methyl 3-(azidocarbonyl)benzoate

• 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: methyl 3-(azidocarbonyl)benzoate
• 英文别名: 3-(methylcarboxy)benzoyl azide；Methyl 3-carbonazidoylbenzoate；methyl 3-carbonazidoylbenzoate
• 化学式: C₉H₇N₃O₃
• 分子量: 205.173
• InChiKey: HETAOLNHJUSWQZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  57.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 3-(azidocarbonyl)benzoate 以 甲苯 为溶剂， 反应 2.0h， 生成 3-(甲氧基羰基)异氰酸苯酯
  参考文献：
  名称：

  Tyrosine Kinase Inhibitors. 4. Structure-Activity Relationships among N- and 3-Substituted 2,2'-Dithiobis(1H-indoles) for in vitro Inhibition of Receptor and Nonreceptor Protein Tyrosine Kinases

  摘要：

  A series of S-substituted 2,2'-dithiobis(1H-indoles) were synthesized and evaluated for their ability to inhibit the tyrosine kinase activity of both the epidermal growth factor receptor (EGFR) and the nonreceptor pp60(v-src) tyrosine kinase, to extend the available structure-activity relationships for this series. The majority of the compounds were prepared either by reaction of 2-chloro-1-methylindole-3-carbonyl chloride with amines, followed by thiomethylation, demethylation, and oxidative dimerization, or by reaction of isocyanates with the anion of 1-methyl-2-indolinethione followed by dimerization. Overall, inhibitory activity is retained by analogues having a wide variety of side chains. A series of 3-carboxamide analogues had moderate to good activity against isolated EGFR (IC(50)s 1-20 mu M), with monoalkyl substitution of the carboxamide being optimal. Polar side chains were generally less effective than lipophilic ones, with benzyl being particularly effective. However, N,N-disubstitution was the most effective pattern for inhibition of pp60(v-src). A variety of substituted N-phenylcarboxamides had lower activity against EGFR than the parent derivative, and a N-thienylcarboxamide also had low activity. A series of 3-ketones, including methyl, phenyl, and furyl derivatives, showed moderate activity against the pp60(v-src) kinase, but were less effective against EGFR. The mechanism of inhibition of both kinases by these drugs was shown to be noncompetitive with respect to both ATP and peptide substrate. Selected compounds inhibited the growth of Swiss 3T3 cells with IC(50)s in the low micromolar range and inhibited bFGF-mediated intracellular tyrosine phosphorylation in the same cell line. Thiol inhibits the effects of the compounds, suggesting that one possible mechanism of inhibition is thiol-disulfide exchange with thiol-containing residues in the catalytic sites. Crystal structures of two representative compounds show a folded, V-shaped structure, with the disulfide bridge exposed, consistent with this hypothesis.

  DOI：

  10.1021/jm00001a011
• 作为产物：
  描述：

  3-(氯羰基)苯甲酸甲酯 在 sodium azide 作用下， 生成 methyl 3-(azidocarbonyl)benzoate
  参考文献：
  名称：

  使用修饰的斯托丁格反应合成酰基磷酸氨基甲酸酯

  摘要：

  在改良的施陶丁格反应中，采用三甲基甲硅烷基氯作为活化剂，已经开发了由多种官能化的酰基叠氮化物一步合成酰基氨基磷酸酯的方法。该方法进一步适于包括从多种选择的羧酸和酰肼起始合成子中原位产生酰基叠氮化物。反应范围扩大到包括亚氨基二磷酸酯和天然产物Microcin C的合成。

  DOI：

  10.1021/acs.orglett.0c03987

文献信息

• Visible light C–H amidation of heteroarenes with benzoyl azides
  作者：E. Brachet、T. Ghosh、I. Ghosh、B. König

  DOI：10.1039/c4sc02365j

  日期：——

  direct and atom economic C–H amidation of electron rich heteroarenes in the presence of phosphoric acid, a photocatalyst and visible light. Hetero-aromatic amides are obtained in good yields at very mild reaction conditions with dinitrogen as the only by-product. The reaction allows the use of aryl-, heteroaryl- or alkenyl acyl azides and has a wide scope for heteroarenes, including pyrroles, indole

  在磷酸，光催化剂和可见光的存在下，苯甲酰叠氮用于富电子的杂芳烃的直接和原子经济的CHH酰胺化反应。杂芳族酰胺是在非常温和的反应条件下以高收率获得的，二氮是唯一的副产物。该反应允许使用芳基，杂芳基或烯基酰基叠氮化物，并具有广泛的杂芳烃范围，包括吡咯，吲哚，呋喃，苯并呋喃和噻吩，具有良好的区域选择性和产率。
• Synthesis of 7-Azaindole Amidated Derivatives: An Efficient Usage of Acyl Azides as the Nitrogen Source
  作者：Wei-Huan Li、Lin Dong

  DOI：10.1002/adsc.201701336

  日期：2018.3.20

  The dual behaviour of acyl azides in transition‐metal‐catalyzed direct C−H amidation is investigated. Variously substituted acyl azides reacted smoothly with 7‐azaindoles providing a diversity of C−C or C−N 7‐azaindole amidated derivatives. This amidation reaction shows an excellent controllability, which is believed to be dependent on catalyst system.

  研究了酰基叠氮化物在过渡金属催化的直接CH H酰胺化反应中的双重行为。各种取代的酰基叠氮化物可与7-氮杂吲哚平稳反应，从而提供各种C-C或C-N 7-氮杂吲哚酰胺化衍生物。该酰胺化反应显示出优异的可控制性，据信这取决于催化剂体系。
• Synthesis of Acyl Phosphoramidates Employing a Modified Staudinger Reaction
  作者：Iain Currie、Brad E. Sleebs

  DOI：10.1021/acs.orglett.0c03987

  日期：2021.1.15

  A one-step synthesis of acyl phosphoramidates from a variety of functionalized acyl azides has been developed employing trimethylsilyl chloride as an activating agent in a modified Staudinger reaction. The methodology was further adapted to include the in situ generation of the acyl azides from a diverse selection of carboxylic acids and hydrazide starting synthons. The reaction scope was extended

  在改良的施陶丁格反应中，采用三甲基甲硅烷基氯作为活化剂，已经开发了由多种官能化的酰基叠氮化物一步合成酰基氨基磷酸酯的方法。该方法进一步适于包括从多种选择的羧酸和酰肼起始合成子中原位产生酰基叠氮化物。反应范围扩大到包括亚氨基二磷酸酯和天然产物Microcin C的合成。
• Tyrosine Kinase Inhibitors. 4. Structure-Activity Relationships among N- and 3-Substituted 2,2'-Dithiobis(1H-indoles) for in vitro Inhibition of Receptor and Nonreceptor Protein Tyrosine Kinases
  作者：Brian D. Palmer、Gordon W. Rewcastle、Andrew M. Thompson、Maruta Boyd、H. D. Hollis Showalter、Anthony D. Sercel、David W. Fry、Alan J. Kraker、William A. Denny

  DOI：10.1021/jm00001a011

  日期：1995.1

  A series of S-substituted 2,2'-dithiobis(1H-indoles) were synthesized and evaluated for their ability to inhibit the tyrosine kinase activity of both the epidermal growth factor receptor (EGFR) and the nonreceptor pp60(v-src) tyrosine kinase, to extend the available structure-activity relationships for this series. The majority of the compounds were prepared either by reaction of 2-chloro-1-methylindole-3-carbonyl chloride with amines, followed by thiomethylation, demethylation, and oxidative dimerization, or by reaction of isocyanates with the anion of 1-methyl-2-indolinethione followed by dimerization. Overall, inhibitory activity is retained by analogues having a wide variety of side chains. A series of 3-carboxamide analogues had moderate to good activity against isolated EGFR (IC(50)s 1-20 mu M), with monoalkyl substitution of the carboxamide being optimal. Polar side chains were generally less effective than lipophilic ones, with benzyl being particularly effective. However, N,N-disubstitution was the most effective pattern for inhibition of pp60(v-src). A variety of substituted N-phenylcarboxamides had lower activity against EGFR than the parent derivative, and a N-thienylcarboxamide also had low activity. A series of 3-ketones, including methyl, phenyl, and furyl derivatives, showed moderate activity against the pp60(v-src) kinase, but were less effective against EGFR. The mechanism of inhibition of both kinases by these drugs was shown to be noncompetitive with respect to both ATP and peptide substrate. Selected compounds inhibited the growth of Swiss 3T3 cells with IC(50)s in the low micromolar range and inhibited bFGF-mediated intracellular tyrosine phosphorylation in the same cell line. Thiol inhibits the effects of the compounds, suggesting that one possible mechanism of inhibition is thiol-disulfide exchange with thiol-containing residues in the catalytic sites. Crystal structures of two representative compounds show a folded, V-shaped structure, with the disulfide bridge exposed, consistent with this hypothesis.