tert-butyl 4-(o-tolyl)piperazine-1-carboxylate

• 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-(o-tolyl)piperazine-1-carboxylate
• 英文别名: Tert-butyl 4-o-tolylpiperazine-1-carboxylate；tert-butyl 4-(2-methylphenyl)piperazine-1-carboxylate
• 化学式: C₁₆H₂₄N₂O₂
• 分子量: 276.379
• InChiKey: PWBKAWVRUDWXDT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 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-(o-tolyl)piperazine-1-carboxylate 在 Barluenga reagent 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 N-(p-iodo-o-tolyl)-N'-Boc-piperazine
  参考文献：
  名称：

  Synthesis, radiolabeling, and preliminary biological evaluation of [3H]-1-[(S)-N,O-bis-(isoquinolinesulfonyl)-N-methyl-tyrosyl]-4-(o-tolyl)-piperazine, a potent antagonist radioligand for the P2X7 receptor

  摘要：

  The design, synthesis, and preliminary biological evaluation of the first potent radioligand antagonist for the P2X(7) receptor, named [H-3]-1-[(S)-N,O-bis-(isoquinolinesulfonyl)-N-methyl-tyrosyl]-4-(o-tolyl)-piperazine (compound 13), are reported. This compound bound to human P2X(7) receptors expressed in HEK transfected cells with K-D and B-max value of 3.46 +/- 0.1 nM and 727 +/- 73 fmol/mg of protein, respectively. The high affinity and facile labeling makes it a promising radioligand for a further characterization of P2X(7) receptor subtype. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.07.095
• 作为产物：
  描述：

  1-(2-甲基苯基)哌嗪 在 TEA 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 66.0h， 生成 tert-butyl 4-(o-tolyl)piperazine-1-carboxylate
  参考文献：
  名称：

  Synthesis, radiolabeling, and preliminary biological evaluation of [3H]-1-[(S)-N,O-bis-(isoquinolinesulfonyl)-N-methyl-tyrosyl]-4-(o-tolyl)-piperazine, a potent antagonist radioligand for the P2X7 receptor

  摘要：

  The design, synthesis, and preliminary biological evaluation of the first potent radioligand antagonist for the P2X(7) receptor, named [H-3]-1-[(S)-N,O-bis-(isoquinolinesulfonyl)-N-methyl-tyrosyl]-4-(o-tolyl)-piperazine (compound 13), are reported. This compound bound to human P2X(7) receptors expressed in HEK transfected cells with K-D and B-max value of 3.46 +/- 0.1 nM and 727 +/- 73 fmol/mg of protein, respectively. The high affinity and facile labeling makes it a promising radioligand for a further characterization of P2X(7) receptor subtype. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.07.095

文献信息

• Synthesis of Hindered Anilines: Copper-Catalyzed Electrophilic Amination of Aryl Boronic Esters
  作者：Richard P. Rucker、Aaron M. Whittaker、Hester Dang、Gojko Lalic

  DOI：10.1002/anie.201200480

  日期：2012.4.16

  No longer a hindrance: Copper‐catalyzed electrophilic amination of aryl boronic esters is accomplished under mild reaction conditions using 2.5–5.0 mol % of a catalyst derived from copper tert‐butoxide and Xantphos ligand (see scheme). The reaction tolerates a wide range of functional groups and can be used to prepare some of the most hindered anilines made to date.

  不再是障碍：芳基硼酸酯的铜催化亲电胺化反应可在温和的反应条件下，使用2.5-5.0 mol％的叔丁醇铜和Xantphos配体衍生的催化剂完成（参见方案）。该反应可耐受各种官能团，可用于制备迄今为止制备的某些受阻最大的苯胺。
• Compositions, Synthesis, And Methods Of Using Piperazine Based Antipsychotic Agents
  申请人：Bhat Laxminarayan

  公开号：US20090298819A1

  公开（公告）日：2009-12-03

  The present invention provides novel piperazine derivatives which can be advantageously used for treating schizophrenia and related psychoses such as acute manic, bipolar disorder, autistic disorder and depression.

  本发明提供了一种新颖的哌嗪衍生物，可以优势地用于治疗精神分裂症和相关精神病，如急性躁狂、双相情感障碍、自闭症和抑郁症。
• 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] EZH2 INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS D'EZH2 ET LEURS UTILISATIONS
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2016073956A1

  公开（公告）日：2016-05-12

  The present disclosure provides compounds of any one of Formulae (I) and (II). The compounds described herein are inhibitors of histone methyltransferases (e.g., enhancer of zeste homolog 1 (EZH1) and enhancer of zeste homolog 2 (EZH2)) and are useful in treating and/or preventing a broad range of diseases (e.g., proliferative diseases). Also provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including or using a compound described herein. Further provided in the present disclosure are methods of identifying EZH1and/or EZH2 inhibitors.

  本公开提供了任一式（I）和（II）中的化合物。本文描述的化合物是组蛋白甲基转移酶抑制剂（例如增强子齿同源蛋白1（EZH1）和增强子齿同源蛋白2（EZH2）），可用于治疗和/或预防广泛范围的疾病（例如增生性疾病）。本公开还提供了包括或使用本文描述的化合物的药物组合物、试剂盒、方法和用途。本公开还提供了识别EZH1和/或EZH2抑制剂的方法。
• [EN] USE OF COMPOSITIONS MODULATING CHROMATIN STRUCTURE FOR GRAFT VERSUS HOST DISEASE (GVHD)<br/>[FR] UTILISATION DE COMPOSITIONS MODULANT LA STRUCTURE DE LA CHROMATINE CONTRE LA MALADIE DU GREFFON CONTRE L'HÔTE (GVHD)
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2016073903A1

  公开（公告）日：2016-05-12

  In some aspects, the instant disclosure relates to methods of treating chronic graft versus host disease (cGVHD). In some embodiments, the method comprises administering to a subject in need thereof a EZH2 inhibitor, a Bcl6 inhibitor and/or BRD4 inhibitor. The present disclosure is based, at least in part, on the discovery that enhancer of zeste homolog 2 (EZH2) inhibitors, B-cell lymphoma 6 protein (Bcl6) inhibitors and/or bromodomain-containing protein 4 (BRD4) inhibitors can be used to treat chronic graft versus host disease (cGVHD).

  在某些方面，瞬时披露涉及治疗慢性移植物抗宿主病（cGVHD）的方法。在某些实施例中，该方法包括向需要该方法的受试者施用EZH2抑制剂、Bcl6抑制剂和/或BRD4抑制剂。本公开至少部分地基于发现，增强子of zeste同源物2（EZH2）抑制剂、B细胞淋巴瘤6蛋白（Bcl6）抑制剂和/或含有bromodomain的蛋白4（BRD4）抑制剂可用于治疗慢性移植物抗宿主病（cGVHD）。