4-[(3R,11bR)-9,10-dimethoxyspiro[1,3,4,6,7,11b-hexahydrobenzo[a]quinolizine-2,2'-1,3-dioxolane]-3-yl]butan-1-ol | 1091627-94-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 4-[(3R,11bR)-9,10-dimethoxyspiro[1,3,4,6,7,11b-hexahydrobenzo[a]quinolizine-2,2'-1,3-dioxolane]-3-yl]butan-1-ol
• CAS: 1091627-94-9
• 化学式: C₂₁H₃₁NO₅
• 分子量: 377.481
• InChiKey: DFEJEUSONQTNET-SJLPKXTDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  60.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (3R,11bR)-3-[4-[tert-butyl(diphenyl)silyl]oxybutyl]-9,10-dimethoxy-1,3,4,6,7,11b-hexahydrobenzo[a]quinolizin-2-one 、 乙二醇 在 甲烷磺酸 作用下， 反应 20.0h， 以73%的产率得到4-[(3R,11bR)-9,10-dimethoxyspiro[1,3,4,6,7,11b-hexahydrobenzo[a]quinolizine-2,2'-1,3-dioxolane]-3-yl]butan-1-ol
  参考文献：
  名称：

  INTERMEDIATES USEFUL FOR MAKING TETRABENAZINE COMPOUNDS

  摘要：

  一种制备结构I的四苯异赭曲嗪化合物（TBZ化合物）的方法，包括以下步骤：将亲核烯基物种与醛化合物II反应，并氧化所得的烯丙醇以提供烯酮III。去除四氢异喹啉氮上的保护基P1，并使去保护的中间体发生氨基环化反应，以提供具有结构I的产品TBZ化合物。该方法可用于制备四苯异赭曲嗪的任一对映体形式；（+）-四苯异赭曲嗪或（-）-四苯异赭曲嗪。另外，该方法可被改进以提供富含一种四苯异赭曲嗪对映体的混合物、外消旋混合物或四苯异赭曲嗪化合物的非对映异构体混合物。此外，本发明提供了可用于制备四苯异赭曲嗪的任一或两种对映体、四苯异赭曲嗪衍生物和四苯异赭曲嗪类似物的新型合成中间体组合物。

  公开号：

  US20080306269A1

文献信息

• INTERMEDIATES USEFUL FOR MAKING TETRABENAZINE COMPOUNDS
  申请人：Rishel Michael James

  公开号：US20080306269A1

  公开（公告）日：2008-12-11

  A method of preparing a tetrabenazine compound (TBZ compound) having structure I comprising the steps of reacting a nucleophilic alkenyl species with aldehyde compound II and oxidizing the resultant allylic alcohol to provide enone III. The protecting group P 1 on the tetrahydroisoquinoline nitrogen is removed and the resultant deprotected intermediate is induced to undergo an amino cyclization reaction to provide a product TBZ compound having structure I. The method may be used to prepare either enantiomeric form of tetrabenazine; (+)-tetrabenazine or (−)-tetrabenazine. Alternatively the method may be adapted to provide a mixture enriched in one tetrabenazine enantiomer, a racemic mixture, or a diastereomeric mixture of tetrabenazine compounds. In addition, the present invention provides novel synthetic intermediate compositions which may be used to prepare either or both enantiomers of tetrabenazine, derivatives of tetrabenazine, and analogs of tetrabenazine.

  一种制备结构I的四苯异赭曲嗪化合物（TBZ化合物）的方法，包括以下步骤：将亲核烯基物种与醛化合物II反应，并氧化所得的烯丙醇以提供烯酮III。去除四氢异喹啉氮上的保护基P1，并使去保护的中间体发生氨基环化反应，以提供具有结构I的产品TBZ化合物。该方法可用于制备四苯异赭曲嗪的任一对映体形式；（+）-四苯异赭曲嗪或（-）-四苯异赭曲嗪。另外，该方法可被改进以提供富含一种四苯异赭曲嗪对映体的混合物、外消旋混合物或四苯异赭曲嗪化合物的非对映异构体混合物。此外，本发明提供了可用于制备四苯异赭曲嗪的任一或两种对映体、四苯异赭曲嗪衍生物和四苯异赭曲嗪类似物的新型合成中间体组合物。
• ALPHA-FLUOROALKYL TETRABENAZINE AND DIHYDROTETRABENAZINE IMAGING AGENTS AND PROBES
  申请人：Rishel Michael James

  公开号：US20090142265A1

  公开（公告）日：2009-06-04

  The present invention provides novel alpha-fluoroalkyl compounds having structure I and the corresponding dihydrotetrabenazine compounds IV wherein R 1 is a C 1 -C 10 fluorinated aliphatic radical; R 2 is hydrogen or a C 1 -C 10 aliphatic radical; and R 3 is hydrogen or a C 1 -C 10 aliphatic radical. The alpha-fluoroalkyl compounds are provided in both racemic and enantiomerically enriched forms and may comprise either or both of fluorine-18 and fluorine 19. The alpha-fluoroalkyl compounds are shown to possess high affinity for VMAT-2, a biomarker implicated in human diabetes. The alpha-fluoroalkyl compounds comprising a fluorine-18 group are useful as PET imaging agents targeting the VMAT-2 biomarker. The non-radiolabled alpha-fluoroalkyl compounds are useful as probes for the discovery of PET imaging agents.

  本发明提供了具有结构I的新型α-氟烷基化合物和相应的二氢四苯乙烯化合物IV，其中R1是C1-C10氟化脂肪基；R2是氢或C1-C10脂肪基；R3是氢或C1-C10脂肪基。α-氟烷基化合物以外消旋和对映富集形式提供，并且可以包括氟-18和氟-19中的任意一个或两个。已证明α-氟烷基化合物具有高亲和力VMAT-2，这是与人类糖尿病有关的生物标志物。含氟-18基团的α-氟烷基化合物可用作PET成像剂，以靶向VMAT-2生物标志物。非放射性标记的α-氟烷基化合物可用作探针，用于发现PET成像剂。
• ALPHA-FLUOROALKYL DIHYDROTETRABENAZINE IMAGING AGENTS AND PROBES
  申请人：Rishel Michael James

  公开号：US20090142276A1

  公开（公告）日：2009-06-04

  The present invention provides novel alpha-fluoroalkyl dihydrotetrabenazine compounds I wherein R 1 is a C 1 -C 10 fluorinated aliphatic radical; R 2 is hydrogen or a C 1 -C 10 aliphatic radical; R 3 is hydrogen or a C 1 -C 10 aliphatic radical; and R 4 is a C 1 -C 10 aliphatic radical, a C 3 -C 10 cycloaliphatic radical, or a C 3 -C 10 aromatic radical. The alpha-fluoroalkyl dihydrotetrabenazine compounds are provided in both racemic and enantiomerically enriched forms and may comprise either or both of fluorine-18 and fluorine 19. The alpha-fluoroalkyl dihydrotetrabenazine compounds are believed to possess high affinity for VMAT-2, a biomarker implicated in human diabetes. The alpha-fluoroalkyl dihydrotetrabenazine compounds comprising a fluorine-18 group are useful as PET imaging agents targeting the VMAT-2 biomarker. The non-radiolabled alpha-fluoroalkyl dihydrotetrabenazine compounds are useful as probes for the discovery of PET imaging agents.

  本发明提供了新型α-氟烷基二氢四氢异脲白菜碱化合物I，其中R1是C1-C10氟化脂肪基；R2是氢或C1-C10脂肪基；R3是氢或C1-C10脂肪基；R4是C1-C10脂肪基、C3-C10环烷基或C3-C10芳香基。α-氟烷基二氢四氢异脲白菜碱化合物以两种形式提供，即外消旋和对映富集，并且可能包含氟-18和氟-19中的一个或两个。认为α-氟烷基二氢四氢异脲白菜碱化合物具有高亲和力VMAT-2，这是与人类糖尿病有关的生物标志物。含氟-18基团的α-氟烷基二氢四氢异脲白菜碱化合物可用作PET成像剂，针对VMAT-2生物标志物。非放射性α-氟烷基二氢四氢异脲白菜碱化合物可用作探针，用于发现PET成像剂。
• INTERMEDIATES FOR ALPHA-FLUOROALKYL TETRABENAZINE AND DIHYDROTETRABENAZINE IMAGING AGENTS AND PROBES
  申请人：Rishel Michael James

  公开号：US20090143587A1

  公开（公告）日：2009-06-04

  The present invention provides novel fluorophilic compounds having structure VII wherein Q is a carbonyl group, a protected carbonyl group, a hydroxy methine group, or a protected hydroxy methine group; R 1 is a C 1 -C 20 aliphatic, C 2 -C 20 cycloaliphatic, or C 2 -C 20 aromatic radical comprising at least one functional group susceptible to reaction with nucleophilic fluoride ion or an electrophilic fluorinating agent; R 2 is hydrogen or a C 1 -C 10 aliphatic radical; and R 3 is hydrogen or a C 1 -C 10 aliphatic radical. The fluorophilic compounds are provided in both racemic and enantiomerically enriched forms and are useful as intermediates in the preparation of novel PET imaging agents and probes useful in the discovery and performance assessment of PET imaging agents. The fluorophilic compounds are particularly useful in the preparation of PET imaging agents and probes having a high affinity for VMAT-2, a biomarker implicated in human diabetes and other illnesses such as Parkinson's disease.

  本发明提供了具有结构VII的新型亲氟化合物，其中Q是羰基基团，受保护的羰基基团，羟基甲基基团或受保护的羟基甲基基团；R1是C1-C20脂肪族，C2-C20环烷基或C2-C20芳香基，包括至少一个易于与亲核氟离子或亲电氟化试剂反应的官能团；R2是氢或C1-C10脂肪基；R3是氢或C1-C10脂肪基。这些亲氟化合物以外消旋和对映富集的形式提供，并且可用作新型PET成像剂和探针的中间体，这些成像剂和探针可用于发现和评估PET成像剂的性能。这些亲氟化合物在制备对VMAT-2具有高亲和力的PET成像剂和探针方面特别有用，VMAT-2是与人类糖尿病和帕金森病等疾病相关的生物标志物。
• Alpha-fluoroalkyl tetrabenazine and dihydrotetrabenazine imaging agents and probes
  申请人：General Electric Company

  公开号：EP2594568A1

  公开（公告）日：2013-05-22

  The present invention provides novel alpha-fluoroalkyl compounds having structure I and the corresponding dihydrotetrabenazine compounds IV and intermediates useful in the preparation of such compounds. The alpha-fluoroalkyl compounds are provided in both racemic and enantiomerically enriched forms and may comprise either or both of fluorine-18 and fluorine 19. The alpha-fluoroalkyl compounds are shown to possess high affinity for VMAT-2, a biomarker implicated, for example, in human diabetes. The alpha-fluoroalkyl compounds comprising a fluorine-18 group are useful as PET imaging agents targeting the VMAT-2 biomarker. The non-radiolabled alpha-fluoroalkyl compounds are useful as probes for the discovery of PET imaging agents.

  本发明提供了具有结构 I 的新型α-氟烷基化合物和相应的二氢四苯嗪化合物 IV 以及用于制备此类化合物的中间体。本发明提供的α-氟烷基化合物既有外消旋形式，也有对映体富集形式，可以包含氟-18 和氟-19 中的一种或两种。α-氟烷基化合物对 VMAT-2 具有很高的亲和力，VMAT-2 是一种与人类糖尿病等有关的生物标志物。包含一个氟-18 基团的 α-氟烷基化合物可用作针对 VMAT-2 生物标志物的 PET 成像剂。非辐射α-氟烷基化合物可用作发现 PET 成像剂的探针。