[(3R,4S)-4-amino-4-(5-bromo-2-fluorophenyl)oxolan-3-yl]methanol

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [(3R,4S)-4-amino-4-(5-bromo-2-fluorophenyl)oxolan-3-yl]methanol
• 化学式: C₁₁H₁₃BrFNO₂
• 分子量: 290.132
• InChiKey: GOACHKOHAIPAMI-HQJQHLMTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  55.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  苯甲酰基异硫氰酸酯 、 [(3R,4S)-4-amino-4-(5-bromo-2-fluorophenyl)oxolan-3-yl]methanol 在 N,O-双(三甲基硅烷基)三氟乙酰胺 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以94%的产率得到racemic N-((3SR,4RS)-3-(5-bromo-2-fluorophenyl)-4-(hydroxymethyl)tetrahydrofuran-3-ylcarbamothioyl)benzamide
  参考文献：
  名称：

  BACE INHIBITORS

  摘要：

  本发明提供了式I的BACE抑制剂：使用它们的方法、中间体以及它们的制备方法。

  公开号：

  US20110009395A1
• 作为产物：
  描述：

  racemic (3aSR,6aSR)-6a-(5-bromo-2-fluorophenyl)hexahydrofuro[3,4-c]isoxazole 在 溶剂黄146 、 锌 、 水 、 sodium hydroxide 作用下， 反应 5.0h， 以86%的产率得到[(3R,4S)-4-amino-4-(5-bromo-2-fluorophenyl)oxolan-3-yl]methanol
  参考文献：
  名称：

  BACE INHIBITORS

  摘要：

  本发明提供了式I的BACE抑制剂：使用它们的方法、中间体以及它们的制备方法。

  公开号：

  US20110009395A1

文献信息

• Synthesis of BACE Inhibitor LY2886721. Part II. Isoxazolidines as Precursors to Chiral Aminothiazines, Selective Peptide Coupling, and a Controlled Reactive Crystallization
  作者：Marvin M. Hansen、Daniel J. Jarmer、Enver Arslantas、Amy C. DeBaillie、Andrea L. Frederick、Molly Harding、David W. Hoard、Adrienne Hollister、Dominique Huber、Stanley P. Kolis、Jennifer E. Kuehne-Willmore、Thomas Kull、Michael E. Laurila、Ryan J. Linder、Thomas J. Martin、Joseph R. Martinelli、Michael J. McCulley、Rachel N. Richey、Derek R. Starkey、Jeffrey A. Ward、Nikolay Zaborenko、Theo Zweifel

  DOI：10.1021/op500327t

  日期：2015.9.18

  An efficient synthesis of LY2886721 (1) in five steps and 46% overall yield from the chiral nitrone cycloadduct 2 is presented. Minimizing formation of a des-fluoro impurity during hydrogenolysis to cleave the isoxazolidine ring and remove the benzyl chiral auxiliary was a key challenge. Installation of the aminothiazine moiety required careful stoichiometry control of the reagents BzNCS and CDI, including in situ conversion monitoring, to minimize byproduct formation. A remarkably regioselective peptide coupling afforded 1 without competing acylation at the aminothiazine nitrogen or bis-acylation. Consideration of the combined chemistry and crystallization process identified an optimal solvent system for the peptide coupling and a reactive crystallization that afforded 1 in high purity and with physical property control. A slurry milling operation near the end of the crystallization, followed by "pH cycles" to digest fines formed during milling, significantly reduced the crystal aspect ratio and provided desirable API bulk density and powder flow properties.
• TETRAHYDROFURANE-FUSED AMINOHYDROTHIAZINE DERIVATIVES WHICH ARE USEFUL IN THE TREATMENT OF ALZHEIMER'S DISEASE
  申请人：Eli Lilly and Company

  公开号：EP3288949B1

  公开（公告）日：2019-11-06
• BACE INHIBITORS
  申请人：AUDIA James Edmund

  公开号：US20110009395A1

  公开（公告）日：2011-01-13

  The present invention provides BACE inhibitors of Formula I: methods for their use, intermediates, and methods for their preparation.

  本发明提供了式I的BACE抑制剂：使用它们的方法、中间体以及它们的制备方法。