9,9-二甲基-3,7-二氮杂双环[3.3.1]壬烷-2,4,6,8-四酮 | 90961-73-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 9,9-二甲基-3,7-二氮杂双环[3.3.1]壬烷-2,4,6,8-四酮
• 英文名称: 9,9-dimethyl-2,4,6,8-tetraoxo-3,7-diazabicyclo[3.3.1]nonane
• 英文别名: 9,9-dimethyl-3,7-diaza-bicyclo[3.3.1]nonane-2,4,6,8-tetraone；9,9-Dimethyl-3,7-diaza-bicyclo[3.3.1]nonan-2,4,6,8-tetraon；9,9-Dimethyl-3,7-diazabicyclo[3.3.1]nonane-2,4,6,8-tetraone；9,9-dimethyl-3,7-diazabicyclo[3.3.1]nonane-2,4,6,8-tetrone
• CAS: 90961-73-2
• 化学式: C₉H₁₀N₂O₄
• 分子量: 210.189
• InChiKey: NHYOGDTZCYMRNT-UHFFFAOYSA-N

物化性质

• 熔点：
  >250℃
• 密度：
  1.337

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  92.3
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  9,9-二甲基-3,7-二氮杂双环[3.3.1]壬烷-2,4,6,8-四酮 在 sodium hydride 、 红铝 作用下， 以 甲苯 为溶剂， 反应 4.0h， 生成 9,9-Dimethyl-3,7-bis(prop-2-enyl)-3,7-diazabicyclo[3.3.1]nonane
  参考文献：
  名称：

  Synthesis, Pharmacological Characterization, and Quantitative Structure−Activity Relationship Analyses of 3,7,9,9-Tetraalkylbispidines:  Derivatives with Specific Bradycardic Activity

  摘要：

  A series of 3,7,9,9-tetraalkyl-3,7-diazabicyclo[3.3.1]nonane derivatives (bispidines) was synthesized and identified as potential antiischemic agents. Pharmacological experiments in vitro as well as in vivo are described, and the results are listed. For selection of those compounds fitting best to the desired profile of a specific bradycardic antianginal agent-decrease in heart rate without affecting contractility and blood pressure-these results were scored and ranked. Quantitative structure-activity relationship (QSAR) analyses were performed and discussed a posteriori by means of Hansch, nonelementary discriminant and factor analysis to get insight into the molecular features determining the biological profile. Highly significant equations were obtained, indicating hydrophobic and steric effects. Both pharmacological ranking and QSAR considerations showed compound 6 as the optimum within the structural class under investigation. Compound 6 (tedisamil, KC8857) has been selected as the most promising compound and was chosen for further pharmacological and clinical investigations as an antiischemic drug.

  DOI：

  10.1021/jm970120q
• 作为产物：
  描述：

  cis-3,5-dicyano-4,4-dimethyl-2,6-dioxopiperidine 在 硫酸 作用下， 反应 0.58h， 以33%的产率得到9,9-二甲基-3,7-二氮杂双环[3.3.1]壬烷-2,4,6,8-四酮
  参考文献：
  名称：

  从一个常见的四氧代双吡啶中间体中合成（+/-）-α-异天冬氨酸，（+/-）-β-异天冬氨酸和（+/-）-天冬氨酸。

  摘要：

  从一种常见的四氧代双吡啶前体3,7-二烯丙基-2,4,6,8-四氧代-3,7-二氮杂双环[3.3.1]壬烷（16）以立体控制的方式分别制备了三种标题生物碱。通过酸促进Knoevenagel缩合加合物1,1,3,3-丙烷四羧酰胺的丙二酸酯生成双酰亚胺16。（+/-）-α-Isosparteine（dl-2）通过双向合成顺序从16精制，总产率为28％，该合成顺序由以下四个反应组成：烯丙基溴化镁的两次加成，闭环烯烃复分解（RCM），氢化和硼烷介导的还原。（+/-）-β-Isosparteine（dl-3）通过核心合成子的烯丙基化和还原操作的战略逆转以相似的路线作为目标。因此，通过从硼氢化钠介导的还原反应开始的反应顺序，以五个步骤将16推进到dl-3，使总收率提高到12％，然后对所得的双血嘧啶进行双Sakurai型烯丙基化。dl-3的合成通过RCM进行，然后进行整体还原（H2，Pd / C； Li

  DOI：

  10.1021/jo8013512

文献信息

• Thole; Thorpe, Journal of the Chemical Society, 1911, vol. 99, p. 440
  作者：Thole、Thorpe

  DOI：——

  日期：——
• Thorpe; Wood, Journal of the Chemical Society, 1913, vol. 103, p. 1575
  作者：Thorpe、Wood

  DOI：——

  日期：——
• SCHOEN, U.;HACHMEISTER, B.;KEHRBACH, W.;KUEHL, U.;BUSCHMANN, G.
  作者：SCHOEN, U.、HACHMEISTER, B.、KEHRBACH, W.、KUEHL, U.、BUSCHMANN, G.

  DOI：——

  日期：——
• Synthesis, Pharmacological Characterization, and Quantitative Structure−Activity Relationship Analyses of 3,7,9,9-Tetraalkylbispidines:  Derivatives with Specific Bradycardic Activity
  作者：Uwe Schön、Jochen Antel、Reinhard Brückner、Josef Messinger、Rainer Franke、Andreas Gruska

  DOI：10.1021/jm970120q

  日期：1998.1.1

  A series of 3,7,9,9-tetraalkyl-3,7-diazabicyclo[3.3.1]nonane derivatives (bispidines) was synthesized and identified as potential antiischemic agents. Pharmacological experiments in vitro as well as in vivo are described, and the results are listed. For selection of those compounds fitting best to the desired profile of a specific bradycardic antianginal agent-decrease in heart rate without affecting contractility and blood pressure-these results were scored and ranked. Quantitative structure-activity relationship (QSAR) analyses were performed and discussed a posteriori by means of Hansch, nonelementary discriminant and factor analysis to get insight into the molecular features determining the biological profile. Highly significant equations were obtained, indicating hydrophobic and steric effects. Both pharmacological ranking and QSAR considerations showed compound 6 as the optimum within the structural class under investigation. Compound 6 (tedisamil, KC8857) has been selected as the most promising compound and was chosen for further pharmacological and clinical investigations as an antiischemic drug.
• Total Synthesis of (±)-α-Isosparteine, (±)-β-Isosparteine, and (±)-Sparteine from a Common Tetraoxobispidine Intermediate
  作者：Neil R. Norcross、John P. Melbardis、Margarita Ferris Solera、Mark A. Sephton、Colin Kilner、Lev N. Zakharov、Peter C. Astles、Stuart L. Warriner、Paul R. Blakemore

  DOI：10.1021/jo8013512

  日期：2008.10.17

  Bisimide 16 was generated from malonate via acid promoted cyclization of the Knoevenagel condensation adduct 1,1,3,3-propanetetracarboxamide. (+/-)-alpha-Isosparteine (dl-2) was elaborated from 16 in 28% overall yield by a two-directional synthetic sequence composed of four reactions: double addition of allylmagnesium bromide, ring-closing olefin metathesis (RCM), hydrogenation, and borane mediated reduction

  从一种常见的四氧代双吡啶前体3,7-二烯丙基-2,4,6,8-四氧代-3,7-二氮杂双环[3.3.1]壬烷（16）以立体控制的方式分别制备了三种标题生物碱。通过酸促进Knoevenagel缩合加合物1,1,3,3-丙烷四羧酰胺的丙二酸酯生成双酰亚胺16。（+/-）-α-Isosparteine（dl-2）通过双向合成顺序从16精制，总产率为28％，该合成顺序由以下四个反应组成：烯丙基溴化镁的两次加成，闭环烯烃复分解（RCM），氢化和硼烷介导的还原。（+/-）-β-Isosparteine（dl-3）通过核心合成子的烯丙基化和还原操作的战略逆转以相似的路线作为目标。因此，通过从硼氢化钠介导的还原反应开始的反应顺序，以五个步骤将16推进到dl-3，使总收率提高到12％，然后对所得的双血嘧啶进行双Sakurai型烯丙基化。dl-3的合成通过RCM进行，然后进行整体还原（H2，Pd / C； Li