4-bromo-2-(phenylethynyl)-1,3-thiazole | 329203-16-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-bromo-2-(phenylethynyl)-1,3-thiazole
• 英文别名: 2-(phenylethynyl)-4-bromothiazole；4-bromo-2-(phenylethynyl)thiazole；4-bromo-2-phenylethynylthiazole；4-bromo-2-(2-phenylethynyl)-1,3-thiazole
• CAS: 329203-16-9
• 化学式: C₁₁H₆BrNS
• 分子量: 264.145
• InChiKey: UGGAUOOZHDYXNR-UHFFFAOYSA-N

物化性质

• 熔点：
  74 °C
• 沸点：
  371.8±34.0 °C(Predicted)
• 密度：
  1.62±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  41.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-bromo-2-(phenylethynyl)-1,3-thiazole 在 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 正丁基锂 、 dimethyl sulfide borane 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 (R)-2-甲基-CBS-恶唑硼烷 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.33h， 生成 (3S,6R,7S)-((S)-2-methyl-3-(2-(phenylethynyl)thiazol-4-yl)cyclopent-2-enyl) 3,7-dihydroxy-4,4,6,8-tetramethyl-5-oxononanoate
  参考文献：
  名称：

  Small-molecule anticancer agents kill cancer cells by harnessing reactive oxygen species in an iron-dependent manner

  摘要：

  在生成开链环烯菌素类药物库的过程中，我们发现了一类新型的小分子抗癌药物，它对微管蛋白没有影响，而是通过以铁为依赖的方式利用活性氧种类杀死特定的癌细胞系。

  DOI：

  10.1039/c7ob03086j
• 作为产物：
  描述：

  2,4-二溴噻唑 、 苯乙炔 在 copper(l) iodide 、 四(三苯基膦)钯 、 二异丙胺 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以86%的产率得到4-bromo-2-(phenylethynyl)-1,3-thiazole
  参考文献：
  名称：

  Small-molecule anticancer agents kill cancer cells by harnessing reactive oxygen species in an iron-dependent manner

  摘要：

  在生成开链环烯菌素类药物库的过程中，我们发现了一类新型的小分子抗癌药物，它对微管蛋白没有影响，而是通过以铁为依赖的方式利用活性氧种类杀死特定的癌细胞系。

  DOI：

  10.1039/c7ob03086j

文献信息

• Palladium-Catalyzed C–H Bond Direct Alkynylation of 5-Membered Heteroarenes: A Well-Defined Synthetic Route to Azole Derivatives Containing Two Different Alkynyl Groups
  作者：Fumitoshi Shibahara、Yoshimasa Dohke、Toshiaki Murai

  DOI：10.1021/jo3008385

  日期：2012.6.15

  conditions, imidazole and benzimidazole, which are sluggish under similar previously reported oxidative coupling conditions, as well as imidazo[1,5-a]pyridines, oxazole, benzoxazole, thiazole, and benzothiazole could be alkynylated. In addition, the bromine atom on the substrates was intact under the reaction conditions, and conventional Sonogashira coupling did not occur at all. With these reactivities in

  已开发出一种广泛使用的五元杂芳烃和末端炔烃的氧化偶合，它使用钯盐和银盐的组合。在合适的条件下，咪唑和苯并咪唑（在类似的先前报道的氧化偶合条件下反应迟缓）以及咪唑并[1,5- a ]吡啶，恶唑，苯并恶唑，噻唑和苯并噻唑可以被炔基化。另外，在反应条件下，底物上的溴原子是完整的，并且根本不发生常规的Sonogashira偶联。掌握了这些反应活性，即可得到明确定义的合成咪唑的合成路线[1,5- a含有两个不同炔基的对吡啶和噻唑的制备方法很简单。此外，不仅获得的1,3-双（芳基乙炔基）咪唑基[1,5]的C1上，而且C3炔基上的芳烃基团的荧光波长与Hammett取代基常数之间也存在线性关系。 -一]吡啶。
• Synthesis of 2‘-Substituted 4-Bromo-2,4‘-bithiazoles by Regioselective Cross-Coupling Reactions
  作者：Thorsten Bach、Stefan Heuser

  DOI：10.1021/jo025661o

  日期：2002.8.1

  which underwent a second regioselective cross-coupling with another equivalent of 2,4-dibromothiazole (2). The Negishi cross-coupling gave high yields of the 2'-alkyl-4-bromo-2,4'-bithiazoles 1a-g (88-97%). The synthesis of the 2'-phenyl- and 2'-alkynyl-4-bromo-2,4'-bithiazoles 1h-j required a Stille cross-coupling that did not proceed as smoothly as the Negishi cross-coupling (58-62% yield). The title

  从容易获得的2,4-二溴噻唑（2）开始，分两个步骤完成了标题化合物（1）的合成。在区域选择性的Pd（0）催化的交叉偶联步骤中，化合物2被转化为各种2-取代的4-溴噻唑3（10个实例，产率65-85％）。烷基和芳基卤化锌用作亲核试剂以引入烷基或芳基取代基。遵循Sonogashira方案以实现炔基脱溴。碳原子C-4处的溴-锂交换以及随后的重金属转化为锌或锡，将4-溴噻唑3转化为碳亲核试剂，该亲核试剂与另一当量的2,4-二溴噻唑进行了第二区域选择性交叉偶联（2）。Negishi交叉偶联产生了2'-烷基-4-溴-2,4'-联噻唑1a-g（88-97％）的高产率。2'的合成 -苯基-和2'-炔基-4-溴-2,4'-联噻唑1h-j需要进行Stille交叉偶联，但其进展不如Negishi交叉偶联顺利（收率58-62％）。总产率为38-82％的标题化合物是合成2,4'-联噻唑的通用结构单元。
• 2,4-Disubstituted Thiazoles by Regioselective Cross-Coupling or Bromine-Magnesium Exchange Reactions of 2,4-Dibromothiazole
  作者：Thorsten Bach、Stefan Gross、Stefan Heuser、Carolin Ammer、Golo Heckmann

  DOI：10.1055/s-0030-1258373

  日期：2011.1

  Cross-coupling reactions occur on 2,4-dibromothiazole preferentially at the more electron-deficient 2-position. This fact can be favorably used to prepare 2-substituted 4-bromothiazoles, which serve as precursors for 2,4-disubstituted thiazoles. Protocols for regioselective Negishi and Stille cross-coupling reactions are provided. Alternatively, the title compound can be metalated in 2-position by a halogen-metal exchange reaction. As a supplement to the well-established bromine-lithium exchange, the regioselective bromine-magnesium exchange reaction is presented.

  2,4-二溴噻唑的交叉偶联反应优先发生在更缺电子的 2 位。这一事实可用于制备 2-取代的 4-溴噻唑，作为 2,4-二取代噻唑的前体。本研究提供了区域选择性 Negishi 和 Stille 交叉偶联反应的方案。另外，还可以通过卤素-金属交换反应将标题化合物 2 位金属化。作为对成熟的溴-锂交换反应的补充，介绍了具有区域选择性的溴-镁交换反应。
• [EN] HETEROCYCLIC COMPOUNDS AND METHODS OF USE THEREOF<br/>[FR] COMPOSES HETEROCYCLIQUES ET PROCEDES D'UTILISATION DE CEUX-CI
  申请人：MERCK & CO INC

  公开号：WO2001016121A1

  公开（公告）日：2001-03-08

  In accordance with the present invention, there are provided novel class of heterocyclic compounds and methods of use thereof. Compounds of the invention contain a substituted, unsaturated five, six or seven membered heterocyclic ring that includes at least one nitrogen atom and at least one carbon atom. At a ring position adjacent to a ring nitrogen atom, the heterocyclic ring has at least one substituent which includes a moiety, linked to the heterocyclic ring via an alkylene moiety, an alkynylene moiety or an azo group. Invention compounds are capable of a wide variety of uses including modulating physiological processes by functioning as agonists and antagonists of receptors in the nervous system, as insecticides, and as fungicides. The invention further provides methods of modulating the activity of excitatory amino acid receptors using a specifically defined class of heterocyclic compounds including the novel compounds referred to above. In one embodiment, there are provided methods of modulating metabotropic glutamate receptors. The present invention also discloses methods of treating disease using heterocyclic compounds. The invention further discloses methods of preventing disease conditions related to diseases of the pulmonary system, diseases of the nervous system, diseases of the cardiovascular system, diseases of the gastrointestinal system, diseases of the endocrine system, diseases of the exocrine system, diseases of the skin, cancer and diseases of the ophthalmic system. The invention also discloses pharmaceutically acceptable salt forms of the above-described heterocyclic compounds.

  根据本发明，提供了一类新型的杂环化合物及其使用方法。该发明的化合物包含一个取代的、不饱和的五、六或七元杂环环，其中至少包含一个氮原子和至少一个碳原子。在靠近环氮原子的环位置上，杂环环有至少一个取代基，包括一个官能团，通过烷基官能团、炔基官能团或偶氮基团连接到杂环环上。发明的化合物能够广泛应用，包括通过作为神经系统受体的激动剂和拮抗剂来调节生理过程，作为杀虫剂和杀菌剂。本发明还提供了使用特定定义的杂环化合物类来调节兴奋性氨基酸受体活性的方法，包括上述新型化合物。在一种实施例中，提供了调节代谢性谷氨酸受体的方法。本发明还揭示了使用杂环化合物治疗疾病的方法。本发明还揭示了预防与肺系统疾病、神经系统疾病、心血管系统疾病、胃肠系统疾病、内分泌系统疾病、外分泌系统疾病、皮肤疾病、癌症和眼科系统疾病相关的疾病状态的方法。本发明还揭示了上述杂环化合物的药物可接受的盐形式。
• Methods of modulating processes mediated by excitatory amino acid receptors
  申请人：Cosford Nicholas D. P.

  公开号：US06956049B1

  公开（公告）日：2005-10-18

  In accordance with the present invention, there are provided methods of modulating the activity of excitatory amino acid receptors using a specifically defined class of heterocyclic compounds. In one embodiment, there are provided methods of modulating metabotropic glutamate receptors. The present invention also discloses methods of treating disease using heterocyclic compounds. Diseases contemplated include cerebral ischemia, chronic neurodegeneration, psychiatric disorders, schizophrenia, mood disorders, emotion disorders, disorders of extrapyramidal motor function, obesity, disorders of respiration, motor control and function, attention deficit disorders, concentration disorders, pain disorders, neurodegenerative disorders, epilepsy, convulsive disorders, eating disorders, sleep disorders, sexual disorders, circadian disorders, drug withdrawal, drug addiction, compulsive disorders, anxiety, panic disorders, depressive disorders, skin disorders, retinal ischemia, retinal degeneration, glaucoma, disorders associated with organ transplantation, asthma, ischemia and astrocytomas. The invention further discloses methods of preventing disease conditions related to diseases of the pulmonary system, diseases of the nervous system, diseases of the cardiovascular system, diseases of the gastrointestinal system, diseases of the endocrine system, diseases of the exocrine system, diseases of the skin, cancer and diseases of the ophthalmic system. The invention also discloses pharmaceutically acceptable salt forms of heterocyclic compounds.

  根据本发明，提供了使用一类特定定义的杂环化合物来调节兴奋性氨基酸受体活性的方法。在一种实施例中，提供了调节代谢型谷氨酸受体的方法。本发明还揭示了使用杂环化合物治疗疾病的方法。所考虑的疾病包括脑缺血、慢性神经退行性疾病、精神障碍、精神分裂症、情绪障碍、运动功能外围疾病、肥胖症、呼吸、运动控制和功能障碍、注意力缺陷障碍、注意力障碍、疼痛障碍、神经退行性疾病、癫痫、惊厥性障碍、进食障碍、睡眠障碍、性障碍、昼夜节律障碍、药物戒断、药物成瘾、强迫障碍、焦虑、恐慌障碍、抑郁障碍、皮肤疾病、视网膜缺血、视网膜退化、青光眼、与器官移植相关的疾病、哮喘、缺血和星形细胞瘤。本发明还揭示了杂环化合物的药物可接受的盐形式的方法。