1,3,6,8-四氮杂三环[4.3.1.13,8]十一烷 | 125251-91-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三嗪烷类
• 中文名称: 1,3,6,8-四氮杂三环[4.3.1.13,8]十一烷
• 英文名称: 1,3,6,8-tetraazatricyclo[4.3.1.1^3,8]undecane
• 英文别名: 1,3,6,8-Tetraazatricyclo[4.3.1.1~3,8~]undecane；1,3,6,8-tetrazatricyclo[4.3.1.13,8]undecane
• CAS: 125251-91-4
• 化学式: C₇H₁₄N₄
• 分子量: 154.215
• InChiKey: QEPWWLPEGNQLPC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  13
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,3,6,8-四氮杂三环[4.3.1.13,8]十一烷 在 sodium tetrahydroborate 、 溶剂黄146 作用下， 以 乙醇 、 异丙醇 为溶剂， 反应 5.0h， 生成 1-(pyridin-4-yl)-3,6-diazahomoadamantan-9-ol
  参考文献：
  名称：

  Synthesis of 1-(pyridin-4-yl)-3,6-diazahomoadamantane and its derivatives

  摘要：

  Condensation of 1-(pyridin-4-yl)propan-2-one with 1,3,6,8-tetraazatricyclo[4.4.1.1(3,8)]dodecane gave 1-( pyridin-4-yl)-3,6-diazahomoadamantan-9-one as intermediate product in the synthesis of 1-(pyridin-4-yl)-3,6-diazahomoadamantane and its derivatives having functional substituents at the bridging carbon atom in the homoadamantane skeleton.

  DOI：

  10.1134/s1070428010030139
• 作为产物：
  描述：

  1,3,5,7-四氮杂三环[3.3.2.2(3,7)]十二烷 在 氟化铵 作用下， 以 水 为溶剂， 反应 5.0h， 以63%的产率得到1,3,6,8-四氮杂三环[4.3.1.13,8]十一烷
  参考文献：
  名称：

  Preparation of cage amine 1,3,6,8-tetraazatricyclo[4.3.1.13,8]undecane

  摘要：

  Reaction between cage amine 1,3,6,8-tetraazatricyclo[4.4. 1.1(3,8)]dodecane (TATD) and ammonium fluoride affords 1,3,6,8-tetraazatricyclo[4.3.1.1(3,8)]undecane, the missing link between 1,3,5,7-tetraazatricyclo[3.3.1.1(3,7)]decane (urotropine) and TATD. The structure was established mainly from 2D NMR measurements. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2004.08.123

文献信息

• Therapeutic Aryl-Amido-Aryl Compounds and Their Use
  申请人：Corcoran Jonathan Patrick Thomas

  公开号：US20120149737A1

  公开（公告）日：2012-06-14

  The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain aryl-amido-aryl compounds of the following formula (for convenience, collectively referred to herein as “AAA compounds”), which, inter alia, are (selective) retinoic acid receptor α (RARα) agonists. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to (selectively) activate RARα, and in the treatment of diseases and conditions that are mediated by RARα, that are ameliorated by the activation of RARα, etc., including cognitive disorders, memory impairment, memory deficit, senile dementia, Alzheimer's disease, early stage Alzheimer's disease, intermediate stage Alzheimer's disease, late stage Alzheimer's disease, cognitive impairment, and mild cognitive impairment.

  本发明涉及治疗化合物领域，更具体地涉及以下公式的某些芳基酰胺-芳基化合物（为方便起见，以下统称为“AAA化合物”），其为（选择性）视黄酸受体α（RARα）激动剂。本发明还涉及包含这些化合物的药物组合物，以及利用这些化合物和组合物在体外和体内（选择性地）激活RARα，并用于治疗由RARα介导的疾病和症状，以及通过激活RARα改善的疾病和症状，包括认知障碍、记忆障碍、记忆缺陷、老年性痴呆、阿尔茨海默病、早期阿尔茨海默病、中期阿尔茨海默病、晚期阿尔茨海默病、认知损害和轻度认知损害。
• Structural Consequences of Anomeric Effect in 1,3,6,8-tetraazatricyclo[4.3.1.13,8]undecan-1-ium pentachlorophenolate monohydrate
  作者：Augusto Rivera、John Sadat-Bernal、Jaime Ríos-Motta、Michal Dušek、Karla Fejfarová

  DOI：10.1007/s10870-011-0008-8

  日期：2011.4

  The asymmetric unit of the crystal structure contains one molecule of the title compound and one molecule of water. X-ray diffraction spectrum of the ammonium salt of title compound exhibits deviations from the ideal molecular geometry which is explained on the basis of anomeric effect. This conclusion is consistent with the natural bond orbital analysis at the B3LYP/6-311+G** level of the anomeric effect. The molecules are linked via N–H···O hydrogen bonds. This compound crystallizes in monoclinic symmetry, in space group P2 1/n , with lattice constants: a = 12.3850(2) Å, b = 6.8123(1) Å, c = 19.6208(4) Å, α = 90°, β = 94.864(2)°, γ = 90°, V = 1649.45(5) Å3, Z = 4, F(000) = 896, R 1 = 3.3%, wR 2 = 10.6%. .

  晶体结构的非对称单位包含一个所述化合物的分子和一个水分子。所述化合物的铵盐的X射线衍射谱表现出与理想分子几何结构的偏差，这基于异构效应进行了解释。该结论与在B3LYP/6-311+G**水平上对异构效应的自然键轨道分析一致。这些分子通过N–H···O氢键连接。该化合物在单斜对称下结晶，空间组为P2 1/n，具有晶格常数：a = 12.3850(2) Å，b = 6.8123(1) Å，c = 19.6208(4) Å，α = 90°，β = 94.864(2)°，γ = 90°，V = 1649.45(5) ų，Z = 4，F(000) = 896，R1 = 3.3%，wR2 = 10.6%。
• An NMR study of sequential intermediates and collateral products in the conversion of 1,3,6,8-tetraazatricyclo[4.4.1.13,8]dodecane (TATD) to 1,3,6,8-tetraazatricyclo[4.3.1.13,8]undecane (TATU)
  作者：Augusto Rivera、Martín E. Núñez、Eliseo Avella、Jaime Ríos-Motta

  DOI：10.1016/j.tetlet.2008.01.091

  日期：2008.3

  In situ 1H nuclear magnetic resonance spectroscopy was used to investigate the processes that occur during the synthesis of 1,3,6,8-tetraazatricyclo[4.3.1.13,8]undecane (TATU). NMR analysis showed a reaction mixture containing more than one compound. The production of these intermediates and collateral products was rationally supported by a careful 1H NMR monitoring study. We characterized 1,3,5-triazabicyclo[3

  原位1 H核磁共振波谱用于研究1,3,6,8-四氮杂三环[4.3.1.1 3,8 ]十一烷（TATU）合成过程中发生的过程。NMR分析表明反应混合物含有一种以上的化合物。仔细的1 H NMR监测研究合理地支持了这些中间体和附带产品的生产。我们用1 H表征了1,3,5-三氮杂双环[3.2.1]辛烷（TABO，4）和3-（2-氨基乙基）-1,3,5-三氮杂双环[3.2.1]辛烷（AETABO，7）D 2中的13 C NMR和13 C NMRNMR样品管内的O溶液分别作为反应的中间产物和附带产物。此外，进行了1,3,6,8-四氮杂三环[4.4.1.1 3,8 ]十二烷（TATD）与15 N-标记的氯化铵的反应。在15 ÑNMR和GC-MS实验表明15 n为并入到TATU，TABO，和乌洛托品。
• Synthesis of 5,7-nonamethylene-1,3-diazaadamantan-6-one
  作者：I. O. Razenko、T. M. Serova、A. I. Kuznetsov

  DOI：10.1007/s11172-016-1606-6

  日期：2016.10

  5,7-Nonamethylene-1,3-diazaadamantan-6-one has been synthesized by condensation of cyclododecanone with [16]adamanzane. In the condensation of cyclododecanone with [15.21]adamanzane, 1,8-nonamethylene-3,6-diazahomoadamantan-9-one is formed.

  5,7-非戊烯基-1,3-二氮杂阿达曼坦-6-酮是通过环十二酮与[16]阿达曼烷的缩合反应合成的。在环十二酮与[15,21]阿达曼烷的缩合反应中，形成了1,8-非戊烯基-3,6-二氮杂同阿达曼坦-9-酮。
• Mechanochemical synthesis and X-ray structural characterization of three 3-nitrophenol cocrystals with three aminal cage azaadamantanes: the role of the stereoelectronic effect on intermolecular hydrogen-bonding patterns
  作者：Augusto Rivera、Jicli José Rojas、John Sadat-Bernal、Jaime Ríos-Motta、Michael Bolte

  DOI：10.1107/s205322961901516x

  日期：2019.12.1

  The structures of the cocrystalline adducts of 3-nitrophenol (3-NP) with 1,3,5,7-tetraazatricyclo[3.3.1.1^3,7]decane [HMTA, (1)] as the 2:1:1 hydrate, 2C₆H₅NO₃·C₆H₁₂N₄·H₂O, (1a), with 1,3,6,8-tetraazatricyclo[4.3.1.1^3,8]undecane [TATU (2)] as the 2:1 cocrystal, 2C₆H₅NO₃·C₇H₁₄N₄, (2a), and with 1,3,6,8-tetraazatricyclo[4.4.1.1^3,8]dodecane [TATD, (3)] as the 2:1 cocrystal, 2C₆H₅NO₃·C₈H₁₆N₄, (3a), are reported. In the binary crystals (2a) and (3a), the 3-nitrophenol molecules are linked via O—H...N hydrogen bonds into aminal cage azaadamantanes. In (1a), the structure is stabilized by O—H...N and O—H...O hydrogen bonds, and generates ternary cocrystals. There are C—H...O hydrogen bonds present in all three cocrystals, and in (1a), there are also C—H...O and C—H...π interactions present. The presence of an ethylene bridge in the structures of (2) and (3) defines the formation of a hydrogen-bonded motif in the supramolecular architectures of (2a) and (3a). The differences in the C—N bond lengths of the aminal cage structures, as a result of hyperconjugative interactions and electron delocalization, were analysed. These three cocrystals were obtained by the solvent-free assisted grinding method. Crystals suitable for single-crystal X-ray diffraction were grown by slow evaporation from a mixture of hexanes.

  3-nitrophenol (3-NP) 与 1,3,5,7-四氮杂三环[3.3.1.13,7]癸烷 [HMTA, (1)] 的 2:1:1 水合物 2C6H5NO3-C6H12N4-H2O (1a)、与 1,3,6,8- 四氮杂三环[4.3.1.13,8]undecane [TATU, (2)] 的 2:1 共晶体 2C6H5NO3-C7H14N4, (2a)，以及与 1,3,6,8-四氮杂三环[4.4.1.13,8]十二烷 [TATD, (3)] 的 2:1 共晶体 2C6H5NO3-C8H16N4, (3a)。在二元晶体（2a）和（3a）中，3-硝基苯酚分子通过 O-H...N氢键连接成氨基笼扎金刚烷。在(1a)中，该结构通过 O-H...N 和 O-H...O 氢键得到稳定，并生成三元共晶体。三种共晶体中都存在 C-H...O 氢键，在 (1a) 中还存在 C-H...O 和 C-H...π 相互作用。(2)和(3)结构中乙烯桥的存在决定了(2a)和(3a)超分子结构中氢键基团的形成。分析了由于超共轭相互作用和电子脱位而导致的氨基笼结构中 C-N 键长度的差异。这三种共晶体是通过无溶剂辅助研磨法获得的。适合进行单晶 X 射线衍射的晶体是从己烷混合物中缓慢蒸发出来的。