2-benzylsulfanyl-4,6-dichloro-[1,3,5]triazine | 25713-57-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三嗪类
• 英文名称: 2-benzylsulfanyl-4,6-dichloro-[1,3,5]triazine
• 英文别名: 2-benzylsulfanyl-4,6-dichloro-1,3,5-triazine；2-Benzylthio-4,6-dichlor-s-triazin；2-(Benzylsulfanyl)-4,6-dichloro-1,3,5-triazine
• CAS: 25713-57-9
• 化学式: C₁₀H₇Cl₂N₃S
• 分子量: 272.158
• InChiKey: DMEZLIQUTNGCOB-UHFFFAOYSA-N

物化性质

• 沸点：
  149-150 °C(Press: 0.3 Torr)
• 密度：
  1.49±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  64
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-benzylsulfanyl-4,6-dichloro-[1,3,5]triazine 在 四(三苯基膦)钯 、 sodium carbonate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 水 为溶剂， 反应 21.0h， 生成 4-(4-(benzylthio)-6-(2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-yl)-1,3,5-triazin-2-yl)morpholine
  参考文献：
  名称：

  Discovery of Novel and Orally Bioavailable Inhibitors of PI3 Kinase Based on Indazole Substituted Morpholino-Triazines

  摘要：

  A new class of potent PI3K alpha inhibitors is identified based on aryl substituted morpholino-triazine scaffold. The identified compounds showed not only a high level of enzymatic and cellular potency in nanomolar range but also high oral bioavailability. The three lead molecules (based on their in vitro potency) when evaluated further for in vitro metabolic stability as well as pharmacokinetic profile led to the identification of 26, as a candidate for further development. The IC50 and EC50 value of 26 is 60 and 500 nM, respectively, for PI3Ka enzyme inhibitory activity and ovarian cancer (A2780) cell line. The identified lead also showed a high level of microsomal stability and minimal inhibition activity for CYP3A4, CYP2C19, and CYP2D6 at 10 mu M concentrations. The lead compound 26, demonstrated excellent oral bioavailability with an AUG of 5.2 mu M at a dose of 3 mpk in mice and found to be well tolerated in mice when dosed at 30 mpk BID for 5 days.

  DOI：

  10.1021/acsmedchemlett.5b00322
• 作为产物：
  描述：

  三聚氯氰 、 苄硫醇 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以97%的产率得到2-benzylsulfanyl-4,6-dichloro-[1,3,5]triazine
  参考文献：
  名称：

  固相合成1,3,5-取代的三嗪的新型正交策略。

  摘要：

  [反应：见正文]为改进先前合成三嗪文库的正交方法，已通过将硫醚氧化活化为砜开发了另一种策略。通过对这两种方法的比较，证明了砜策略是生成高纯度三嗪文库化合物的一种增强方法。

  DOI：

  10.1021/ol027195v

文献信息

• Novel Orthogonal Strategy toward Solid-Phase Synthesis of 1,3,5-Substituted Triazines
  作者：Jacqueline T. Bork、Jae Wook Lee、Sonya M Khersonsky、Ho-Sang Moon、Young-Tae Chang

  DOI：10.1021/ol027195v

  日期：2003.1.1

  [reaction: see text] To improve upon the previous orthogonal method for synthesis of a triazine library, an alternative strategy has been developed via oxidation-activation of the thioether to the sulfone. Through a comparison between these two methods, the sulfone strategy was demonstrated as an enhanced method in the generation of highly pure triazine library compounds.

  [反应：见正文]为改进先前合成三嗪文库的正交方法，已通过将硫醚氧化活化为砜开发了另一种策略。通过对这两种方法的比较，证明了砜策略是生成高纯度三嗪文库化合物的一种增强方法。
• Solid phase synthesis of novel biaryl triazine library by suzuki cross coupling
  申请人：NEW YORK UNIVERSITY

  公开号：US20040225125A1

  公开（公告）日：2004-11-11

  Two methods are used to produce diaryl trisubstituted triazines. In the first method, cyanuric chloride is first reacted with a 4-alkoxybenzylamine. The product of this reaction is then reacted with a resin-bound amine, such as 4-alkoxybenzylamine, to ensure that the final compound will be bound to a resin. The product of this reaction is then reacted with boronic acid to produce a trisubstituted diaryl triazine. In the second method, cyanuric chloride is reacted with a benzenealkanethiol. The product of this reaction is then reacted with a resin-bound amine, such as 4-alkoxybenzylamine, to ensure that the final compound will be bound to a resin. The product of this reaction is then reacted with m-CPBA to form a sulfone, which is then reacted with a 4-alkoxybenzylamine to form the desired trisubstituted biaryltriazine.

  有两种方法可以制备二苯基三取代三嗪。第一种方法是，首先将氰尿酸氯与4-烷氧基苯甲胺反应。然后将该反应产物与树脂结合胺（如4-烷氧基苯甲胺）反应，以确保最终化合物与树脂结合。然后将该反应产物与硼酸反应，以产生三取代二苯基三嗪。第二种方法是，将氰尿酸氯与苯基烷硫醇反应。然后将该反应产物与树脂结合胺（如4-烷氧基苯甲胺）反应，以确保最终化合物与树脂结合。然后将该反应产物与m-CPBA反应形成烷基磺酰，然后再与4-烷氧基苯甲胺反应形成所需的三取代联苯三嗪。
• Terminal alkyne-functionalized triazine by Sonogashira coupling: synthesis of a potential cell signalling inhibitor via click chemistry
  作者：Caroline Courme、Sophie Gillon、Nohad Gresh、Michel Vidal、Christiane Garbay、Jean-Claude Florent、Emmanuel Bertounesque

  DOI：10.1016/j.tetlet.2008.05.050

  日期：2008.7

  Introduction of the acetylene group on the 1,3,5-triazine scaffold was studied under various conditions. We describe here a new method to functionalize a triazine ring using Sonogashira coupling between 2-benzylsulfanyl-4,6-dichloro-1,3,5-triazine and trimethylsilylacetylene to give the corresponding 2-benzylsulfanyl-4-chloro-6-(trimethylsilyl)ethynyl-1,3,5-triazine. The latter was then used to obtain

  在各种条件下研究了在1,3,5-三嗪支架上乙炔基的引入。我们在这里描述了一种新的方法来使用2-苄基硫烷基-4,6-二氯-1,3,5-三嗪和三甲基甲硅烷基乙炔之间的Sonogashira偶联功能化三嗪环，以给出相应的2-苄基硫烷基-4-氯-6-（三甲基甲硅烷基）乙炔基1,3,5-三嗪。然后将后者用于获得磷酸单-4- [4-（4-氨基-6-苄基硫烷基-1,3,5-三嗪-2-基）-1,2,3-三唑-1-基通过点击化学，通过Huisgen 1,3-偶极环加成反应得到]-苯基}酯。
• Palladium-catalyzed cross-coupling reaction of resin-bound chlorotriazines
  作者：Jacqueline T Bork、Jae Wook Lee、Young-Tae Chang

  DOI：10.1016/s0040-4039(03)01451-5

  日期：2003.8

  To introduce the biaryl structure as a triazine functionality, we have developed a new synthetic route via the Suzuki cross-coupling reaction of resin-bound chlorotriazines. The Suzuki cross-coupling reaction was achieved using various arylboronic acids, Pd(PPh3)(4), Cs2CO3, and dioxane. With the integration of this chemistry and our previous orthogonal methodology, the triazine library is greatly expanded to a biaryl scaffold. (C) 2003 Elsevier Ltd. All rights reserved.
• KELAREV, V. I.;KARAXANOV, R. A.;MALYSHEV, V. A.;PATALAX, I. I., TEZ. DOKL. SEMIN.-SOVESHCH.-4 ZHOTREBITELI I PROIZVODITELI ORGAN. REAKTIV+
  作者：KELAREV, V. I.、KARAXANOV, R. A.、MALYSHEV, V. A.、PATALAX, I. I.

  DOI：——

  日期：——