tert-butyl 4-(4-chlorophenyl)piperazine-1-carboxylate | 1070716-32-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: tert-butyl 4-(4-chlorophenyl)piperazine-1-carboxylate
• CAS: 1070716-32-3
• 化学式: C₁₅H₂₁ClN₂O₂
• 分子量: 296.797
• InChiKey: KWGJPILHSLHTNW-UHFFFAOYSA-N

物化性质

• 沸点：
  410.8±40.0 °C(Predicted)
• 密度：
  1.178±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(4-chlorophenyl)piperazine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以420 mg的产率得到1-(4-氯苯基)哌嗪
  参考文献：
  名称：

  Optimization of 5-substituted thiazolyl ureas and 6-substituted imidazopyridines as potential HIV-1 latency reversing agents

  摘要：

  A persistent latent reservoir of virus in CD4(+) T cells is a major barrier to cure HIV. Activating viral transcription in latently infected cells using small molecules is one strategy being explored to eliminate latency. We previously described the use of a FlpIn.FM HEK293 cellular assay to identify and then optimize the 2-acylaminothiazole class to exhibit modest activation of HIV gene expression. Here, we implement two strategies to further improve the activation of viral gene expression and physicochemical properties of this class. Firstly, we explored rigidification of the central oxy-carbon linker with a variety of saturated heterocycles, and secondly, investigated bioisosteric replacement of the 2-acylaminothiazole moiety. The optimization process afforded lead compounds (74 and 91) from the 2-piperazinyl thiazolyl urea and the imidazopyridine class. The lead compounds from each class demonstrate potent activation of HIV gene expression in the FlpIn.FM HEK293 cellular assay (both with LTR EC(50)s of 80 nM) and in the Jurkat Latency 10.6 cell model (LTR EC50 220 and 320 nM respectively), but consequently activate gene expression non-specifically in the FlpIn.FM HEK293 cellular assay (CMV EC50 70 and 270 nM respectively) manifesting in cellular cytotoxicity. The lead compounds have potential for further development as novel latency reversing agents. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112254
• 作为产物：
  描述：

  4-溴氯苯 、 N-Boc-哌嗪 在 三乙烯二胺 、 nickel(II) bromide trihydrate 、 tris(1,10-phenanthroline)osmium(II) hexafluorophosphate 作用下， 以 二甲基亚砜 为溶剂， 以55 %的产率得到tert-butyl 4-(4-chlorophenyl)piperazine-1-carboxylate
  参考文献：
  名称：

  克服金属光氧化还原催化中的光化学限制：红光驱动的 C-N 交叉偶联

  摘要：

  芳基胺化是医药、工艺和材料化学的重要转变。除了经典的 Buchwald-Hartwig 胺化条件外，蓝光驱动的金属光氧化还原催化已成为 C-N 交叉偶联的重要工具。然而，蓝光对反应介质的渗透率低，限制了其在工业用途上的可扩展性。此外，蓝光会促进金属光氧化还原催化（即加氢脱卤）中不需要的副产物形成。低能量光，例如深红光 (DR) 或近红外光 (NIR)，提供了解决此问题的方法，因为与高能量波长相比，它可以增强通过反应介质的穿透力。在此处，我们表明，低能光还可以通过抑制不需要的加氢脱卤来增强金属光氧化还原催化中所需的反应性。我们假设减少的副产物是由高能光直接光解芳基镍键形成的，导致芳基自由基的产生。使用深红色或近红外光和锇光催化剂，我们证明了（杂）芳基溴化物和胺基亲核试剂的范围扩大，加氢脱卤副产物的形成最少。

  DOI：

  10.1021/jacs.2c09745

文献信息

• MONOACYLGLYCEROL LIPASE INHIBITORS
  申请人：Stichting Het Nederlands Kanker Instituut- Antoni van Leeuwenhoek Ziekenhuis

  公开号：EP3875452A1

  公开（公告）日：2021-09-08

  Provided are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof: Also provided are compositions comprising compounds of formula (I). The compounds and compositions are also provided for use as medicaments, for example as medicaments useful in the treatment of a condition modulated by monoacylglycerol lipase (MAGL). Also provided are the use of compounds and compositions for the inhibition of monoacylglycerol lipase (MAGL).

  提供的是式(I)的化合物，或其药学上可接受的盐或溶剂： 还提供了包含式(I)化合物的组合物。这些化合物和组合物还可用作药物，例如用于治疗由单酰基甘油脂酶（MAGL）调节的疾病的药物。还提供了利用这些化合物和组合物来抑制单酰基甘油脂酶（MAGL）的用途。
• An Improved Protocol for the Pd-Catalyzed α-Arylation of Aldehydes with Aryl Halides
  作者：Rubén Martín、Stephen L. Buchwald

  DOI：10.1021/ol8017775

  日期：2008.10.16

  An improved protocol for the Pd-catalyzed alpha-arylation of aldehydes with aryl halides has been developed. The new catalytic system allows for the coupling of an array of substrates including challenging electron-rich aryl bromides and less reactive aryl chlorides. The utility of this method has been demonstrated in a new total synthesis of (+/-)-sporochnol.

  已经开发出用于钯与芳基卤化物的醛催化的α-芳基化的改进方案。新的催化系统允许偶联一系列底物，包括具有挑战性的富电子的芳基溴化物和反应性较低的芳基氯化物。该方法的实用性已在新的（+/-）-亚砜醇的全合成中得到证明。
• Efficient copper-catalyzed cross-coupling of 1-Boc-piperazine with aryl iodides and its application in the synthesis of trazodone
  作者：Fui-Fong Yong、Yong-Chua Teo、Khee-Ngiap Tan

  DOI：10.1016/j.tetlet.2013.07.104

  日期：2013.9

  convenient and practical strategy is developed for the cross-coupling of N-Boc protected piperazines with aryl iodides using CuBr/1,1′-bi-2-naphthol as the catalyst and K3PO4 as the base. The protocol affords N-arylated piperazine products in moderate to good yields under the optimized conditions. The application of this catalytic system to the synthesis of trazodone is also successfully demonstrated using commercially

  提出了一种方便实用的策略，以CuBr / 1,1'-bi-2-萘酚为催化剂，K 3 PO 4为碱，将N - Boc保护的哌嗪与芳基碘交叉偶联。该协议在优化条件下以中等到良好的产率提供了N-芳基哌嗪产品。使用市场上可买到的底物也成功地证明了该催化体系在合成曲唑酮中的应用。
• [EN] LOW AFFINITY POLY(AD-RIBOSE) POLYMERASE 1 DEPENDENT CYTOTOXIC AGENTS<br/>[FR] AGENTS CYTOTOXIQUES DÉPENDANT DE LA POLY(AD-RIBOSE) POLYMÉRASE-1 DE FAIBLE AFFINITÉ
  申请人：UNIV PENNSYLVANIA

  公开号：WO2019169156A1

  公开（公告）日：2019-09-06

  The present disclosure provides compounds of Formula (I) or (II), pharmaceutically acceptable salt, isotopic variant, stereoisomer, or a mixture thereof. Also provided are pharmaceutical compositions comprising a compound, methods of treating a poly(ADP-ribose)polymerase-1-mediated disease or disorder in a subject, methods of detecting a poly(ADP-ribose)polymerase-1-mediated neurodegenerative disease or disorder, or methods of monitoring cancer treatment in a subject. In some embodiments, the poly(ADP-ribose)polymerase-1-mediated disease or disorder is a neurodegenerative disease or cancer.

  本公开提供公式（I）或（II）的化合物，药学上可接受的盐、同位素变体、立体异构体或其混合物。还提供了包含该化合物的制药组合物，治疗受体内聚合酶-1介导的疾病或障碍的方法，检测聚合酶-1介导的神经退行性疾病或障碍的方法，或监测受体内癌症治疗的方法。在某些实施例中，聚合酶-1介导的疾病或障碍是神经退行性疾病或癌症。
• HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK
  申请人：McCall John M.

  公开号：US20120165318A1

  公开（公告）日：2012-06-28

  Disclosed herein are new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.

  本文公开了新的杂环化合物和组合物，以及它们作为药物治疗疾病的应用。还提供了抑制人或动物主体中PAS激酶（PASK）活性的方法，用于治疗糖尿病等疾病。