2,4-dichloro-5-ethoxyacetanilide | 65979-66-0

• 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: 2,4-dichloro-5-ethoxyacetanilide
• 英文别名: 4,6-dichloro-3-ethoxyacetanilide；5-Ethoxy-2,4-dichloracetanilid；N-(2,4-dichloro-5-ethoxyphenyl)acetamide
• CAS: 65979-66-0
• 化学式: C₁₀H₁₁Cl₂NO₂
• 分子量: 248.109
• InChiKey: IRERCDWUZFQCST-UHFFFAOYSA-N

物化性质

• 熔点：
  144.0 °C
• 沸点：
  391.1±42.0 °C(Predicted)
• 密度：
  1.327±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,4-dichloro-5-ethoxyacetanilide 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以88%的产率得到2,4-二氯-5-乙氧基苯胺
  参考文献：
  名称：

  Optimization of 4-Phenylamino-3-quinolinecarbonitriles as Potent Inhibitors of Src Kinase Activity

  摘要：

  Subsequent to the discovery of 4-[(2,4-dichlorophenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile (1a) as an inhibitor of Src kinase activity (IC50 = 30 nM), several additional analogues were prepared. Optimization of the C-4 anilino group of la led to le, which contains a 2,4-dichloro-5-methoxy-substituted aniline. Replacement of the methoxy group at C-7 of le with a 3-(morpholin-4-yl)propoxy group provided 2c, resulting in increased inhibition of both Src kinase activity and Src-mediated cell proliferation. Analogues of 2c, with other trisubstituted anilines at C-4 were also potent Src inhibitors, and the propoxy group of 2c was preferred over ethoxy, butoxy, or pentoxy. Replacement of the morpholine group of 2c with a 4-methylpiperazine group provided 31a, which had an IC50 of 1.2 nM in the Src enzymatic assay, an IC50 of 100 nM for the inhibition of Src-dependent cell proliferation and was selective for Src over non-Src family kinases. Compound 31a, which had higher 1 and 4 h plasma levels than 2c, effectively inhibited tumor growth in xenograft models.

  DOI：

  10.1021/jm0102250
• 作为产物：
  描述：

  3-乙氧基乙酰苯胺 在 benzyltrimethylazanium tetrachloro-λ³-iodanuide 、 溶剂黄146 作用下， 反应 24.0h， 以93%的产率得到2,4-dichloro-5-ethoxyacetanilide
  参考文献：
  名称：

  使用季铵多卤化物的卤化。二十四。用四氯碘酸苄基三甲基铵氯化乙酰苯胺

  摘要：

  在室温或 70°C 下，乙酰苯胺与计算量的四氯碘酸苄基三甲基铵在乙酸中的反应，选择性地以良好的产率得到所需的氯代乙酰苯胺。

  DOI：

  10.1246/bcsj.63.941

文献信息

• Solvent-free aromatic C–H functionalisation/halogenation reactions
  作者：Robin B. Bedford、Jens U. Engelhart、Mairi F. Haddow、Charlotte J. Mitchell、Ruth L. Webster

  DOI：10.1039/c0dt00385a

  日期：——

  The solvent-free, palladium-catalysed reaction of anilides with CuCl2 in the presence or absence of copper acetate yields ortho-chlorinated anilides in good to excellent yields, even on a large scale (100 mmol). By contrast, the equivalent reactions with copper bromide, either solvent free or in 1,2-dichloroethane, in the presence or absence of palladium, under air or inert conditions, gave the products

  无溶剂 钯催化的苯甲酸酯与 氯化铜2 在存在或不存在的情况下 醋酸铜即使大规模（100 mmol），也能以良好或优异的收率得到邻氯代苯甲酸酯。相比之下，与溴化铜，无溶剂或在 1,2-二氯乙烷，无论是否存在 钯在空气或惰性条件下，得到简单的亲电子溴化产物。机理研究突显了Palladacyclic中间体的参与，其中之一在结晶学上已得到表征，随后会与之发生反应。铜（II），氯化 产生氯化苯胺产品。
• Mild CH Halogenation of Anilides and the Isolation of an Unusual Palladium(I)-Palladium(II) Species
  作者：Robin B. Bedford、Mairi F. Haddow、Charlotte J. Mitchell、Ruth L. Webster

  DOI：10.1002/anie.201101606

  日期：2011.6.6

  Reducing the load: A facile palladium‐catalyzed ortho‐selective bromination and chlorination of anilides occurs under aerobic conditions at room temperature when N‐halosuccinimides (NXS) are used in the presence of p‐toluenesulfonic acid (PTSA). The orthopalladated PTSA complex is not only catalytically competent but also undergoes a reductive process to yield an unusual PdI–PdII tetramer (see structure;

  减少负荷：在有氧条件下，在对甲苯磺酸（PTSA）的存在下使用N-卤代琥珀酰亚胺（NXS）时，在室温下好氧条件下，钯的催化邻位溴化和氯离子氯化很容易进行。正统的PTSA配合物不仅具有催化能力，而且还经过还原过程生成不寻常的Pd I –Pd II四聚体（见结构； Pd绿色，O红色，S黄色和C灰色）。
• KAJIGAESHI, SHOJI;SHINMASU, YOICHI;FUJISAKI, SHIZUO;KAKINAMI, TAKAAKI, BULL. CHEM. SOC. JAP., 63,(1990) N, C. 941-943
  作者：KAJIGAESHI, SHOJI、SHINMASU, YOICHI、FUJISAKI, SHIZUO、KAKINAMI, TAKAAKI

  DOI：——

  日期：——
• WO2023/43803
  申请人：——

  公开号：——

  公开（公告）日：——
• Optimization of 4-Phenylamino-3-quinolinecarbonitriles as Potent Inhibitors of Src Kinase Activity
  作者：Diane H. Boschelli、Fei Ye、Yanong D. Wang、Minu Dutia、Steve L. Johnson、Biqi Wu、Karen Miller、Dennis W. Powell、Deanna Yaczko、Mairead Young、Mark Tischler、Kim Arndt、Carolyn Discafani、Carlo Etienne、Jay Gibbons、Janet Grod、Judy Lucas、Jennifer M. Weber、Frank Boschelli

  DOI：10.1021/jm0102250

  日期：2001.11.1

  Subsequent to the discovery of 4-[(2,4-dichlorophenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile (1a) as an inhibitor of Src kinase activity (IC50 = 30 nM), several additional analogues were prepared. Optimization of the C-4 anilino group of la led to le, which contains a 2,4-dichloro-5-methoxy-substituted aniline. Replacement of the methoxy group at C-7 of le with a 3-(morpholin-4-yl)propoxy group provided 2c, resulting in increased inhibition of both Src kinase activity and Src-mediated cell proliferation. Analogues of 2c, with other trisubstituted anilines at C-4 were also potent Src inhibitors, and the propoxy group of 2c was preferred over ethoxy, butoxy, or pentoxy. Replacement of the morpholine group of 2c with a 4-methylpiperazine group provided 31a, which had an IC50 of 1.2 nM in the Src enzymatic assay, an IC50 of 100 nM for the inhibition of Src-dependent cell proliferation and was selective for Src over non-Src family kinases. Compound 31a, which had higher 1 and 4 h plasma levels than 2c, effectively inhibited tumor growth in xenograft models.