奎硫平去羟乙基杂质 | 329216-67-3

• 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 - 有机杂环化合物 - 苯并硫氮卓类
• 中文名称: 奎硫平去羟乙基杂质
• 英文名称: O-Dealkyl Quetiapine
• 英文别名: 2-(4-dibenzo[b,f][1,4]thiazepin-11-yl-piperazin-1-yl)-ethanol；11-(4-(2-hydroxyethyl)-1-piperazinyl)dibenzo-[b,f][1,4]-thiazepine；(E)-2-(4-(dibenzo[b,f][1,4]thiazepin-11-yl)piperazin-1-yl)ethanol；11-[4-(2-hydroxyethyl)-1-piperazinyl]dibenzo[b,f][l,4]thiazepine；2-(4-dibenzo[b,f][1,4]thiazepine-11-yl-piperazine-1-yl)-ethanol；2-(4-(dibenzo[b,f][1,4]thiazepin-11-yl)piperazin-1-yl)ethanol；Quetiapine Hydroxy Impurity；2-(4-benzo[b][1,4]benzothiazepin-6-ylpiperazin-1-yl)ethanol
• CAS: 329216-67-3
• 化学式: C₁₉H₂₁N₃OS
• 分子量: 339.461
• InChiKey: OFLMIXVKBNAUIB-UHFFFAOYSA-N

物化性质

• 熔点：
  >50°C (dec.)
• 沸点：
  523.4±60.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)
• 溶解度：
  氯仿（微溶）、DMSO（微溶）、乙醇（微溶）、甲醇（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  64.4
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 储存条件：
  2-8°C

反应信息

• 作为反应物：
  描述：

  奎硫平去羟乙基杂质 、 苄基-2-氯乙醚 在 sodium hydroxide 、 四丁基硫酸氢铵 、 盐酸 、 氨 作用下， 以 水 、 甲苯 为溶剂， 反应 9.08h， 以93%的产率得到11-{4-[2-(2-benzyloxy-ethoxy)ethyl]-piperazin-1-yl}-dibenzo[b,f][1,4]thiazepine
  参考文献：
  名称：

  [EN] PROCEDURE FOR PREPARING 11-(4`2-(2-HYDROXYETHOXY )ETHYL!-1-PIPERAZINYL!-DIBENZO`B,F!`1,4!THIAZEPINE
  [FR] PROCEDE DE PREPARATION D'UN COMPOSE PHARMACEUTIQUEMENT ACTIF

  摘要：

  公开号：

  WO2005014590A3
• 作为产物：
  描述：

  二苯并[b,f][1,4]硫氮杂卓-11-[10H]酮 在 N,N-二甲基苯胺 、 三氯氧磷 作用下， 以 xylene 为溶剂， 反应 4.0h， 生成 奎硫平去羟乙基杂质
  参考文献：
  名称：

  Behavioral Approach to Nondyskinetic Dopamine Antagonists:  Identification of Seroquel

  摘要：

  A great need exists for antipsychotic drugs which will not induce extrapyramidal symptoms (EPS) and tardive dyskinesias (TDs). These side effects are deemed to be a consequence of nonselective blockade of nigrostriatal and mesolimbic dopamine D2 receptors. Nondyskinetic clozapine (1) is a low-potency D2 dopamine receptor antagonist which appears to act selectively in the mesolimbic area. In this work dopamine antagonism was assessed in two mouse behavioral assays: antagonism of apomorphine-induced climbing and antagonism of apomorphine-induced disruption of swimming. The potential for the liability of dyskinesias was determined in haloperidol-sensitized Cebus monkeys. Initial examination of a few close cogeners of 1 enhanced confidence in the Cebus model as a predictor of dyskinetic potential. Considering dibenzazepines, 2 was not dyskinetic whereas 2a was dyskinetic. Among dibenzodiazepines, 1 did not induce dyskinesias where as its N-2-(2-hydroxyethoxy)ethyl analogue 3 was dyskinetic. The emergence of such distinctions presented an opportunity. Thus, aromatic and N-substituted analogues of 6-(piperazin-1-yl)-11H-dibenz[b,e]azepines and 11-(piperazin-1-yl)dibenzo[b,f][1,4]thiazepines and -oxazepines were prepared and evaluated. 11-(4-[2-(2-Hydroxyethoxy)ethyl]piperazin-1-yl)dibenzo[b,f][1,4]thiazepine (23) was found to be an apomorphine antagonist comparable to clozapine. It was essentially nondyskinetic in the Cebus model. With 23 as a platform, a number of N-substituted analogues were found to be good apomorphine antagonists but all were dyskinetic.

  DOI：

  10.1021/jm000242+

文献信息

• [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]。
• DIBENZOTHIAZEPINE MODULATORS OF DOPAMINE, ALPHA ADRENERGIC, AND SEROTONIN RECEPTORS
  申请人：Gant Thomas G.

  公开号：US20100069356A1

  公开（公告）日：2010-03-18

  The present invention relates to new dibenzothiazepine modulators of D1 receptors, D2 receptors, alpha-1 adrenergic receptors, alpha-2 adrenergic receptors, H1 receptors, 5-HT1A receptors, and/or 5-HT2 receptors, pharmaceutical compositions thereof, and methods of use thereof.

  本发明涉及新的二苯并噻吩D1受体、D2受体、α-1肾上腺素受体、α-2肾上腺素受体、H1受体、5-HT1A受体和/或5-HT2受体调节剂，其药物组合物以及其使用方法。
• DIBENZOTHIAZEPINE DERIVATIVES
  申请人：Tung Roger

  公开号：US20090291152A1

  公开（公告）日：2009-11-26

  This invention relates to novel 11-[4-[2-(2-Hydroxyethoxy)ethyl]piperazin-1-yl]dibenzo[b,f][1,4]thiazepine derivatives, their acceptable acid addition salts, solvates, hydrates and polymorphs thereof. The invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions beneficially treated by antagonists of seratonergic 5HT1A and 5HT2 receptors, dopaminergic D1 and D2 receptor, histaminergic H1 receptors, and/or adrenergic α1 and α2 receptors.

  本发明涉及新型11-[4-[2-(2-羟乙氧基)乙基]哌嗪-1-基]二苯并[b,f][1,4]噻唑啉衍生物，其可接受的酸加盐、溶剂化合物、水合物和多晶形态。本发明还提供了包含本发明化合物的组合物，并且利用这些组合物治疗抗血清素5HT1A和5HT2受体拮抗剂、多巴胺D1和D2受体、组胺H1受体和/或肾上腺素α1和α2受体治疗有益的疾病和病状的方法。
• Process For The Preparation Of An 11-(4-Substituted-I- Piperazinyl)Dibenzo[B,F][1,4:rsqb; Thiazepine Derivative
  申请人：Comely Alexander Christian

  公开号：US20080171869A1

  公开（公告）日：2008-07-17

  A process for the preparation of an 11-(4-substituted-1-piperazinyl)dibenzo[b,f][1,4]thiazepine derivative, of general Formula (I), where A is hydrogen or a —(CH 2 ) 2 —OH group or a —(CH 2 ) 2 -0-(CH 2 ) 2 —OH group, or of a salt thereof, comprises a step in which 10H-dibenzo[b,f][1,4]thiazepin-11-one is reacted with a piperazine derivative in the presence of a titanium alkoxide of general formula Ti(OR) 4 , where R is a straight or branched alkyl group, having from one to eight carbon atoms to obtain said Formula I derivative or a salt thereof. Where A is —CH 2 ) 2 -0-(CH 2 ) 2 —OH, then the piperazine derivative is 1-(2-(2-hydroxyethoxy)ethyl)piperazine and the 11-(4-substituted-1-piperazinyl)dibenzo[b,f][1,4]thiazepine is quetiapine, (11-(4-(2-(2-hydroxyethoxy)ethyl)-1-piperazinyl)dibenzo[b,f][1,4]thiazepine). The process may comprise an additional step of reacting the quetiapine with fumaric acid to obtain quetiapine hemifumarate.

  一种制备通式（I）的11-（4-取代-1-哌嗪基）二苯并[b，f][1,4]噻唑啉衍生物的方法，其中A是氢或—（CH2）2—OH基或—（CH2）2-0-（CH2）2—OH基，或其盐之一，包括一步，在钛醇的存在下，将10H-二苯并[b，f][1,4]噻唑啉-11-酮与哌嗪衍生物反应，其中钛醇的通式为Ti（OR）4，其中R是一种直链或支链烷基，具有从一到八个碳原子，以获得所述的通式I衍生物或其盐。当A是—（CH2）2-0-（CH2）2—OH时，哌嗪衍生物是1-（2-（2-羟乙氧基）乙基）哌嗪，而11-（4-取代-1-哌嗪基）二苯并[b，f][1,4]噻唑啉是喹硫平（11-（4-（2-（2-羟乙氧基）乙基）-1-哌嗪基）二苯并[b，f][1,4]噻唑啉）。该过程还可以包括将喹硫平与富马酸反应以获得喹硫平半富马酸盐的附加步骤。
• WO2008/66620
  申请人：——

  公开号：——

  公开（公告）日：——