1,3-dimethyl-3-(2-aminoethyl)-5-methoxyoxindole | 110691-50-4

• 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: 1,3-dimethyl-3-(2-aminoethyl)-5-methoxyoxindole
• 英文别名: 3-(2-amino-ethyl)-5-methoxy-1,3-dimethyl-1,3-dihydro-indol-2-one；3-(2-amino-ethyl)-5-methoxy-1,3-dimethyl-indolin-2-one；3-(2-Amino-aethyl)-5-methoxy-1,3-dimethyl-indolin-2-on；3-(2-Aminoethyl)-5-methoxy-1,3-dimethyl-2-indolone；3-(2-aminoethyl)-5-methoxy-1,3-dimethylindol-2-one
• CAS: 110691-50-4
• 化学式: C₁₃H₁₈N₂O₂
• 分子量: 234.298
• InChiKey: XEEBADQXIMNBQG-UHFFFAOYSA-N

物化性质

• 沸点：
  201-203 °C(Press: 9 Torr)
• 密度：
  1.116±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,3-dimethyl-3-(2-aminoethyl)-5-methoxyoxindole 在 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (+)-esermethole
  参考文献：
  名称：

  Synthesis of (−)- and (+)-esermethole via chemical resolution of 1,3-dimethyl-3-(2-aminoethyl)-5-methoxyoxindole

  摘要：

  A new synthesis of (-)- and (+)-esermethole (2 and 7 respectively), penultimate intermediates to (-)- and (+)-physostigmine, is described. Phase-transfer catalyzed dimethylation of 3-cyanomethyl -5-methoxyoxindole (3) and successive hydrogenation of the cyano group gave 1,3-dimethyl-3-(2-aminoethyl)-5-methoxyoxindole (5), which was efficiently resolved with optically active tartaric acids. Subsequent conversion to a carbamate and reductive cyclization performed by a standard method afforded both the enantiomers of esermethole. The enantiomeric excesses, determined by chiral HPLC analysis, were greater than 99.5%. In particular, analytical HPLC resolution of 5, previously reported as unfeasible, was achieved.

  DOI：

  10.1016/s0957-4166(00)80490-5
• 作为产物：
  描述：

  (5-methoxy-1,3-dimethyl-2-oxo-2,3-dihydro-1H-indol-3-yl)acetonitrile 在 platinum(IV) oxide 盐酸 、 氢气 作用下， 以 甲醇 为溶剂， 反应 15.0h， 生成 1,3-dimethyl-3-(2-aminoethyl)-5-methoxyoxindole
  参考文献：
  名称：

  Synthesis of (−)- and (+)-esermethole via chemical resolution of 1,3-dimethyl-3-(2-aminoethyl)-5-methoxyoxindole

  摘要：

  A new synthesis of (-)- and (+)-esermethole (2 and 7 respectively), penultimate intermediates to (-)- and (+)-physostigmine, is described. Phase-transfer catalyzed dimethylation of 3-cyanomethyl -5-methoxyoxindole (3) and successive hydrogenation of the cyano group gave 1,3-dimethyl-3-(2-aminoethyl)-5-methoxyoxindole (5), which was efficiently resolved with optically active tartaric acids. Subsequent conversion to a carbamate and reductive cyclization performed by a standard method afforded both the enantiomers of esermethole. The enantiomeric excesses, determined by chiral HPLC analysis, were greater than 99.5%. In particular, analytical HPLC resolution of 5, previously reported as unfeasible, was achieved.

  DOI：

  10.1016/s0957-4166(00)80490-5

文献信息

• Decarboxylative Synthesis of Functionalized Oxindoles via An Iron-Initiated Radical Chain Process and Application in Constructing Diverse Fused-Indoline Heterocycles
  作者：Zhihao Cui、Da-Ming Du

  DOI：10.1002/adsc.201700976

  日期：2018.1.4

  Rapid construction of diverse fused‐indoline−heterocycle (FIH) frameworks including high‐value pyrroloindolines, furoindolines and thienoindolines in a two‐step sequence has been described. The key to success hinges on the adoption of peresters as α‐heteroatom alkyl radical precusors, which can smoothly react with N‐arylacrylamides via a radical chain process initiated by inexpensive FeCl2⋅4H2O to

  已经描述了以两个步骤快速构建包括高价值吡咯并吲哚啉，呋喃并吲哚啉和硫代吲哚啉在内的各种稠合吲哚杂环化合物（FIH）框架的方法。关于通过过酸酯为α -杂烷基precusors的，其可以与平滑反应以成功铰链键Ñ通过由廉价的FeCl引发的自由基链过程-arylacrylamides 2 ⋅4H 2 O操作得到官能化的羟吲哚，关键中间体FIH骨骼。该方法具有操作简单，底物范围广和条件温和的特点。
• Fragmentation of Optically Active (1-Phenylethyl)- and (1-Naphthylethyl)ureas in Refluxing Alcohols: Easy Preparation of Optically Active Amines of High Optical Purity
  作者：Bernhard Schönenberger、Arnold Brossi

  DOI：10.1002/hlca.19860690620

  日期：1986.9.10

  (1-Phenylethyl)- and (1-naphthylethyl)ureas, obtained in the reaction of racemic amines with optically pure isocyanates, are separated and then decomposed in refluxing alcohols, to afford optically pure secondary amines and optically pure alkyl carbamates in quantitative yields. The scope of this fragmentation for the resolution of racemic mixtures of amines is illustrated by several examples of biologically

  将在外消旋胺与旋光纯的异氰酸酯反应中获得的（1-苯乙基）-和（1-萘基乙基）脲分离，然后在回流的醇中分解，以定量收率得到旋光纯的仲胺和旋光的氨基甲酸烷基酯。用于拆分胺的外消旋混合物的这种裂解作用的范围由生物学上重要的化合物的几个例子说明。通过这种裂解获得的氨基甲酸酯可以容易地再循环。
• Process for the chemical resolution of 5-alkoxy-substituted (+/-)-1,3-dimethyloxindolylethylamines
  申请人：HOECHST-ROUSSEL PHARMACEUTICALS INCORPORATED

  公开号：EP0418770A2

  公开（公告）日：1991-03-27

  A process for chemically resolving a mixture of enantiomers of primary amines, such as enantiomers of 1,3-dimethyl-5-methoxyoxindolylethylamine, provides one of the enantiomers in the form of a tartaric acid salt. In carrying out the process, an enantiomeric mixture is contacted with a chiral acid in an amount sufficient to preferentially precipitate a salt of the chiral acid and one of the enantiomers. The resulting precipitate can then be recovered. The chiral acid is selected from the group consisting of dibenzoyl-D-tartaric acid, dibenzoyl-L-tartaric acid, ditoluoyl-D-tartaric acid, and ditoluoyl-L-tartaric acid. The precipitates can be used in the synthesis of stereospecific forms of physostigmine.

  一种对伯胺对映体混合物（如 1,3-二甲基-5-甲氧基吲哚乙胺的对映体）进行化学分解的工艺可提供酒石酸盐形式的其中一种对映体。在实施该工艺时，将对映体混合物与手性酸接触，接触量足以优先沉淀出手性酸和其中一种对映体的盐。然后回收沉淀物。手性酸选自二苯甲酰基-D-酒石酸、二苯甲酰基-L-酒石酸、二托洛尔-D-酒石酸和二托洛尔-L-酒石酸组成的组。沉淀物可用于合成立体特异形式的酞丁斯的明。
• A metal-free synthesis of oxindoles by a radical addition-cyclization onto N-arylacrylamides with xanthates
  作者：Shucheng Wang、Xuhu Huang、Bowen Li、Zemei Ge、Xin Wang、Runtao Li

  DOI：10.1016/j.tet.2015.01.049

  日期：2015.3

  A convenient, high yielding synthesis of oxindoles by metal-free di-functionalization of alkenes with xanthates has been developed. This transformation involves a radical addition/cyclization process. Various arylalkylation products including alkyl ester-, benzyl-, cyano-, ketone-, amine-, and amide-substituted oxindoles were prepared in good to excellent yields. (C) 2015 Elsevier Ltd. All rights reserved.
• Kolosow; Preobrashenskii, Zhurnal Obshchei Khimii, 1953, vol. 23, p. 1922,1924; engl. Ausg. S. 2035, 2036
  作者：Kolosow、Preobrashenskii

  DOI：——

  日期：——