methyl 2-(2,6-dichlorophenyl)acrylate | 1203555-33-2

• 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 2-(2,6-dichlorophenyl)acrylate
• 英文别名: methyl 2-(2,6-dichlorophenyl)prop-2-enoate
• CAS: 1203555-33-2
• 化学式: C₁₀H₈Cl₂O₂
• 分子量: 231.078
• InChiKey: AUMSGBUAXMTMTE-UHFFFAOYSA-N

物化性质

• 熔点：
  47-48 °C
• 沸点：
  327.3±32.0 °C(Predicted)
• 密度：
  1.289±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  methyl 2-(2,6-dichlorophenyl)acrylate 在 sodium methylate 、 sodium hydride 作用下， 以 甲醇 、 二甲基亚砜 、 mineral oil 为溶剂， 反应 5.0h， 生成 4-amino-6-(2,6-dichlorophenyl)-8-methyl-2-(phenylamino)pyrido[2,3-d]pyrimidin-7(8H)-one
  参考文献：
  名称：

  4-Amino-2-arylamino-6-(2,6-dichlorophenyl)-pyrido[2,3-d]pyrimidin-7-(8H)-ones as BCR kinase inhibitors for B lymphoid malignancies

  摘要：

  A new family of 4-aminopyrido[2,3-d]pyrimidines active against non-Hodgkin's lymphomas (NHLs) is described. Among these compounds, 19 inhibits the most upstream tyrosine kinases in the B cell receptor (BCR) signaling pathway which are involved in the mature B cell neoplasms. Thus, 19 showed anti-proliferative activity at 24 h and 48 h against a panel of 20 NHLs cell lines with GI(50) ranging from 1.3 to 6.91 mu M at 24 h, and 1.4-7.2 mu M at 48 h, being this effect related to a significant (20-90%) inhibition of the phosphorylation of the BCR-related kinases Btk, Syk, and Lyn. Most importantly, 19 was able to induce a 63% reduction in Rec-1 cell proliferation, which was significantly greater than the 31% and 3% blockade of proliferation observed after cell treatment with R406, a Syk inhibitor, and ibrutinib, a Btk inhibitor, respectively. The computational blind docking and ligand binding within the pockets of Btk, Syk and Lyn kinases showed that compound 19 presents the same kind of interactions of described cocrystallized inhibitors. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.09.018
• 作为产物：
  描述：

  聚合甲醛 、 2,6-二氯苯乙酸甲酯 在 potassium carbonate 、 calcium oxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以94%的产率得到methyl 2-(2,6-dichlorophenyl)acrylate
  参考文献：
  名称：

  3,3-二甲氧基丙烷腈对2-芳基丙烯酸酯的不寻常迈克尔加成：通往4-未取代的5,6-二氢吡啶并[2,3- d ]嘧啶的便捷途径

  摘要：

  2-芳基取代的丙烯酸酯和3,3-二甲氧基丙腈之间的不寻常的迈克尔加成，这取决于反应温度（分别为60或-78°C），导致生成4-甲氧基亚甲基取代的4-氰基丁酸酯或描述了4-二甲氧基甲基4-氰基丁酸酯。在微波辐射下用胍系统处理后，这些化合物可随后转化为4-未取代的吡啶并[2,3- d ]嘧啶。

  DOI：

  10.1021/jo902345r

文献信息

• Design, synthesis and biological evaluation of pyrido[2,3-d]pyrimidin-7-(8H)-ones as HCV inhibitors
  作者：Marta Camarasa、Raimon Puig de la Bellacasa、Àlex L. González、Raül Ondoño、Roger Estrada、Sandra Franco、Roger Badia、José Esté、Miguel Ángel Martínez、Jordi Teixidó、Bonaventura Clotet、José I. Borrell

  DOI：10.1016/j.ejmech.2016.03.055

  日期：2016.6

  design and selection of a combinatorial library of pyrido[2,3-d]pyrimidin-7(8H)-ones (4) has allowed the synthesis of 121 compounds, using known and new synthetic methodologies, and the evaluation of the inhibitory activity against hepatitis C virus (HCV) genotype 1b replicon. Among these compounds, 214,10} and 242,10} presented very high activities [EC50 = 0.027 μM (CC50 = 5.3 μM) and EC50 = 0.034 μM

  吡啶并[2,3 - d ]嘧啶-7（8 H）-ones（4）的组合文库的设计和选择已允许使用已知的和新的合成方法合成121种化合物，并对其抑制性进行评估抗丙型肝炎病毒（HCV）基因型1b复制子的活性。在这些化合物中，21 4,10 }和24 2,10 }表现出非常高的活性[分别为EC 50  = 0.027μM（CC 50  = 5.3μM）和EC 50  = 0.034μM（CC 50  = 13.5μM）]和高选择性指数196和397。这些值类似于EC 50索非布韦（2）（0.048μM ）使用相似的方法学方法和相同的病毒亚型报道。21 4,10 }和24 2,10 }是通过比sofosbuvir短的合成路线而获得的，而24 2,10 }是非手性的，与sofosbuvir具有4个立体生成中心相反。计算机研究表明21 4,10 }和24 2,10 }通过变构位点结合抑制NS5B聚合酶。
• 4-Amino-2-arylamino-6-(2,6-dichlorophenyl)-pyrido[2,3-d]pyrimidin-7-(8H)-ones as BCR kinase inhibitors for B lymphoid malignancies
  作者：Raimon Puig de la Bellacasa、Gaël Roué、Patricia Balsas、Patricia Pérez-Galán、Jordi Teixidó、Dolors Colomer、José I. Borrell

  DOI：10.1016/j.ejmech.2014.09.018

  日期：2014.10

  A new family of 4-aminopyrido[2,3-d]pyrimidines active against non-Hodgkin's lymphomas (NHLs) is described. Among these compounds, 19 inhibits the most upstream tyrosine kinases in the B cell receptor (BCR) signaling pathway which are involved in the mature B cell neoplasms. Thus, 19 showed anti-proliferative activity at 24 h and 48 h against a panel of 20 NHLs cell lines with GI(50) ranging from 1.3 to 6.91 mu M at 24 h, and 1.4-7.2 mu M at 48 h, being this effect related to a significant (20-90%) inhibition of the phosphorylation of the BCR-related kinases Btk, Syk, and Lyn. Most importantly, 19 was able to induce a 63% reduction in Rec-1 cell proliferation, which was significantly greater than the 31% and 3% blockade of proliferation observed after cell treatment with R406, a Syk inhibitor, and ibrutinib, a Btk inhibitor, respectively. The computational blind docking and ligand binding within the pockets of Btk, Syk and Lyn kinases showed that compound 19 presents the same kind of interactions of described cocrystallized inhibitors. (C) 2014 Elsevier Masson SAS. All rights reserved.
• An Unusual Michael Addition of 3,3-Dimethoxypropanenitrile to 2-Aryl Acrylates: A Convenient Route to 4-Unsubstituted 5,6-Dihydropyrido[2,3-<i>d</i>]pyrimidines
  作者：Xavier Berzosa、Xavier Bellatriu、Jordi Teixidó、José I. Borrell

  DOI：10.1021/jo902345r

  日期：2010.1.15

  An unusual Michael addition between 2-aryl-substituted acrylates and 3,3-dimethoxypropanenitrile which leads, depending on the reaction temperature (60 or −78 °C, respectively), to a 4-methoxymethylene-substituted 4-cyanobutyric ester or to a 4-dimethoxymethyl 4-cyanobutyric ester is described. These compounds can be subsequently converted to 4-unsubstituted pyrido[2,3-d]pyrimidines upon treatment

  2-芳基取代的丙烯酸酯和3,3-二甲氧基丙腈之间的不寻常的迈克尔加成，这取决于反应温度（分别为60或-78°C），导致生成4-甲氧基亚甲基取代的4-氰基丁酸酯或描述了4-二甲氧基甲基4-氰基丁酸酯。在微波辐射下用胍系统处理后，这些化合物可随后转化为4-未取代的吡啶并[2,3- d ]嘧啶。