1-(4-氟苯基)-1,3-二氢-1-[3-(甲基氨基)丙基]异苯并呋喃-5-甲腈 | 62498-67-3

• 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)-1,3-二氢-1-[3-(甲基氨基)丙基]异苯并呋喃-5-甲腈
• 中文别名: 西酞普兰去甲基杂质；草酸艾司西酞普兰去甲基杂质；去甲西酞普兰；西酞普兰杂质28
• 英文名称: rac-desmethylcitalopram
• 英文别名: Desmethylcitalopram；demethylcitalopram；N-desmethylcitalopram；1-(4-fluorophenyl)-1-[3-(methylamino)propyl]-3H-2-benzofuran-5-carbonitrile
• CAS: 62498-67-3
• 化学式: C₁₉H₁₉FN₂O
• 分子量: 310.371
• InChiKey: PTJADDMMFYXMMG-UHFFFAOYSA-N

物化性质

• 保留指数：
  2441.7;2429.2

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  45
• 氢给体数：
  1
• 氢受体数：
  4

ADMET

代谢

去甲基西酞普兰已知的人类代谢物包括N,N-去二甲基西酞普兰。

Desmethylcitalopram has known human metabolites that include N,N-Didesmethylcitalopram.

来源:NORMAN Suspect List Exchange

反应信息

• 作为反应物：
  描述：

  1-(4-氟苯基)-1,3-二氢-1-[3-(甲基氨基)丙基]异苯并呋喃-5-甲腈 在 四氢吡咯 、 盐酸 、 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 乙醚 、 乙醇 、 1,2-二氯乙烷 为溶剂， 生成 1-(3-((4-(1H-indol-3-yl)cyclohex-3-en-1-yl)(methyl)amino)-propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile
  参考文献：
  名称：

  Design and Synthesis of 1-(3-(Dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (Citalopram) Analogues as Novel Probes for the Serotonin Transporter S1 and S2 Binding Sites

  摘要：

  The serotonin transporter (SERT) is the primary target for antidepressant drugs. The existence of a high affinity primary orthosteric binding site (S1) and a low affinity secondary site (S2) has been described, and their relation to antidepressant pharmacology has been debated. Herein, structural modifications to the N, 4, 5, and 4' positions of (+/-)citalopram (1) are reported. All of the analogues were SERT-selective and demonstrated that steric bulk was tolerated at the SERT Si site, including two dimeric ligands (15 and 51). In addition, eight analogues were identified with similar potencies to S-1 for decreasing the dissociation of [H-3]S-1 from the S1 site via allosteric modulation at S2. Both dimeric compounds had similar affinities for the SERT Si site (K-i = 19.7 and 30.2 nM, respectively), whereas only the N-substituted analogue, 51, was as effective as S-1 in allosterically modulating the binding of [H-3]S-1 via S2.

  DOI：

  10.1021/jm4014136
• 作为产物：
  描述：

  西酞普兰 在 氯甲酸氯甲酯 、 甲醇 、 氨 作用下， 以 1,2-二氯乙烷 、 水 为溶剂， 生成 1-(4-氟苯基)-1,3-二氢-1-[3-(甲基氨基)丙基]异苯并呋喃-5-甲腈
  参考文献：
  名称：

  Process for the preparation of escitalopram

  摘要：

  该发明涉及一种用于制备艾司西酞普兰的新工艺，包括：(ii)去甲基化(±)-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（式II）（西酞普兰）以产生(±)-1-[3-(甲基氨基)丙基]-1-(4-氟苯基)-1,3-二氢-5-异苯并呋喃碳腈（去甲基西酞普兰）（XII），(iii)分离纯的去甲基西酞普兰（XII），(iv)用旋光酸将对映体从纯的去甲基西酞普兰（XII）中分离出来，得到(S)-(+)-1-[3-(甲基氨基)丙基]-1-(4-氟苯基)-1,3-二氢-5-异苯并呋喃碳腈（(S)-(+)-去甲基西酞普兰）（XIII），(v)使用适当的甲基化剂对对映体纯化合物（XIII）进行甲基化，以产生艾司西酞普兰（I）。

  公开号：

  EP2017271A1

文献信息

• [EN] PREPARATION OF ESCITALOPRAM<br/>[FR] PREPARATION D'ESCITALOPRAME
  申请人：REDDYS LAB INC DR

  公开号：WO2005047274A1

  公开（公告）日：2005-05-26

  Enantiomerically enriched citalopram is prepared by methylating enantiomerically enriched didesmethylcitalopram, obtained by directly resolving racemic didesmethylcitalopram using a chiral acid.

  对映富集的西酞普兰是通过对映富集的二去甲基西酞普兰进行甲基化制备的，后者是通过使用手性酸直接拆分混合的二去甲基西酞普兰得到的。
• [EN] IMPROVED PROCESS FOR THE MANUFACTURE OF CITALOPRAM HYDROBROMIDE<br/>[FR] PROCEDE AMELIORE DE PREPARATION D'HYDROBROMURE DE CITALOPRAM
  申请人：WOCKHARDT LTD

  公开号：WO2005042473A1

  公开（公告）日：2005-05-12

  The present invention describes an improved process for the preparation of extremely pure 1-(4'-Fluorophenyl)-1-(3-dimethylaminopropyl)-5-phthalanecarbonitrile and its bromide salt (citalopram hydrobromide), which is a well known antidepressant. Other aspect of the invention are isolation of crystalline (4-Bromo-2-hydroxymethyl)phenyl-(4-fluorophenyl)-3-(dimethylaminopropyl)methanol (Bromodiol) and conversion of desmethylcitalopram which is formed during the cyanide exchange reaction, to Citalopram by heating with a mixture of formaldhyde and formic acid in chloroform. The resulting citalopram is conventionally purified using extraction methodology.

  该发明描述了一种改进的工艺，用于制备极纯的1-(4'-氟苯基)-1-(3-二甲基氨丙基)-5-邻苯二甲腈及其溴化盐（西酞普兰盐酸盐），后者是一种众所周知的抗抑郁药。该发明的另一个方面是分离结晶的(4-溴-2-羟甲基)苯基-(4-氟苯基)-3-(二甲基氨丙基)甲醇（溴二醇）以及将在氰化物交换反应期间形成的去甲基西酞普兰转化为西酞普兰，方法是在氯仿中与甲醛和甲酸混合物加热。所得的西酞普兰通常使用萃取方法进行纯化。
• Method for the preparation of citalopram
  申请人：H. Lundbeck A/S

  公开号：US20030092761A1

  公开（公告）日：2003-05-15

  The invention relates to a method for the preparation of citalopram comprising reaction of a compound of formula II 1 with a compound having the formula 2 wherein R is halogen or —O—SO 2 -X, wherein X is alkyl, alkenyl, alkynyl or optionally alkyl substituted aryl or aralkyl, and R 1 is dimethylamino, halogen, —O—SO 2 -X wherein X is as defined above, provided that R is not halogen when R 1 is dimethylamino; and if R 1 is dimethylamino followed by isolation of citalopram base or a pharmaceutically acceptable acid addition salt thereof, and if R 1 is halogen or —O—SO 2 -X, wherein X is as defined above, followed by conversion of the resulting compound of formula 3 wherein R 2 is halogen or a group of formula —O—SO 2 -X wherein X is as defined above to citalopram, followed by isolation of citalopram base or a pharmaceutically acceptable acid addition salt thereof.

  该发明涉及一种制备西酞普兰的方法，包括将式II1的化合物与具有式2的化合物反应，其中R是卤素或—O—SO2-X，其中X是烷基、烯基、炔基或可选地被烷基取代的芳基或芳基烷基，R1是二甲基氨基、卤素、—O—SO2-X，其中X如上定义，前提是当R1是二甲基氨基时，R不是卤素；如果R1是二甲基氨基，则随后分离西酞普兰碱或其药学上可接受的酸盐，如果R1是卤素或—O—SO2-X，其中X如上定义，则随后将得到的式3的化合物转化为西酞普兰，其中R2是卤素或式—O—SO2-X的基团，其中X如上定义，随后分离西酞普兰碱或其药学上可接受的酸盐。
• Method for the preparation of pure citalopram
  申请人：H. Lundbeck A/S

  公开号：US20020120005A1

  公开（公告）日：2002-08-29

  The present invention relates to the process for the preparation and purification of citalopram (I) 1 in which a compound of formula (II) 2 wherein Z is iodo, bromo, chloro or CF 3—(CF 2 ) n —SO 2 —O—, n being 0, 1, 2, 3, 4, 5, 6, 7 or 8, is subjected to a cyanide exchange reaction with a cyanide source; the resultant crude citalopram product is optionally subjected to some initial purification and subsequently treated with an amide or an amide-like group forming agent; the reaction mixture is then subjected to an acid/base wash and/or crystallisation and recrystallisation of citalopram in order to remove the amides formed from the crude citalopram mixture; and the resulting citalopram product is optionally further purified, worked up and isolated as the base or a pharmaceutically acceptable salt thereof.

  本发明涉及西酞普兰（I）的制备和纯化过程，其中将式（II）的化合物进行氰化物交换反应，其中Z为碘、溴、氯或CF3—(CF2)n—SO2—O—，n为0、1、2、3、4、5、6、7或8；所得的粗西酞普兰产品可选择性地经过一些初步纯化，随后与酰胺或类似酰胺基团形成剂反应；然后将反应混合物进行酸碱洗涤和/或西酞普兰的结晶和再结晶，以去除从粗西酞普兰混合物中形成的酰胺；最终得到的西酞普兰产品可选择性地进一步纯化、处理和作为其碱性或药用可接受盐进行分离。
• Process for the Preparation of Escitalopram
  申请人：Rao Dharmaraj Ramachandra

  公开号：US20100204493A1

  公开（公告）日：2010-08-12

  The present invention provides a novel process for the preparation of a compound of Formula III, and novel processes for preparing escitalopram using the compound of Formula III.

  本发明提供了一种制备化合物III的新型工艺，以及利用化合物III制备艾司西酞普兰的新工艺。