(2S,6S)-hydroxynorketamine hydrochloride | 1430202-70-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2S,6S)-hydroxynorketamine hydrochloride
• 英文别名: (2S,6S)-2-amino-2-(2-chlorophenyl)-6-hydroxycyclohexanone hydrochloride；[(1S,3S)-1-(2-chlorophenyl)-3-hydroxy-2-oxocyclohexyl]azanium;chloride
• CAS: 1430202-70-2
• 化学式: C₁₂H₁₄ClNO₂*ClH
• 分子量: 276.163
• InChiKey: ZQJVHBJDLMIKJK-JGAZGGJJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.03
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  63.3
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-氨基-2-(2-氯苯基)环己酮盐酸盐 在 D-酒石酸 、 间氯过氧苯甲酸 、 三氟乙酸 、 lithium diisopropyl amide 、 苯 作用下， 以 四氢呋喃 、 乙醇 、 正庚烷 、 二氯甲烷 、 乙基苯 、 甲苯 为溶剂， 反应 38.03h， 生成 (2S,6S)-hydroxynorketamine hydrochloride
  参考文献：
  名称：

  (2R,6R)-羟基去甲氯胺酮和(2S,6S)-羟基去甲氯胺酮的晶型和合成方法

  摘要：

  本公开提供用于合成游离碱形式的(2R,6R)‑羟基去甲氯胺酮(HNK)和(2S,6S)‑羟基去甲氯胺酮的方法。在一个实施方式中，(2R,6R)‑羟基去甲氯胺酮(HNK)的合成包括通过使用L‑焦谷氨酸的手性拆分通过从外消旋去甲氯胺酮中手性拆分而制备(R)‑去甲氯胺酮。本公开还提供相应的(2R,6R)‑羟基去甲氯胺酮(HNK)盐酸盐和(2S,6S)‑羟基去甲氯胺酮盐酸盐的晶型。

  公开号：

  CN109311801B

文献信息

• Simple Enantioselective Syntheses of (2<i>R</i>,6<i>R</i>)-Hydroxynorketamine and Related Potential Rapid-Onset Antidepressants
  作者：Yixin Han、Karla Mahender Reddy、E. J. Corey

  DOI：10.1021/acs.orglett.7b02498

  日期：2017.10.6

  A novel strategy for accessing cyclic α-amino ketones enantioselectively has opened a simple synthetic route to the antidepressant (2R,6R)-hydroxynorketamine and numerous analogues. Mechanistically guided catalyst selection was essential in an initial olefin epoxidation step. In a second crucial step, the epoxide was subjected to a novel O → N displacement that occurred with retention of configuration

  对映选择性地获得环状α-氨基酮的新策略为抗抑郁药（2 R，6 R）-羟基降甲胺酮和许多类似物开辟了一条简单的合成途径。在初始烯烃环氧化步骤中，机械引导的催化剂选择至关重要。在第二个关键步骤中，通过使用基于Al或Ti的叠氮化物，使环氧化物经受新的O→N置换，并保留了构型，从而促进了环氧化物的活化和N 3内向碳的顺式传递。
• Crystal forms and methods of synthesis of (2R, 6R)-hydroxynorketamine and (2S, 6S)-hydroxynorketamine
  申请人：The United States of America, As Represented by the Secretary, Department of Health and Human Services

  公开号：US10919842B2

  公开（公告）日：2021-02-16

  The disclosure provides a method for synthesizing free base forms of (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hydroxynorketamine. In an embodiment synthesis of (2R,6R)-hydroxynorketamine (HNK) includes preparation of (R)-norketamine via chiral resolution from racemic norketamine via a chiral resolution with L-pyroglutamic acid. The disclosure also provided crystal forms of the corresponding (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hydroxynorketamine hydrochloride salts.

  本公开提供了一种合成游离碱形式的 (2R,6R)-hydroxynorketamine (HNK) 和 (2S,6S)-hydroxynorketamine 的方法。在一个实施方案中，(2R,6R)-羟基炔诺酮胺（HNK）的合成包括通过外消旋炔诺酮胺与 L-焦谷氨酸的手性解析，通过手性解析制备 (R)-炔诺酮胺。该公开还提供了相应的 (2R,6R)-hydroxynorketamine (HNK) 和 (2S,6S)-hydroxynorketamine 盐酸盐的晶体形式。
• METHODS OF USING (2R, 6R)-HYDROXYNORKETAMINE AND (2S, 6S)-HYDROXYNORKETAMINE IN THE TREATMENT OF DEPRESSION, ANXIETY, ANHEDONIA, FATIGUE, SUICIDAL IDEATION, AND POST TRAUMATIC STRESS DISORDERS
  申请人：The Uinited States of America, as represented by the Secretary, Department of Health and Human Serv

  公开号：US20190083420A1

  公开（公告）日：2019-03-21

  Disclosed is a method of treating Psychotic Depression, Suicidal Ideation, Disruptive Mood Dysregulation Disorder, Persistent Depressive Disorder (Dysthymia), Premenstrual Dysphoric Disorder, Substance/Medication-Induced Depressive Disorder, Depressive Disorder Due to Another Medical Condition, Other Specified Depressive Disorder, Unspecified Depressive Disorder, Separation Anxiety Disorder, Selective Mutism, Specific Phobia, Social Anxiety Disorder (Social Phobia), Panic Disorder, Panic Attack (Specifier), Agoraphobia, Generalized Anxiety Disorder, Substance/Medication-Induced Anxiety Disorder, Anxiety Disorder Due to Another Medical, Other Specified Anxiety Disorder, Unspecified Anxiety Disorder, or fatigue the method including administering a pharmaceutical composition containing an effective amount of an active agent, wherein the active agent is purified (2R,6R)-hydroxynorketamine, purified (2S,6S)-hydroxynorketamine, or a combination thereof, or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier to a patient in need of such treatment.
• CRYSTAL FORMS AND METHODS OF SYNTHESIS OF (2R, 6R)-HYDROXYNORKETAMINE AND (2S, 6S)-HYDROXYNORKETAMINE
  申请人：The United States of America, As Represented by the Secretary, Department of Health and Human Serv

  公开号：US20190135732A1

  公开（公告）日：2019-05-09

  The disclosure provides a method for synthesizing free base forms of (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hydroxynorketamine. In an embodiment synthesis of (2R,6R)-hydroxynorketamine (HNK) includes preparation of (R)-norketamine via chiral resolution from racemic norketamine via a chiral resolution with L-pyroglutamic acid. The disclosure also provided crystal forms of the corresponding (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hydroxynorketamine hydrochloride salts.
• (2R,6R)-羟基去甲氯胺酮和(2S,6S)-羟基去甲氯胺酮的晶型和合成方法
  申请人：美国政府健康及人类服务部

  公开号：CN109311801B

  公开（公告）日：2022-07-26

  本公开提供用于合成游离碱形式的(2R,6R)‑羟基去甲氯胺酮(HNK)和(2S,6S)‑羟基去甲氯胺酮的方法。在一个实施方式中，(2R,6R)‑羟基去甲氯胺酮(HNK)的合成包括通过使用L‑焦谷氨酸的手性拆分通过从外消旋去甲氯胺酮中手性拆分而制备(R)‑去甲氯胺酮。本公开还提供相应的(2R,6R)‑羟基去甲氯胺酮(HNK)盐酸盐和(2S,6S)‑羟基去甲氯胺酮盐酸盐的晶型。