methyl 2-bromo-1H-indole-6-carboxylate | 1240045-34-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: methyl 2-bromo-1H-indole-6-carboxylate
• CAS: 1240045-34-4
• 化学式: C₁₀H₈BrNO₂
• 分子量: 254.083
• InChiKey: OJTIJVJZLDVMSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  42.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  methyl 2-bromo-1H-indole-6-carboxylate 在 tetrahydroxyborate 、 XPhos Pd G2 、 potassium acetate 、 Selectfluor 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 24.0h， 生成 methyl 2-(4-amino-1-(tert-butyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-3-fluoro-1H-indole-6-carboxylate
  参考文献：
  名称：

  [EN] HETEROCYCLIC COMPOUNDS AS RET KINASE INHIBITORS
  [FR] COMPOSÉS HÉTÉROCYCLIQUES UTILISÉS EN TANT QU'INHIBITEURS DE KINASE RET

  摘要：

  本发明涉及具有以下结构的Formula I化合物，其作为RET（重排基因转座）激酶酶活性的抑制剂：其中HET，键a、b、c和d，X1、X2、X3、X4、R2和R3在此处各自定义。本发明还涉及制备这些化合物的方法，包括它们的药物组合物，以及它们在治疗增殖性疾病（如癌症）以及其他涉及RET激酶活性的疾病或症状中的用途。

  公开号：

  WO2017178844A1
• 作为产物：
  描述：

  3-氨基-4-(2,2-二溴乙烯基)-苯甲酸甲酯 在 copper(I) iodide 、 sodium hydroxide 作用下， 以 水 为溶剂， 反应 15.0h， 以72%的产率得到methyl 2-bromo-1H-indole-6-carboxylate
  参考文献：
  名称：

  Application of nanoparticle mediated N-arylation of amines for the synthesis of pharmaceutical entities using vit-E analogues as amphiphiles in water

  摘要：

  首次在水中开发了以维生素E类似物为两性分子的CuI纳米颗粒催化的胺的分子内和分子间N-芳基化反应，并扩展到唑类化合物、取代吲哚、生物活性天然产物和药物实体的中间体。

  DOI：

  10.1039/c4ra15267k

文献信息

• The facile synthesis of 2-bromoindoles via Cs₂CO₃-promoted intramolecular cyclization of 2-(gem-dibromovinyl)anilines under transition-metal-free conditions
  作者：Pinhua Li、Yong Ji、Wei Chen、Xiuli Zhang、Lei Wang

  DOI：10.1039/c2ra22172a

  日期：——

  2-Bromoindoles were readily prepared through a facile Cs2CO3-promoted intramolecular cyclization of 2-(gem-bromovinyl)-N-methylsulfonylanilines in excellent yields under transition-metal-free conditions. This methodology could be extended to the synthesis of corresponding 2-chloroindoles. The reaction mechanism suggested that cyclization occurs through a key intermediate, phenylethynyl bromide, followed by cyclization in one-pot.

  在不含过渡金属的条件下，通过 Cs2CO3 促进的 2-(偕溴乙烯基)-N-甲基磺酰基苯胺的分子内环化，可以轻松制备 2-溴吲哚，收率优异。该方法可以扩展到相应的 2-氯吲哚的合成。反应机理表明，环化是通过关键中间体苯乙炔基溴发生的，然后是一锅环化。
• Heterocyclic compounds as ret kinase inhibitors
  申请人：Cancer Research Technology Limited

  公开号：US10954241B2

  公开（公告）日：2021-03-23

  The present invention relates to compounds of Formula I that function as inhibitors of RET (rearranged during transfection) kinase enzyme activity: wherein HET, bonds a, b, c and d, X1, X2, X3, X4, R2, and R3 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which RET kinase activity is implicated.

  本发明涉及作为 RET（转染过程中重排）激酶酶活性抑制剂的式 I 化合物： 其中HET、键a、b、c和d、X1、X2、X3、X4、R2和R3各自如本文所定义。本发明还涉及这些化合物的制备工艺、包含这些化合物的药物组合物，以及它们在治疗增殖性疾病（如癌症）和其他涉及 RET 激酶活性的疾病或病症中的用途。
• The Role of Reversible Oxidative Addition in Selective Palladium(0)-Catalyzed Intramolecular Cross-Couplings of Polyhalogenated Substrates: Synthesis of Brominated Indoles
  作者：Stephen G. Newman、Mark Lautens

  DOI：10.1021/ja1052335

  日期：2010.8.25

  A Pd(0)-catalyzed C-N bond-forming reaction leading to the synthesis of brominated indoles is described. The use of the phosphine ligand PtBu3 is necessary for reactivity. It is proposed that the bulky ligand serves to prevent inhibition of the catalyst by facilitating reversible oxidative addition into the product C-Br bond. Intramolecular coupling of a vinyl bromide in the presence of an aryl iodide can take place, demonstrating unprecedented levels of selectivity.
• HETEROCYCLIC COMPOUNDS AS RET KINASE INHIBITORS
  申请人：Cancer Research Technology Limited

  公开号：EP3442980B1

  公开（公告）日：2021-06-09
• Heterocyclic Compounds as RET Kinase Inhibitors
  申请人：Cancer Research Technology Limited

  公开号：US20210155628A1

  公开（公告）日：2021-05-27

  The present invention relates to compounds of Formula I that function as inhibitors of RET (rearranged during transfection) kinase enzyme activity: wherein HET, bonds a, b, c and d, X 1 , X 2 , X 3 , X 4 , R 2 , and R 3 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which RET kinase activity is implicated.