(S)-methyl 3-(3,4-bis(difluoromethoxy)phenyl)-2-(tert-butoxycarbonylamino)propanoate | 1373754-41-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-methyl 3-(3,4-bis(difluoromethoxy)phenyl)-2-(tert-butoxycarbonylamino)propanoate
• 英文别名: methyl (2S)-3-[3,4-bis(difluoromethoxy)phenyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate
• CAS: 1373754-41-6
• 化学式: C₁₇H₂₁F₄NO₆
• 分子量: 411.35
• InChiKey: XXDLLLGPXMFAQQ-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (S)-methyl 3-(3,4-bis(difluoromethoxy)phenyl)-2-(tert-butoxycarbonylamino)propanoate 在 isobutyl chloroformate 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 5.5h， 生成 (S)-tert-butyl 1-(3,4-bis(difluoromethoxy)phenyl)-4-diazo-3-oxobutan-2-ylcarbamate
  参考文献：
  名称：

  Design and Preparation of a Potent Series of Hydroxyethylamine Containing β-Secretase Inhibitors That Demonstrate Robust Reduction of Central β-Amyloid

  摘要：

  A series of potent hydroxyethyl amine (HEA) derived inhibitors of beta-site APP cleaving enzyme (BACE1) was optimized to address suboptimal pharmacokinetics and poor CNS partitioning. This work identified a series of benzodioxolane analogues that possessed improved metabolic stability and increased oral bioavailability. Subsequent efforts focused on improving CNS exposure by limiting susceptibility to Pgp-mediated efflux and identified an inhibitor which demonstrated robust and sustained reduction of CNS beta-amyloid (A beta) in Sprague-Dawley rats following oral administration.

  DOI：

  10.1021/jm300119p
• 作为产物：
  描述：

  trimethyl 2-(tert-butoxycarbonylamino)phosphonoacetate 在 (1R,2S)-2-tert-butyl-1-((1R,2S)-2-tertbutyl-2,3-dihydro-1H-isophosphindol-1-yl)-2,3-dihydro-1H-isophosphindole 、 氢气 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、344.75 kPa 条件下， 反应 4.33h， 生成 (S)-methyl 3-(3,4-bis(difluoromethoxy)phenyl)-2-(tert-butoxycarbonylamino)propanoate
  参考文献：
  名称：

  Design and Preparation of a Potent Series of Hydroxyethylamine Containing β-Secretase Inhibitors That Demonstrate Robust Reduction of Central β-Amyloid

  摘要：

  A series of potent hydroxyethyl amine (HEA) derived inhibitors of beta-site APP cleaving enzyme (BACE1) was optimized to address suboptimal pharmacokinetics and poor CNS partitioning. This work identified a series of benzodioxolane analogues that possessed improved metabolic stability and increased oral bioavailability. Subsequent efforts focused on improving CNS exposure by limiting susceptibility to Pgp-mediated efflux and identified an inhibitor which demonstrated robust and sustained reduction of CNS beta-amyloid (A beta) in Sprague-Dawley rats following oral administration.

  DOI：

  10.1021/jm300119p