1-piperazinyldibenzo[b,f][1,4]thiazepine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并硫氮卓类
• 英文名称: 1-piperazinyldibenzo[b,f][1,4]thiazepine
• 英文别名: 7-piperazin-1-ylbenzo[b][1,4]benzothiazepine
• 化学式: C₁₇H₁₇N₃S
• 分子量: 295.408
• InChiKey: QAIMUVOMLPNKKY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  52.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  哌嗪 、 11-(1-哌嗪基)二苯并[B,F][1,4]硫氮杂卓 、 11-氯-二苯并[b,f][1,4]硫氮杂卓 、 正丁醇 以 水 、 甲苯 为溶剂， 生成 1-piperazinyldibenzo[b,f][1,4]thiazepine
  参考文献：
  名称：

  Process for preparing quetiapine fumarate

  摘要：

  提供了喹硫平和药用可接受盐的改进合成方法。

  公开号：

  US20080241949A1

文献信息

• DIBENZOTHIAZEPINE DERIVATIVES AND USES THEREOF - 424
  申请人：Brown Dean

  公开号：US20090318415A1

  公开（公告）日：2009-12-24

  Compounds the following formula: wherein Z is as described in the specification, pharmaceutically acceptable salts thereof, compositions comprising the same, and methods of treating bipolar disorder, an anxiety disorder, a mood disorder or schizophrenia or other psychotic disorder with said compounds.

  合成以下公式：其中Z如规范中所述，其药学上可接受的盐，包含相同物质的组合物，以及使用该化合物治疗双相情感障碍、焦虑障碍、情绪障碍或精神分裂症或其他精神障碍的方法。
• [EN] PROCESS FOR PRODUCING 11-[4-[2-(2-HYDROXYETHOXY)ETHYL]-1-PIPERAZINYL]DIBENZO[b,f][1,4]THIAZEPINE AND A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF<br/>[FR] PROCEDE DE PRODUCTION DE 11-[4-[2-(2-HYDROXYETHOXY)ETHYL]-1-PIPERAZINYL]DIBENZO[B,F][1,4]THIAZEPINE ET D'UN SEL ACCEPTABLE SUR LE PLAN PHARMACEUTIQUE ASSOCIE
  申请人：JUBILANT ORGANOSYS LTD

  公开号：WO2006027789A1

  公开（公告）日：2006-03-16

  A process for producing 11-[4-[2-(2-hydroxyethoxy)ethyl]-l-piperazinyl]dibenzo [b,f][1,4]thiazepine [I] and a pharmaceutically suitable acid addition salt is disclosed. Accordingly, thiosalicylic acid [XVI] is reacted with o-halonitrobenzene [XVII] using a phase transfer catalyst to obtain 2-nitro-2'-carboxydiphenylsulphide [XI]. It is hydrogenated in the presence of a noble metal catalyst to obtain 2-amino-2' carboxydiphenyl sulphide [X]. The 2-amino-2'-carboxydiphenylsulphide [X] is reacted with halide or oxyhalide of the phosphorous to obtain in situ iminohalide [VI], which further reacts as such with 1-hydroxyethoxyethylpiperazine or condenses with piperazine to obtain 11-piperazinyldi.benzo[b,f][1,4]thiazepine [XIX] which further reacts with 2- chloroethoxyethanol or reacts with 1-(2-hydroxyethyl)piperazine to give 11-[4-(2-hydroxyethyl)piperazine-1-yl]dibenzo[b,f][ 1,4]thiazepine [XXXI] which further converts to an intermediate 11-[4-(2-substitutedethyl)piperazin-1- yl)dibenzo[b,f][1,4]thiazepine wherein the substituent at the 2-position is selected from mesyloxy or tosyloxy or halo group [XXXII] followed by reaction with ethylene glycol to give quetiapine [1].

  揭示了一种生产11-[4-[2-(2-羟基乙氧基)乙基]-1-哌嗪基]二苯并[b,f][1,4]噻吩[I]及其药用合适的酸盐的方法。因此，巯基水杨酸[XVI]与o-卤代硝基苯[XVII]在相转移催化剂的作用下反应，得到2-硝基-2'-羧基二苯硫醚[XI]。在贵金属催化剂的存在下加氢得到2-氨基-2'-羧基二苯硫醚[X]。2-氨基-2'-羧基二苯硫醚[X]与磷的卤代物或氧卤代物反应，得到原位亚胺卤化物[VI]，后者直接与1-羟乙氧乙基哌嗪反应或与哌嗪缩合，得到11-哌嗪二.苯并[b,f][1,4]噻吩[XIX]，它进一步与2-氯乙氧乙醇反应或与1-(2-羟乙基)哌嗪反应，得到11-[4-(2-羟乙基)哌嗪-1-基]二苯并[b,f][1,4]噻吩[XXXI]，它进一步转化为中间体11-[4-(2-取代乙基哌嗪-1-基)二苯并[b,f][1,4]噻吩，其中2-位置的取代基选择自mesyloxy或tosyloxy或卤素基[XXXII]，然后与乙二醇反应得到喹硫平[1]。
• [EN] PROCESS FOR THE PREPARATION OF QUETIAPINE FUMARATE<br/>[FR] PROCEDE DE PREPARATION DE FUMARATE DE QUETIAPINE
  申请人：RANBAXY LAB LTD

  公开号：WO2010100623A1

  公开（公告）日：2010-09-10

  The present invention relates to an improved process for the preparation of quetiapine and pharmaceutically acceptable salts. It also relates to improved process for the preparation of intermediates of quetiapine.

  本发明涉及一种改进的制备喹硫平和药用可接受盐的方法。它还涉及一种改进的制备喹硫平中间体的方法。
• [EN] PROCESS FOR THE PREPARATION OF 11-(4-[2-(2-HYDROXYETHOXY)ETHYL]-I-PIPERAZINYL)DIB ENZO[b,f][l,4]THIAZEPINE<br/>[FR] PROCEDE DE PREPARATION DE 11-(4-[2-(2-HYDROXYETHOXY)ETHYL]-I-PIPERAZINYL)DIB ENZO[B,F][L,4]THIAZEPINE
  申请人：SK CORP

  公开号：WO2006001619A1

  公开（公告）日：2006-01-05

  Disclosed is a process for the preparation of l l-(4-[2-(2-hydroxyethoxy)ethyl]-l- piperazinyl)-dibenzo[b,f][l,4]thiazepine. In the process, low-priced 2,2'-dithiosalicylic acid as starting material is subjected to bond formation reaction with l-chloro-2- 5 nitrobenzene in a basic aqueous solution, a nitro group reduction reaction is conducted, cyclization and chlorination reactions are simultaneously carried out in the presence of a equivalent amount of halogenating agent, a reaction with piperazine is continuously conducted without separation, and a reaction with 2-haloethoxyethanol is conducted, thereby it is possible to economically producing Quetiapine, that is, l l-(4-[2-(2- 10 hydroxyethoxy)ethyl]-l-piperazinyl)-dibenzo[b,fj[l,4]thiazepine, in an environmentally friendly manner. Particularly, the process is advantageous in that economic efficiency is assured because of use of the low-priced starting material, use of an organic solvent is minimized because a reaction is conducted in an aqueous solution, and it is possible to achieve the environmentally friendly and economical process having high commercial 15 usefulness because the number of reaction steps of the process is reduced and because generation of acidic waste is minimized.

  公开了一种制备 l l-(4-[2-(2-羟基乙氧基)乙基]-l-哌嗪基)-二苯并[b,f][1,4]噻二嗪的过程。在该过程中，以低价的2,2'-二硫基水杨酸作为起始物质，经过与1-氯-2-5-硝基苯基的键合反应，在碱性水溶液中进行硝基还原反应，同时在存在等量卤化剂的情况下进行环化和氯化反应，与哌嗪的反应连续进行而不分离，并进行与2-卤乙氧基乙醇的反应，从而可以在环保的方式下经济地生产奎提亚平，即l l-(4-[2-(2-羟基乙氧基)乙基]-l-哌嗪基)-二苯并[b,f][1,4]噻二嗪。特别是，该过程具有经济效益，因为使用了低价的起始物质，由于反应在水溶液中进行，有机溶剂的使用被最小化，并且由于减少了过程的反应步骤和酸性废物的生成，可以实现具有高商业实用性的环保和经济过程。
• Method of treating anxiety disorders
  申请人：Davis C. Patricia

  公开号：US20060217367A1

  公开（公告）日：2006-09-28

  A method of treating at least one symptom or condition associated with but not limited to: Anxiety Disorders including but not limited to Panic Disorder Without Agoraphobia, Panic Disorder With Agoraphobia, Agoraphobia Without History of Panic Disorder, Specific Phobia, Social Phobia, Obsessive-Compulsive Disorder, Postaumatic Stress Disorder, Acute Stress Disorder, Generalized Anxiety Disorder and Generalized Anxiety Disorder Due to a General Medical Condition comprising administering an effective amount of Formula I or its pharmaceutically acceptable salt. In another aspect of the invention a pharmaceutical composition is provided comprising an effective amount of Formula I or its pharmaceutically acceptable salt and at least one pharmaceutically acceptable carrier or diluent.

  一种治疗至少一种与以下症状或疾病相关但不限于：焦虑障碍，包括但不限于无广场恐惧症的恐慌障碍，有广场恐惧症的恐慌障碍，无恐慌障碍史的广场恐惧症，特定恐惧症，社交恐惧症，强迫症，创伤后应激障碍，急性应激障碍，广泛性焦虑障碍和由一般医学状况引起的广泛性焦虑障碍的方法，包括给予有效量的公式I或其药学上可接受的盐。在发明的另一个方面，提供了一种制药组合物，其包括有效量的公式I或其药学上可接受的盐和至少一种药学上可接受的载体或稀释剂。