ethyl N-(benzyloxycarbonyl)-3-aza-6,6-difluorobicyclo[3.3.0]octane-2-carboxylate | 783326-24-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl N-(benzyloxycarbonyl)-3-aza-6,6-difluorobicyclo[3.3.0]octane-2-carboxylate
• 英文别名: (1S,3aR,6aS)-2-benzyl 1-ethyl 4,4-difluorohexahydrocyclopenta[c]pyrrole-1,2(1H)-dicarboxylate；2-O-benzyl 3-O-ethyl 6,6-difluoro-1,3,3a,4,5,6a-hexahydrocyclopenta[c]pyrrole-2,3-dicarboxylate
• CAS: 783326-24-9
• 化学式: C₁₈H₂₁F₂NO₄
• 分子量: 353.366
• InChiKey: YLOPDALMJMDJEG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl N-(benzyloxycarbonyl)-3-aza-6,6-difluorobicyclo[3.3.0]octane-2-carboxylate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 17.0h， 生成 N-(benzyloxycarbonyl)-3-aza-6,6-difluorobicyclo[3.3.0]octane-2-carboxylic acid
  参考文献：
  名称：

  [EN] [C]-FUSED BICYCLIC PROLINE DERIVATIVES AND THEIR USE FOR TREATING ARTHRITIC CONDITIONS
  [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

  摘要：

  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。

  公开号：

  WO2004092134A1
• 作为产物：
  描述：

  ethyl N-(benzyloxycarbonyl)-3-aza-6-oxobicyclo[3.3.0]octane-2-carboxylate 在 [双(2-甲氧基乙基)胺]三氟化硫 、 碳酸氢钠 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 72.0h， 以66%的产率得到ethyl N-(benzyloxycarbonyl)-3-aza-6,6-difluorobicyclo[3.3.0]octane-2-carboxylate
  参考文献：
  名称：

  [EN] [C]-FUSED BICYCLIC PROLINE DERIVATIVES AND THEIR USE FOR TREATING ARTHRITIC CONDITIONS
  [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

  摘要：

  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。

  公开号：

  WO2004092134A1