N-(2,5-dimethoxybenzyl)-N-(2-phenoxyphenyl)amine | 220553-76-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(2,5-dimethoxybenzyl)-N-(2-phenoxyphenyl)amine
• 英文别名: N-(2,5-dimethoxybenzyl)-2-phenoxyaniline；N-[(2,5-dimethoxyphenyl)methyl]-2-phenoxyaniline
• CAS: 220553-76-4
• 化学式: C₂₁H₂₁NO₃
• 分子量: 335.403
• InChiKey: RXKFQBYMQOILEO-UHFFFAOYSA-N

物化性质

• 熔点：
  55 °C
• 沸点：
  467.7±40.0 °C(Predicted)
• 密度：
  1.163±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  39.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(2,5-dimethoxybenzyl)-N-(2-phenoxyphenyl)amine 在 potassium fluoride 、 三乙胺 作用下， 以 二氯甲烷 、 二乙二醇 为溶剂， 反应 6.0h， 生成 PBR06
  参考文献：
  名称：

  Synthesis of [11C]PBR06 and [18F]PBR06 as agents for positron emission tomographic (PET) imaging of the translocator protein (TSPO)

  摘要：

  The translocator protein 18 kDa (TSPO) is an attractive target for molecular imaging of neuroinflammation and tumor progression. [F-18]PBR06, a fluorine-18 labeled form of PBR06, is a promising PET TSPO radioligand originally developed at NIMH. [C-11]PBR06, a carbon-11 labeled form of PBR06, was designed and synthesized for the first time. The standard PBR06 was synthesized from 2,5-dimethoxybenzaldehyde in three steps with 71% overall chemical yield. The radiolabeling precursor desmethyl-PBR06 was synthesized from 2-hydroxy-5-methoxybenzaldehyde in five steps with 12% overall chemical yield. The target tracer [C-11]PBR06 was prepared by O-[C-11]methylation of desmethyl-PBR06 with [C-11]CH3OTf in CH3CN at 80 degrees C under basic condition and isolated by HPLC combined with SPE purification with 40-60% decay corrected radiochemical yield and 222-740 GBq/mu mol specific activity at EOB. On the similar grounds, [F-18]PBR06 was also designed and synthesized. The previously described Br-PBR06 precursor was synthesized from 2,5-dimethoxybenzaldehyde in two steps with 78% overall chemical yield. A new radiolabeling precursor tosyloxy-PBR06, previously undescribed tosylate congener of PBR06, was designed and synthesized from ethyl 2-hydroxyacetate, 4-methylbenzene-1-sulfonyl chloride, and N-(2,5-dimethoxybenzyl)-2-phenoxyaniline in four steps with 50% overall chemical yield. [F-18]PBR06 was prepared by the nucleophilic substitution of either new tosyloxy-PBR06 precursor or known Br-PBR06 precursor in DMSO at 140 degrees C with K[F-18]F/Kryptofix 2.2.2 for 15 min and HPLC combined with SPE purification in 20-60% decay corrected radiochemical yield, >99% radiochemical purity, 87-95% chemical purity, and 37-222 GBq/mu mol specific activity at EOB. Radiosynthesis of [F-18]PBR06 using new tosylated precursor gave similar radiochemical purity, and higher specific activity, radiochemical yield and chemical purity in comparison with radiosynthesis using bromine precursor. (C) 2011 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2011.06.012
• 作为产物：
  描述：

  2,5-dimethoxy-N-(2-phenoxyphenyl)benzamide 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 以1.35 g的产率得到N-(2,5-dimethoxybenzyl)-N-(2-phenoxyphenyl)amine
  参考文献：
  名称：

  Single-Step High-Yield Radiosynthesis and Evaluation of a Sensitive ¹⁸F-Labeled Ligand for Imaging Brain Peripheral Benzodiazepine Receptors with PET

  摘要：

  Elevated levels of peripheral benzodiazepine receptors (PBR) are associated with activated microglia in their response to inflammation. Hence, PBR imaging in vivo is valuable for investigating brain inflammatory conditions. Sensitive, easily prepared, and readily available radioligands for imaging with positron emission tomography (PET) are desirable for this purpose. We describe a new F-18-labeled PBR radioligand, namely [F-18]N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline ([F-18]9). [F-18]9 was produced easily through a single and highly efficient step, the reaction of [F-18]fluoride ion with the corresponding bromo precursor, 8. Ligand 9 exhibited high affinity for PBR in vitro. PET showed that [F-18]9 was avidly taken into monkey brain and gave a high ratio of PBR-specific to nonspecific binding. [F-18]9 was devoid of defluorination in rat and monkey and gave predominantly polar radiometabolite(s). In rat, a low level radiometabolite of intermediate lipophilicity was identified as [F-18]2-fluoro-N-(2-phenoxyphenyl)acetamide ([F-18]11). [F-18]9 is a promising radioligand for future imaging of PBR in living human brain.

  DOI：

  10.1021/jm8011855
• 作为试剂：
  描述：

  2-chloro-2-oxoethyl 4-methylbenzenesulfonate 、 N-(2,5-dimethoxybenzyl)-N-(2-phenoxyphenyl)amine 在 N-(2,5-dimethoxybenzyl)-N-(2-phenoxyphenyl)amine 作用下， 以92的产率得到2-((2,5-dimethoxybenzyl)(2-phenoxyphenyl)amino)-2-oxoethyl-4-methylbenzenesulfonate
  参考文献：
  名称：

  Steroids 2011, 76, 1331-1340

  摘要：

  DOI：

文献信息

• Synthesis ofN-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)[carbonyl-11C]acetamide ([carbonyl-11C]DAA1106) and analogues using [11C]carbon monoxide and palladium(0) complex
  作者：Obaidur Rahman、Bengt Långström

  DOI：10.1002/jlcr.1437

  日期：2007.11

  N-(2,5-Dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide (DAA1106), a potent and selective ligand for peripheral benzodiazepine receptor, and eight structurally related analogues were labelled with 11C at the carbonyl position using a low concentration of [11C]carbon monoxide and the micro-autoclave technique. A combinatorial approach was applied to synthesize the analogues using similar reaction conditions. Palladium-mediated carbonylation using tetrakis(triphenylphosphine)palladium, various amines and methyl iodide or iodobenzene was employed in the synthesis. The 11C-labelled products were obtained with 10–55% decay-corrected radiochemical yields and the final product was more than 97% pure in all cases. Specific radioactivity was determined for the compound [carbonyl-11C]DAA1106 using a single experiment and a 10-µA h bombardment. The specific radioactivity, measured 36 min after end of bombardment, was 455 GBq/µmol. Synthetic routes to the precursors and reference compounds were also developed. The presented approach is a novel method for the synthesis of [carbonyl-11C]DAA1106 and its analogues, and allows the formation of a library of 11C-labelled DAA1106 analogues which can be used to optimize the performance as a potential positron emission tomography tracer. Copyright © 2007 John Wiley & Sons, Ltd.

  N-(2,5-二甲氧基苄基)-N-(5-氟-2-苯氧苯基)乙酰胺（DAA1106），一种强效且选择性的外周苯二氮卓受体配体，及其八个结构相关的类似物，使用低浓度的[11C]一氧化碳和微型高压釜技术在羰基位置进行了11C标记。采用组合方法，利用相似的反应条件合成了这些类似物。合成中使用了四(三苯膦)钯介导的羰基化反应，并结合了各种胺和甲基碘或碘苯。所得的11C标记产物具有10-55%的衰变校正放射化学产率，所有情况下最终产物纯度均超过97%。通过单次实验和10µA h轰击，测定了化合物[羰基-11C]DAA1106的比活度。轰击结束后36分钟测得的比活度为455 GBq/µmol。还开发了合成前体和参考化合物的路线。所提出的方法是一种新颖的[羰基-11C]DAA1106及其类似物的合成方法，并能够形成一系列11C标记的DAA1106类似物库，这些类似物可用于优化其作为潜在正电子发射断层扫描示踪剂的性能。版权所有 © 2007 John Wiley & Sons, Ltd.
• Aryloxyaniline derivatives
  申请人：Taisho Pharmaceutical Co., Ltd.

  公开号：US06333358B1

  公开（公告）日：2001-12-25

  An aryloxyaniline derivative represented by the formula: wherein Ar1 and Ar2 are each a substituted or unsubstituted phenyl group, pyridyl group or naphthyl group, R1 is a hydrogen atom, an alkyl group, etc., X1 is a hydrogen atom, an alkyl group, etc., y1 is a branched or unbranched alkylene group having 1 to 6 carbon atoms or a single bond; or a pharmaceutically acceptable salt thereof can provide medicines having a high affinity for MDR, and therefore, exhibiting a therapeutic or preventive effect on anxiety, related diseases thereto, depression, etc.

  由以下公式表示的一种芳基氧基苯胺衍生物：其中Ar1和Ar2分别是取代或未取代的苯基、吡啶基或萘基，R1是氢原子、烷基等，X1是氢原子、烷基等，y1是具有1至6个碳原子的分支或非分支烷基基团或单键；或其药学上可接受的盐，可以提供对多药耐药性(MDR)具有高亲和力的药物，因此对焦虑、相关疾病、抑郁等具有治疗或预防作用。
• Heterocycle substituted aryloxyaniline derivatives and their use as MDR ligands
  申请人：Taisho Pharmaceutical Co., Ltd.

  公开号：US06476056B2

  公开（公告）日：2002-11-05

  An aryloxyaniline derivative represented by the formula: wherein Ar1 and Ar2 are the same or different, and are each a substituted or unsubstituted phenyl group, a substituted or unsubstituted pyridyl group or a naphthyl group, provided that Ar1 and Ar2 are not both phenyl or both naphthyl and are not phenyl and naphthyl, R1 is a hydrogen atom, a substituted or unsubstituted alkyl group having 1 to 10 carbon atoms, an alkoxy group having 1 to 10 carbon atoms, a substituted or unsubstituted phenyl group or a group of the formula: —NR2(R3) (wherein R2 and R3 are the same or different, and are each a hydrogen atom or an alkyl group having 1 to 10 carbon atoms, X1 is a hydrogen atom, an alkyl group having 1 to 5 carbon atoms, an alkoxy group having 1 to 5 carbon atoms, a phenoxy group, a halogen atom, a trifluoromethyl group, a carbamoyl group or an aminosulfonyl group, Y1 is a branched or unbranched alkylene group having 1 to 6 carbon atoms or a single bond; and pharmaceutically acceptable salts thereof.

  一种芳氧基苯胺衍生物，其化学式如下：其中Ar1和Ar2相同或不同，每个都是取代或未取代的苯基、取代或未取代的吡啶基或萘基，但要求Ar1和Ar2不能同时是苯基或萘基，也不能同时是苯基和萘基；R1是氢原子，具有1至10个碳原子的取代或未取代的烷基、具有1至10个碳原子的烷氧基、取代或未取代的苯基或化学式为- NR2（R3）（其中R2和R3相同或不同，每个都是氢原子或具有1至10个碳原子的烷基），X1是氢原子、具有1至5个碳原子的烷基、具有1至5个碳原子的烷氧基、苯氧基、卤素原子、三氟甲基基团、氨基甲酰基或氨基磺酰基，Y1是具有1至6个碳原子的分支或非分支烷基或单键；以及其药学上可接受的盐。
• J. Med. Chem. 2009, 52, 688-699
  作者：

  DOI：——

  日期：——
• ARYLOXYANILINE DERIVATIVES
  申请人：TAISHO PHARMACEUTICAL CO., LTD

  公开号：EP1004573B1

  公开（公告）日：2002-10-30