8-氟-5-甲基-6-氧代-4H-咪唑并[1,5-a][1,4]苯并二氮杂-3-羧酸乙酯 | 92745-42-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 中文名称: 8-氟-5-甲基-6-氧代-4H-咪唑并[1,5-a][1,4]苯并二氮杂-3-羧酸乙酯
• 英文名称: [11C]flumazenil
• 英文别名: Flumazenil C-11；ethyl 8-fluoro-5-(111C)methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate
• CAS: 92745-42-1
• 化学式: C₁₅H₁₄FN₃O₃
• 分子量: 302.282
• InChiKey: OFBIFZUFASYYRE-JVVVGQRLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  64.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  8-氟-5-甲基-6-氧代-4H-咪唑并[1,5-a][1,4]苯并二氮杂-3-羧酸乙酯 在 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以95%的产率得到8-fluoro-5-(111C)methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylic acid
  参考文献：
  名称：

  A single-mode microwave cavity for reducing radiolabelling reaction times, demonstrated by alkylations with [11C]alkyl halides

  摘要：

  考虑到正电子发射放射性核素屏蔽工作空间的典型空间限制，为微观反应建造了一个单模微波腔。演示了微波腔中的微波场对典型反应介质的影响。与文献中报道的相应热程序相比，用[11C]甲基碘和[2-11C]异丙基碘对神经受体配体进行放射性标记的反应时间大大缩短。

  DOI：

  10.1002/jlcr.2580341008
• 作为产物：
  描述：

  8-氟-5,6-二氢-6-氧代-4H-咪唑并[1,5-a][1,4]苯并二氮杂卓-3-羧酸乙酯 、 [11C]methyl triflate 在 sodium hydroxide 作用下， 以 丙酮 为溶剂， 反应 0.02h， 以75%的产率得到8-氟-5-甲基-6-氧代-4H-咪唑并[1,5-a][1,4]苯并二氮杂-3-羧酸乙酯
  参考文献：
  名称：

  Methylation of amide and thiol functions with [11C]methyl triflate, as exemplified by [11C]NMSP[11C]flumazenil and [11C]methionine

  摘要：

  DOI：

  10.1002/(sici)1099-1344(1998090)41:9<831::aid-jlcr129>3.0.co;2-e

文献信息

• Rapid preparation of [11C]flumazenil: captive solvent synthesis combined with purification by analytical sized columns
  作者：Marcel C. Cleij、John C. Clark、Jean-Claude Baron、Franklin I. Aigbirhio

  DOI：10.1002/jlcr.1152

  日期：——

  To produce the radioligand [N-methyl-11C]flumazenil at very high specific radioactivity for our small animal imaging studies we have developed procedures for its rapid synthesis, purification and analysis. We have developed ‘micro-reactor’ apparatus which are assembled from analytical HPLC guard columns packed with stainless steel powder for performing the carbon-11 methylation reactions. These highly efficient reaction columns enable high radiochemical yields to be obtained with very small amounts of precursor (20–40 µg). The very small amount of reactants used enables the use of small analytical-sized HPLC columns for the rapid purification of the radioligand. Combining these techniques has enabled us to consistently prepare [N-methyl-11C]flumazenil from [11C]iodomethane with radiochemical yields of 80% (decay corrected). This results in 8–10 GBq of [N-methyl-11C]flumazenil at very high specific radioactivities of 520–600 GBq/µmol at the end-of-synthesis. The total preparation time from end-of-bombardment of cyclotron-produced [11C]carbon dioxide to end-of-synthesis is 20 min. A quality control method based on very rapid HPLC analysis (completed within 2 min) on a micro-analytical HPLC column has also being developed to reduce the time from the end-of-synthesis to injection for imaging. Copyright © 2007 John Wiley & Sons, Ltd.

  为了在我们的动物成像研究中制备高比活度的放射性配体[N-甲基-11C]氟马西尼，我们开发了快速合成、纯化和分析的方法。我们开发了由填充不锈钢粉末的分析型HPLC保护柱组装而成的“微反应器”设备，用于进行碳-11甲基化反应。这些高效的反应柱能够在非常少量的前体物质（20-40微克）下获得高的放射化学产率。使用非常少量的反应物使得可以采用小型的分析尺寸HPLC柱进行放射性配体的快速纯化。结合这些技术，我们能够从[11C]碘甲烷一致性地制备[N-甲基-11C]氟马西尼，放射化学产率达到80%（衰变校正）。这结果在合成结束时获得8-10 GBq的[N-甲基-11C]氟马西尼，比活度高达520-600 GBq/微摩尔。从回旋加速器产生的[11C]二氧化碳轰击结束到合成结束的总制备时间为20分钟。我们还开发了一种基于微型分析HPLC柱的快速HPLC分析（在2分钟内完成）的质量控制方法，以减少从合成结束到成像注射的时间。版权所有 © 2007 John Wiley & Sons, Ltd.
• The use of tetrabutylammonium fluoride to promote<i>N</i>- and<i>O</i>-¹¹C-methylation reactions with iodo[¹¹C]methane in dimethyl sulfoxide
  作者：Tatsuya Kikuchi、Katsuyuki Minegishi、Hiroki Hashimoto、Ming-Rong Zhang、Koichi Kato

  DOI：10.1002/jlcr.3092

  日期：2013.11

  The N- or O-methylation reactions of compounds bearing amide, aniline, or phenol moieties using iodo[11C]methane (1) with the aid of a base are frequently applied to the preparation of 11C-labeled radiopharmaceuticals. Although sodium hydride and alkaline metal hydroxides are commonly employed as bases in these reactions, their poor solubility properties in organic solvents and hydrolytic activities have sometimes limited their application and made the associated 11C-methylation reactions difficult. In contrast to these bases, tetrabutylammonium fluoride (TBAF) is moderately basic, highly soluble in organic solvents, and weakly nucleophilic. Although it was envisaged that TBAF could be used as the preferred base for 11C-methylation reactions using 1, studies concerning the use of TBAF to promote 11C-methylation reactions are scarce. Herein, we have evaluated the efficiency of the 11C-methylation reactions of 13 model compounds using TBAF and 1. In most cases, the N-11C-methylations were efficiently promoted by TBAF in dimethyl sulfoxide at ambient temperature, whereas the O-11C-methylations required heating in some cases. Comparison studies revealed that the efficiencies of the 11C-methylation reactions with TBAF were comparable or sometimes greater than those conducted with sodium hydride. Based on these results, TBAF should be considered as the preferred base for 11C-methylation reactions using 1.

  含有酰胺、苯胺或酚基团的化合物在碘[11C]甲烷（1）作用下，借助碱进行的N-或O-甲基化反应通常用于制备11C标记的放射药物。尽管氢化钠和碱金属氢氧化物在这些反应中常被用作碱，但它们在有机溶剂中的溶解性差以及水解活性，有时限制了其应用，使得相关的11C-甲基化反应变得困难。与这些碱相比，四丁基氟铵（TBAF）具有适中的碱性，高度溶于有机溶剂，并且亲核性较弱。尽管有预想TBAF可以作为11C-甲基化反应的优选碱，但关于TBAF促进11C-甲基化反应的研究却很少。在此，我们评估了使用TBAF和1对13个模型化合物进行11C-甲基化反应的效率。在大多数情况下，TBAF在室温下能有效促进二甲基亚硫酰胺中的N-11C-甲基化，而在某些情况下O-11C-甲基化则需要加热。比较研究表明，使用TBAF进行的11C-甲基化反应的效率可比或有时大于使用氢化钠的反应。基于这些结果，TBAF应被视为使用1进行11C-甲基化反应的优选碱。
• Highlighting the versatility of the Tracerlab synthesis modules. Part 2: fully automated production of [11C]-labeled radiopharmaceuticals using a Tracerlab FXC-Pro
  作者：Xia Shao、Raphaël Hoareau、Adam C. Runkle、Louis J. M. Tluczek、Brian G. Hockley、Bradford D. Henderson、Peter J. H. Scott

  DOI：10.1002/jlcr.1937

  日期：2011.12

  Herein, we continue our series of articles showcasing the versatility of the Tracerlab FX synthesis modules by presenting straightforward, fully automated methods for preparing a range of carbon‐11 labeled radiopharmaceuticals using a Tracerlab FXC‐Pro. Strategies for production of [11C]acetate, [11C]carfentanil, [11C]choline, [11C]3‐amino‐4‐[2‐[(di(methyl)amino)methyl]phenyl]sulfanylbenzonitrile ([11C]DASB)

  放射化学领域正在朝着自动合成模块的专用化方向发展，以生产临床放射药物剂量。这样的举动不仅具有许多优势，而且还给放射化学工作者带来了重新配置合成模块的挑战，以生产需要非常规放射化学同时又要保持全自动的放射性药物。在此，我们将继续介绍一系列文章，展示通过使用Tracerlab FX C-Pro制备一系列碳11标记的放射性药物的直接，全自动方法，来展示Tracerlab FX合成模块的多功能性。产生[ 11 C]乙酸盐，[ 11 C]芬太尼，[ 11 C]胆碱，[ 11C] 3-氨基-4- [2-[（（（（二（甲基）氨基）甲基]苯基]硫烷基苄腈（[ 11 C] DASB），（+）-[ 11 C]二氢萜烯嗪（[ 11 C] DTBZ） ，[ 11 C]氟马西尼（[ 11 C] FMZ），间羟基麻黄碱（[ 11 C] HED），[ 11 C]蛋氨酸，[ 11 C] PBR28，[ 11 C]匹兹堡化合物B（[
• [11C]methyl iodide from [11C]methane and iodine using a non-thermal plasma method
  作者：Jonas Eriksson、Johan Ulin、Bengt Långström

  DOI：10.1002/jlcr.1135

  日期：2006.11

  radioactivity of 84 GBq/mmol from 10 GBq of [11C]carbon monoxide. [1-11C]Propyl iodide was synthesized with a specific radioactivity of 270 GBq/mmol from 12 GBq and [1-11C]butyl iodide with 146 GBq/mmol from 8 GBq.Palladium-mediated hydroxycarbonylation of acetylene was used in the synthesis of [1-11C]acrylic acid. The labelled carboxylic acid was converted to its acid chloride and subsequently treated with

  用 11C（β+，t1/2 = 20.4 分钟）标记的化合物用于正电子发射断层扫描 (PET)，这是一种定量的非侵入性分子成像技术。它利用计算机重建方法生成活体放射性分布的时间分辨图像。探讨了通过单次通过非热等离子体反应器从[11C]甲烷和碘制备[11C]甲基碘的可行性。通过 [11C] 二氧化碳 (24 GBq) 的催化氢化和随后的碘化，在 6 分钟内以 13 ± 3% 衰减校正的放射化学产率获得了具有 412 ± 32 GBq/µmol 比放射性的 [11C] 甲基碘，电子碰撞。标记的乙基碘、丙基碘和丁基碘在 15 分钟内通过使用 [11C] 一氧化碳的钯介导的羰基化合成。羰基化产物，标记为羧酸、酯和醛，被还原为相应的醇并转化为烷基碘。[1-11C] 乙基碘是通过钯介导的甲基碘羰基化获得的，衰减校正的放射化学产率为 55 ± 5%。[1-11C] 碘化丙烷和 [1-11C] 碘化丁酯是
• Non Thermal Plasma Method to Prepare [11C] Methyl Iodide From [11C] Methane and Iodine Methane and Iodine
  申请人：Eriksson Jonas

  公开号：US20080306313A1

  公开（公告）日：2008-12-11

  A method and an apparatus for preparing [ 11 C]methyl iodide from [ 11 C]methane and iodine in a single pass through a non-thermal plasma reactor has been developed. The plasma was created by applying high voltage (400 V/31 kHz) to electrodes in a stream of helium gas at reduced pressure. The [ 11 C]methane used in the experiments was produced from [ 11 C]carbon dioxide via reduction with hydrogen over nickel. [ 11 C]Methyl iodide was obtained with a specific radioactivity of 412±32 GBq/μmol within 6 min from approximately 24 GBq of [ 11 C]carbon dioxide. The decay corrected radiochemical yield was 13±3% based on [ 11 C]carbon dioxide at start of synthesis. [ 11 C]Flumazenil was synthesized via a N-alkylation with the prepared [ 11 C]methyl iodide. Kit and apparatus for preparing [ 11 C]methyl iodide by a non thermal plasma method are also provided.

  一种从[11C]甲烷和碘在单次通过非热等离子体反应器制备[11C]甲基碘的方法和装置已经开发出来。等离子体是通过在减压氦气流中施加高电压（400 V/31 kHz）于电极上来创建的。实验中使用的[11C]甲烷是通过在镍催化下与氢还原[11C]二氧化碳产生的。在约24 GBq的[11C]二氧化碳中，6分钟内获得了具有412±32 GBq/μmol的特定放射性的[11C]甲基碘。校正衰变的放射化学产率基于合成开始时的[11C]二氧化碳为13±3%。使用制备的[11C]甲基碘通过N-烷基化合成[11C]氟马西尼。还提供了用于通过非热等离子体方法制备[11C]甲基碘的试剂盒和装置。