4-[2-oxo-2-(3-trifluoromethyl-phenyl)-ethylcarbamoyl]piperidine-1-carboxylic acid tert-butyl ester | 1082949-93-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-[2-oxo-2-(3-trifluoromethyl-phenyl)-ethylcarbamoyl]piperidine-1-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl 4-(2-oxo-2-(3-(trifluoromethyl)phenyl)ethylcarbamoyl)piperidine-1-carboxylate；Tert-butyl 4-((2-oxo-2-(3-(trifluoromethyl)phenyl)ethyl)carbamoyl)piperidine-1-carboxylate；tert-butyl 4-[[2-oxo-2-[3-(trifluoromethyl)phenyl]ethyl]carbamoyl]piperidine-1-carboxylate
• CAS: 1082949-93-6
• 化学式: C₂₀H₂₅F₃N₂O₄
• 分子量: 414.425
• InChiKey: NOGILORWSQYUJQ-UHFFFAOYSA-N

物化性质

• 沸点：
  533.8±50.0 °C(Predicted)
• 密度：
  1.240±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  75.7
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-[2-oxo-2-(3-trifluoromethyl-phenyl)-ethylcarbamoyl]piperidine-1-carboxylic acid tert-butyl ester 在 乙醇 、 氯化铵 作用下， 120.0~160.0 ℃ 、1.38 MPa 条件下， 反应 16.0h， 以75%的产率得到4-[4-(3-trifluoromethylphenyl)-1H-imidazol-2-yl]piperidine
  参考文献：
  名称：

  WO2008/140947

  摘要：

  公开号：
• 作为产物：
  描述：

  间三氟甲基苯乙酮 在 sodium azide 、 溴 、 1-丙基磷酸酐 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 10.42h， 生成 4-[2-oxo-2-(3-trifluoromethyl-phenyl)-ethylcarbamoyl]piperidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Rapid Development and Scale-Up of a 1H-4-Substituted Imidazole Intermediate Enabled by Chemistry in Continuous Plug Flow Reactors

  摘要：

  The development of reactions in a continuous fashion in plug flow tube reactors (PFR) offers unique advantages to the drug development and scale-up process and can also enable chemistry that would be difficult to perform via batch processing. Herein, we report the development of two different continuous flow approaches to a key 1H-4-substituted imidazole intermediate (5). In a first generation approach, rapid optimization and scale-up of a challenging cyclization reaction was demonstrated in a PFR under GMP conditions to afford 29 kg of protected product 2. This material was further processed in batch equipment to deliver di-HCl salt 4. This first generation approach highlights the rapid development of chemistry in research-scale PFRs and speed to material delivery through linear scale up to a pilot-scale PFR under GMP conditions. In a second generation effort, a more efficient synthetic route was developed, and PFRs with automated sampling, dilution, and analytical analysis allowed for rapid and data-rich reaction optimization of both a key cyclization reaction and thermal removal of a Boc protecting group. This work culminated in 1 kg demonstration runs in a 0.22 L PFR for both continuous steps and shows the potential of commercialization from a lab hood footprint (1-2 MT/year).

  DOI：

  10.1021/op200351g

文献信息

• P70 S6 kinase inhibitors
  申请人：Eli Lilly and Company

  公开号：US08093383B2

  公开（公告）日：2012-01-10

  The present invention provides p70 S6 kinase inhibitors of the formula: pharmaceutical formulations comprising them, and methods for their use.

  本发明提供了式为p70 S6激酶抑制剂的制剂：包括它们的药物制剂，以及使用它们的方法。
• P70 S6 KINASE INHIBITORS
  申请人：Dally Robert Dean

  公开号：US20120071490A1

  公开（公告）日：2012-03-22

  The present invention provides p70 S6 kinase inhibitors of the formula: pharmaceutical formulations comprising them, and methods for their use.

  本发明提供了公式为：p70 S6激酶抑制剂的制剂，以及包含它们的药物制剂和使用它们的方法。
• US8093383B2
  申请人：——

  公开号：US8093383B2

  公开（公告）日：2012-01-10
• [EN] P70 S6 KINASE INHIBITORS<br/>[FR] INHIBITEURS DE LA P70 S6 KINASE
  申请人：LILLY CO ELI

  公开号：WO2008140947A1

  公开（公告）日：2008-11-20

  [EN] The present invention provides p70 S6 kinase inhibitors of the formula: pharmaceutical formulations comprising them, and methods for their use.
  [FR] La présente invention concerne des inhibiteurs de la p70 S6 kinase de formule : des formulations pharmaceutiques comprenant ces inhibiteurs et leurs procédés d'utilisation.