N-(5-bromo-2-phenoxyphenyl)-N-(2,5-dimethoxybenzyl)acetamide | 909109-24-6

• 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-(5-bromo-2-phenoxyphenyl)-N-(2,5-dimethoxybenzyl)acetamide
• 英文别名: N-(5-bromo-2-phenoxyphenyl)-N-[(2,5-dimethoxyphenyl)methyl]acetamide
• CAS: 909109-24-6
• 化学式: C₂₃H₂₂BrNO₄
• 分子量: 456.336
• InChiKey: DKFDUNFXEUYUNE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(5-bromo-2-phenoxyphenyl)-N-(2,5-dimethoxybenzyl)acetamide 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 Cu(OTf)2(py)4 、 potassium acetate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.33h， 生成 [¹⁸F]DAA1106
  参考文献：
  名称：

  Enhanced copper-mediated ¹⁸F-fluorination of aryl boronic esters provides eight radiotracers for PET applications

  摘要：

  使用铜介导的非载体添加亲核性¹⁸F-氟化技术，从芳基硼酸酯前体中分离出了八种临床相关的放射性示踪剂。

  DOI：

  10.1039/c6cc03295h
• 作为产物：
  描述：

  对二甲氧基苯甲醇 在 盐酸 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 N-(5-bromo-2-phenoxyphenyl)-N-(2,5-dimethoxybenzyl)acetamide
  参考文献：
  名称：

  N-(5-Fluoro-2-phenoxyphenyl)-N-(2-[¹³¹I]iodo-5-methoxybenzyl)acetamide:  A Potent Iodinated Radioligand for the Peripheral-type Benzodiazepine Receptor in Brain

  摘要：

  To image the peripheral-type benzodiazepine receptor (PBR) in vivo, we previously developed two positron emission tomography (PET) ligands, N-(2-[C-11],5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide ([C-11]1a) and its [F-18]fluoroethyl analogue ([F-18]1b), for the investigation of PBR in the living human brain. This time, using 1a as a leading compound, we designed two novel iodinated analogues, N-(5-fluoro-2-phenoxyphenyl)-N-(2-iodo-5-methoxybenzyl)acetamide (3a) and N-(2,5-dimethoxybenzyl)-N-(5-iodo-2-phenoxyphenyl)acetamide (3b) for the PBR imaging. Ligands 3 were synthesized by the iodination of tributystannyl precursors 10. Radiolabeling for 3 with I-131 was carried out by the reaction of 10 with [I-131]NaI using H2O2 as an oxidizing agent. In vitro competition experiments determined that 3a exhibited both high affinity and selectivity for PBR (IC50: 7.8 nM) vs CBR (> 1 mu M). Biodistribution study in mice determined that [I-131]3a had a high radioactivity level (1.69% dose/g) in the brain, and its distribution pattern in the brain was consistent with the known distribution of PBR in rodents. Ex vivo autoradiography of the rat brain gave visual evidence that [I-131]3a was a potent and specific radioligand for PBR.

  DOI：

  10.1021/jm061127n

文献信息

• A General Copper-Mediated Nucleophilic¹⁸F Fluorination of Arenes
  作者：Matthew Tredwell、Sean M. Preshlock、Nicholas J. Taylor、Stefan Gruber、Mickael Huiban、Jan Passchier、Joël Mercier、Christophe Génicot、Véronique Gouverneur

  DOI：10.1002/anie.201404436

  日期：2014.7.21

  describe the realization of these requirements with the production of 18F arenes from pinacol‐derived aryl boronic esters (arylBPin) upon treatment with [18F]KF/K222 and [Cu(OTf)2(py)4] (OTf=trifluoromethanesulfonate, py=pyridine). This method tolerates electron‐poor and electron‐rich arenes and various functional groups, and allows access to 6‐[18F]fluoro‐L‐DOPA, 6‐[18F]fluoro‐m‐tyrosine, and the translocator

  标有氟18的分子用作正电子发射断层扫描的放射性示踪剂。一个重要的挑战是芳烃不适于芳香亲核取代（S的标记Ñ AR）与[ 18 F]˚F - 。在理想情况下，这些底物的18 F氟化反应将通过[ 18 F] KF与耐贮存稳定且易于获得的前体进行反应，并采用适用于自动化的广泛应用的方法。在此，我们描述了实现这些要求的生产的18个处理后从频哪醇衍生的芳基硼酸酯（arylBPin）的F芳烃与[ 18 F] KF / K 222和物[Cu（OTF）2（py）4 ]（OTf ＝三氟甲磺酸盐，py ＝吡啶）。此方法容许贫电子和富电子的芳烃和各种官能团，并允许访问6- [ 18 F]氟-大号-DOPA，6- [ 18 F]氟-米-酪氨酸，和转运蛋白（TSPO ）PET配体[ 18 F] DAA1106。
• RADIOACTIVE HALOGEN-LABELED PHENYLOXYANILINE DERIVATIVES
  申请人：TAISHO PHARMACEUTICAL CO., LTD

  公开号：EP1854781A1

  公开（公告）日：2007-11-14

  A radioactive halogen-labeled phenyoxyaniline derivative represented by the following formula: wherein R1 represents a group such as an alkyl group; X1, X2, X3 and X4 represent each a hydrogen atom, an alkyl group, an alkoxy group, an alkoxy group carrying 11C introduced thereinto or a radioactive halogen atom, provided that at least one of X1, X2, X3 and X4 represents an alkoxy group carrying 11C introduced thereinto or a radioactive halogen atom; which is a compound useful as a PBR ligand having a high affinity and a high selectivity. In in vitro measurement of PBR, a PBR ligand having a high affinity and a high selectivity is labeled with a radioactive halogen nuclear species so as to enable the measurement of PBR in vivo with the use of means including not only PET but also SPECT. Thus, a compound which is useful in early diagnosing, preventing and treating diseases such as Alzheimer type dementia can be obtained.

  一种放射性卤素标记的苯氧胺衍生物，其化学式如下：其中R1代表类似烷基的基团；X1、X2、X3和X4分别代表氢原子、烷基、烷氧基、携带11C的烷氧基或放射性卤素原子，至少其中之一代表携带11C的烷氧基或放射性卤素原子；该化合物作为具有高亲和力和高选择性的PBR配体而有用。在体外测量PBR时，将具有高亲和力和高选择性的PBR配体标记为放射性卤素核种，以便使用PET和SPECT等手段在体内测量PBR。因此，可以获得一种在早期诊断、预防和治疗阿尔茨海默型痴呆等疾病中有用的化合物。
• METHOD FOR SYNTHESIZING RADIOACTIVE LIGAND HAVING 18F-LABELED FLUOROBENZENE RING
  申请人：Suzuki Kazutoshi

  公开号：US20090069592A1

  公开（公告）日：2009-03-12

  A phenyl tin compound is synthesized by using a derivative having various functional groups and a bromo- or iodo-benzene ring as a labeling material of a radioactive ligand. On the other hand, a novel hydroxytosyl iodobenzene compound having an electron-donating group is obtained by oxidizing iodobenzene having one or more electron-donating groups and reacting it with tosylic acid. Then, a diphenyliodonium salt which is a labeling precursor is synthesized by reacting the resulting compound with various phenyl tin compounds. Finally, a 18 F-labeled ligand having various functional groups and a [ 18 F] fluorobenzene ring is synthesized by reacting the resulting diphenyliodonium salt with [ 18 F]F − .

  使用具有各种功能基团和溴苯或碘苯环的衍生物作为放射性配体的标记物质，合成了一种苯基锡化合物。另一方面，通过氧化具有一个或多个电子给予基团的碘苯并与对甲苯磺酸反应，得到了一种具有电子给予基团的新型羟基对甲苯碘苯化合物。然后，通过将所得化合物与各种苯基锡化合物反应合成了一种标记前体二苯碘铵盐。最后，通过将所得二苯碘铵盐与[18F]F-反应，合成了具有各种功能基团和[18F]氟苯环的18F标记配体。
• Copper-Mediated Aromatic Radiofluorination Revisited: Efficient Production of PET Tracers on a Preparative Scale
  作者：Boris D. Zlatopolskiy、Johannes Zischler、Philipp Krapf、Fadi Zarrad、Elizaveta A. Urusova、Elena Kordys、Heike Endepols、Bernd Neumaier

  DOI：10.1002/chem.201405586

  日期：2015.4.7

  Two novel methods for copper‐mediated aromatic nucleophilic radiofluorination were recently reported. Evaluation of these methods reveals that, although both are efficient in small‐scale experiments, they are inoperative for the production of positron emission tomography (PET) tracers. Since high base content turned out to be responsible for low radiochemical conversions, a “low base” protocol has

  最近报道了两种铜介导的芳香族亲核放射性氟化的新方法。对这些方法的评估表明，尽管这两种方法在小规模实验中都是有效的，但它们对于生产正电子发射断层扫描（PET）示踪剂是无效的。由于事实证明高碱含量是造成低放射性化学转化的原因，因此开发了一种“低碱”方案，该方案可从二芳基碘鎓盐和芳基频哪醇硼酸酯中以合理的产率提供18 F标记的芳烃。此外，实施我们的“极简主义”方法来处理（间苯二甲酰基）（芳基）碘鎓盐的铜介导的[ 18 F]-氟化反应，可以制备18具有出色RCC的F标签芳烃。新颖的放射性氟化方法避免了费时的共沸干燥，并且避免了利用碱和其他添加剂（例如穴状配体）。此外，该程序可以生产临床相关的PET示踪剂。[ 18 F] FDA，4- [ 18 F] FPhe和[ 18 F] DAA1106以良好的分离放射化学产率获得。此外，[ 18 F] DAA1106已在大鼠中风模型中进行了评估，并证明了可视化
• A practical route for synthesizing a PET ligand containing [18F]fluorobenzene using reaction of diphenyliodonium salt with [18F]F−
  作者：Ming-Rong Zhang、Katsushi Kumata、Kazutoshi Suzuki

  DOI：10.1016/j.tetlet.2007.10.025

  日期：2007.12

  route for preparing a fluorine-18 ([18F]) labelled ligand ([18F]1) containing [18F]fluorobenzene ring by employing the reaction of diphenyliodonium salt with [18F]F−. Diphenyliodonium tosylate (2) was synthesized from tributylphenylstannyl compound (6) with [hydroxy(tosyloxy)iodo]benzene (7). Using this method, [18F]DAA1106 ([18F]3a), a positron emission tomography ligand for imaging peripheral-type benzodiazepine

  这项研究的目的是通过使用二苯基碘鎓盐与[ 18 F ]的反应，开发一种制备包含[ 18 F]氟苯环的氟18（[ 18 F]）标记的配体（[ 18 F] 1）的实用途径。F的- 。二苯基碘鎓甲苯磺酸酯（2）从tributylphenylstannyl化合物（合成6与）[羟基（甲苯磺酰氧基）碘]苯（7）。使用这种方法，制备了[ 18 F] DAA1106（[ 18 F] 3a），这是一种用于对周围型苯并二氮杂receptor受体成像的正电子发射断层成像配体。