2-azido-N-benzyl-N-methylacetamide | 1013663-31-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-azido-N-benzyl-N-methylacetamide
• 英文别名: 2-azido-N-methyl-N-(phenylmethyl)acetamide
• CAS: 1013663-31-4
• 化学式: C₁₀H₁₂N₄O
• 分子量: 204.231
• InChiKey: PJDKQGOYUWTLLZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  34.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-azido-N-benzyl-N-methylacetamide 在 盐酸 、 copper(ll) sulfate pentahydrate 、 sodium ascorbate 、 三乙胺 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 叔丁醇 为溶剂， 反应 8.0h， 生成 N-benzyl-2-(4-{[(7-chloroquinolin-4-yl)amino]methyl}-1H-1,2,3-triazol-1-yl)-N-methylacetamide
  参考文献：
  名称：

  In vitro antimalarial activity, β-haematin inhibition and structure–activity relationships in a series of quinoline triazoles

  摘要：

  A novel series of quinoline triazole amide analogues (38-51) has been synthesized. Analogues 38-44 had a Cl substituent at the 7-position of the quinoline ring, while 45-51 had a CN substituent at this position. Compounds 40,45 and 49 were found to be the most active in the series against the Plasmodium falciparum chloroquine-sensitive D10 strain, with IC50 values in the range of 349-1247 nM, with 40 and 45, but not 49 also exhibiting similar activity against the chloroquine-resistant 1(1 strain of parasite. Quinoline triazoles 40 and 44 were the most active beta-haematin inhibitors, with 50% inhibitory concentrations of 14.7 and 8.9 1tM respectively. In vitro antimalarial activity of the 7-C1 bearing analogues 38 -44 exhibited a strong linear dependence of log(1/IC50) on log P. Thus, the more lipophilic, the more active it was found be. The 7-CN series 45-51 showed no such dependence. The resistance index (IC50 K1 /IC50 D10) also exhibited a linear dependence on log P, with a substantially steeper slope in the case of the 7-CI series. The findings demonstrate the feasibility of producing hydrophilic analogues with strong activity and low cross-resistance with chloroquine. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.08.046
• 作为产物：
  描述：

  N-苄基-2-氯-N-甲基乙酰胺 在 sodium azide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2-azido-N-benzyl-N-methylacetamide
  参考文献：
  名称：

  In vitro antimalarial activity, β-haematin inhibition and structure–activity relationships in a series of quinoline triazoles

  摘要：

  A novel series of quinoline triazole amide analogues (38-51) has been synthesized. Analogues 38-44 had a Cl substituent at the 7-position of the quinoline ring, while 45-51 had a CN substituent at this position. Compounds 40,45 and 49 were found to be the most active in the series against the Plasmodium falciparum chloroquine-sensitive D10 strain, with IC50 values in the range of 349-1247 nM, with 40 and 45, but not 49 also exhibiting similar activity against the chloroquine-resistant 1(1 strain of parasite. Quinoline triazoles 40 and 44 were the most active beta-haematin inhibitors, with 50% inhibitory concentrations of 14.7 and 8.9 1tM respectively. In vitro antimalarial activity of the 7-C1 bearing analogues 38 -44 exhibited a strong linear dependence of log(1/IC50) on log P. Thus, the more lipophilic, the more active it was found be. The 7-CN series 45-51 showed no such dependence. The resistance index (IC50 K1 /IC50 D10) also exhibited a linear dependence on log P, with a substantially steeper slope in the case of the 7-CI series. The findings demonstrate the feasibility of producing hydrophilic analogues with strong activity and low cross-resistance with chloroquine. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.08.046

文献信息

• Catalytic Enantioselective Intramolecular C(sp ³ )−H Amination of 2‐Azidoacetamides
  作者：Zijun Zhou、Shuming Chen、Jie Qin、Xin Nie、Xingwen Zheng、Klaus Harms、Radostan Riedel、K. N. Houk、Eric Meggers

  DOI：10.1002/anie.201811927

  日期：2019.1.21

  An enantioselective ring‐closing C(sp3)−H amination of 2‐azidoacetamides is catalyzed by a chiral‐at‐metal ruthenium complex and provides chiral imidazolidin‐4‐ones in 31–95 % yield, with enantioselectivities of up to 95 % ee, and at catalyst loadings down to 0.1 mol % (turnover number (TON)=740). To our knowledge, this is the first example of a highly enantioselective C(sp3)−H amination with aliphatic

  手性金属钌配合物催化2-叠氮基乙酰胺的对映选择性闭环C（sp 3）-H胺化反应，提供手性咪唑啉丁-4-酮，产率为31-95％，对映选择性高达95％ee，并且催化剂负载量低至0.1 mol％（周转数（TON）= 740）。据我们所知，这是用脂肪族叠氮化物进行高对映选择性的C（sp 3）-H胺化反应的第一个例子。机理实验揭示了酰胺基的重要性，这大概可以使2-叠氮基乙酰胺与催化剂进行初步的双齿配位。DFT计算表明，导致主要对映异构体的过渡态具有更好的空间适应性，并且在底物和催化剂骨架之间具有良好的π-π堆积。
• Acceleration of 1,3-Dipolar Cycloadditions by Integration of Strain and Electronic Tuning
  作者：Jesús M. Dones、Nile S. Abularrage、Namrata Khanal、Brian Gold、Ronald T. Raines

  DOI：10.1021/jacs.1c03133

  日期：2021.6.30

  α-azidoacetamides and α-diazoacetamides than its constitutional isomer, dibenzoazacyclooctyne (DIBAC). ABC and DIBAC have comparable chemical stability in a biomimetic solution. Both ABC and DIBO are accessible in three steps by the alkylidene carbene-mediated ring expansion of commercial cycloheptanones. Our findings enhance the accessibility and utility of 1,3-dipolar cycloadditions and encourage further innovation

  叠氮化物和炔烃之间的 1,3-偶极环加成为探测和控制生物过程提供了新的方法。一个主要挑战是使用稳定的试剂实现高反应速率。炔基试剂的优化依赖于两种策略：增加应变和调整电子。我们报告了这些策略的整合。计算分析表明，二苯并环辛炔 (DIBO) 中的 CH → N 芳基取代可能是有益的。在过渡态中，2-氮杂苯并-苯并环辛炔 (ABC) 的氮与 α-叠氮基乙酰胺的 C=O 发生 n→π* 相互作用，并与 α-重氮乙酰胺的 N-H 形成氢键。这些偶极特异性相互作用与应变 π 键的电子激活协同作用以增加反应性。我们发现 ABC 确实比其结构异构体二苯并氮杂环辛炔 (DIBAC) 与 α-叠氮基乙酰胺和 α-重氮乙酰胺反应更快。ABC 和 DIBAC 在仿生溶液中具有相当的化学稳定性。ABC 和 DIBO 都可以通过亚烷基卡宾介导的商业环庚酮的扩环分三步获得。我们的研究结果提高了 1,3-偶极环加成的可及性和实用性，并鼓励进一步的创新。
• Synthesis of Staudinger-type Molecular Probe for Catch-and-release Purification of the Binding Protein for Potassium Isolespedezate, a Leaf-closing Substance of Leguminous Plant
  作者：Tomohiko Fujii、Nobuki Kato、Izumi Iwakura、Yoshiyuki Manabe、Minoru Ueda

  DOI：10.1246/cl.2008.52

  日期：2008.1.5

  We synthesized azide-containing photoaffinity probe 1 based on the structure of potassium isolespedezate. This probe can be used for catch-and-release-mechanism purification of binding protein for 1: photo-crosslinking with 1 gave azide-labeled receptor which can be captured by phosphane-linked gel matrix by the Staudinger ligation. After washing the gel, the caught binding protein can be released by the reductive cleavage of disulfide bond in 1. This process can be used as a convenient method for the purification of binding protein for bioactive natural product.

  我们根据异双哌酸钾的结构合成了含叠氮化物的光亲和探针1。该探针可用于结合蛋白的捕获和释放机制纯化，与 1 个给定叠氮化物标记的受体进行 1: 光交联，该受体可通过 Staudinger 连接被磷烷连接的凝胶基质捕获。洗涤凝胶后，捕获的结合蛋白可通过1中二硫键的还原断裂而释放。该过程可作为纯化具有生物活性的天然产物的结合蛋白的便捷方法。
• Cyclooctynes for click chemistry
  申请人：Massachusetts Institute of Technology

  公开号：US11377424B1

  公开（公告）日：2022-07-05

  Provided herein are dibenzocyclooctyne compounds useful as reagents in 1,3-dipolar cycloaddition reactions, and methods for their preparation.

  本文提供了二苯并环辛炔化合物，可用作1,3-二极体环加成反应的试剂，并提供了它们的制备方法。
• CYCLOOCTYNES FOR CLICK CHEMISTRY
  申请人：Massachusetts Institute of Technology

  公开号：US20220402876A1

  公开（公告）日：2022-12-22

  Provided herein are dibenzocyclooctyne compounds useful as reagents in 1,3-dipolar cycloaddition reactions, and methods for their preparation.