4-(吡啶-4-基甲基)苯酚 | 66414-18-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 中文名称: 4-(吡啶-4-基甲基)苯酚
• 英文名称: 4-(pyridin-4-ylmethyl)phenol
• 英文别名: 4-(4-hydroxybenzyl)pyridine；4-[4]Pyridylmethyl-phenol
• CAS: 66414-18-4
• 化学式: C₁₂H₁₁NO
• 分子量: 185.225
• InChiKey: FQNZRIMTMGOVMD-UHFFFAOYSA-N

物化性质

• 熔点：
  176.3 °C
• 沸点：
  353.8±22.0 °C(Predicted)
• 密度：
  1.154±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  33.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(吡啶-4-基甲基)苯酚 生成 4-[(1-methyl-3,6-dihydro-2H-pyridin-4-yl)methyl]phenol;hydrochloride
  参考文献：
  名称：

  EFANGE, S. M. N.;MICHELSON, R. H.;REMMEL, R. P.;BOUDREAU, R. J.;DUTTA, A.+, J. MED. CHEM., 33,(1990) N2, C. 3133-3138

  摘要：

  DOI：
• 作为产物：
  描述：

  (4-methoxyphenyl)(pyridin-4-yl)methanol 在 甲酸 、 氢溴酸 、 锌 作用下， 以 溶剂黄146 为溶剂， 反应 22.0h， 生成 4-(吡啶-4-基甲基)苯酚
  参考文献：
  名称：

  Flexible N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analog: synthesis and monoamine oxidase catalyzed bioactivation

  摘要：

  Eighteen analogues of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were synthesized and evaluated as substrates of monoamine oxidase. In general, the flexible analogues, characterized by the presence of a methylene (or ethylene) bridge between the aryl/heteroaryl and tetrahydropyridyl moieties, were better substrates of the enzyme than the conformationally restricted MPTP. It is suggested that the increased oxidative activity of these flexible analogues reflects enhanced binding due to the ability of the C-4-aryl/heteroaryl substituent to gain access to a hydrophobic pocket within the substrate binding site.

  DOI：

  10.1021/jm00174a007

文献信息

• Identification and Development of an Efficient Route to SB-649915
  作者：Mark Armitage、Guillaume Bret、Bernie M. Choudary、Mike Kingswood、Mike Loft、Steve Moore、Steve Smith、Michael W. J. Urquhart

  DOI：10.1021/op300185s

  日期：2012.10.19

  an efficient manufacturing route to the SSRI-5-HT1A receptor antagonist 6-[(1-2-[(2-methyl-5-quinolinyl)oxy]ethyl}-4-piperidinyl)methyl]-2H-1,4-benzoxazin-3(4H)-one (SB-649915) 1 is described. The existing route to 1 involved coupling quinoline 6 with piperidine 5 and was considered lengthy as a consequence of the nine synthetic steps required to prepare 5. Two new routes to the key piperidine intermediate

  SSRI-5-HT1A受体拮抗剂6-[[（1- 2-[（2-甲基-5-喹啉基）氧基]乙基} -4-哌啶基）甲基] -2的高效生产途径的发现和发展描述了H -1，4-苯并恶嗪-3（4 H）-1（SB-649915）1。现有的通往1的途径涉及将喹啉6与哌啶5偶联，由于制备5所需的九个合成步骤而被认为是冗长的。通往关键哌啶中间体5的两条新路线可以分别使用新颖的锂化法和Friedel-Crafts方法从容易获得的材料中分五步和两步分离出该化合物。这两种途径中的后者已成功地以5 L的规模进行了演示，可提供700 g的5。还描述了向喹啉6的替代物甲烷磺酸盐34的发展，是哌啶5与该甲烷磺酸盐34的最终烷基化反应，以输送SB-649915 1。
• Lewis Acid Promoted Benzylic Cross-Couplings of Pyridines with Aryl Bromides
  作者：Stéphanie Duez、Andreas K. Steib、Sophia M. Manolikakes、Paul Knochel

  DOI：10.1002/anie.201103074

  日期：2011.8.8

  Either ZnCl2, Sc(OTf)3 , or BF3⋅OEt2 can promote the palladium‐catalyzed arylation of methylpyridines and related heterocycles (see example). The complexation of the Lewis acid to the nitrogen atom in the heterocycle facilitates the reductive elimination, leading to various arylated pyridines in high yields. BF3⋅OEt2 was also found to promote highly regioselective metalations in the case of 2,4‐lutidine

  ZnCl 2，Sc（OTf）3 或BF 3 OEt 2均可促进钯催化的甲基吡啶和相关杂环的芳基化（参见示例）。路易斯酸与杂环中氮原子的络合有助于还原消除，从而以高收率产生各种芳基化吡啶。BF 3 ⋅OEt 2还发现，以促进2,4-二甲基吡啶的情况下，高度选择性metalations。
• 3,4-Dihydro-2H-benzoxazinones are 5-HT1A receptor antagonists with potent 5-HT reuptake inhibitory activity
  作者：Peter J. Atkinson、Steven M. Bromidge、Mark S. Duxon、Laramie M. Gaster、Michael S. Hadley、Beverley Hammond、Christopher N. Johnson、Derek N. Middlemiss、Stephanie E. North、Gary W. Price、Harshad K. Rami、Graham J. Riley、Claire M. Scott、Tracey E. Shaw、Kathryn R. Starr、Geoffrey Stemp、Kevin M. Thewlis、David R. Thomas、Mervyn Thompson、Antonio K.K. Vong、Jeannette M. Watson

  DOI：10.1016/j.bmcl.2004.11.030

  日期：2005.2

  Starting from a high throughput screening hit, a series of 3,4-dihydro-2H-benzoxazinones has been identified with both high affinity for the 5-HT1A receptor and potent 5-HT reuptake inhibitory activity. The 5-(2-methyl)quinolinyloxy derivative combined high 5-HT1A/1B/1D receptor affinities with low intrinsic activity and potent inhibition of the 5-HT reuptake site (pK(i) 8.2). This compound also had good oral bioavailability and brain penetration in the rat. (C) 2004 Elsevier Ltd. All rights reserved.
• US5399575A
  申请人：——

  公开号：US5399575A

  公开（公告）日：1995-03-21
• Flexible N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analog: synthesis and monoamine oxidase catalyzed bioactivation
  作者：S. Mbera Ngale Efange、R. H. Michelson、R. P. Remmel、R. J. Boudreau、A. K. Dutta、A. Freshler

  DOI：10.1021/jm00174a007

  日期：1990.12

  Eighteen analogues of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were synthesized and evaluated as substrates of monoamine oxidase. In general, the flexible analogues, characterized by the presence of a methylene (or ethylene) bridge between the aryl/heteroaryl and tetrahydropyridyl moieties, were better substrates of the enzyme than the conformationally restricted MPTP. It is suggested that the increased oxidative activity of these flexible analogues reflects enhanced binding due to the ability of the C-4-aryl/heteroaryl substituent to gain access to a hydrophobic pocket within the substrate binding site.