4-[¹⁸F]fluoroaniline | 93639-14-6

• 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: 4-[¹⁸F]fluoroaniline
• 英文别名: 4-(18F)fluoranylaniline
• CAS: 93639-14-6
• 化学式: C₆H₆FN
• 分子量: 110.12
• InChiKey: KRZCOLNOCZKSDF-JZRMKITLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  8
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  26
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-[¹⁸F]fluoroaniline 在 羟胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 0.13h， 生成 4-(18)F-fluorosuberoylanilide hydroxamic acid
  参考文献：
  名称：

  In Vivo PET Imaging of Histone Deacetylases by ¹⁸F-Suberoylanilide Hydroxamic Acid (¹⁸F-SAHA)

  摘要：

  Histone deacetylases (HDACs) are a group of enzymes that modulate gene expression and cell state by deacetylation of both histone and non-histone proteins. A variety of HDAC inhibitors (HDACi) have already undergone clinical testing in cancer. Real-time in vivo imaging of HDACs and their inhibition would be invaluable; however, the development of appropriate imaging agents has remained a major challenge. Here, we describe the development and evaluation of F-18-suberoylanilide hydroxamic acid (F-18-SAHA 1a), a close analogue of the most clinically relevant HDAC inhibitor suberoylanilide hydroxamic acid (SAHA). We demonstrate that 1a has near identical biochemical activity profiles to that of SAHA and report findings from pharmacokinetic studies. Using a murine ovarian. cancer model, we likewise show that HDAC inhibitor target binding efficacy can be quantitated within 24 h of administration. 1a thus represents the first F-18-positron emission tomography (PET) HDAC imaging agent, which also exhibits low nanomolar potency and is pharmacologically analogous to a clinically relevant HDAC inhibitor.

  DOI：

  10.1021/jm200620f
• 作为产物：
  描述：

  1-azido-4-[¹⁸F]fluorobenzene 在 三苯基膦 作用下， 以 乙腈 为溶剂， 反应 0.17h， 生成 4-[¹⁸F]fluoroaniline
  参考文献：
  名称：

  通过施陶丁格还原方便地获得 18F 标记胺

  摘要：

  Fluorine-18 在正电子发射断层扫描 (PET) 成像中具有出色的衰变特性。因此，它非常适合临床应用。因此，改进将氟-18纳入生物活性分子的策略至关重要。使用氨基功能化合成子进行间接 18F 标记是合成各种 PET 示踪剂的一种方便且通用的方法。在此，我们报告了一种通过施陶丁格还原将 18F 标记的叠氮化物转化为伯胺的方法。脂肪族和芳香族18F标记的叠氮化物被转化为相应的胺，转化率很高。该方法很容易实现自动化。从更广泛的角度来看，所应用的策略从单个前体产生两个有用的合成子，从而增加了以最少的合成工作标记不同化学支架的灵活性。

  DOI：

  10.1002/ejoc.201801457

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。
• 4-[18F]fluorophenyl ureas via carbamate-4-nitrophenyl esters and 4-[18F]fluoroaniline
  作者：Sebastian Olma、Johannes Ermert、Heinz H. Coenen

  DOI：10.1002/jlcr.1121

  日期：2006.10.30

  Four different no carrier added (n.c.a.) 4-[18F]fluorophenylurea derivatives are synthesized as model compounds via two alternative routes. In both cases carbamate-4-nitrophenylesters are used as intermediates. Either n.c.a. 4-[18F]fluoroaniline reacts with carbamates of several amines, or the carbamate of n.c.a. 4-[18F]fluoroaniline is formed at first and an amine is added subsequently to yield the urea derivative. The choice of the appropriate way of reaction depends on the possibilities of precursor synthesis. The radiochemical yields reach up to 80% after 50 min of synthesis time while no radiochemical by-products can be determined. These high yields were possible due to an optimized preparation of n.c.a. 4-[18F]fluoroaniline with a radiochemical yield of up to 90%. From the various ways of its radiosynthesis, the substitution with n.c.a. [18F]fluoride on dinitrobenzene is chosen, using phosphorous acid and palladium black for reduction of the second nitro group. Copyright © 2006 John Wiley & Sons, Ltd.

  合成了四种不同的无载体添加（n.c.a.）4-[18F]氟苯基尿酸酯衍生物作为模型化合物，采用了两种不同的合成路径。在这两种情况下，碳酸酯-4-硝基苯酯被用作中间体。无载体添加的4-[18F]氟苯胺与几种胺的碳酸酯反应，或者先形成无载体添加的4-[18F]氟苯胺的碳酸酯，再随后添加胺以生成尿酸酯衍生物。选择适当的反应路径取决于前体合成的可能性。 合成时间为50分钟时，放射化学产率可达80%，而未检测到放射化学副产物。这些高产率的获得归功于优化的无载体添加4-[18F]氟苯胺的制备，其放射化学产率高达90%。在多种放射合成方式中，选择了在二硝基苯上用无载体[18F]氟化物进行取代，并采用磷酸和黑色铂进行第二个硝基的还原。 版权所有 © 2006 John Wiley & Sons, Ltd.
• Rapid microfluidic flow hydrogenation for reduction or deprotection of 18F-labeled compounds
  作者：Steven H. Liang、Thomas Lee Collier、Benjamin H. Rotstein、Rebecca Lewis、Mia Steck、Neil Vasdev

  DOI：10.1039/c3cc45166f

  日期：——

  We have combined the benefits of both microfluidics and flow hydrogenation to provide facile access to previously underutilized reduction and protecting group chemistries for PET imaging applications. The rapid removal of an O-benzyl protecting group to prepare 2-[18F]fluoroquinolin-8-ol and the reduction of a nitro group in the synthesis of 4-[18F]fluoroaniline were achieved within 3 minutes.

  我们结合了微流体技术和流动氢化的优势，为PET成像应用提供了便捷的未充分利用的还原和保护基团化学的访问。O-苄基保护基团的快速去除，以制备2-[18F]氟喹啉-8-醇，以及在合成4-[18F]氟苯胺过程中对硝基的还原，均在3分钟内完成。
• Reaction of [18F]4-fluorobenzenediazonium cations with cysteine or the cysteinyl group: preparation of18F-labeled S-aryl-cysteine and a radiolabeled peptide
  作者：J. T. Patt、M. Patt

  DOI：10.1002/jlcr.635

  日期：2002.12

  A reaction route for the preparation of no-carrier-added (n.c.a.) [18F]S-4-fluorophenylcysteine 7 via the [18F]-4-fluorobenzenediazonium ion 4 is described. The key step in this radiosynthesis is the reaction of 4 with cysteine forming [18F]4-fluorophenyldiazocysteine 6, which is subsequently converted into 7 by irradiation with 366 nm light. 4 was synthesized by reacting 1,4-dinitrobenzene 1 with [18F]-fluoride in acetonitrile in a PEEK-capillary in a microwave oven. After dilution of the reaction mixture with methanol, the resulting [18F]4-fluoro-1-nitrobenzene 2 was submitted to reduction by means of H2 with Pd on C catalyst. The resulting [18F]4-fluoroaniline 3 was purified by HPLC and diazotized to 4. The preparation of 4 was optimized with regard to yield and purity. The radiochemical yield of 6 was >90% (based on 3) while after UV irradiation and HPLC purification 45% of 7 (based on 3) was obtained (yields corrected for decay). The suitability of this method for labeling peptides with fluorine-18 was demonstrated by application to the tripeptide, glutathione (GSH; γ-L-glutamyl-L-cysteinyglycine) 8. Copyright © 2002 John Wiley & Sons, Ltd.

  描述了一种通过[18F]-4-氟苯二氮离子4制备无载体添加（n.c.a.）[18F]S-4-氟苯丙氨酸7的反应路线。本放射合成的关键步骤是4与半胱氨酸反应形成[18F]4-氟苯基二氮半胱氨酸6，随后通过366纳米光照射转化为7。4的合成是通过将1,4-二硝基苯1与[18F]-氟化物在微波炉中的PEEK毛细管中于乙腈中反应得到的。在用甲醇稀释反应混合物后，得到的[18F]4-氟-1-硝基苯2通过Pd/C催化剂与氢气还原。得到的[18F]4-氟苯胺3经过HPLC纯化并重氮化为4。4的制备在产率和纯度上得到了优化。6的放射化学产率超过90%（基于3），而在紫外线照射和HPLC纯化后，获得了7的产率为45%（基于3，已校正衰变）。通过应用于三肽谷胱甘肽（GSH；γ-L-谷氨酸-L-半胱氨酸-甘氨酸）8，证明了该方法在用氟-18标记肽类方面的适用性。版权 © 2002 John Wiley & Sons, Ltd.
• [EN] METHOD OF PREPARING FLUORINE-18 LABELED CABOZANTINIB AND ITS ANALOGS<br/>[FR] PROCÉDÉ DE PRÉPARATION DE CABOZANTINIB MARQUÉ AU FLUOR-18 ET D'ANALOGUES DE CELUI-CI
  申请人：EXELIXIS INC

  公开号：WO2016019285A1

  公开（公告）日：2016-02-04

  The present invention relates to a method of preparing Cabozantinib (Cyclopropane- 1,1-dicarboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-phenylo]amide (4-fluoro- phenyl)amide) and 18F labeled Cabozantinib.

  本发明涉及一种制备卡博替尼（环丙烷-1,1-二甲酸[4-(6,7-二甲氧基喹啉-4-基氧基)-苯基]酰胺(4-氟苯基)酰胺)和18F标记卡博替尼的方法。