Methanesulfonic acid 3-(2-{3-[4-(1H-indol-3-yl)-1-methyl-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-indol-1-yl}-ethoxy)-4-trityloxy-butyl ester | 203250-18-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: Methanesulfonic acid 3-(2-{3-[4-(1H-indol-3-yl)-1-methyl-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-indol-1-yl}-ethoxy)-4-trityloxy-butyl ester
• 英文别名: [3-[2-[3-[4-(1H-indol-3-yl)-1-methyl-2,5-dioxopyrrol-3-yl]indol-1-yl]ethoxy]-4-trityloxybutyl] methanesulfonate
• CAS: 203250-18-4
• 化学式: C₄₇H₄₃N₃O₇S
• 分子量: 793.94
• InChiKey: LSURNKFJYCBVLS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  58
• 可旋转键数：
  16
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  128
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Methanesulfonic acid 3-(2-{3-[4-(1H-indol-3-yl)-1-methyl-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-indol-1-yl}-ethoxy)-4-trityloxy-butyl ester 以78的产率得到6,7,10,11-tetrahydro-19-methyl-9-[(triphenylmethoxy)methyl]-9H,18H,-5,21:12,17-dimethenodibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecine-18,20(19H)-dione
  参考文献：
  名称：

  Synthesis of bisindolylmaleimides

  摘要：

  本发明提供了一种新型合成式(I)化合物的方法：##STR1## 该化合物的产率高且不需要使用昂贵的色谱分离。该合成方法尤其有优势，因为它是立体选择性的。

  公开号：

  US05541347A1
• 作为产物：
  描述：

  3-(1-{2-[3-(tert-Butyl-diphenyl-silanyloxy)-1-trityloxymethyl-propoxy]-ethyl}-1H-indol-3-yl)-4-(1H-indol-3-yl)-1-methyl-pyrrole-2,5-dione 在 四丁基氟化铵 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 Methanesulfonic acid 3-(2-{3-[4-(1H-indol-3-yl)-1-methyl-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-indol-1-yl}-ethoxy)-4-trityloxy-butyl ester
  参考文献：
  名称：

  Macrocyclic Bisindolylmaleimides:  Synthesis by Inter- and Intramolecular Alkylation

  摘要：

  Macrocyclic bisindolylmaleimides 1-4 have been identified as competitive reversible inhibitors of PKC beta(1) and beta(2) and are being advanced to the clinic for evaluation as a treatment of retinopathy associated with diabetic complications. Highly convergent and stereoselective syntheses of 1-4 have been developed. The key synthetic step involves intermolecular alkylation of symmetrical bisindolylmaleimide 9 with chiral bisalkylating agent 8c and is amenable to the preparation of multikilogram quantities of these compounds. The synthetic sequence to 1, the most active compound, proceeds in 11 steps and 26% overall yield (>98% ee) from (R)-1-chloro-2,3-propanediol. No chromatographic purifications are required throughout the process and the final product is isolated in >97% purity after crystallization from DMF/MeOH. Synthesis of 1-4 by intramolecular alkylation proved less efficient, requiring 1? steps and affording 1-4 in lower overall yields of 6.0-8.5%.

  DOI：

  10.1021/jo971980h

文献信息

• Synthesis of bisindolylmaleimides
  申请人：Eli Lilly and Company

  公开号：US05541347A1

  公开（公告）日：1996-07-30

  The present invention provides a novel synthesis of the compounds of Formula (I): ##STR1## The compounds are produced in high yield and without utilizing expensive chromatographic separations. The synthesis is particularly advantageous because it is stereoselective.

  本发明提供了一种新型合成式(I)化合物的方法：##STR1## 该化合物的产率高且不需要使用昂贵的色谱分离。该合成方法尤其有优势，因为它是立体选择性的。
• J. Org. Chem. 1998, 63, 1961-1973
  作者：

  DOI：——

  日期：——
• J. Med. Chem. 1996, 39, 2664-2671
  作者：

  DOI：——

  日期：——
• Macrocyclic Bisindolylmaleimides:  Synthesis by Inter- and Intramolecular Alkylation
  作者：Margaret M. Faul、Leonard L. Winneroski、Christine A. Krumrich、Kevin A. Sullivan、James R. Gillig、David A. Neel、Christopher J. Rito、Michael R. Jirousek

  DOI：10.1021/jo971980h

  日期：1998.3.1

  Macrocyclic bisindolylmaleimides 1-4 have been identified as competitive reversible inhibitors of PKC beta(1) and beta(2) and are being advanced to the clinic for evaluation as a treatment of retinopathy associated with diabetic complications. Highly convergent and stereoselective syntheses of 1-4 have been developed. The key synthetic step involves intermolecular alkylation of symmetrical bisindolylmaleimide 9 with chiral bisalkylating agent 8c and is amenable to the preparation of multikilogram quantities of these compounds. The synthetic sequence to 1, the most active compound, proceeds in 11 steps and 26% overall yield (>98% ee) from (R)-1-chloro-2,3-propanediol. No chromatographic purifications are required throughout the process and the final product is isolated in >97% purity after crystallization from DMF/MeOH. Synthesis of 1-4 by intramolecular alkylation proved less efficient, requiring 1? steps and affording 1-4 in lower overall yields of 6.0-8.5%.