(S)-2-((2R,3R)-2-(3-chlorophenyl)-3-(4-chlorophenyl)-3-hydroxypropyl)-N-((S)-1-hydroxybutan-2-yl)-2-methylpent-4-enamide | 1388625-18-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: (S)-2-((2R,3R)-2-(3-chlorophenyl)-3-(4-chlorophenyl)-3-hydroxypropyl)-N-((S)-1-hydroxybutan-2-yl)-2-methylpent-4-enamide
• 英文别名: (2S)-2-[(2R,3R)-2-(3-chlorophenyl)-3-(4-chlorophenyl)-3-hydroxypropyl]-N-[(2S)-1-hydroxybutan-2-yl]-2-methylpent-4-enamide
• CAS: 1388625-18-0
• 化学式: C₂₅H₃₁Cl₂NO₃
• 分子量: 464.432
• InChiKey: CYGYGFCIRNSCCZ-AANQFLQQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  31
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  69.6
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-2-((2R,3R)-2-(3-chlorophenyl)-3-(4-chlorophenyl)-3-hydroxypropyl)-N-((S)-1-hydroxybutan-2-yl)-2-methylpent-4-enamide 在 2,6-二甲基吡啶 、 水 、 碳酸氢钠 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-3-methylpiperidin-2-one
  参考文献：
  名称：

  An Expeditious Synthesis of the MDM2–p53 Inhibitor AM-8553

  摘要：

  The development of the structurally complex MDM2/p53 inhibitor AM-8553 was impeded by the low yield of the initial synthesis. A second generation synthesis is described that features a Noyori dynamic kinetic resolution, a highly diastereoselective allylation, and a novel oxazoline-assisted piperidinone forming reaction to provide AM-8553 in 35.6% yield and 11 steps.

  DOI：

  10.1021/ja305123v
• 作为产物：
  描述：

  methyl 4-(3-chlorophenyl)-5-(4-chlorophenyl)-2-methyl-5-oxopentanoate 在 RuCI₂[(R)xylbinap][(R)-daipen] 、 potassium tert-butylate 、 水 、 4-甲基苯磺酸吡啶 、 lithium hydroxide 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， -35.0~100.0 ℃ 、344.75 kPa 条件下， 反应 117.5h， 生成 (S)-2-((2R,3R)-2-(3-chlorophenyl)-3-(4-chlorophenyl)-3-hydroxypropyl)-N-((S)-1-hydroxybutan-2-yl)-2-methylpent-4-enamide
  参考文献：
  名称：

  An Expeditious Synthesis of the MDM2–p53 Inhibitor AM-8553

  摘要：

  The development of the structurally complex MDM2/p53 inhibitor AM-8553 was impeded by the low yield of the initial synthesis. A second generation synthesis is described that features a Noyori dynamic kinetic resolution, a highly diastereoselective allylation, and a novel oxazoline-assisted piperidinone forming reaction to provide AM-8553 in 35.6% yield and 11 steps.

  DOI：

  10.1021/ja305123v

文献信息

• An Expeditious Synthesis of the MDM2–p53 Inhibitor AM-8553
  作者：Brian S. Lucas、Benjamin Fisher、Lawrence R. McGee、Steven H. Olson、Julio C. Medina、Eugene Cheung

  DOI：10.1021/ja305123v

  日期：2012.8.1

  The development of the structurally complex MDM2/p53 inhibitor AM-8553 was impeded by the low yield of the initial synthesis. A second generation synthesis is described that features a Noyori dynamic kinetic resolution, a highly diastereoselective allylation, and a novel oxazoline-assisted piperidinone forming reaction to provide AM-8553 in 35.6% yield and 11 steps.