2,3-dihydro-1H,5H-pyrrolo[2,1-a]isoindole-9b-carboxylic acid tert-butyl ester | 401504-03-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2,3-dihydro-1H,5H-pyrrolo[2,1-a]isoindole-9b-carboxylic acid tert-butyl ester
• 英文别名: 2,3-dihydro-1H,5H-pyrrolo[2,1-α]isoindole-9b-carboxylic acid tert-butyl ester；2,3-Dihydro-1h, 5h-pyrrolo[2,1-a]isoindole-9b-carboxylic acid tert-butyl ester；tert-butyl 1,2,3,5-tetrahydropyrrolo[2,1-a]isoindole-9b-carboxylate
• CAS: 401504-03-8
• 化学式: C₁₆H₂₁NO₂
• 分子量: 259.348
• InChiKey: ICUQRCUJZSSEQS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,3-dihydro-1H,5H-pyrrolo[2,1-a]isoindole-9b-carboxylic acid tert-butyl ester 在 盐酸 、 5% rhodium-on-charcoal 、 水 、 氢气 作用下， 以 乙醇 为溶剂， 60.0 ℃ 、413.7 kPa 条件下， 反应 74.0h， 生成 octahydropyrrolo[2,1-a]isoindole-9b-carboxylic acid hydrochloride
  参考文献：
  名称：

  Synthesis and Characterization of Novel Bi- and Tricyclic α-Amino Acids

  摘要：

  As part of a medicinal chemistry collaboration, a number of novel bi- and tricyclic alpha-amino acids were prepared through various routes and characterized by H-1 nuclear Overhauser effect difference experiments. The syntheses provide a number of routes to access some highly substituted amino acid derivatives that have not been reported previously. It is envisaged that the chemistry described here could be applied to the synthesis of other unique substrates.

  DOI：

  10.1080/00397911.2010.515354
• 作为产物：
  描述：

  proline tert-butyl ester 在 tris(dibenzylideneacetone)dipalladium (0) 、 dicyclohexyl(2'-(dimethylamino)[1,1'-biphenyl]-2-yl)phosphine oxide 、 potassium carbonate 、 lithium tert-butoxide 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 35.0h， 生成 2,3-dihydro-1H,5H-pyrrolo[2,1-a]isoindole-9b-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Palladium-Catalyzed Intramolecular α-Arylation of α-Amino Acid Esters

  摘要：

  The Pd-catalyzed intramolecular alpha-arylation of alpha-amino acid esters is described. Starting from readily available amino acids, the synthesis of a variety of isoindolines and tetrahydroisoquinoline carboxylic acid esters has been accomplished. Additionally, fused tricyclic systems can be efficiently prepared from cyclic amino acid esters. Reaction conditions have been found that allow the use of tert-butyl ester and N-(benzyloxycarbonyl) protecting groups.

  DOI：

  10.1021/jo0107756

文献信息

• [EN] [C]-FUSED BICYCLIC PROLINE DERIVATIVES AND THEIR USE FOR TREATING ARTHRITIC CONDITIONS<br/>[FR] DERIVES DE PROLINE BICYCLIQUES 20041028US2003008861A1LIN LINUS S [US], et al20030109example 10, step C example 11, step A example 29, step c (starting material)X2,8XBERGMEIER S C ET AL: "Synthesis of Bicyclic Proline Analogs Using a Formal [3 + 2] Intramolecular Aziridine-Allylsilane Cycloaddition Reaction", TETRAHEDRON, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 55, no. 26, 25 June 1999 (1999-06-25), pages 8025 - 8038, XP004168571, ISSN: 0040-4020BERGMEIER S C ET ALSynthesis of Bicyclic Proline Analogs Using a Formal [3 + 2] Intramolecular Aziridine-Allylsilane Cycloaddition ReactionTETRAHEDRON, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL1999062555260040-40208025803845Scheme 7X2XDATABASE BEILSTEIN BEILSTEIN INSTITUTE FOR ORGANIC CHEMISTRY, FRANKFURT-MAIN, DE; XP002288925, Database accession no. BRN:388906BEILSTEINBEILSTEIN INSTITUTE FOR ORGANIC CHEMISTRY, FRANKFURT-MAIN, DEBRN:388906AX4XMURAYAMA ET AL, YAKUGAKU ZASSHI, vol. 85, 1965, pages 765 - 769MURAYAMA ET ALYAKUGAKU ZASSHI196585765769WO0027808A1AVENTIS PHARMA GMBH [DE]20000518214814211517A1-9AWO03074048A1WARNER LAMBERT CO [US], et al2003091235253626PX1-9PXOTHMAN M ET AL: "New Fused Lactones from Indolizinediones via N-Acyliminium Ions", TETRAHEDRON, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 54, no. 30, 23 July 1998 (1998-07-23), pages 8737 - 8744, XP004124041, ISSN: 0040-4020OTHMAN M ET ALNew Fused Lactones from Indolizinediones via N-Acyliminium IonsTETRAHEDRON, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL1998072354300040-4020873787443A-EScheme 1X1XGUILLERM G ET AL: "Synthesis of Hydroxylated Pyrrolidines Derivatives as Potential Inhibitors of SAH/MTA Nucleosidase", TETRAHEDRON LETTERS, vol. 28, no. 5, 1987, pages 535 - 538, XP002288924GUILLERM G ET ALSynthesis of Hydroxylated Pyrrolidines Derivatives as Potential Inhibitors of SAH/MTA NucleosidaseTETRAHEDRON LETTERS19872855355384AScheme 2X1X
  申请人：WARNER LAMBERT CO

  公开号：WO2004092134A1

  公开（公告）日：2004-10-28

  This invention relates to a compound which is [c]-fused bicyclic proline derivative, or a pharmaceutically acceptable salt thereof; a pharmaceutical composition comprising the compound or the salt thereof, and methods of treating diseases, including, but not limited to, methods of preventing or inhibiting joint cartilage damage and preventing or treating diseases characterized by joint cartilage damage, joint inflammation, or joint pain. The [c]-fused bicyclic proline derivatives are compounds of Formula I as described above. Diseases characterized by joint cartilage damage or joint pain include, for example, osteoarthritis and rheumatoid arthritis. Rheumatoid arthritis is also characterized by joint inflammation. This invention also relates to methods of synthesizing and preparing the [c]-fused bicyclic proline derivatives, or a pharmaceutically acceptable salt thereof.

  本发明涉及一种[c]-融合的双环脯氨酸衍生物，或其药用可接受的盐；包括该化合物或其盐的药物组合物；以及治疗疾病的方法，包括但不限于预防或抑制关节软骨损伤，以及预防或治疗以关节软骨损伤、关节炎或关节疼痛为特征的疾病的方法。[c]-融合的双环脯氨酸衍生物是如上所述的I式化合物。以关节软骨损伤或关节疼痛为特征的疾病包括，例如，骨关节炎和类风湿性关节炎。类风湿性关节炎还以关节炎为特征。本发明还涉及合成和制备[c]-融合的双环脯氨酸衍生物或其药用可接受的盐的方法。
• [C]-fused bicyclic proline derivatives and their use for treating arthritic conditions
  申请人：Guzzo R. Peter

  公开号：US20050137215A1

  公开（公告）日：2005-06-23

  This invention relates to a compound which is [c]-fused bicyclic proline derivative, or a pharmaceutically acceptable salt thereof; a pharmaceutical composition comprising the compound or the salt thereof, and methods of treating diseases, including, but not limited to, methods of preventing or inhibiting joint cartilage damage and preventing or treating diseases characterized by joint cartilage damage, joint inflammation, or joint pain. The [c]-fused bicyclic proline derivatives are compounds of Formula I as described above. Diseases characterized by joint cartilage damage or joint pain include, for example, osteoarthritis and rheumatoid arthritis. Rheumatoid arthritis is also characterized by joint inflammation. This invention also relates to methods of synthesizing and preparing the [c]-fused bicyclic proline derivatives, or a pharmaceutically acceptable salt thereof.

  本发明涉及一种[c]-融合的双环脯氨酸衍生物化合物或其药学上可接受的盐；一种包括该化合物或其盐的制药组合物，以及治疗疾病的方法，包括但不限于预防或抑制关节软骨损伤和预防或治疗以关节软骨损伤、关节炎或关节疼痛为特征的疾病的方法。[c]-融合的双环脯氨酸衍生物是如上所述的化合物I。以关节软骨损伤或关节疼痛为特征的疾病包括骨关节炎和类风湿性关节炎等。类风湿性关节炎还表现为关节炎。本发明还涉及合成和制备[c]-融合的双环脯氨酸衍生物或其药学上可接受的盐的方法。
• [EN] QUINAZOLINE AMINE DERIVATIVES AS KRAS INHIBITORS<br/>[FR] DÉRIVÉS DE QUINAZOLINE AMINE EN TANT QU'INHIBITEURS DE KRAS
  申请人：NIKANG THERAPEUTICS INC

  公开号：WO2022187528A1

  公开（公告）日：2022-09-09

  The present disclosure provides certain quinazoline derivatives that inhibit certain K-Ras proteins and are therefore useful for the treatment of cancers mediated by such proteins. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

  本公开提供了某些喹唑啉衍生物，其抑制某些K-Ras蛋白质，因此可用于治疗由此类蛋白质介导的癌症。还提供了含有这些化合物的药物组合物以及制备这些化合物的方法。
• TETRACYCLIC DERIVATIVES AS KRAS INHIBITORS
  申请人：[en]NIKANG THERAPEUTICS, INC.

  公开号：WO2024051721A1

  公开（公告）日：2024-03-14

  The present disclosure provides certain tetracyclic derivatives that inhibit certain K-Ras proteins and are therefore useful for the treatment of cancers mediated by such proteins. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.
• [EN] ALKYLIDENE DERIVATIVES AS KRAS INHIBITORS<br/>[FR] DÉRIVÉS D'ALKYLIDÈNE EN TANT QU'INHIBITEURS DE KRAS
  申请人：[en]NIKANG THERAPEUTICS, INC.

  公开号：WO2023284730A1

  公开（公告）日：2023-01-19

  The present disclosure provides certain alkylidenyl derivatives that inhibit certain K-Ras proteins and are therefore useful for the treatment of cancers mediated by such proteins. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds. 114342739v.1