tert-butyl 4-(4-(3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidine-1-carboxylate | 1082950-40-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: tert-butyl 4-(4-(3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidine-1-carboxylate
• 英文别名: tert-butyl 4-[5-[3-(trifluoromethyl)phenyl]-1H-imidazol-2-yl]piperidine-1-carboxylate
• CAS: 1082950-40-0
• 化学式: C₂₀H₂₄F₃N₃O₂
• 分子量: 395.425
• InChiKey: HXZJTMNTYSDUCE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  58.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(4-(3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidine-1-carboxylate 、 碘甲烷 在 sodium hydride 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 13.0h， 以76%的产率得到tert-butyl 4-(1-methyl-4-(3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidine-1-carboxylate
  参考文献：
  名称：

  WO2008/140947

  摘要：

  公开号：
• 作为产物：
  描述：

  2-溴-1-(3-(三氟甲基)苯基)乙酮 在 sodium azide 、 ammonium acetate 、 1-丙基磷酸酐 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 水 、 乙酸乙酯 为溶剂， 反应 11.42h， 生成 4-[4-(3-trifluoromethylphenyl)-1H-imidazol-2-yl]piperidine 、 tert-butyl 4-(4-(3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidine-1-carboxylate
  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
• WO2008/140947
  申请人：——

  公开号：——

  公开（公告）日：——
• Rapid Development and Scale-Up of a 1<i>H</i>-4-Substituted Imidazole Intermediate Enabled by Chemistry in Continuous Plug Flow Reactors
  作者：Scott A. May、Martin D. Johnson、Timothy M. Braden、Joel R. Calvin、Brian D. Haeberle、Amy R. Jines、Richard D. Miller、Edward F. Plocharczyk、Gregory A. Rener、Rachel N. Richey、Christopher R. Schmid、Radhe K. Vaid、Hannah Yu

  DOI：10.1021/op200351g

  日期：2012.5.18

  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).