tert-butyl 4-(2-((1H-benzo[d]imidazol-2-yl)thio)ethyl)piperazine-1-carboxylate | 698976-81-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: tert-butyl 4-(2-((1H-benzo[d]imidazol-2-yl)thio)ethyl)piperazine-1-carboxylate
• 英文别名: 1-[2-(benzimidazol-2-ylthio)ethyl]-4-(tert-butoxycarbonyl)-piperazine；1-[2-(Benzimidazol-2-ylthio)ethyl]-4-tert-butoxycarbonyl piperazine；tert-butyl 4-[2-(1H-benzimidazol-2-ylsulfanyl)ethyl]piperazine-1-carboxylate
• CAS: 698976-81-7
• 化学式: C₁₈H₂₆N₄O₂S
• 分子量: 362.496
• InChiKey: JUTZNHMXHHMXSO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  86.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(2-((1H-benzo[d]imidazol-2-yl)thio)ethyl)piperazine-1-carboxylate 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 14.0h， 生成 2-(4-(2-((1H-benzo[d]imidazol-2-yl)thio)ethyl)piperazin-1-yl)-N-(6-methyl-2-(methyl-sulfinyl)-4-(methylthio)pyridin-3-yl)acetamide
  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 四氢呋喃 、 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 4.08h， 以64%的产率得到tert-butyl 4-(2-((1H-benzo[d]imidazol-2-yl)thio)ethyl)piperazine-1-carboxylate
  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 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
• US7214796B2
  申请人：——

  公开号：US7214796B2

  公开（公告）日：2007-05-08