1,2,3-trideoxy-3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-5-O-[(4-methylphenyl)sulfonyl]-L-threo-pent-1-enitol | 1016161-42-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 1,2,3-trideoxy-3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-5-O-[(4-methylphenyl)sulfonyl]-L-threo-pent-1-enitol
• 英文别名: [(2R,3S)-3-(1,3-dioxoisoindol-2-yl)-2-hydroxypent-4-enyl] 4-methylbenzenesulfonate
• CAS: 1016161-42-4
• 化学式: C₂₀H₁₉NO₆S
• 分子量: 401.44
• InChiKey: JSVSPZGSCJBOMH-ROUUACIJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1,2,3-trideoxy-3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-5-O-[(4-methylphenyl)sulfonyl]-L-threo-pent-1-enitol 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 甲苯 为溶剂， 反应 1.0h， 生成 4,5-anhydro-1,2,3-trideoxy-3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-L-threo-pent-1-enitol
  参考文献：
  名称：

  Large-scale synthesis of SB-462795, a cathepsin K inhibitor: the RCM-based approaches

  摘要：

  Two stereoselective syntheses of SB-462795, a highly potent cathepsin K inhibitor, are described. Both routes feature a C5-C6 disconnection by ring closing metathesis to construct an azepane ring and are amenable to large-scale manufacturing. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2009.06.022
• 作为产物：
  描述：

  4,5-anhydro-1,2,3-trideoxy-3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-L-threo-pent-1-enitol 、 对甲苯磺酸 在 四乙基对甲苯磺酸铵 作用下， 以 甲苯 为溶剂， 生成 1,2,3-trideoxy-3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-5-O-[(4-methylphenyl)sulfonyl]-L-threo-pent-1-enitol
  参考文献：
  名称：

  Large-scale synthesis of SB-462795, a cathepsin K inhibitor: the RCM-based approaches

  摘要：

  Two stereoselective syntheses of SB-462795, a highly potent cathepsin K inhibitor, are described. Both routes feature a C5-C6 disconnection by ring closing metathesis to construct an azepane ring and are amenable to large-scale manufacturing. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2009.06.022

文献信息

• Development of a Robust Ring-Closing Metathesis Reaction in the Synthesis of SB-462795, a Cathepsin K Inhibitor
  作者：Huan Wang、Steven N. Goodman、Qunying Dai、Gregory W. Stockdale、William M. Clark

  DOI：10.1021/op700288p

  日期：2008.3.1

  The development of a robust and high-yielding ring-closing metathesis (RCM) reaction and its demonstration on multikilogram scale are described. A detailed understanding of the impact of impurities on the RCM reaction was achieved using a variety of chemical and statistical methods. Specifically, individual impurities were evaluated in spiking studies to identify those that negatively affected the RCM reaction. Projection methods (PCA and PLS) were applied to historical data to identify the main sources of variation in starting material quality and determine the main detrimental impurities that impeded the RCM reaction. The synthesis of the starting material was then modified to adequately control these key impurities, which in turn ensured a robust RCM process. Finally, the robustness of the RCM reaction was assessed using a probability-based approach.