替来他明中间体2 | 94139-04-5

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 替来他明中间体2
• 英文名称: (1-Bromocyclopentyl)-2-thienyl ketone
• 英文别名: (1-bromocyclopentyl)-thiophen-2-ylmethanone
• CAS: 94139-04-5
• 化学式: C₁₀H₁₁BrOS
• 分子量: 259.167
• InChiKey: ZUMUBEYQNBPOND-UHFFFAOYSA-N

物化性质

• 沸点：
  337.8±22.0 °C(Predicted)
• 密度：
  1.542±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿、可溶于二氯甲烷、乙酸乙酯

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  45.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  替来他明中间体2 在 正丁基锂 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 2.5h， 生成
  参考文献：
  名称：

  用于构建第四纪立体中心的催化对映选择性频哪醇和 Meinwald 重排

  摘要：

  对映选择性频哪醇重排的发展极具挑战性，因为碳鎓中间体可能参与其中，这使得催化剂和底物之间的立体化学通讯难以实现。在此，我们报告了手性 N-三氟甲基磷酰胺催化的 1,2-叔二醇的对映选择性频哪醇重排和机械相关的四取代环氧化物的 Meinwald 重排，用于合成对映体富集的 2-炔基-2-芳基环己酮和 2,2-环己酮二芳基分别。还记录了以催化对映选择性频哪醇重排为关键战略步骤的 (+)-膜的全合成。

  DOI：

  10.1021/jacs.9b04551
• 作为产物：
  描述：

  环戊基噻吩-2-基酮 在 溴 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 替来他明中间体2
  参考文献：
  名称：

  用于构建第四纪立体中心的催化对映选择性频哪醇和 Meinwald 重排

  摘要：

  对映选择性频哪醇重排的发展极具挑战性，因为碳鎓中间体可能参与其中，这使得催化剂和底物之间的立体化学通讯难以实现。在此，我们报告了手性 N-三氟甲基磷酰胺催化的 1,2-叔二醇的对映选择性频哪醇重排和机械相关的四取代环氧化物的 Meinwald 重排，用于合成对映体富集的 2-炔基-2-芳基环己酮和 2,2-环己酮二芳基分别。还记录了以催化对映选择性频哪醇重排为关键战略步骤的 (+)-膜的全合成。

  DOI：

  10.1021/jacs.9b04551

文献信息

• Process for the production of cyclopentyl 2-thienyl ketone
  申请人：GREAT LAKES CHEMICAL CORPORATION

  公开号：EP1029858A1

  公开（公告）日：2000-08-23

  A water-scavenging solvent, such a polyphosphoric acid, can be used for the synthesis of cyclopentyl 2-thienyl ketone by the direct acylation of cyclopentanecarboxylic acid without first reacting the cyclopentanecarboxylic acid with thionylchloride to form the acid chloride, while achieving new and unexpected yields. A tiletamine-free base can be made from the cyclopentyl 2-thienyl ketone with a halide in the presence of a solvent for the cyclopentyl 2-thienyl ketone to form a halogenated cyclopentane 2-thienyl ketone; aminating the halogenated cyclopentane 2-thienyl ketone by reaction with an amine; and subjecting the reaction product to thermal rearrangement, in a suitable solvent, and at a sufficient temperature to form tiletamine free base. Each step for the formation of tiletamine free base can be accomplished using the same solvent, e.g., dichlorobenzene so that intermediates need not be isolated between reactions.

  在通过环戊烷羧酸的直接酰化合成环戊烷-2-噻吩基酮时，可使用一种清水溶剂，如聚磷酸，而无需先使环戊烷羧酸与亚硫酰氯反应生成酰氯，同时还可获得意想不到的新产率。无瓦塔胺碱可以由环戊烷-2-噻吩基酮与卤化物在环戊烷-2-噻吩基酮溶剂存在下生成卤代环戊烷-2-噻吩基酮；通过与胺反应将卤代环戊烷-2-噻吩基酮胺化；以及在合适的溶剂中和足够的温度下将反应产物进行热重排以形成无瓦塔胺碱。形成游离瓦他敏碱的每个步骤都可以使用相同的溶剂（如二氯苯）来完成，这样就不需要在反应之间分离中间产物。
• Discovery of novel ketamine‐inspired derivatives as a protective agent against renal ischemic/reperfusion injury in Wistar rats
  作者：Li Zhu、Yin Zhang

  DOI：10.1111/cbdd.14011

  日期：2022.7

  AbstractRenal ischemia‐reperfusion (I/R) injury is a limiting factor for the success of renal grafts and is deemed greatly responsible for the mortality. A novel series of ketamine‐inspired compounds was synthesized and subjected to NF‐ĸB transcriptional inhibitory activity in LPS‐stimulated RAW264.7 cells, where entire set of compounds showed mild‐to‐moderate significant NF‐ĸB transcriptional inhibitory activity (IC50 6.53–67.52 µM). Compound 6d showed highest inhibitory activity among the tested series (IC50 2.62 µM) and found more potent as compared to ketamine as standard. The effect of compound 6d was further quantified in I/R injury in Wistar rats, where it dose‐dependently improves kidney function of rats with significant amelioration of kidney injury as suggested by histopathologic examination of renal tissues. It further showed reduction in the generation of pro‐inflammatory cytokines and improves the antioxidant status of experimental rats. Compound 6d inhibited apoptosis and increases the expression of Bcl2 and decreases Bax, and cleaved caspase‐3 level. It further reduces TLR‐4 and NF‐κB expression in renal cells of rats, with increases in IκB‐α level in Western blot analysis as compared to I/R group. In summary, our current study showed the development of a novel class of ketamine‐inspired derivatives against renal ischemia/reperfusion injury.
• US5969159A
  申请人：——

  公开号：US5969159A

  公开（公告）日：1999-10-19
• US6147226A
  申请人：——

  公开号：US6147226A

  公开（公告）日：2000-11-14
• [EN] PROCESS FOR THE PRODUCTION OF CYCLOPENTYL 2-THIENYL KETONE<br/>[FR] PROCEDE DE PRODUCTION DE CYCLOPENTYL 2-THIENYL CETONE
  申请人：GREAT LAKES CHEMICAL CORP

  公开号：WO2000049012A1

  公开（公告）日：2000-08-24

  Solid, non-tin-containing catalysts can be used for the synthesis of cyclopentyl 2-thienyl ketone by the reaction of cyclopentanecarboxylic acid chloride and thiophene, while achieving new and unexpected yields. Aluminum trichloride is both cheaper than stannic chloride and it is easier to deal with as a waste stream. The successful use of graphite as a catalyst for the reaction of cyclopentanecarboxylic acid chloride and thiophene provides a mild and ecologically friendly method for carrying out the Friedel-Crafts reaction. A tiletamine-free base can be made from the cyclopentyl 2-thienyl ketone with a halide in the presence of a solvent for the cyclopentyl 2-thienyl ketone to form a halogenated cyclopentane 2-thienyl ketone; aminating the halogenated cyclopentane 2-thienyl ketone by reaction with an amine; and subjecting the reaction product to thermal rearrangement, in a suitable solvent, and at a sufficient temperature to form tiletamine free base. Each step for the formation of tiletamine free base can be accomplished using the same solvent, e.g., dichlorobenzene so that intermediates need not be isolated between reactions.