公开（公告）日：2003-07-31

  Process for preparing purified citalopram or one of its salts that comprises the purification of citalopram by selective extractions of citalopram or of its impurities with organic solvents and water under specific conditions of pH and temperature. The crude citalopram can be prepared by a process that comprises reacting 1-[3-(dimethylamine)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-bromoisobenzofuran with copper cyanide.

  制备纯化西酞普兰或其盐的过程包括通过在特定pH和温度条件下使用有机溶剂和水有选择性地提取西酞普兰或其杂质来纯化西酞普兰。粗西酞普兰可以通过将1-[3-(二甲胺基)丙基]-1-(4-氟苯基)-1,3-二氢-5-溴异苯并呋喃与氰化铜反应的过程来制备。
• CRYSTALLINE BASE OF ESCITALOPRAM AND ORODISPERSIBLE TABLETS COMPRISING ESCITALOPRAM BASE
  申请人：Dancer Robert

  公开号：US20070021499A1

  公开（公告）日：2007-01-25

  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-isobenzofurancarbonitrile, 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.

  本发明涉及著名抗抑郁药埃司他普兰的结晶基础，即S-1-[3-(二甲基氨基)丙基]-1-(4-氟苯基)-1,3-二氢-5-异苯并呋喃基碳腈的配方，所述基础的制备过程，用于制备埃司他普兰的纯化盐（如草酸盐）的过程，以及通过该过程获得的盐和含有此类盐的配方，以及用氢溴酸盐制备纯化埃司他普兰游离基或埃司他普兰盐（如草酸盐）的过程，通过该过程获得的盐和含有此类盐的配方。最后，本发明涉及一种口崩片，其硬度至少为22N，口服溶解时间小于120秒，并包含吸附在水溶性填料上的活性药物成分，其中活性药物成分的熔点在40-100°C范围内，以及制备这种口崩片的方法。
• Process for the preparation of 1 - (3-dimethylaminopropyl) -1 - (4-fluorophenyl) -1,3-dihydroisobenzofuran-5-carbonitrile
  申请人：Hilden Leif

  公开号：US20050209467A1

  公开（公告）日：2005-09-22

  The present invention is directed to novel processes for the preparation of citalopram comprising halogenation of a phthalide compound of formula II, wherein R is a suitable group to be changed to CN, to afford an acid halogenide compound of formula III wherein R is as defined as above and X is halogen, and thereafter obtaining citalopram through two successive reactions with suitable organometallic halides or organoboranes or by a reaction with organometallic 4-fluorophenylhalide or 4-fluorophenylborane followed by reduction and alkylation, and an exchange of R to cyano to afford citalopram. The order of the reactions can be varied depending for example on the starting compound used.

  本发明涉及制备西酞普兰的新工艺，包括对式II的邻苯二酸酐化合物进行卤代反应，其中R是适当的基团，可被改变为CN，以得到式III的酸卤化合物，其中R如上所定义，X为卤素，然后通过与适当的有机金属卤化物或有机硼烷进行两步连续反应，或通过与有机金属4-氟苯基卤化物或4-氟苯基硼烷反应后还原和烷基化，以及将R交换为氰基以得到西酞普兰。反应的顺序可以根据所使用的起始化合物进行变化。
• CRYSTALLINE BASE OF ESCITALOPRAM AND ORODISPERSIBLE TABLETS COMPRISING ESCITALOPRAM BASE
  申请人：Dancer Robert

  公开号：US20080161388A1

  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.

  本发明涉及著名抗抑郁药物艾司西酞普兰的结晶基础，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-碳腈的配方，使用该基础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及含有这种盐的配方，以及使用氢溴酸盐制备纯化艾司西酞普兰自由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及含有这种盐的配方。最后，本发明涉及一种口崩片，硬度至少为22 N，口服崩解时间小于120 s，包含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℃范围内，以及制备这种口崩片的方法。