1-[(1SR,9SR,10RS)-10-(hydroxymethyl)-8-methyl-8,12-diazatricyclo[7.3.1.0^2,7]trideca-2(7),3,5-trien-12-yl]ethan-1-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 1-[(1SR,9SR,10RS)-10-(hydroxymethyl)-8-methyl-8,12-diazatricyclo[7.3.1.0^2,7]trideca-2(7),3,5-trien-12-yl]ethan-1-one
• 英文别名: rac-1-[(1S,9S,10R)-10-hydroxymethyl-8-methyl-8,12-diazatricyclo[7.3.1.0(2,7)]trideca-2(7),3,5-trien-12-yl]ethanone；(1S,9Z,12R,16S)-N-(2,4-dimethoxyphenyl)-15-methyl-14-oxa-8-thia-10,15-diazatetracyclo[8.7.0.02,7.012,16]heptadeca-2,4,6-trien-9-imine；1-[(1S,9S,10R)-10-(hydroxymethyl)-8-methyl-8,12-diazatricyclo[7.3.1.02,7]trideca-2,4,6-trien-12-yl]ethanone
• 化学式: C₁₅H₂₀N₂O₂
• 分子量: 260.336
• InChiKey: ULBXUWCGRFTMGZ-CQDKDKBSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  丁二酰亚胺 、 1-[(1SR,9SR,10RS)-10-(hydroxymethyl)-8-methyl-8,12-diazatricyclo[7.3.1.0^2,7]trideca-2(7),3,5-trien-12-yl]ethan-1-one 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以90%的产率得到1-{[(1RS,9RS,10SR)-12-acetyl-8-methyl-8,12-diazatricyclo[7.3.1.0^2,7]trideca-2(7),3,5-trien-10-yl]methyl}pyrrolidine-2,5-dione
  参考文献：
  名称：

  Multicomponent, Mannich-type assembly process for generating novel, biologically-active 2-arylpiperidines and derivatives

  摘要：

  A multicomponent, Mannich-type assembly process commencing with commercially available bromobenzaldehydes was sequenced with [3+2] dipolar cycloaddition reactions involving nitrones and azomethine ylides to generate collections of fused, bicyclic scaffolds based on the 2-arylpiperidine subunit. Use of the 4-pentenoyl group, which served both as an activator in the Mannich-type reaction and a readily-cleaved amine protecting group, allowed sub-libraries to be prepared through piperidine N-functionalization and cross-coupling of the aryl bromide. A number of these derivatives displayed biological activities that had not previously been associated with this substructure. Methods were also developed that allowed rapid conversion of these scaffolds to novel, polycyclic dihydroquinazolin-2-ones, 2-imino-1,3-benzothiazinanes, dihydroisoquinolin-3-ones, and bridged tetrahydroquinolines. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2014.06.045
• 作为产物：
  描述：

  1-((2SR,4SR,5RS)-2-(2-bromophenyl)-5-(hydroxymethyl)-4-(methylamino)piperidin-1-yl)ethanone 在 palladium diacetate 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 甲苯 为溶剂， 反应 14.0h， 以70%的产率得到1-[(1SR,9SR,10RS)-10-(hydroxymethyl)-8-methyl-8,12-diazatricyclo[7.3.1.0^2,7]trideca-2(7),3,5-trien-12-yl]ethan-1-one
  参考文献：
  名称：

  Multicomponent Assembly and Diversification of Novel Heterocyclic Scaffolds Derived from 2-Arylpiperidines

  摘要：

  A collection of structurally diverse, polyheterocyclic scaffolds comprising a 2-arylpiperidine subunit were synthesized using a Mannich-type multicomponent assembly process, followed by appropriately sequenced ring-forming reactions. An Improved procedure for removal of N-4-pentenoyl groups was developed; one-pot sequences for tandem urea/thiourea formation and cyclization and tandem enolate arylation/alkylation were discovered. A novel entry to bridged tetrahydroquinoline scaffolds exploiting A(1,3) strain was also invented. Derivatization of several scaffolds was achieved by cross-coupling and N-functionalization.

  DOI：

  10.1021/ol201010s

文献信息

• Multicomponent Assembly and Diversification of Novel Heterocyclic Scaffolds Derived from 2-Arylpiperidines
  作者：Simon Hardy、Stephen F. Martin

  DOI：10.1021/ol201010s

  日期：2011.6.17

  A collection of structurally diverse, polyheterocyclic scaffolds comprising a 2-arylpiperidine subunit were synthesized using a Mannich-type multicomponent assembly process, followed by appropriately sequenced ring-forming reactions. An Improved procedure for removal of N-4-pentenoyl groups was developed; one-pot sequences for tandem urea/thiourea formation and cyclization and tandem enolate arylation/alkylation were discovered. A novel entry to bridged tetrahydroquinoline scaffolds exploiting A(1,3) strain was also invented. Derivatization of several scaffolds was achieved by cross-coupling and N-functionalization.
• Multicomponent, Mannich-type assembly process for generating novel, biologically-active 2-arylpiperidines and derivatives
  作者：Simon Hardy、Stephen F. Martin

  DOI：10.1016/j.tet.2014.06.045

  日期：2014.10

  A multicomponent, Mannich-type assembly process commencing with commercially available bromobenzaldehydes was sequenced with [3+2] dipolar cycloaddition reactions involving nitrones and azomethine ylides to generate collections of fused, bicyclic scaffolds based on the 2-arylpiperidine subunit. Use of the 4-pentenoyl group, which served both as an activator in the Mannich-type reaction and a readily-cleaved amine protecting group, allowed sub-libraries to be prepared through piperidine N-functionalization and cross-coupling of the aryl bromide. A number of these derivatives displayed biological activities that had not previously been associated with this substructure. Methods were also developed that allowed rapid conversion of these scaffolds to novel, polycyclic dihydroquinazolin-2-ones, 2-imino-1,3-benzothiazinanes, dihydroisoquinolin-3-ones, and bridged tetrahydroquinolines. (C) 2014 Elsevier Ltd. All rights reserved.