6-(3-methoxyphenyl)-2,3,4,5-tetrahydropyridine | 509953-50-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 6-(3-methoxyphenyl)-2,3,4,5-tetrahydropyridine
• 英文别名: 2-(3-anisyl)-3,4,5,6-tetrahydropyridine
• CAS: 509953-50-8
• 化学式: C₁₂H₁₅NO
• 分子量: 189.257
• InChiKey: PLLTVVJOSWQUQA-UHFFFAOYSA-N

物化性质

• 沸点：
  291.9±32.0 °C(Predicted)
• 密度：
  1.05±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  21.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-(3-methoxyphenyl)-2,3,4,5-tetrahydropyridine 在 盐酸 、 氢溴酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 18.5h， 生成 3-(3,4,5,6-tetrahydropyridin-2-yl)phenol hydrochloride
  参考文献：
  名称：

  Modification of the anabaseine pyridine nucleus allows achieving binding and functional selectivity for the α3β4 nicotinic acetylcholine receptor subtype

  摘要：

  We report the design, synthesis and pharmacological screening of a group of analogues of anabaseine 2, a naturally occurring unselective nicotinic agonist. The novel nAChR ligands 5-15 were planned following a molecular modeling analysis which suggested the replacement of the pyridine ring of 2 with a 3 substituted benzene ring as a means to gain selectivity for the alpha 3 beta 4 nAChR subtype. Overall, from binding experiments, the synthesized compounds showed high values of alpha 3 beta 4 affinity and alpha 3 beta 4 vs alpha 3 beta 4 selectivity, although they poorly discriminated the homomeric alpha 7 subtype. The three analogues 6,12 and 13 were also evaluated in electrophysiological assays, and 12 [6-(3-iodophenyl)-2,3,4,5-tetrahydropyridine] emerged as a rather interesting nicotinic ligand. Indeed, in addition to a note-worthy affinity (K-i = 4.7 nM) for the alpha 3 beta 4 subtype and to an excellent alpha 3 beta 4 vs alpha 3 beta 4 subtype selectivity (806 -fold), compound 12 selectively activated the alpha 3 beta 4 nAChR (EC50 = 7.4 mu M) while eliciting a negligible response at the alpha 7 subtype and no effect at the alpha 3 beta 4 subtype. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.11.045
• 作为产物：
  描述：

  (5-oxo-5-(3-methoxyphenyl)-pentyl)-carbamic acid tert-butyl ester 在 三氟乙酸 作用下， 以71%的产率得到6-(3-methoxyphenyl)-2,3,4,5-tetrahydropyridine
  参考文献：
  名称：

  Modification of the anabaseine pyridine nucleus allows achieving binding and functional selectivity for the α3β4 nicotinic acetylcholine receptor subtype

  摘要：

  We report the design, synthesis and pharmacological screening of a group of analogues of anabaseine 2, a naturally occurring unselective nicotinic agonist. The novel nAChR ligands 5-15 were planned following a molecular modeling analysis which suggested the replacement of the pyridine ring of 2 with a 3 substituted benzene ring as a means to gain selectivity for the alpha 3 beta 4 nAChR subtype. Overall, from binding experiments, the synthesized compounds showed high values of alpha 3 beta 4 affinity and alpha 3 beta 4 vs alpha 3 beta 4 selectivity, although they poorly discriminated the homomeric alpha 7 subtype. The three analogues 6,12 and 13 were also evaluated in electrophysiological assays, and 12 [6-(3-iodophenyl)-2,3,4,5-tetrahydropyridine] emerged as a rather interesting nicotinic ligand. Indeed, in addition to a note-worthy affinity (K-i = 4.7 nM) for the alpha 3 beta 4 subtype and to an excellent alpha 3 beta 4 vs alpha 3 beta 4 subtype selectivity (806 -fold), compound 12 selectively activated the alpha 3 beta 4 nAChR (EC50 = 7.4 mu M) while eliciting a negligible response at the alpha 7 subtype and no effect at the alpha 3 beta 4 subtype. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.11.045

文献信息

• An (<i>R</i>)-Imine Reductase Biocatalyst for the Asymmetric Reduction of Cyclic Imines
  作者：Shahed Hussain、Friedemann Leipold、Henry Man、Elizabeth Wells、Scott P. France、Keith R. Mulholland、Gideon Grogan、Nicholas J. Turner

  DOI：10.1002/cctc.201402797

  日期：2015.2

  enantiomerically pure chiral amines continues to expand, few existing methods provide access to secondary amines. To address this shortcoming, we have over-expressed the gene for an (R)-imine reductase [(R)-IRED] from Streptomyces sp. GF3587 in Escherichia coli to create a recombinant whole-cell biocatalyst for the asymmetric reduction of prochiral imines. The (R)-IRED was screened against a panel of cyclic imines

  尽管可用于合成对映体纯的手性胺的生物催化剂的范围不断扩大，但现有的方法很少能提供仲胺的途径。为了解决这个缺点，我们过量表达了链霉菌属（Streptomyces sp。）的（R）-亚胺还原酶[（R）-IRED]的基因。GF3587在大肠杆菌中创建重组全细胞生物催化剂，用于不对称还原前手性亚胺。针对一组环状亚胺和两个亚胺离子筛选了（R）-IRED，结果显示该催化剂具有较高的催化活性和对映选择性。从亚胺前体的制备规模的生物碱（R）-亚氨酸的合成规模（90％收率； 99％ee）以克为单位进行。酶活性位点的同源模型，基于来自链霉菌的紧密相关的（R）-IRED的结构，
• Palladium‐Catalyzed Arylation of Endocyclic 1‐Azaallyl Anions: Concise Synthesis of Unprotected Enantioenriched <i>cis</i>‐2,3‐Diarylpiperidines
  作者：Biao Zhang、Junhao Ruan、Daniel Seidel、Weijie Chen

  DOI：10.1002/anie.202307638

  日期：2023.9.4

  Unprotected cis-2,3-diarylpiperidines are synthesized from readily available piperidines in only three operations. The key step is a palladium-catalyzed cross-coupling reaction between aryl halides and endocyclic 1-azallyl anions, elusive intermediates derived from the in situ deprotonation of 2-aryl-1-piperideines. This cross-coupling reaction can be achieved enantioselectively with a chiral mono-phosphine

  仅通过三个操作即可从容易获得的哌啶合成未保护的顺式-2,3-二芳基哌啶。关键步骤是芳基卤化物和环内 1-氮杂丙烯基阴离子之间的钯催化交叉偶联反应，这是源自 2-芳基-1-哌啶原位去质子化的难以捉摸的中间体。这种交叉偶联反应可以通过手性单膦配体对映选择性地实现。
• A One-Pot Process for the Enantioselective Synthesis of Amines via Reductive Amination under Transfer Hydrogenation Conditions
  作者：Glynn D. Williams、Richard A. Pike、Charles E. Wade、Martin Wills

  DOI：10.1021/ol035746r

  日期：2003.10.1

  Cyclic amines may be prepared via a sequence of deprotection followed by intramolecular reductive amination of t-Boc-protected amino ketones under asymmetric transfer hydrogenation conditions. In cases where the corresponding imine reaction proceeds with high enantioselectivity, this is reflected in the one-step process.
• ——
  作者：A. B. Koldobskii、V. E. Vakhmistrov、E. V. Solodova、O. S. Shilova、V. N. Kalinin

  DOI：10.1023/a:1021118204730

  日期：——