1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-isobenzofuran

• 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: 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-isobenzofuran
• 英文别名: [3-[1-(4-fluorophenyl)-1,3 dihydro-isobenzofuran-1-yl]propyl]dimethyl amine；3-[1-(4-fluorophenyl)-3H-2-benzofuran-1-yl]-N,N-dimethylpropan-1-amine
• 化学式: C₁₉H₂₂FNO
• 分子量: 299.388
• InChiKey: CGVBIXZVEMXIQU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  22
• 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

• 作为产物：
  描述：

  3-(5-溴-1-(4-氟苯基)-1,3-二氢异苯并呋喃-1-基)-N,N-二甲基丙烷-1-胺 在 5%-palladium/activated carbon 甲酸铵 作用下， 以 乙酸乙酯 为溶剂， 反应 7.0h， 生成 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-isobenzofuran
  参考文献：
  名称：

  A process for hydrogenolysis of [1-(3-dimethylamino)propyl)]-1-(4-fluorophenyl)-1,3-dihydro-5-halo-isobenzofuran.

  摘要：

  本发明提供了一种降低[1-(3-二甲基氨基)丙基)]-1-(4-氟苯基)-1,3-二氢-5-卤异苯并呋喃的含量的方法，该化合物的化学式为1，其中X为卤素，通过将存在于粗1-[3-(二甲基氨基)丙基]-1-(4-氟苯基)-1,3-二氢-5-异苯并呋喃碳腈中的[1-(3-二甲基氨基)丙基)]-1-(4-氟苯基)-1,3-二氢-5-卤异苯并呋喃转化为化合物的化学式3，包括将其进行氢解。

  公开号：

  EP1486492A3

文献信息

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

  公开号：US20020077353A1

  公开（公告）日：2002-06-20

  Method for the preparation of citalopram comprising reaction of a compound of Formula (IV) 1 wherein R is halogen, or CF 3 —(CF 2 ) n —SO 2 —, n being 0 to 8, with a cyanide source in the presence of a palladium catalyst and a catalytic amount of C + or Zn 2+ , or with Zn(CN) 2 in the presence of a palladium catalyst.

  制备西酞普兰的方法包括在存在钯催化剂和催化量的C+或Zn2+的情况下，将化合物IV的反应物（其中R为卤素，或CF3—(CF2)n—SO2—，n为0至8）与氰化物源反应，或在存在钯催化剂的情况下将其与Zn(CN)2反应。
• 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。
• [EN] AN IMPROVED PROCESS FOR THE PREPARATION OF CITALOPRAM HYDROBROMIDE<br/>[FR] PROCEDE AMELIORE DE PREPARATION D'HYDROBROMURE DE CITALOPRAM
  申请人：NATCO PHARMA LTD

  公开号：WO2004094399A1

  公开（公告）日：2004-11-04

  The present invention discloses an improved process for the preparation of citalopram hydrobromide of formula (I) from citalopram base of formula (III) without isolating and crystallizing the latter. The citalopram base of formula (III) is prepared according to earlier known method from the isobenzofuran of formula (II). Accordingly, the organic layer containing citalopram base is directly treated with aqueous hydrobromic acid to get the citalopram hydrobromide.

  本发明揭示了一种改进的制备盐酸西酞普兰的方法，该方法从西酞普兰碱的公式（III）制备而来，而无需分离和结晶后者。公式（III）的西酞普兰碱是根据早期已知方法从公式（II）的异苯并呋喃制备而来。因此，含有西酞普兰碱的有机层直接用水溶性氢溴酸处理，以得到盐酸西酞普兰。
• METHOD FOR THE PREPARATION OF CITALOPRAM
  申请人：Petersen Hans

  公开号：US20090088469A1

  公开（公告）日：2009-04-02

  Method for the preparation of citalopram comprising reaction of a compound of Formula (IV) wherein R is halogen, or CF 3 —(CF 2 ) n —SO 2 —, n being 0 to 8, with a cyanide source in the presence of a palladium catalyst and a catalytic amount of Cu + or Zn 2+ , or with Zn(CN) 2 in the presence of a palladium catalyst.

  制备西酞普兰的方法包括在钯催化剂和催化量的Cu+或Zn2+的存在下，将式（IV）化合物与氰源反应，其中R是卤素或CF3—（CF2）n—SO2—，n为0至8，或在钯催化剂的存在下与Zn（CN）2反应。
• PROCESS FOR PREPARATION OF CITALOPRAM AND ENANTIOMERS
  申请人：Nagarajan Periyandi

  公开号：US20080177096A1

  公开（公告）日：2008-07-24

  The present invention provides a process for preparation of 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofuran car-bonitrile comprising reacting a compound of formula IVa, in the presence of a base with a compound of formula RX, wherein R is selected from alkyl, alkenyl, aryl and heteroaryl which may be optionally substituted with electron withdrawing groups and X is selected from F, Cl, Br, I, CN, OTf and OR 1 , wherein Tf represents trifluoromethanesulfonyl group, and R 1 is optionally substituted alkyl, Z is a cyano group or a group that may be converted to a cyano group; further wherein RX is selected such that an intermediate ether derivative, a compound of formula Va formed from said reaction cyclizes to a compound of formula VI, and where Z is not a cyano group, conversion of the group Z in the compound of formula VI to a cyano group to form 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofuran carbonitrile. The present invention also provides novel ether compound, a compound of formula Va and a process for preparation thereof.

  本发明提供了一种制备1-[3-(二甲基氨基)丙基]-1-(4-氟苯基)-1,3-二氢-5-异苯并呋喃-2-碳腈的方法，包括在碱存在下，将式IVa的化合物与式RX的化合物反应，其中R选择从烷基，烯基，芳基和杂环芳基中选择，可以选择用电子吸引基替代，X选择从F，Cl，Br，I，CN，OTf和OR1中选择，其中Tf代表三氟甲烷磺酰基，R1是可选择的取代基烷基，Z是氰基或可转化为氰基的基团；进一步，选择RX使得从所述反应中形成的化合物Va的中间醚衍生物，环化为式VI的化合物，其中Z不是氰基，则将化合物VI中的基团Z转化为氰基，以形成1-[3-(二甲基氨基)丙基]-1-(4-氟苯基)-1,3-二氢-5-异苯并呋喃-2-碳腈。本发明还提供了一种新的醚化合物，式为Va的化合物及其制备方法。