(1s,4s)-6'-fluoro-N,N-dimethyl-4-phenyl-4',9'-dihydro-3'H-spiro[cyclohexane-1,1'-pyrano[3,4-b]indole]-4-amine | 863513-93-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (1s,4s)-6'-fluoro-N,N-dimethyl-4-phenyl-4',9'-dihydro-3'H-spiro[cyclohexane-1,1'-pyrano[3,4-b]indole]-4-amine
• 英文别名: 6'-fluoro-4',9'-dihydro-N,N-dimethyl-4-phenyl-spiro[cyclohexane-1,1'(3'H)-pyrano[3,4-b]indol]-4-amine
• CAS: 863513-93-3
• 化学式: C₂₄H₂₇FN₂O
• 分子量: 378.49
• InChiKey: CSMVOZKEWSOFER-PSWAGMNNSA-N

物化性质

• 沸点：
  547.5±50.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  5.11
• 重原子数：
  28.0
• 可旋转键数：
  2.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  28.26
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  (1s,4s)-6'-fluoro-N,N-dimethyl-4-phenyl-4',9'-dihydro-3'H-spiro[cyclohexane-1,1'-pyrano[3,4-b]indole]-4-amine 、 柠檬酸 以 乙醇 为溶剂， 以548 mg的产率得到
  参考文献：
  名称：

  [EN] PROCESS FOR THE PREPARATION OF (1R,4R)-6'-FLUORO-(N,N-DIMETHYL- AND N-METHYL)-4-PHENYL-4',9'-DIHYDRO-3'H-SPIRO[CYCLOHEXANE-1,1'-PYRANO-[3,4,B]INDOL]-4-AMINE
  [FR] PROCÉDÉ DE PRÉPARATION DE (1R,4R)-6'-FLUORO-(N,N-DIMÉTHYL- ET N-MÉTHYL)- 4-PHÉNYL-4',9'-DIHYDRO-3'H-SPIRO[CYCLOHEXANE-1,1'-PYRANO[3,4-B]INDOL]- 4-AMINE

  摘要：

  本发明涉及一种制备(1r,4r)-6'-氟-N,N-二甲基-4-苯基-4',9'-二氢-3'H-螺[环己烷-1,1'-吡喃[3,4b]吲哚]-4-胺和(1r,4r)-6'-氟-N-甲基-4-苯基-4',9'-二氢-3'H-螺[环己烷-1,1'-吡喃[3,4b]吲哚]-4-胺或其生理上可接受的酸盐的过程。

  公开号：

  WO2013087589A1
• 作为产物：
  描述：

  4-dimethylamino-4-phenylcyclohexanone, ethylene ketal hydrochloride 在 盐酸 、 磷酸 、 水 、 溶剂黄146 作用下， 以 乙醚 为溶剂， 反应 16.0h， 生成 (1s,4s)-6'-fluoro-N,N-dimethyl-4-phenyl-4',9'-dihydro-3'H-spiro[cyclohexane-1,1'-pyrano[3,4-b]indole]-4-amine
  参考文献：
  名称：

  Discovery of a Potent Analgesic NOP and Opioid Receptor Agonist: Cebranopadol

  摘要：

  In a previous communication, our efforts leading from 1 to the identification of spiro[cyclohexane-dihydropyrano[3,4-b]indole]-amine 2a as analgesic NOP and opioid receptor agonist were disclosed and their favorable in vitro and in vivo pharmacological properties revealed. We herein report our efforts to further optimize lead 2a, toward trans-6'-fluoro-4',9'-dihydro-N,N-dimethyl-4-phenyl-spiro[cyclohexane-1,1'(3'H)-pyrano[3,4-b]indol]-4-amine (cebranopadol, 3a), which is currently in clinical development for the treatment of severe chronic nociceptive and neuropathic pain.

  DOI：

  10.1021/ml500117c

文献信息

• CRYSTALLINE (1R,4R)-6'-FLUORO-N,N-DIMETHYL-4-PHENYL-4',9'-DIHYDRO-3'H-SPIRO[CYCLOHEXANE-1,1'-PYRANO[3,4,B]INDOL]-4-AMINE
  申请人：Gruss Michael

  公开号：US20130012563A1

  公开（公告）日：2013-01-10

  Crystalline forms of (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4,b]indol]-4-amine, pharmaceutical compositions and medicaments comprising these crystalline modifications, the use of these modifications as well as a process for the enrichment of such crystalline modifications.

  (1r,4r)-6'-氟-N,N-二甲基-4-苯基-4',9'-二氢-3'H-螺[环己烷-1,1'-吡喃[3,4,b]吲哚]-4-胺的晶体形态，包括这些晶体修饰的药物组合物和药物，以及这些修饰的用途，以及用于富集此类晶体修饰的过程。
• [EN] PROCESS FOR THE PREPARATION OF (1R,4R)-6'-FLUORO-(N,N-DIMETHYL- AND N-METHYL)-4-PHENYL-4',9'-DIHYDRO-3'H-SPIRO[CYCLOHEXANE-1,1'-PYRANO-[3,4,B]INDOL]-4-AMINE<br/>[FR] PROCÉDÉ DE PRÉPARATION DE (1R,4R)-6'-FLUORO-(N,N-DIMÉTHYL- ET N-MÉTHYL)- 4-PHÉNYL-4',9'-DIHYDRO-3'H-SPIRO[CYCLOHEXANE-1,1'-PYRANO[3,4-B]INDOL]- 4-AMINE
  申请人：GRUENENTHAL GMBH

  公开号：WO2013087589A1

  公开（公告）日：2013-06-20

  The present invention relates to a process for the preparation of (1r,4r)-6'-fluoro-N,N-dimethyl-4-phenyl-4',9'-dihydro-3'H-spiro[cyclohexane-1,1'-pyrano[3,4b]indol]-4-amine and (1r,4r)-6'-fluoro-N-methyl-4-phenyl-4',9'-dihydro-3'H-spiro[cyclohexane-1,1'-pyrano[3,4b]- indol]-4-amine or physiologically acceptable acid addition salts thereof.

  本发明涉及一种制备(1r,4r)-6'-氟-N,N-二甲基-4-苯基-4',9'-二氢-3'H-螺[环己烷-1,1'-吡喃[3,4b]吲哚]-4-胺和(1r,4r)-6'-氟-N-甲基-4-苯基-4',9'-二氢-3'H-螺[环己烷-1,1'-吡喃[3,4b]吲哚]-4-胺或其生理上可接受的酸盐的过程。
• [EN] SOLID FORMS OF (1R,4R)-6'-FLUORO-N,N-DIMETHYL-4-PHENYL-4',9'-DIHYDRO-3'H-SPIRO-[CYCLOHEXANE-1,1'-PYRANO[3,4,B]INDOL]-4-AMINE HYDROCHLORIDE<br/>[FR] FORMES SOLIDES DE CHLORHYDRATE DE (1R,4R)-6'-FLUORO-N,N-DIMÉTHYL-4-PHÉNYL-4',9'-DIHYDRO-3'H-SPIRO-[CYCLOHEXANE-1,1'-PYRANO[3,4,B]INDOL]-4-AMINE
  申请人：GRUENENTHAL GMBH

  公开号：WO2013087590A1

  公开（公告）日：2013-06-20

  The present invention relates to solid forms of (1 r,4r)-6'-fluoro-N,N-dimethyl-4-phenyl-4',9'- dihydro-3'H-spiro[cyclohexane-1,1'-pyrano[3,4,b]indol]-4-amine hydrochloride, in particular crystalline forms and/or amorphous forms thereof, pharmaceutical compositions and medicaments comprising these solid forms, the use of these solid forms as well as to a process for obtaining them.

  本发明涉及(1 r,4r)-6'-氟-N,N-二甲基-4-苯基-4',9'-二氢-3'H-螺[环己烷-1,1'-吡喃[3,4,b]吲哚]-4-胺盐酸盐的固态形式，特别是其晶体形式和/或非晶形式、包含这些固态形式的制药组合物和药物、这些固态形式的用途以及获得它们的方法。
• [EN] SOLID FORMS OF (1R,4R)-6'-FLUORO-(N,N-DIMETHYL)-4-PHENYL-4',9'-DIHYDRO-3'H-SPIRO-[CYCLOHEXANE-1,1'-PYRANO-[3,4,B]INDOL]-4-AMINE AND SULFURIC ACID<br/>[FR] FORMES SOLIDES DE (1R,4R)-6'-FLUORO-(N,N-DIMÉTHYL)-4-PHÉNYL-4',9'- DIHYDRO-3'H-SPIRO[CYCLOHEXANE-1,1'-PYRANO[3,4-B]INDOL]-4-AMINE ET D'ACIDE SULFURIQUE
  申请人：GRUENENTHAL GMBH

  公开号：WO2013087591A1

  公开（公告）日：2013-06-20

  The invention relates to solid forms of (1r,4r)-6'-fluoro-N,N-dimethyl-4-phenyl-4',9'-dihydro- 3'H-spiro[cyclohexane-1,1'-pyrano[3,4b]indol]-4-amine and sulfuric acid such as (1r,4r)-6'- fluoro-N,N-dimethyl-4-phenyl-4',9'-dihydro-3'H-spiro[cyclohexane-1,1'-pyrano[3,4b]indol]-4- amine sulfate or hemi-sulfate, in particular crystalline forms and/or amorphous forms thereof, pharmaceutical compositions and medicaments comprising these solid forms, the use of these solid forms as well as to a process for obtaining them.

  本发明涉及(1r,4r)-6'-氟-N,N-二甲基-4-苯基-4',9'-二氢-3'H-螺[环己烷-1,1'-吡喃[3,4b]吲哚]-4-胺及其硫酸盐的固态形式，例如(1r,4r)-6'-氟-N,N-二甲基-4-苯基-4',9'-二氢-3'H-螺[环己烷-1,1'-吡喃[3,4b]吲哚]-4-胺硫酸盐或半硫酸盐，特别是其结晶形式和/或非晶形式，包括这些固态形式的制药组合物和药物，以及这些固态形式的用途以及获得它们的过程。
• Solid forms of (1r,4r)-6'-fluoro-N,N-dimethyl-4-phenyl-4',9'-dihydro-3' H-spiro-[cyclohexane-1,1'-pyrano-[3,4,b]indol]-4-amine hydrochloride
  申请人：Gruenenthal GmbH

  公开号：US20130150420A1

  公开（公告）日：2013-06-13

  Solid forms of (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4,b]indol]-4-amine hydrochloride, in particular crystalline forms and/or amorphous forms thereof, pharmaceutical compositions and medicaments containing these solid forms, the use of these solid forms, and a process for obtaining such solid forms.

  (1R,4R)-6'-氟-N,N-二甲基-4-苯基-4',9'-二氢-3'H-螺[环己烷-1,1'-吡喃[3,4,b]吲哚]-4-胺盐酸盐的固态形式，特别是其晶体形式和/或非晶形式，包括这些固态形式的药物组合物和药物，这些固态形式的用途以及获得这些固态形式的过程。