5-氟-1H-吲哚-2-羧酸甲酯 | 167631-84-7

• 物质功能分类: 医药中间体 - 杂环化合物
• 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
• 中文名称: 5-氟-1H-吲哚-2-羧酸甲酯
• 英文名称: methyl 5-fluoro-1H-indole-2-carboxylate
• 英文别名: 5-fluoro-1H-indole-2-carboxylic acid methyl ester
• CAS: 167631-84-7
• 化学式: C₁₀H₈FNO₂
• mdl: MFCD04972072
• 分子量: 193.177
• InChiKey: QUZGGDBUGGJROM-UHFFFAOYSA-N

物化性质

• 熔点：
  201 °C(Solv: ethyl acetate (141-78-6))
• 沸点：
  335.3±22.0 °C(Predicted)
• 密度：
  1.341±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 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：
  3

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  5-氟-1H-吲哚-2-羧酸甲酯 在 氢氧化钾 、 碘 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.25h， 生成 methyl 5-fluoro-3-iodo-1H-indole-2-carboxylate
  参考文献：
  名称：

  Bicyclic compositions and methods for modulating a kinase cascade

  摘要：

  该发明涉及化合物和方法，用于调节激酶级联中的一个或多个组分。

  公开号：

  US20080004241A1
• 作为产物：
  描述：

  methyl 2-azido-3-(3-fluorophenyl)prop-2-enoate 以 甲苯 为溶剂， 反应 0.17h， 以84%的产率得到5-氟-1H-吲哚-2-羧酸甲酯
  参考文献：
  名称：

  Extending the versatility of the Hemetsberger–Knittel indole synthesis through microwave and flow chemistry

  摘要：

  Microwave, flow and combination methodologies have been applied to the synthesis of a number of substituted indoles. Based on the Hemetsberger-Knittel (HK) process, modifications allow formation of products rapidly and in high yield. Adapting the methodology allows formation of 2-unsubstituted indoles and derivatives, and a route to analogs of the antitumor agent PLX-4032 is demonstrated. The utility of the HK substrates is further demonstrated through bioconjugation and subsequent ring closure and via Huisgen type [3+2] cycloaddition chemistry, allowing formation of peptide adducts which can be subsequently labeled with fluorine tags. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.01.066

文献信息

• INDOLE DERIVATIVES
  申请人：Beke Gyula

  公开号：US20130217702A1

  公开（公告）日：2013-08-22

  The present invention relates to the indole derivatives of formula (I), wherein R 1 -R 6 and X are defined in the claims and optical antipodes or racemates and/or salts thereof which are selective antagonists of bradykinin B1 to process for producing these compounds, pharmacological compositions containing them and to their use in therapy or prevention of painful and inflammatory conditions.

  本发明涉及式(I)的吲哚衍生物，其中R1-R6和X在权利要求中定义，并且其光学对映体或消旋体和/或盐是布雷金肽B1的选择性拮抗剂，用于制备这些化合物的方法，含有它们的药理学组合物以及它们在治疗或预防疼痛和炎症症状中的用途。
• Mild Esterification of Carboxylic Acids via Continuous Flow Diazotization of Amines
  作者：Clément Audubert、Hélène Lebel

  DOI：10.1021/acs.orglett.7b02231

  日期：2017.8.18

  A new continuous flow protocol for the diazotization of methylamine with 1,3-propanedinitrite in THF is reported. The synthesis of methyl esters was achieved in high yields from a variety of carboxylic acids in 20 min at 90 °C. Additionally, this protocol was extended to other aryl and alkyl amines, namely secondary amines, to produce various substituted esters in high yield using 2-MeTHF as a solvent

  报道了一种新的连续流方案，用于在THF中将甲胺与1,3-丙炔重氮化。在90°C下20分钟内可以从多种羧酸中高收率地合成甲酯。另外，该方案扩展到其他芳基和烷基胺，即仲胺，以使用2-MeTHF作为溶剂以高收率生产各种取代的酯。反应条件与许多官能团相容，即含氮杂环，炔烃，烯烃，醇和酚。机理研究表明，反应似乎是通过瞬态重氮物质而不是重氮中间体进行的。
• [Fe(F₂₀TPP)Cl]-Catalyzed Amination with Arylamines and {[Fe(F₂₀TPP)(NAr)](PhINAr)} + . Intermediate Assessed by High-Resolution ESI-MS and DFT Calculations
  作者：Yungen Liu、Guo-Qiang Chen、Chun-Wai Tse、Xianguo Guan、Zheng-Jiang Xu、Jie-Sheng Huang、Chi-Ming Che

  DOI：10.1002/asia.201402580

  日期：2015.1

  Amination of CH bonds catalyzed by transition metal complexes via nitrene/imide insertion is an appealing strategy for CN bond formation, and the use of iminoiodinanes, or their in situ generated forms from ‘PhI(OAc)2+primary amides (such as sulfonamides, sulfamates, and carbamates)’, as nitrogen sources for the amination reaction has been well documented. In this work, a ‘metal catalyst+PhI(OAc)2+primary

  的Ç胺化经由氮烯/酰亚胺插入由过渡金属配合物催化的H键是对于C一个有吸引力的策略 N键的形成，以及使用iminoiodinanes的，或从“岛（OAC）其在原位产生的形式2个+伯酰胺（如磺酰胺，氨基磺酸盐和氨基甲酸酯等，作为胺化反应的氮源已被充分证明。在这项工作中，使用[Fe（F 20 TPP）Cl]（H 2 F 20 TPP = meso- tetrakis（五氟苯基）卟啉）作为“金属催化剂+ PhI（OAc）2 +伯芳基胺”的胺化方案已被开发出来。催化剂。该催化方法适用于sp的分子内和分子间胺化2个SP 3 Ç  H键（> 27个实施例），得到氨基化的产品，包括天然产物如吴茱萸，在中度至良好的产率。ESI-MS分析和DFT计算借给的参与支持[铁（F 20 TPP）（NC 6 H ^ 4 - p -NO 2）]（PHI = NC 6 H ^ 4 - p -NO 2）}在中间催化。
• Palladium(0)‐Catalyzed Intermolecular Asymmetric Cascade Dearomatization Reaction of Indoles with Propargyl Carbonate
  作者：Lu Ding、Run‐Duo Gao、Shu‐Li You

  DOI：10.1002/chem.201900425

  日期：2019.3.21

  An intermolecular asymmetric cascade dearomatization reaction of indole derivatives with propargyl carbonate was developed. The challenges associated with both the chemoselectivity between the carbon and nitrogen nucleophile and the enantioselective control during the formation of an all‐carbon quaternary stereogenic center were well addressed by a Pd catalytic system derived from the Feringa ligand

  进行了吲哚衍生物与碳酸炔丙酯的分子间不对称级联脱芳香化反应。碳和氮亲核试剂之间的化学选择性和对映选择性控制在全碳季铵立体异构中心形成过程中所面临的挑战，都可以通过源自Feringa配体的Pd催化体系很好地解决。一系列对映体富集的乘法取代的稠合假吲哚在良好的产率（71-86％）具有优异的对映选择性（91-96％是提供 EE（）和化学选择性3 / 4：1在大多数情况下> 19）。
• New indole derivatives as factor Xa inhibitors
  申请人：——

  公开号：US20030199689A1

  公开（公告）日：2003-10-23

  The present invention relates to compounds of formula I, 1 in which R 0 ; R 1 ; R 2 ; R 3 ; R 4 ; R 5 ; R 6 ; R 7 ; Q; V, G and M have the meanings indicated in the claims. The compounds of formula I are valuable pharmacologically active compounds. They exhibit a strong antithrombotic effect and are suitable, for example, for the therapy and prophylaxis of cardiovascular disorders like thromboembolic diseases or restenoses. They are reversible inhibitors of the blood clotting enzymes factor Xa (FXa) and/or factor VIIa (FVIIa), and can in general be applied in conditions in which an undesired activity of factor Xa and/or factor VIIa is present or for the cure or prevention of which an inhibition of factor Xa and/or factor VIIa is indicated. The invention furthermore relates to processes for the preparation of compounds of formula I, their use, in particular as pharmaceuticals for treating the foregoing conditions, and pharmaceutical preparations comprising them.

  本发明涉及具有式I的化合物，其中R0；R1；R2；R3；R4；R5；R6；R7；Q；V，G和M具有索赔中指示的含义。式I的化合物是有价值的药理活性化合物。它们表现出强烈的抗血栓作用，例如，适用于治疗和预防心血管疾病如血栓栓塞疾病或再狭窄。它们是血凝酶因子Xa（FXa）和/或因子VIIa（FVIIa）的可逆抑制剂，通常可应用于存在因子Xa和/或因子VIIa不良活性的情况，或者在其治疗或预防需要抑制因子Xa和/或因子VIIa的情况下。此外，本发明还涉及制备式I化合物的方法，它们的用途，特别是作为用于治疗上述疾病的药物，以及包含它们的制剂。