2-bromo-N-(2-phenoxyphenyl)acetamide

• 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: 2-bromo-N-(2-phenoxyphenyl)acetamide
• 化学式: C₁₄H₁₂BrNO₂
• mdl: MFCD02131358
• 分子量: 306.159
• InChiKey: KTKDDFXYNFVUQH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.071
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-bromo-N-(2-phenoxyphenyl)acetamide 在 potassium fluoride 、 palladium 10% on activated carbon 、 氢气 、 sodium hydride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 mineral oil 、 二乙二醇 为溶剂， 150.0 ℃ 、413.7 kPa 条件下， 反应 12.0h， 生成 2-fluoro-N-(2-hydroxy-5-methoxybenzyl)-N-(2-phenoxyphenyl)-acetamide
  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：

  溴乙酰溴 、 2-氨基二苯醚 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以86%的产率得到2-bromo-N-(2-phenoxyphenyl)acetamide
  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

文献信息

• 11H-dibenzo[b,e]azepines. Part 1. Synthesis and ir spectra of dibenzo[b,f][1,4]oxazepines
  作者：V. G. Noskov、L. N. Kalinina、M. N. Noskova、Yu. L. Kruglyak、O. G. Strukov、A. P. Bezrukov、V. K. Kurochkin

  DOI：10.1007/bf02464359

  日期：1997.8
• Single-Step High-Yield Radiosynthesis and Evaluation of a Sensitive ¹⁸F-Labeled Ligand for Imaging Brain Peripheral Benzodiazepine Receptors with PET
  作者：Emmanuelle Briard、Sami S. Zoghbi、Fabrice G. Siméon、Masao Imaizumi、Jonathan P. Gourley、H. Umesha Shetty、Shuiyu Lu、Masahiro Fujita、Robert B. Innis、Victor W. Pike

  DOI：10.1021/jm8011855

  日期：2009.2.12

  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.
• [EN] THIOAZEPINONE DERIVATIVES, PREPARATION METHOD AND INTERMEDIATES THEREFOR, USE AS MEDICINES AND PHARMACEUTICAL COMPOSITIONS CONTAINING SAME<br/>[FR] DERIVES DE THIOAZEPINONE, PROCEDE DE PREPARATION ET INTERMEDIAIRES DE CE PROCEDE, APPLICATION COMME MEDICAMENTS ET COMPOSITIONS PHARMACEUTIQUES LES CONTENANT
  申请人：HOECHST MARION ROUSSEL INC

  公开号：WO2000005246A1

  公开（公告）日：2000-02-03

  L'invention a pour objet un dérivé de thioazepinone de formule (I) dans laquelle R1, R2, R3, R4, R5, X, [A1], A2 et U ont les significations indiquées dans la description, leurs sels et leurs promédicaments. L'invention de plus a pour objet les procédés de préparation des composés de formule (I), les intermédiaires de ce procédé, leur application à titre de médicaments, notamment comme inhibiteurs du domaine Src SH2 et inhibiteurs de la résorption osseuse médiée par les ostéoclastes, et les compositions pharmaceutiques les renfermant.
• [EN] MU-OPIOID RECEPTOR BINDING COMPOUNDS<br/>[FR] COMPOSÉS SE FIXANT AU RÉCEPTEUR DES OPIOÏDES DE TYPE MU
  申请人：ALGYNOMICS INC

  公开号：WO2012166891A2

  公开（公告）日：2012-12-06

  A pharmaceutical composition, comprising (i) a mu opioid receptor modulating compound selected from the group consisting of Group I compounds, Matching Compounds, and their pharmaceutically acceptable derivatives, (ii) a pharmaceutically acceptable carrier, and (iii) optionally, another therapeutic agent. Also described are therapeutic methods of administering mu opioid receptor modulating compounds, and cocktail formulations with other mu opioid receptor compounds, e.g., morphine, (+)-morphine, methadone, (+)-methadone, 3-methoxynaltrexone, etorphine, or naltrexone.
• Synthesis of [11C]PBR06 and [18F]PBR06 as agents for positron emission tomographic (PET) imaging of the translocator protein (TSPO)
  作者：Min Wang、Mingzhang Gao、Kathy D. Miller、Qi-Huang Zheng

  DOI：10.1016/j.steroids.2011.06.012

  日期：2011.11

  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.