(1-(tert-butoxycarbonyl)piperidin-4-yl)zinc(II) bromide | 1309607-10-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (1-(tert-butoxycarbonyl)piperidin-4-yl)zinc(II) bromide
• 英文别名: bromo({1-[(tert-butoxy)carbonyl]piperidin-4-yl})zinc；bromo(1-tert-butoxycarbonyl-4-piperidyl)zinc
• CAS: 1309607-10-0
• 化学式: C₁₀H₁₈BrNO₂Zn
• 分子量: 329.552
• InChiKey: XJYIMHJZLCCWRV-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  15.0
• 可旋转键数：
  1.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  29.54
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  (1-(tert-butoxycarbonyl)piperidin-4-yl)zinc(II) bromide 在 copper(l) iodide 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 ethyl 2-({6-[(1,3-benzothiazol-2-yl)amino]-5-methylpyridazin-3-yl}(methyl)amino)-5-(piperidin-4-yl)-1,3-thiazole-4-carboxylate
  参考文献：
  名称：

  WO2021018857A5

  摘要：

  公开号：

  WO2021018857A5
• 作为产物：
  描述：

  4-溴-N-Boc-哌啶 、 锌 在 三甲基氯硅烷 、 1-溴-2-氯乙烷 作用下， 以 四氢呋喃 为溶剂， 生成 (1-(tert-butoxycarbonyl)piperidin-4-yl)zinc(II) bromide
  参考文献：
  名称：

  叔酰胺和烷基卤化物形成 C(sp3)–C(sp3) 键的全自动流程方案

  摘要：

  在此，我们提出了一种新颖的 C(sp 3 )–C(sp 3 ) 键形成方案，通过丰富的叔酰胺与由相应的烷基卤化物原位制备的有机锌试剂进行还原偶联。使用多步全自动流程方案，该反应可用于从实验室稳定试剂开始的克级文库合成和目标分子合成。此外，优异的化学选择性和官能团耐受性使其成为药物分子后期多样化的理想选择。

  DOI：

  10.1021/acs.orglett.3c01390

文献信息

• Coupling of Reformatsky Reagents with Aryl Chlorides Enabled by Ylide‐Functionalized Phosphine Ligands
  作者：Zhiyong Hu、Xiao‐Jing Wei、Jens Handelmann、Ann‐Katrin Seitz、Ilja Rodstein、Viktoria H. Gessner、Lukas J. Gooßen

  DOI：10.1002/anie.202016048

  日期：2021.3.15

  organozinc reagents with aryl electrophiles using a cyclohexyl‐YPhos ligand bearing an ortho‐tolyl‐substituent in the backbone. This highly electron‐rich, bulky ligand enables the use of aryl chlorides in room temperature couplings of Reformatsky reagents. The reaction scope covers diversely functionalized arylacetic and arylpropionic acid derivatives. Aryl bromides and chlorides can be converted selectively

  芳基氯化物与Reformatsky试剂的偶联是构建α-芳基酯的理想策略，但由于各种可能的副反应带来许多挑战，到目前为止，在基质范围上已受到很大的限制。现在，通过调整内酯官能化的膦以满足Negishi联轴器的要求，克服了这一局限性。使用在主链上带有邻甲苯基取代基的环己基-YPhos配体，在钯催化的有机锌试剂与芳基亲电试剂的芳基化中达到了创纪录的活性。这种高度电子富集的庞大配体使得可以在Reformatsky试剂的室温偶联中使用芳基氯化物。反应范围包括各种官能化的芳酸和芳基丙酸衍生物。
• Pd-PEPPSI-IPent^Cl: A Highly Effective Catalyst for the Selective Cross-Coupling of Secondary Organozinc Reagents
  作者：Matthew Pompeo、Robert D. J. Froese、Niloufar Hadei、Michael G. Organ

  DOI：10.1002/anie.201205747

  日期：2012.11.5

  of new N‐heterocyclic carbene based Pd complexes has been created and evaluated in the Negishi cross‐coupling of aryl and heteroaryl chlorides, bromides, and triflates with a variety of secondary alkylzinc reagents (see scheme). The direct elimination product is nearly exclusively formed; in most examples there is no migratory insertion at all.

  没有迁移吗？没问题！在芳基和杂芳基氯化物，溴化物和三氟甲磺酸与各种仲烷基锌试剂的Negishi交叉偶联中，已经创建并评估了一系列基于N杂环卡宾的新型Pd配合物（参见方案）。直接消除产物几乎是排他性的；在大多数示例中，根本没有迁移插入。
• [EN] SUBSTITUTED PYRAZOLO[1,5-A]PYRIMIDINE-7-AMINE COMPOUNDS AS CDK INHIBITORS AND THEIR THERAPEUTIC USE<br/>[FR] COMPOSÉS DE PYRAZOLO[1,5-A]PYRIMIDINE-7-AMINE SUBSTITUÉS EN TANT QU'INHIBITEURS DE CDK ET LEUR UTILISATION THÉRAPEUTIQUE
  申请人：CARRICK THERAPEUTICS LTD

  公开号：WO2022263604A1

  公开（公告）日：2022-12-22

  The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain substituted pyrazolo[1,5-a]pyrimidine-7-amine compounds PPA that, inter alia, inhibit cyclin-dependent protein kinases (CDKs), especially CDK12 and/or CDK13, and are selective, for example, for CDK12 and/or CDK13 as compared to CDK7. In addition to selectively inhibiting CDK12 and/or CDK13, the compounds also act as selective Cyclin K degraders thereby removing the key cofactor required for CDK12 and/or CDK13 activation; this confers additional cellular potency and selectivity. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CDK, especially CDK12 and/or CDK13; and to treat disorders including: disorders that are associated with CDK, especially CDK12 and/or CDK13; disorders that result from an inappropriate activity of a CDK, especially CDK12 and/or CDK13; disorders that are associated with CDK mutation, especially CDK12 and/or CDK13mutation; disorders that are associated with CDK overexpression, especially CDK12 and/or CDK13 overexpression; disorders that are associated with upstream pathway activation of CDK, especially CDK12 and/or CDK13; disorders that are ameliorated by the inhibition of CDK, especially CDK12 and/or CDK13; proliferative disorders; cancer; viral infections (including HIV); neurodegenerative disorders (including Alzheimer's disease and Parkinson's disease); ischaemia; renal diseases; cardiovascular disorders (including atherosclerosis); autoimmune disorders (including rheumatoid arthritis); and disorders caused by dysfunction of translation in cells (including muscular dystrophy). Optionally, the treatment further comprises treatment (e.g., simultaneous or sequential treatment) with a further active agent which is, e.g., a DNA repair inhibitor, an immune checkpoint inhibitor, an agent stimulating the immune system, a cell cycle checkpoint inhibitor, a Her2 blocker, a transcriptional inhibitor, a cytotoxic chemotherapeutic agent, etc.

  本发明涉及治疗化合物领域。更具体地说，本发明涉及某些取代的吡唑并[1,5-a]嘧啶-7-胺化合物PPA，这些化合物在抑制细胞周期依赖蛋白激酶（CDKs）方面具有选择性，特别是CDK12和/或CDK13，并且相对于CDK7具有选择性。除了选择性地抑制CDK12和/或CDK13外，这些化合物还作为选择性的Cyclin K降解剂，从而去除了CDK12和/或CDK13激活所需的关键辅因子；这赋予了额外的细胞效力和选择性。本发明还涉及包含这些化合物的制药组合物以及在体内外使用这些化合物和组合物来抑制CDK，特别是CDK12和/或CDK13，并治疗与CDK，特别是CDK12和/或CDK13相关的疾病，包括：由CDK，特别是CDK12和/或CDK13引起的疾病；由CDK突变，特别是CDK12和/或CDK13突变引起的疾病；由CDK过表达，特别是CDK12和/或CDK13过表达引起的疾病；由CDK上游通路激活，特别是CDK12和/或CDK13激活引起的疾病；由抑制CDK，特别是CDK12和/或CDK13抑制改善的增殖性疾病；癌症；病毒感染（包括艾滋病毒）；神经退行性疾病（包括阿尔茨海默病和帕金森病）；缺血；肾脏疾病；心血管疾病（包括动脉粥样硬化）；自身免疫性疾病（包括类风湿性关节炎）；以及由细胞翻译功能障碍引起的疾病（包括肌萎缩性侧索硬化症）。可选地，治疗还进一步包括与另一种活性剂的治疗（例如，同时或顺序治疗），该活性剂可以是DNA修复抑制剂、免疫检查点抑制剂、刺激免疫系统的剂、细胞周期检查点抑制剂、Her2阻断剂、转录抑制剂、细胞毒化学治疗剂等。
• Development of an Air-Stable, Broadly Applicable Nickel Source for Nickel-Catalyzed Cross-Coupling
  作者：Javier Magano、Sebastien Monfette

  DOI：10.1021/acscatal.5b00498

  日期：2015.5.1

  The synthesis of NiCl(o-tolyl)(TMEDA) (3; TMEDA = tetramethylethylenediamine) and its application in coupling reactions is described. In combination with a suitable ligand, precatalyst 3 was applied to a wide range of transformations, such as Suzuki, amination, Kumada, Negishi, Heck, borylation, and reductive coupling. Yields of products obtained with 3 are equal or superior to those obtained with common Ni sources such as Ni(cod)(2) (1) and NiCl2(dme) (2). Importantly, and unlike 1, complex 3 is stable for months in air as a solid, which eliminates the need for a glovebox and greatly facilitates the reaction setup. Thus, complex 3 is the first highly versatile Ni source that combines the broad applicability of 1 with the air stability of 2.