3-(2-(2-methylthiazol-4-yl)ethynyl)-5-bromobenzonitrile | 686768-53-6

• 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: 3-(2-(2-methylthiazol-4-yl)ethynyl)-5-bromobenzonitrile
• 英文别名: 3-bromo-5-((2-(methyl)thiazol-4-yl)ethynyl)benzonitrile；3-bromo-5-((2-methylthiazol-4-yl)ethynyl)benzonitrile；3-bromo-5-[(2-methyl-1,3-thiazol-4-yl)ethynyl]benzonitrile；3-bromo-5-[2-(2-methyl-1,3-thiazol-4-yl)ethynyl]benzonitrile
• CAS: 686768-53-6
• 化学式: C₁₃H₇BrN₂S
• 分子量: 303.182
• InChiKey: YNNDAGNEIADYLF-UHFFFAOYSA-N

物化性质

• 沸点：
  429.2±40.0 °C(Predicted)
• 密度：
  1.61±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  64.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(2-(2-methylthiazol-4-yl)ethynyl)-5-bromobenzonitrile 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 N,N-二甲基乙酰胺 、 Cu(OTf)2(py)4 、 potassium acetate 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 1.0h， 生成 3-[¹⁸F]fluoro-5-[(2-methyl-1,3-thiazol-4-yl)ethynyl]benzonitrile
  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：

  3,5-二溴苯甲酰胺 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 氯化亚砜 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 3-(2-(2-methylthiazol-4-yl)ethynyl)-5-bromobenzonitrile
  参考文献：
  名称：

  Potent mGluR5 antagonists: Pyridyl and thiazolyl-ethynyl-3,5-disubstituted-phenyl series

  摘要：

  We report the synthesis of four series of 3,5-disubstituted-phenyl ligands targeting the metabotropic glutamate receptor subtype 5: (2-methylthiazol-4-yl)ethynyl (1a-j,), (6-methylpyridin-2-yl)ethynyl (2a-j), (5-methylpyridin-2-yl)ethynyl (3a-j,), and (pyridin-2-yl)ethynyl (4a-j,). The compounds were evaluated for antagonism of glutamate-mediated mobilization of internal calcium in an mGluR5 in vitro assay. All compounds were found to be full antagonists and exhibited low nanomolar to subnanomolar activity. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.047

文献信息

• Alkyne derivatives as tracers for metabotropic glutamate receptor binding
  申请人：Cosford Peter Nicholas David

  公开号：US20070060618A1

  公开（公告）日：2007-03-15

  The present invention is directed to isotopically labeled alkyne derivative compounds, particularly 11 C, 13 C, 14 C, 18 F, 15 O, 13 N, 35 S, 2 H, and 3 H labeled compounds. In particular, the present invention is directed to 11 C, 13 C, 14 C, 18 F, 15 O, 13 N, 35 S, 2 H, and 3 H labeled heterocyclic alkynes and methods of their preparation. The present invention further includes a method of use of the 11 C, 18 F, 15 O, or 13 N labeled heterocyclic alkyne compounds as tracers in positron emission tomography (PET) imaging, particularly in the study of metabolic conditions in mammals, specifically conditions modulated by metabotropic glutamate receptors subtype 5 (mGluR5).

  本发明涉及同位素标记的炔基衍生物化合物，特别是11C、13C、14C、18F、15O、13N、35S、2H和3H标记的化合物。具体而言，本发明涉及11C、13C、14C、18F、15O、13N、35S、2H和3H标记的杂环炔烃及其制备方法。本发明还包括将11C、18F、15O或13N标记的杂环炔烃化合物用作正电子发射断层扫描（PET）成像中的示踪剂的使用方法，特别是在哺乳动物代谢状况的研究中，特别是通过代谢型谷氨酸受体亚型5（mGluR5）调节的状况。
• [EN] FLUORINATION METHOD<br/>[FR] PROCÉDÉ DE FLUORATION
  申请人：ISIS INNOVATION

  公开号：WO2015140572A1

  公开（公告）日：2015-09-24

  The present invention relates to a process for producing an organic compound comprising an 18F atom. The compounds comprising an 18F can be useful as PET ligands for use in diagnostics and/or scanning. The process of the invention comprises treating an organoboron compound, which organoboron compound comprises a boron atom bonded to an sp2 hybridised carbon atom, with (i) 18F – and (ii) a copper compound. The invention also provides the use of an organoboron compound, which organoboron compound comprises a boron atom bonded to an sp2 hybridised carbon atom, in a process for producing an organic compound comprising an 18F atom, which process comprises treating the organoboron compound with (i) 18F – and (ii) a copper compound. The invention also provides a compound of formula (XXXVII): wherein: each PGA is independently H or an alcohol protecting group; PGB is H or a carboxylic acid protecting group; each PGC is independently an amine protecting group; Z is a group selected from a boronic ester group, a boronic acid group, a borate group, and a trifluoroborate group; and a is an integer from 0 to 4.

  本发明涉及一种制备含有18F原子的有机化合物的方法。含有18F的化合物可用作PET配体，用于诊断和/或扫描。该发明的方法包括处理一种含有有机硼化合物，该有机硼化合物包括与sp2杂化碳原子键合的硼原子，与（i）18F-和（ii）铜化合物。该发明还提供了一种有机硼化合物的用途，该有机硼化合物包括与sp2杂化碳原子键合的硼原子，在制备含有18F原子的有机化合物的方法中，该方法包括处理该有机硼化合物与（i）18F-和（ii）铜化合物。该发明还提供了一种化合物的公式（XXXVII）：其中：每个PGA独立地为H或醇保护基；PGB为H或羧酸保护基；每个PGC独立地为胺保护基；Z为从硼酯基团、硼酸基团、硼酸盐基团和三氟硼酸盐基团中选择的基团；a为0到4之间的整数。
• Syntheses of mGluR5 PET radioligands through the radiofluorination of diaryliodonium tosylates
  作者：Sanjay Telu、Joong-Hyun Chun、Fabrice G. Siméon、Shuiyu Lu、Victor W. Pike

  DOI：10.1039/c1ob05555k

  日期：——

  3-Fluoro-1-((thiazol-4-yl)ethynyl)benzenes constitute an important class of high-affinity metabotropic glutamate subtype 5 receptor (mGluR5) ligands, some of which have been labeled with fluorine-18 (t1/2 = 109.7 min), to provide radioligands for molecular imaging of brain mGluR5 in living animal and human subjects with positron emission tomography (PET). Labeling in the 3-fluoro position of such ligands can be achieved through aromatic nucleophilic substitution of a halide leaving group with [18F]fluoride ion when a weakly activating m-nitrile group is present, but is generally very low yielding (<8%). Here we used a microfluidic reaction platform to show that greatly enhanced (up to 6-fold) radiochemical yields can be achieved from suitably synthesized diaryliodonium tosylate precursors. The presence of a m-nitrile or other activating group is not required. Similar conditions were adopted in a more conventional automated radiochemistry platform having a single-pot reactor, to produce mGluR5 radioligands with useful radioactivities for PET imaging.

  3-氟-1-((噻唑-4-基)乙炔基)苯系物是一类重要的高亲和性代谢谷氨酸亚型 5 受体（mGluR5）配体，其中一些已用氟-18（t1/2 = 109.7 分钟）标记，为正电子发射断层扫描（PET）对活体动物和人体脑部 mGluR5 进行分子成像提供了放射性配体。当存在弱活化间腈基团时，可通过芳香族亲核取代卤化物离去基团与[18F]氟离子来实现此类配体 3-氟位置的标记，但通常产率很低（<8%）。在这里，我们利用微流体反应平台证明，通过适当合成二芳碘对甲苯磺酸盐前体，可大大提高放射化学产率（高达 6 倍）。无需存在间腈或其他活化基团。在具有单锅反应器的更传统的自动化放射化学平台中也采用了类似的条件，以生产具有 PET 成像有用放射性活性的 mGluR5 放射性配体。
• Fluorination method
  申请人：Oxford University Innovation Limited

  公开号：US10287220B2

  公开（公告）日：2019-05-14

  The present invention relates to a process for producing an organic compound comprising an 18F atom. The compounds comprising an 18F can be useful as PET ligands for use in diagnostics and/or scanning. The process of the invention comprises treating an organoboron compound, which organoboron compound comprises a boron atom bonded to an sp2 hybridized carbon atom, with (i) 18F— and (ii) a copper compound. The invention also provides the use of an organoboron compound, which organoboron compound comprises a boron atom bonded to an sp2 hybridized carbon atom, in a process for producing an organic compound comprising an 18F atom, which process comprises treating the organoboron compound with (i)18F— and (ii) a copper compound. The invention also provides a compound of formula (XXXVII): wherein: each PGA is independently H or an alcohol protecting group; PGB is H or a carboxylic acid protecting group; each PGC is independently an amine protecting group; Z is a group selected from a boronic ester group, a boronic acid group, a borate group, and a trifluoroborate group; and a is an integer from 0 to 4.

  本发明涉及一种生产含有 18F 原子的有机化合物的工艺。含有 18F 的化合物可用作 PET 配体，用于诊断和/或扫描。本发明的工艺包括用(i)18F-和(ii)铜化合物处理有机硼化合物，该有机硼化合物包括与sp2杂化碳原子键合的硼原子。本发明还提供了有机硼化合物在生产包含 18F 原子的有机化合物的工艺中的用途，该有机硼化合物包含与 sp2 杂化碳原子键合的硼原子，该工艺包括用(i)18F- 和(ii)铜化合物处理该有机硼化合物。本发明还提供了式(XXXVII)的化合物： 其中：每个 PGA 独立地为 H 或醇保护基；PGB 为 H 或羧酸保护基；每个 PGC 独立地为胺保护基；Z 为选自硼酸酯基、硼酸基、硼酸盐基和三氟硼酸盐基的基团；以及 a 为 0 至 4 的整数。
• ALKYNE DERIVATIVES AS TRACERS FOR METABOTROPIC GLUTAMATE RECEPTOR BINDING
  申请人：Merck & Co., Inc.

  公开号：EP1556142A2

  公开（公告）日：2005-07-27