2-azido-1-(3-(trifluoromethyl)phenyl)ethanone | 61062-57-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-azido-1-(3-(trifluoromethyl)phenyl)ethanone
• 英文别名: 2-Azido-3'-trifluormethylacetophenon；2-Azido-1-[3-(trifluoromethyl)phenyl]ethan-1-one；2-azido-1-[3-(trifluoromethyl)phenyl]ethanone
• CAS: 61062-57-5
• 化学式: C₉H₆F₃N₃O
• mdl: MFCD09745932
• 分子量: 229.161
• InChiKey: KPJZFNJMPHEHRB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.222
• 拓扑面积：
  31.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-azido-1-(3-(trifluoromethyl)phenyl)ethanone 在 ammonium acetate 、 1-丙基磷酸酐 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 为溶剂， 反应 11.42h， 生成 (4-[4-(3-trifluoromethyl-phenyl)-1H-imidazol-2-yl]-piperidine) dihydrochloride
  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
• 作为产物：
  描述：

  间三氟甲基苯乙酮 在 sodium azide 、 oxone 、 溴化铵 作用下， 以 甲醇 、 水 、 丙酮 为溶剂， 生成 2-azido-1-(3-(trifluoromethyl)phenyl)ethanone
  参考文献：
  名称：

  松萝酸烯胺酮偶联的1,2,3-三唑类用作抗菌剂和抗结核剂。

  摘要：

  （+）-尿酸是地衣中的二次代谢产物，具有广泛的生物学特性，例如抗肿瘤，抗微生物，抗病毒，抗炎和杀虫活性。对这些药理活性感兴趣并挖掘其潜力，我们在此介绍新的松萝酸烯胺酮偶联的1,2,3-三唑10-44作为抗分枝杆菌药的合成和生物学评估。将（+）-松香酸与炔丙基胺缩合，得到具有末端乙炔基部分的松香酸烯胺酮8。在铜催化下，它进一步与各种叠氮化物A1-A35反应，以高收率得到三唑10-44。在合成的化合物中，糖精衍生物36被证明是活性最高的类似物，在MIC值为2.5μM时可抑制结核分枝杆菌（Mtb）。类似物16和27，以及3，4-二氟苯酰基和2-酰基萘单元分别在MIC值为5.4和5.3μM时抑制Mtb。在测试的革兰氏阳性和革兰氏阴性细菌中，新衍生物对枯草芽孢杆菌具有活性，化合物18 [3-（三氟甲基）苯甲酰基]和29（N-酰基吗啉基）分别显示抑制浓度41和90.7μM，而它们对其他测试细菌菌株没有

  DOI：

  10.1021/acs.jnatprod.9b00475

文献信息

• Semipinacol rearrangements involving trifluoromethylphenyl groups
  作者：Fernando E. Blanco、Francis L. Harris

  DOI：10.1021/jo00425a023

  日期：1977.3
• Usnic Acid Enaminone-Coupled 1,2,3-Triazoles as Antibacterial and Antitubercular Agents
  作者：Pavan K. Bangalore、Siva K. Vagolu、Rakesh K. Bollikanda、Dileep K. Veeragoni、Pallavi C. Choudante、Sunil Misra、Dharmarajan Sriram、Balasubramanian Sridhar、Srinivas Kantevari

  DOI：10.1021/acs.jnatprod.9b00475

  日期：2020.1.24

  be the most active analogue, inhibiting Mycobacterium tuberculosis (Mtb) at an MIC value of 2.5 μM. Analogues 16 and 27, with 3,4-difluorophenacyl and 2-acylnaphthalene units, respectively, inhibited Mtb at MIC values of 5.4 and 5.3 μM, respectively. Among the tested Gram-positive and Gram-negative bacteria, the new derivatives were active on Bacillus subtilis, with compounds 18 [3-(trifluoromethyl)phenacyl]

  （+）-尿酸是地衣中的二次代谢产物，具有广泛的生物学特性，例如抗肿瘤，抗微生物，抗病毒，抗炎和杀虫活性。对这些药理活性感兴趣并挖掘其潜力，我们在此介绍新的松萝酸烯胺酮偶联的1,2,3-三唑10-44作为抗分枝杆菌药的合成和生物学评估。将（+）-松香酸与炔丙基胺缩合，得到具有末端乙炔基部分的松香酸烯胺酮8。在铜催化下，它进一步与各种叠氮化物A1-A35反应，以高收率得到三唑10-44。在合成的化合物中，糖精衍生物36被证明是活性最高的类似物，在MIC值为2.5μM时可抑制结核分枝杆菌（Mtb）。类似物16和27，以及3，4-二氟苯酰基和2-酰基萘单元分别在MIC值为5.4和5.3μM时抑制Mtb。在测试的革兰氏阳性和革兰氏阴性细菌中，新衍生物对枯草芽孢杆菌具有活性，化合物18 [3-（三氟甲基）苯甲酰基]和29（N-酰基吗啉基）分别显示抑制浓度41和90.7μM，而它们对其他测试细菌菌株没有
• 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).