(2S,3S,5S,6R,8S)-8-allyl-6-(3-chlorophenyl)-5-(4-chlorophenyl)-3-ethyl-2,8-dimethyl-2,3,5,6,7,8-hexahydrooxazolo[3,2-a]pyridin-4-ium trifluromethanesulfonate | 1352072-36-6

• 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: (2S,3S,5S,6R,8S)-8-allyl-6-(3-chlorophenyl)-5-(4-chlorophenyl)-3-ethyl-2,8-dimethyl-2,3,5,6,7,8-hexahydrooxazolo[3,2-a]pyridin-4-ium trifluromethanesulfonate
• 英文别名: (2S,3S,5S,6R,8S)-6-(3-chlorophenyl)-5-(4-chlorophenyl)-3-ethyl-2,8-dimethyl-8-prop-2-enyl-3,5,6,7-tetrahydro-2H-[1,3]oxazolo[3,2-a]pyridin-4-ium
• CAS: 1352072-36-6
• 化学式: C₂₆H₃₀Cl₂NO
• 分子量: 443.436
• InChiKey: QIUKRPAMRKUFLL-XSEYPUOTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  12.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (2S,3S,5S,6R,8S)-8-allyl-6-(3-chlorophenyl)-5-(4-chlorophenyl)-3-ethyl-2,8-dimethyl-2,3,5,6,7,8-hexahydrooxazolo[3,2-a]pyridin-4-ium trifluromethanesulfonate 在 potassium permanganate 、 四丁基氯化铵 、 溶剂黄146 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 0.5h， 生成 (2S,3S,5S,6R,7aR,10aS)-6-(3-chlorophenyl)-5-(4-chlorophenyl)-3-ethyl-2,7a-dimethylhexahydrofuro[2,3-b]oxazolo[3,2-a]pyridin-9(5H)-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：

  间氯溴苯 在 2,6-二甲基吡啶 、 RuCI₂[(R)xylbinap][(R)-daipen] 、 potassium tert-butylate 、 水 、 4-甲基苯磺酸吡啶 、 三乙胺 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 lithium hydroxide 、 lithium hexamethyldisilazane 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 甲苯 为溶剂， -50.0~90.0 ℃ 、344.75 kPa 条件下， 反应 244.5h， 生成 (2S,3S,5S,6R,8S)-8-allyl-6-(3-chlorophenyl)-5-(4-chlorophenyl)-3-ethyl-2,8-dimethyl-2,3,5,6,7,8-hexahydrooxazolo[3,2-a]pyridin-4-ium trifluromethanesulfonate
  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

• PIPERIDINONE DERIVATIVES AS MDM2 INHIBITORS FOR THE TREATMENT OF CANCER
  申请人：BARTBERGER Michael David

  公开号：US20110319378A1

  公开（公告）日：2011-12-29

  The present invention provides MDM2 inhibitor compounds of Formula I, wherein the variables are defined above, which compounds are useful as therapeutic agents, particularly for the treatment of cancers. The present invention also relates to pharmaceutical compositions that contain an MDM2 inhibitor.

  本发明提供了公式I的MDM2抑制剂化合物，其中变量如上所定义，这些化合物可用作治疗剂，特别是用于治疗癌症。本发明还涉及含有MDM2抑制剂的药物组合物。
• Piperidinone Derivatives as MDM2 Inhibitors for the Treatment of Cancer
  申请人：AMGEN INC.

  公开号：US20160137667A1

  公开（公告）日：2016-05-19

  The present invention provides MDM2 inhibitor compounds of Formula I, wherein the variables are defined above, which compounds are useful as therapeutic agents, particularly for the treatment of cancers. The present invention also relates to pharmaceutical compositions that contain an MDM2 inhibitor.

  本发明提供了式I的MDM2抑制剂化合物，其中变量如上所定义，该化合物可用作治疗剂，特别是用于治疗癌症。本发明还涉及含有MDM2抑制剂的制药组合物。
• US8569341B2
  申请人：——

  公开号：US8569341B2

  公开（公告）日：2013-10-29
• US9296736B2
  申请人：——

  公开号：US9296736B2

  公开（公告）日：2016-03-29
• 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.