2-cyano-1,3,4-trimethyl-3-piperideine | 73657-70-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-cyano-1,3,4-trimethyl-3-piperideine
• 英文别名: 1,4,5-trimethyl-3,6-dihydro-2H-pyridine-6-carbonitrile
• CAS: 73657-70-2
• 化学式: C₉H₁₄N₂
• 分子量: 150.224
• InChiKey: MIQUNXLIWZVSSY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  27
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-cyano-1,3,4-trimethyl-3-piperideine 在 锌 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 3.75h， 生成 2-carboethoxymethyl-2-(p-methoxybenzyl)-1,3,4-trimethyl-1,2,5,6-tetrahydropyridine
  参考文献：
  名称：

  Synthesis of C-2 substituted 1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocines: binding studies on opioid receptors

  摘要：

  The racemic C-2 substituted 1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocines 8a-k were prepared in three steps from the readily available 2-cyano-1,2,5,6-tetrahydropyridines 4a-c. This involved alkylation of the anion of 4a-c with the appropriate alkyl halide, displacement of thc cyano group in 5 or 6 by reaction with a Grignard reagent and cyclization under Grewe conditions (HBr, reflux). The equilibrium binding affinities of compounds 8a-k for the mu, delta and kappa-opioid receptor types were determined. Compounds 8c, 8e, 8j and 8k bearing a phenyl or olefinic substituent at C-2 display high kappa-receptor binding affinities demonstrating that the presence of a substituent at this position is important for kappa-receptor binding. The insensitivity of the binding of compounds 8j and 8k to sodium ions and guanine nucleotides at both mu and kappa-sites suggests that these 2-substituted 1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocines could behave as partial agonists or antagonists. The binding of the molecule 8e to mu and kappa sites was inhibited in the presence of these allosteric effectors, whereas N-methyl-2-phenyl-1,2,3,4,5.6-hexahydro-2,6-methano-3-benzazocine 8c appears to display the same kappa-agonist/mu-antagonist pharmacological profile as bremazocine 2.

  DOI：

  10.1016/0223-5234(92)90150-y
• 作为产物：
  描述：

  1,3,4-trimethyl-1,2,5,6-tetrahydropyridine N-oxide 在 potassium cyanide 、 sodium acetate 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 1.5h， 生成 2-cyano-1,3,4-trimethyl-3-piperideine
  参考文献：
  名称：

  Synthesis and chemistry of 5,6-dihydropyridinium salt adducts. Synthons for general electrophilic and nucleophilic substitution of the piperidine ring system

  摘要：

  DOI：

  10.1021/ja00523a026

文献信息

• 2-Cyano Δ3 Piperideines XIV: Facile synthesis of 1-substituted benzomorphans
  作者：P. Jimonet、D.S. Grierson、H.P. Husson

  DOI：10.1016/s0040-4039(00)61840-3

  日期：1987.1

  Two complementary routes have been developped for the preparation of the key intermediate leading to a series of 1-substituted benzomorphons 8. Final cyclization to the title compounds was achieved under standard Grewe conditions (HBr,Δ).

  已开发出两条互补的路线来制备关键中间体，从而产生一系列1取代的苯并吗啡酮8。在标准Grewe条件（HBr，Δ）下实现了标题化合物的最终环化。
• GRIERSON D. S.; HARRIS M.; HUSSON H.-P., J. AMER. CHEM. SOC., 1980, 102, NO 3, 1064-1082
  作者：GRIERSON D. S.、 HARRIS M.、 HUSSON H.-P.

  DOI：——

  日期：——
• JIMONET, P.;GRIERSON, D. S.;HUSSON, H. -P., TETRAHEDRON LETT., 28,(1987) N 49, 6179-6182
  作者：JIMONET, P.、GRIERSON, D. S.、HUSSON, H. -P.

  DOI：——

  日期：——
• Synthesis of C-2 substituted 1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocines: binding studies on opioid receptors
  作者：B Frances、C Gouarderes、C Moisand、J Cros、P Jimonet、L Moy、A Chiaroni、C Riche、DS Grierson、HP Husson

  DOI：10.1016/0223-5234(92)90150-y

  日期：1992.6

  The racemic C-2 substituted 1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocines 8a-k were prepared in three steps from the readily available 2-cyano-1,2,5,6-tetrahydropyridines 4a-c. This involved alkylation of the anion of 4a-c with the appropriate alkyl halide, displacement of thc cyano group in 5 or 6 by reaction with a Grignard reagent and cyclization under Grewe conditions (HBr, reflux). The equilibrium binding affinities of compounds 8a-k for the mu, delta and kappa-opioid receptor types were determined. Compounds 8c, 8e, 8j and 8k bearing a phenyl or olefinic substituent at C-2 display high kappa-receptor binding affinities demonstrating that the presence of a substituent at this position is important for kappa-receptor binding. The insensitivity of the binding of compounds 8j and 8k to sodium ions and guanine nucleotides at both mu and kappa-sites suggests that these 2-substituted 1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocines could behave as partial agonists or antagonists. The binding of the molecule 8e to mu and kappa sites was inhibited in the presence of these allosteric effectors, whereas N-methyl-2-phenyl-1,2,3,4,5.6-hexahydro-2,6-methano-3-benzazocine 8c appears to display the same kappa-agonist/mu-antagonist pharmacological profile as bremazocine 2.
• Synthesis and chemistry of 5,6-dihydropyridinium salt adducts. Synthons for general electrophilic and nucleophilic substitution of the piperidine ring system
  作者：David S. Grierson、Martin Harris、Henri Philippe Husson

  DOI：10.1021/ja00523a026

  日期：1980.1