1-(1-溴-2-氟丙烷-2-基)-4-碘苯 | 865101-46-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 1-(1-溴-2-氟丙烷-2-基)-4-碘苯
• 英文名称: 1-(2-bromo-1-fluoro-1-methyl-ethyl)-4-iodo-benzene
• 英文别名: 1-(1-Bromo-2-fluoropropan-2-YL)-4-iodobenzene
• CAS: 865101-46-8
• 化学式: C₉H₉BrFI
• 分子量: 342.977
• InChiKey: HDQIQCMEONAWRQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-(1-溴-2-氟丙烷-2-基)-4-碘苯 在 四丁基溴化铵 、 potassium carbonate 、 钯 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 丙醇 、 乙醇 、 甲基叔丁基醚 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 41.93h， 生成 (S)-4'-[1-fluoro-1-methyl-2-(propane-2-sulfonylamino)-ethyl]-biphenyl-4-carboxylic acid methylamide
  参考文献：
  名称：

  Diastereomeric Salt Resolution Based Synthesis of LY503430, an AMPA (α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid) Potentiator

  摘要：

  This article describes the development and optimization of chemical reactions and subsequent preparation of the API LY503430 under cGMPs to fund first human dose (FHD) clinical evaluation as a potential therapeutic agent for Parkinson's disease. Reasons and rationale are presented for changes in solvents and reagents. One of the major developments presented here is the replacement of a chiral chromatography with a diastereomeric salt resolution. This article also discusses a preferred orientation issue with LY503430 which complicated the XRPD analysis.

  DOI：

  10.1021/op0500741
• 作为产物：
  描述：

  1-碘-4-丙-1-烯-2-基苯 在 N-溴代丁二酰亚胺(NBS) 、 triethylamine tris(hydrogen fluoride) 作用下， 以 正庚烷 、 二氯甲烷 为溶剂， 以36.4 kg的产率得到1-(1-溴-2-氟丙烷-2-基)-4-碘苯
  参考文献：
  名称：

  Diastereomeric Salt Resolution Based Synthesis of LY503430, an AMPA (α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid) Potentiator

  摘要：

  This article describes the development and optimization of chemical reactions and subsequent preparation of the API LY503430 under cGMPs to fund first human dose (FHD) clinical evaluation as a potential therapeutic agent for Parkinson's disease. Reasons and rationale are presented for changes in solvents and reagents. One of the major developments presented here is the replacement of a chiral chromatography with a diastereomeric salt resolution. This article also discusses a preferred orientation issue with LY503430 which complicated the XRPD analysis.

  DOI：

  10.1021/op0500741

文献信息

• GluR2 receptor modulators
  申请人：Gouaux James Eric

  公开号：US20090270508A1

  公开（公告）日：2009-10-29

  The present invention provides for compositions and methods for modulating the GluR2 receptor. It is based, at least in part, on the discovery, by X-ray crystallography, that a known GluR2 agonist binds to the receptor in two different orientations, thereby diminishing its potency. The present invention provides for structural alternatives in which alternative binding possibilities are substantially eliminated.

  本发明提供了调节GluR2受体的组合物和方法。该发明至少部分基于X射线晶体学的发现，即已知的GluR2激动剂以两种不同的方向结合到受体上，从而降低了其效力。本发明提供了结构上的替代方案，在其中替代性结合可能性被大大消除。
• Diastereomeric Salt Resolution Based Synthesis of LY503430, an AMPA (α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid) Potentiator
  作者：Nicholas A. Magnus、James A. Aikins、Jason S. Cronin、William D. Diseroad、Amy D. Hargis、Michael E. LeTourneau、Bruce E. Parker、Susan M. Reutzel-Edens、John P. Schafer、Michael A. Staszak、Gregory A. Stephenson、Shella L. Tameze、Lisa M. H. Zollars

  DOI：10.1021/op0500741

  日期：2005.9.1

  This article describes the development and optimization of chemical reactions and subsequent preparation of the API LY503430 under cGMPs to fund first human dose (FHD) clinical evaluation as a potential therapeutic agent for Parkinson's disease. Reasons and rationale are presented for changes in solvents and reagents. One of the major developments presented here is the replacement of a chiral chromatography with a diastereomeric salt resolution. This article also discusses a preferred orientation issue with LY503430 which complicated the XRPD analysis.