4-[2-(1H-苯并咪唑-2-基硫基)乙基]-1-哌嗪甲醛 | 561023-88-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 中文名称: 4-[2-(1H-苯并咪唑-2-基硫基)乙基]-1-哌嗪甲醛
• 英文名称: 4-(2-((1H-benzo[d]imidazol-2-yl)thio)ethyl)piperazine-1-carbaldehyde
• 英文别名: 1-[2-(benzimidazol-2-ylthio)ethyl]-4-formylpiperazine；1-formyl-4-[2-(benzimidazol-2-ylthio)ethyl]piperazine；4-[2-(1H-benzimidazol-2-ylsulfanyl)ethyl]piperazine-1-carbaldehyde
• CAS: 561023-88-9
• 化学式: C₁₄H₁₈N₄OS
• 分子量: 290.389
• InChiKey: QCIZFRFTFQBPMJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  77.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[2-(1H-苯并咪唑-2-基硫基)乙基]-1-哌嗪甲醛 在 盐酸 作用下， 以 甲醇 、 水 为溶剂， 以97%的产率得到1-[2-(benzimidazol-2-ylthio)ethyl]piperazine hydrochloride
  参考文献：
  名称：

  Syntheses and pharmacokinetic evaluations of four metabolites of 2-(4-(2-((1H-benzo[d]imidazol-2-yl)thio)ethyl)piperazin-1-yl)-N-(6-methyl-2,4-bis-(methylthio)pyridin-3-yl)acetamide hydrochloride [K-604], an acyl-CoA:cholesterol O-acyltransferase-1 inhibitor

  摘要：

  We synthesized and identified four metabolites of acyl-coenzyme A:cholesterol O-acyltransferase (ACAT)-1 inhibitor, K-604 (1). Two of the metabolites M1 and M2, were prepared from 1 using a combination reagent of hydrogen peroxide and sodium tungstate with either phosphoric acid or trifluoroethanol as the solvent to control the regioselectivity. Upon exposure of 4b to tert-butyl hypochlorite at -78 degrees C, the monosulfoxidation afforded synthetic intermediate of M3 in excellent yield. The efficient synthesis of M4 was established. The in vitro metabolic study exhibited a high clearance value (720 mu L/min/mg protein) of 1 using human liver microsomes. We orally administered a single dose of 10 mg/kg of 1 to monkeys because the in vitro metabolic patterns are quite similar. Fortunately, the drug concentration of 1 was much higher than those of M1, M2, M3 and M4.

  DOI：

  10.1016/j.bmc.2020.115457
• 作为产物：
  描述：

  1H-苯并咪唑-2-硫醇 在 4-二甲氨基吡啶 、 18-冠醚-6 甲基磺酰氯 、 三乙胺 、 potassium carbonate 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 2.75h， 以74%的产率得到4-[2-(1H-苯并咪唑-2-基硫基)乙基]-1-哌嗪甲醛
  参考文献：
  名称：

  PROCESS FOR PRODUCTION OF 1- 2-(BENZIMIDAZOL-2-YL- THIO)ETHYL PIPERAZINE OR SALTS THEREOF

  摘要：

  公开号：

  EP1566381B1

文献信息

• Process for production of cyclic diamine compounds or salts thereof
  申请人：Shibuya Kimiyuki

  公开号：US20050032814A1

  公开（公告）日：2005-02-10

  The present invention is directed to a process for producing cyclic diamine compounds (4) or salts or intermediates thereof according to the following reaction scheme: (wherein R is a protective group and Ar is an optionally substituted aryl group). According to the present invention, the cyclic diamine compounds (4) useful as drugs or salts or intermediates thereof can be produced at high levels of yield and purity in terms of industrially advantageous productivity.

  本发明涉及一种生产环状二胺化合物（4）或其盐或中间体的方法，该方法根据以下反应方程式进行：（其中R是保护基，Ar是可选取代的芳基基团）。根据本发明，这种环状二胺化合物（4）作为药物或其盐或中间体可以以工业上有利的生产率高水平地产生，同时保证高收率和纯度。
• Process for production of 1-[2-(benzimidazol-2-yl- thio)ethy]piperazine or salts thereof
  申请人：Shibuya Kimiyuki

  公开号：US20060035906A1

  公开（公告）日：2006-02-16

  This invention relates to a method for producing 1-[2-(benzimidazol-2-ylthio)ethyl]piperadine (5) or its salt by the following reaction scheme: This invention enables efficient production of 1-[2-(benzimidazol-2-ylthio) ethyl]piperadine or its salt which is an intermediate in the production of a cyclic diamine compound which is useful as a ACAT inhibitor.

  本发明涉及一种通过以下反应方案生产1-[2-(苯并咪唑-2-基硫基)乙基]哌嗪(5)或其盐的方法：本发明使得1-[2-(苯并咪唑-2-基硫基)乙基]哌嗪或其盐的高效生产成为可能，该化合物是生产环状二胺化合物的中间体，后者是一种有用的ACAT抑制剂。
• Process for production of 1-[2-(benzimidazol-2-yl-thio)ethyl]piperazine or salts thereof
  申请人：Kowa Co., Ltd.

  公开号：US07214796B2

  公开（公告）日：2007-05-08

  This invention relates to a method for producing 1-[2-(benzimidazol-2-ylthio)ethyl]piperazine (5) or its salt by the following reaction scheme: This invention enables efficient production of 1-[2-(benzimidazol-2-ylthio) ethyl]piperazine or its salt which is an intermediate in the production of a cyclic diamine compound which is useful as a ACAT inhibitor.

  本发明涉及一种通过以下反应方案生产1-[2-(苯并咪唑-2-基硫基)乙基]哌嗪（5）或其盐的方法：本发明使得1-[2-(苯并咪唑-2-基硫基)乙基]哌嗪或其盐的高效生产成为可能，该化合物是一种用作ACAT抑制剂的环状二胺化合物的中间体。
• PROCESS FOR PRODUCTION OF 1- 2-(BENZIMIDAZOL-2-YL- THIO)ETHYL ]PIPERAZINE OR SALTS THEREOF
  申请人：Kowa Co., Ltd.

  公开号：EP1566381A1

  公开（公告）日：2005-08-24

  This invention relates to a method for producing 1-[2-(benzimidazol-2-ylthio)ethyl]piperadine (5) or its salt by the following reaction scheme: This invention enables efficient production of 1-[2-(benzimidazol-2-ylthio)ethyl]piperadine or its salt which is an intermediate in the production of a cyclic diamine compound which is useful as a ACAT inhibitor.

  本发明涉及一种通过以下反应方案生产 1-[2-(苯并咪唑-2-基硫基)乙基]哌拉啶 (5) 或其盐的方法： 本发明能够高效生产 1-[2-(苯并咪唑-2-基硫基)乙基]哌啶或其盐，该盐是生产环二胺化合物的中间体，可用作 ACAT 抑制剂。
• PROCESSES FOR PRODUCTION OF CYCLIC DIAMINE COMPOUNDS OR SALTS THEREOF
  申请人：Kowa Co., Ltd.

  公开号：EP1460065B1

  公开（公告）日：2012-12-05