3-cyclopentyl-2-(2-pyridyl)-N-methylindole-6-carboxylic acid methyl ester | 865173-50-8

• 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: 3-cyclopentyl-2-(2-pyridyl)-N-methylindole-6-carboxylic acid methyl ester
• 英文别名: 3-cyclopentyl-1-methyl-2-pyridin-2-yl-1H-indole-6-carboxylic acid methyl ester；methyl 3-cyclopentyl-1-methyl-2-pyridin-2-ylindole-6-carboxylate
• CAS: 865173-50-8
• 化学式: C₂₁H₂₂N₂O₂
• 分子量: 334.418
• InChiKey: ZWFSMIQWGWEZLV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-cyclopentyl-2-(2-pyridyl)-N-methylindole-6-carboxylic acid methyl ester 在 sodium hydroxide 、 溶剂黄146 作用下， 以 丙醇 、 水 为溶剂， 反应 2.0h， 以77%的产率得到3-cyclopentyl-1-methyl-2-pyridin-2-yl-1H-indole-6-carboxylic acid
  参考文献：
  名称：

  [EN] PROCESS FOR CROSS COUPLING INDOLES
  [FR] PROCEDE DE COUPLAGE CROISE D'INDOLES

  摘要：

  本发明提供了一种制备通式(I)化合物的方法，其中：R = H或C1-8烷基；X = C3-C8环烷基，C3-C8芳基或C3-C8烷基；Y = 杂芳基或芳基；Z = H，HO2C-，C1-8烷基O2C-，C1-6烷基HNC(O)-，以及如本文所述。

  公开号：

  WO2005092855A1
• 作为产物：
  描述：

  6-吲哚甲酸 在 copper(l) iodide 、 正丁基锂 、 20% Pd(OH)2/C 、 氢气 、 溴 、 sodium acetate 、 potassium carbonate 、 三苯基膦 、 lithium chloride 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 醋酸异丙酯 、 水 、 N,N-二甲基甲酰胺 为溶剂， -72.0~100.0 ℃ 、101.33 kPa 条件下， 反应 46.75h， 生成 3-cyclopentyl-2-(2-pyridyl)-N-methylindole-6-carboxylic acid methyl ester
  参考文献：
  名称：

  Discovery of the First Thumb Pocket 1 NS5B Polymerase Inhibitor (BILB 1941) with Demonstrated Antiviral Activity in Patients Chronically Infected with Genotype 1 Hepatitis C Virus (HCV)

  摘要：

  Combinations of direct acting antivirals (DAAs) that have the potential to suppress emergence of resistant virus and that can be used in interferon-sparing regimens represent a preferred option for the treatment of chronic HCV infection. We have discovered allosteric (thumb pocket 1) non-nucleoside inhibitors of HCV NS5B polymerase that inhibit replication in replicon systems. Herein, we report the late-stage optimization of indole-based inhibitors, which began with the identification of a metabolic liability common to many previously reported inhibitors in this series. By use of parallel synthesis techniques, a sparse matrix of inhibitors was generated that provided a collection of inhibitors satisfying potency criteria and displaying improved in vitro ADME profiles. "Cassette" screening for oral absorption in rat provided a short list of potential development candidates. Further evaluation led to the discovery of the first thumb pocket 1 NS5B inhibitor (BILB 1941) that demonstrated antiviral activity in patients chronically infected with genotype 1 HCV.

  DOI：

  10.1021/jm3006788

文献信息

• Process for preparing 2, 3-disubstituted indoles
  申请人：Khodabocus Ahmad

  公开号：US20060183752A1

  公开（公告）日：2006-08-17

  Disclosed are processes for making 2,3 disubstituted indole compounds such as compounds of general formula I comprised of the steps of a) reacting a bromoindole compound (i) with a dialkoxyl C 1-5 borane in the presence of a ligand, a palladium catalyst and a base to make a compound of general formula (ii); or alternatively reacting compound (i) with a trialkyl magnesiate reagent, followed by treatment with a borate; b) reacting the product of step a with a R2-Hal where R2-Hal is defined herein.

  披露了制备2,3-二取代吲哚化合物的方法，例如通式I所示的化合物，包括以下步骤： a) 在存在配体、钯催化剂和碱的情况下，将溴吲哚化合物(i)与二烷氧基C1-5硼烷反应，制备通式(ii)化合物；或者将化合物(i)与三烷基镁试剂反应，然后用硼酸盐处理；b) 将步骤a的产物与R2-Hal反应，其中R2-Hal在此处定义。
• Palladium catalyzed indolization of 2-bromo or chloroanilines
  申请人：Li Guisheng

  公开号：US20050209465A1

  公开（公告）日：2005-09-22

  The present invention provides a method for making substituted indole compounds of general formula III comprising the step of: (a) reacting a 2-bromoaniline or 2-chloroaniline of general formula (I) (I) wherein: X, R and R 1 are defined herein with a substituted acetylene of formula (II) wherein R 2 and R 3 in the presence of a palladium catalyst, a ligand, and a base in a solvent at a suitable temperature to give a compound of formula (III);

  本发明提供了一种制备通式III的取代吲哚化合物的方法，包括以下步骤：(a)将通式(I)的2-溴苯胺或2-氯苯胺（I中X、R和R1的定义见本文）与通式(II)的取代乙炔（其中R2和R3）在钯催化剂、配体和碱的存在下，在适当温度下的溶剂中反应，得到通式(III)的化合物；
• [EN] PROCESS FOR CROSS COUPLING INDOLES<br/>[FR] PROCEDE DE COUPLAGE CROISE D'INDOLES
  申请人：BOEHRINGER INGELHEIM PHARMA

  公开号：WO2005092855A1

  公开（公告）日：2005-10-06

  The present invention provides a process for making a compound of general formula (I) wherein: R = H or C1-8 alkyl X = C3 -C8 cycloalkyl, C3 -C8 aryl or C3 -C8 alkyl; Y = heteroaryl or aryl; Z = H, HO2C-, C1-8 alkyl O2C-, C1-6 alkyl HNC(O)- and as described herein.

  本发明提供了一种制备通式(I)化合物的方法，其中：R = H或C1-8烷基；X = C3-C8环烷基，C3-C8芳基或C3-C8烷基；Y = 杂芳基或芳基；Z = H，HO2C-，C1-8烷基O2C-，C1-6烷基HNC(O)-，以及如本文所述。
• PROCESS FOR PREPARING 2,3-DISUBSTITUTED INDOLES
  申请人：KHODABOCUS Ahmad

  公开号：US20090264655A1

  公开（公告）日：2009-10-22

  Disclosed are processes for making 2, 3 disubstituted indole compounds such as compounds of general formula I comprised of the steps of a) reacting a bromoindole compound (i) with a dialkoxyl C 1-5 borane in the presence of a ligand, a palladium catalyst and a base to make a compound of general formula (ii); or alternatively reacting compound (i) with a trialkyl magnesiate reagent, followed by treatment with a borate; b) reacting the product of step a with a R2-Hal where R2-Hal is defined herein.

  公开了制备2,3-二取代吲哚化合物的方法，例如由公式I组成的化合物，包括以下步骤：a)在配体、钯催化剂和碱的存在下，将溴吲哚化合物（i）与二烷氧基C1-5硼烷反应，制备公式（ii）的化合物；或者将化合物（i）与三烷基镁试剂反应，然后用硼酸盐处理；b)将步骤a的产物与R2-Hal反应，其中R2-Hal的定义如本文所述。
• 2-Bromoanaline and 2-chloroaniline compounds
  申请人：Boehringer Ingelheim International GmbH

  公开号：US07408076B2

  公开（公告）日：2008-08-05

  Disclosed are 2-bromoaniline or 2-chloroaniline compounds of formula (I): wherein R, R1 and X are as defined. The compounds are useful as intermediates for preparing indole compounds.

  本发明涉及式(I)的2-溴苯胺或2-氯苯胺化合物：其中R，R1和X如定义。这些化合物可用作制备吲哚化合物的中间体。