(5S,6R,E)-6-((tert-butyldimethylsilyl)oxy)-5-isobutyl-10,11-dimethoxy-2,3,5,6-tetrahydrobenzo[d]azecin-4(1H)-one | 1228458-05-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (5S,6R,E)-6-((tert-butyldimethylsilyl)oxy)-5-isobutyl-10,11-dimethoxy-2,3,5,6-tetrahydrobenzo[d]azecin-4(1H)-one
• 英文别名: (5S,6R,7E)-6-[tert-butyl(dimethyl)silyl]oxy-10,11-dimethoxy-5-(2-methylpropyl)-2,3,5,6-tetrahydro-1H-3-benzazecin-4-one
• CAS: 1228458-05-6
• 化学式: C₂₅H₄₁NO₄Si
• 分子量: 447.69
• InChiKey: QYONEXFWFHHBSF-HRZVIGLNSA-N

物化性质

• 熔点：
  172 °C
• 沸点：
  549.5±50.0 °C(Predicted)
• 密度：
  1.03±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.44
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  56.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (5S,6R,E)-6-((tert-butyldimethylsilyl)oxy)-5-isobutyl-10,11-dimethoxy-2,3,5,6-tetrahydrobenzo[d]azecin-4(1H)-one 在 对甲苯磺酸 作用下， 以 甲苯 、 乙腈 为溶剂， 以18.3 g的产率得到(2R,3S,11 bR)-2-hydroxy-3-isobutyl-9,10-dimethoxy-1,2,3,6,7,11b-hexahydro-4H-pyrido[2,1-a]isoquinolin-4-one
  参考文献：
  名称：

  PROCESS FOR MAKING A PHARMACEUTICAL COMPOUND

  摘要：

  This invention relates to a novel process for making dihydrotetrabenazines, and in particular (+)-α-dihydrotetrabenazine, novel synthetic intermediates for use in the process and processes for making the intermediates.

  公开号：

  US20230331667A1
• 作为产物：
  描述：

  (R,E)-1-[1-(2-(tert-butyldimethylsilyloxy)vinyl)-6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl]-4-methylpentan-1-one 在 异丙基氯化镁 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 以100 %的产率得到(5S,6R,E)-6-((tert-butyldimethylsilyl)oxy)-5-isobutyl-10,11-dimethoxy-2,3,5,6-tetrahydrobenzo[d]azecin-4(1H)-one
  参考文献：
  名称：

  PROCESS FOR MAKING A PHARMACEUTICAL COMPOUND

  摘要：

  This invention relates to a novel process for making dihydrotetrabenazines, and in particular (+)-α-dihydrotetrabenazine, novel synthetic intermediates for use in the process and processes for making the intermediates.

  公开号：

  US20230331667A1

文献信息

• A Ring-Closing Metathesis-Based Approach to the Synthesis of (+)-Tetrabenazine
  作者：Manuel Johannes、Karl-Heinz Altmann

  DOI：10.1021/ol301612q

  日期：2012.7.20

  A modular stereoselective synthesis of the vesicular monoamine transport inhibitors (+)-tetrabenazine ((+)-1) and (+)-alpha-dihydrotetrabenazine ((+)-2) has been developed. The approach is based on amine 4 and acid 5 as the key building blocks, which were elaborated into macrolactam 3 by amide coupling and a subsequent highly E-selective RCM reaction. Macrolactam 3 could be converted into tetrabenazine in three known steps.
• A Concise Total Synthesis of (+)-Tetrabenazine and (+)-α-Dihydrotetrabenazine
  作者：Seung-Mann Paek、Nam-Jung Kim、Dongyun Shin、Jae-Kyung Jung、Jong-Wha Jung、Dong-Jo Chang、Hyunyoung Moon、Young-Ger Suh

  DOI：10.1002/chem.200902591

  日期：2010.4.19

  AbstractHighly concise asymmetric total syntheses of (+)‐tetrabenazine (1), a drug for the treatment of chorea associated with Huntington’s disease, and of (+)‐α‐dihydrotetrabenazine (2), an active metabolite of 1, have been accomplished. Our synthetic route features a trans‐selective enol etherification, followed by an unprecedented cation‐dependent aza‐Claisen rearrangement to establish the carbon framework and two stereogenic centers of tetrabenazine. The syntheses consist of seven steps (34 % overall yield) for (+)‐2 and eight steps (22 % overall yield) for (+)‐1.