methyl 3-bromo-4-(3-isopropoxy-4-methoxyphenyl)-5-(4-isopropoxy-3-methoxyphenyl)-1H-pyrrole-2-carboxylate | 1519002-16-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: methyl 3-bromo-4-(3-isopropoxy-4-methoxyphenyl)-5-(4-isopropoxy-3-methoxyphenyl)-1H-pyrrole-2-carboxylate
• 英文别名: methyl 3-bromo-5-(3-methoxy-4-propan-2-yloxyphenyl)-4-(4-methoxy-3-propan-2-yloxyphenyl)-1H-pyrrole-2-carboxylate
• CAS: 1519002-16-4
• 化学式: C₂₆H₃₀BrNO₆
• 分子量: 532.431
• InChiKey: ZQMOKNUPUIZUJQ-UHFFFAOYSA-N

物化性质

• 沸点：
  583.3±50.0 °C(Predicted)
• 密度：
  1.282±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  79
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 3-bromo-4-(3-isopropoxy-4-methoxyphenyl)-5-(4-isopropoxy-3-methoxyphenyl)-1H-pyrrole-2-carboxylate 在 1,1'-双(二苯基膦)二茂铁 、 三氟甲磺酸三甲基硅酯 、 sodium carbonate 、 caesium carbonate 、 对甲苯磺酸 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 作用下， 以 甲醇 、 乙二醇二甲醚 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 59.75h， 生成 3,11-diisopropoxy-14-(3-isopropoxy-4-methoxyphenyl)-2,12-dimethoxy-9-(phenylsulfanyl)-8,9-dihydro-6H-[1]-benzopyrano[4′,3′:4,5]pyrrolo[2,1-a]isoquinolin-6-one
  参考文献：
  名称：

  Modular Synthesis of Lamellarins via Regioselective Assembly of 3,4,5-Differentially Arylated Pyrrole-2-carboxylates

  摘要：

  A modular synthesis of lamellarins via 3,4,5-differentially arylated pyrrole-2-carboxylate intermediates has been developed. The key reactions employed are Br-Li exchange-methoxycarbonylation of 2,5-dibromo-1-(tert-butoxycarbonyl)-1H-pyrrole (1) followed by palladium-catalyzed iterative Suzuki-Miyaura coupling of the pyrrole core. The 3,4,5-triarylpyrrole 4 thus synthesized was readily converted to 5,6-saturated lamellarin L (2) and 5,6-unsaturated lamellarin N (3) via lactonization followed by annulation of the pyrrole nitrogen and lateral aromatic ring at C5 using 2-bromoethyl phenyl sulfide or bromoacetaldehyde dimethyl acetal as two-carbon homologation agents. In principle, this strategy allows the production of diverse lamellarins in short steps with high yields using readily accessible arylboronic acids as aromatic modules.

  DOI：

  10.1021/jo402181w
• 作为产物：
  描述：

  3-异丙氧基-4-甲氧基苯硼酸 在 N-溴代丁二酰亚胺(NBS) 、 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 methyl 3-bromo-4-(3-isopropoxy-4-methoxyphenyl)-5-(4-isopropoxy-3-methoxyphenyl)-1H-pyrrole-2-carboxylate
  参考文献：
  名称：

  Modular Synthesis of Lamellarins via Regioselective Assembly of 3,4,5-Differentially Arylated Pyrrole-2-carboxylates

  摘要：

  A modular synthesis of lamellarins via 3,4,5-differentially arylated pyrrole-2-carboxylate intermediates has been developed. The key reactions employed are Br-Li exchange-methoxycarbonylation of 2,5-dibromo-1-(tert-butoxycarbonyl)-1H-pyrrole (1) followed by palladium-catalyzed iterative Suzuki-Miyaura coupling of the pyrrole core. The 3,4,5-triarylpyrrole 4 thus synthesized was readily converted to 5,6-saturated lamellarin L (2) and 5,6-unsaturated lamellarin N (3) via lactonization followed by annulation of the pyrrole nitrogen and lateral aromatic ring at C5 using 2-bromoethyl phenyl sulfide or bromoacetaldehyde dimethyl acetal as two-carbon homologation agents. In principle, this strategy allows the production of diverse lamellarins in short steps with high yields using readily accessible arylboronic acids as aromatic modules.

  DOI：

  10.1021/jo402181w

文献信息

• Design, synthesis, and evaluation of A-ring-modified lamellarin N analogues as noncovalent inhibitors of the EGFR T790M/L858R mutant
  作者：Tsutomu Fukuda、Teppei Umeki、Keiji Tokushima、Gao Xiang、Yuki Yoshida、Fumito Ishibashi、Yusuke Oku、Naoyuki Nishiya、Yoshimasa Uehara、Masatomo Iwao

  DOI：10.1016/j.bmc.2017.10.030

  日期：2017.12

  series of A-ring-modified lamellarin N analogues were designed, synthesized, and evaluated as potential noncovalent inhibitors of the EGFR T790M/L858R mutant, a causal factor in the drug-resistant non-small cell lung cancer. Several water-soluble ammonium- or guanidinium-tethered analogues exhibited good kinase inhibitory activities. The most promising analogue, 14f, displayed an excellent inhibitory

  设计，合成和评估了一系列A环修饰的lamellarin N类似物，作为EGFR T790M / L858R突变体的潜在非共价抑制剂，EGFR T790M / L858R突变体是耐药性非小细胞肺癌的致病因素。几种水溶性铵盐或胍盐系的类似物表现出良好的激酶抑制活性。最有前途的类似物14f对T790M / L858R突变体表现出优异的抑制作用[IC 50（WT）= 31.8 nM; IC 50（T790M / L858R）= 8.9 nM]。通过对接研究合理化了A环取代基对活性的影响。
• FOURTH-GENERATION EGFR TYROSINE KINASE INHIBITOR
  申请人：NAGASAKI UNIVERSITY

  公开号：US20210122759A1

  公开（公告）日：2021-04-29

  Provided is a compound having a tyrosine kinase inhibitory activity specific to C797S resistant mutant EGFR (particularly C797S tertiary-resistant mutant EGFR) and is useful as a C797S resistant mutant EGFR (particularly C797S mutant tertiary-resistant EGFR) specific tyrosine kinase inhibitor, an agent for preventing and/or treating non-small cell lung cancer with resistance mutant EGFR and the like, and the like. A compound represented by the formula (I): wherein X is O or NH, R 1 and R 2 are each independently a hydrogen atom or an optionally substituted hydrocarbon group; R 3 and R 4 are each independently a hydrogen atom, a halogen atom or an optionally substituted hydrocarbon group, and R 5 and R 6 are each independently an optionally substituted hydrocarbon group, excluding the following compounds: or a salt thereof.

  提供一种具有特异性抑制C797S耐药突变EGFR的酪氨酸激酶抑制活性的化合物（特别是C797S三级耐药突变EGFR），并且可用作C797S耐药突变EGFR（特别是C797S突变三级耐药EGFR）特异性酪氨酸激酶抑制剂，用于预防和/或治疗具有耐药突变EGFR的非小细胞肺癌等药剂等。一种由以下式（I）表示的化合物：其中X为O或NH，R1和R2分别为氢原子或可选择取代的碳氢基团；R3和R4分别为氢原子、卤素原子或可选择取代的碳氢基团，而R5和R6分别为可选择取代的碳氢基团，但不包括以下化合物：或其盐。