2-phenyl-4-(1-(S)-amino-2-phenylethyl)-1H-imidazole | 852248-39-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-phenyl-4-(1-(S)-amino-2-phenylethyl)-1H-imidazole
• 英文别名: (1S)-2-phenyl-1-(2-phenyl-1H-imidazol-5-yl)ethanamine
• CAS: 852248-39-6
• 化学式: C₁₇H₁₇N₃
• 分子量: 263.342
• InChiKey: QWDACSZUGZZZDC-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  54.7
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-phenyl-4-(1-(S)-amino-2-phenylethyl)-1H-imidazole 在 吡啶 、 双(2-氧代-3-恶唑烷基)次磷酰氯 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 生成 trans-4-(aminomethyl)-N-((S)-2-phenyl-1-(2-phenyl-1H-imidazol-4-yl)ethyl)cyclohexanecarboxamide bis(trifluoroacetic acid) salt
  参考文献：
  名称：

  Phenylimidazoles as Potent and Selective Inhibitors of Coagulation Factor XIa with in Vivo Antithrombotic Activity

  摘要：

  Novel inhibitors of FXIa containing an (S)-2-phenyl-1-(4-phenyl-1H-imidazol-2-yl)ethanamine core have been optimized to provide compound 16b, a potent, reversible inhibitor of FXIa (K-i = 0.3 nM) having in vivo antithrombotic efficacy in the rabbit AV-shunt thrombosis model (ID50 = 0.6 mg/kg + 1 mg kg(-1) h(-1)). Initial analog selection was informed by molecular modeling using compounds 11a and 11h overlaid onto the X-ray crystal structure of tetrahydroquinoline 3 complexed to FXIa. Further optimization was achieved by specific modifications derived from careful analysis of the X-ray crystal structure of the FXIa/11h complex. Compound 16b was well tolerated and enabled extensive pharmacologic evaluation of the FXIa mechanism up to the ID90 for thrombus inhibition.

  DOI：

  10.1021/jm5010607
• 作为产物：
  描述：

  (S)-3-Z-氨基-1-重氮基-3-苯基-2-丁酮 在 palladium on activated charcoal 氢溴酸 、 氢气 、 potassium hydrogencarbonate 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 1.0h， 生成 2-phenyl-4-(1-(S)-amino-2-phenylethyl)-1H-imidazole
  参考文献：
  名称：

  Chiral imidazole derivatives synthesis from enantiopure N-protected α-amino acids

  摘要：

  A route to the preparation of enantiopure ligands based on a 2-phenylimidazol ring is described. The stereogenic centre is placed into the chain bonded to the fourth carbon of the imidazole ring. The synthesis starts from inexpensive and readily available N-protected alpha-amino acids, as the source of chirality, which are converted into appropriate alpha-diazoketones and, consequently, into alpha-bromoketones. These alpha-bromoketones are good precursors for reactions with amidines to provide the imidazole ring. The deprotection into the final products was carried out using hydrogen. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2005.01.049

文献信息

• Imidazole-based Potential Bi- and Tridentate Nitrogen Ligands: Synthesis, Characterization and Application in Asymmetric Catalysis
  作者：Roman Sívek、Filip Bureš、Oldřich Pytela、Jiří Kulhánek

  DOI：10.3390/molecules13092326

  日期：——

  Twelve new imidazole-based potential bi- and tridentate ligands were synthesized and characterized. Whereas in the first series the α-amino acid and imidazole moieties were linked by an amino bond, in the second series the tridentate ligands, containing two imidazole groups, were separated by an amide bond. The first series was obtained by the reductive amination of 2-phenylimidazole-4-carboxaldehyde with α-amino acid esters. The tridentate ligands were prepared from 2-phenylimidazole-4-carboxylic acid and chiral amines. In the Henry reaction, the amines were revealed as a more reactive species than the less nucleophilic amides, however the enantiomeric excesses were generally poor.

  合成并表征了十二种新的基于咪唑的潜在双齿和三齿配体。第一系列中，α-氨基酸和咪唑部分通过氨基键连接，而在第二系列中，含有两个咪唑基团的三齿配体通过酰胺键分隔。第一系列是通过2-苯基咪唑-4-醛与α-氨基酸酯的还原胺化反应获得的。三齿配体则是由2-苯基咪唑-4-羧酸和手性胺制备而成。在亨利反应中，胺显示出比亲核性较低的酰胺更具反应性，然而，通常情况下，外消旋过量较低。
• Novel nitrogen ligands based on imidazole derivatives and their application in asymmetric catalysis
  作者：Filip Bureš、Tomáš Szotkowski、Jiří Kulhánek、Oldřich Pytela、Miroslav Ludwig、Michal Holčapek

  DOI：10.1016/j.tetasy.2006.03.005

  日期：2006.3

  spectroscopy. The structures of the prepared ligands were also confirmed by APCI mass spectroscopy. Both chiral amines and tridentate compounds have been applied as ligands in copper (II)-catalyzed nitroaldol reactions (Henry reaction). Various reaction conditions for the Henry reaction have been studied (influence of temperature, molar ratio, solvent or copper (II) precursors). The compounds prepared with

  最近制备的手性胺已用于基于咪唑环和附加的（杂）环的新型三齿配体的制备。通过手性胺与合适的醛（2-苯基咪唑-4-甲醛，2-羟基苯甲醛或吡啶-2-甲醛）在还原条件（H 2 / Pd或NaBH 4）下反应进行合成。制备的所有配体在d 6 -DMSO溶液中均显示强氢键，从而导致咪唑互变异构现象受阻。观察到的受阻互变异构现象由1进行研究1 H NMR光谱。制备的配体的结构也通过APCI质谱法确认。手性胺和三齿化合物都已被用作铜（II）催化的硝基醛醇缩合反应（亨利反应）中的配体。已经研究了亨利反应的各种反应条件（温度，摩尔比，溶剂或铜（II）前体的影响）。与其他手性胺相比，用两个咪唑环制备的化合物显示出快速的反应时间和对映选择性的逆转。
• Phenylimidazoles as Potent and Selective Inhibitors of Coagulation Factor XIa with in Vivo Antithrombotic Activity
  作者：Jon J. Hangeland、Todd J. Friends、Karen A. Rossi、Joanne M. Smallheer、Cailan Wang、Zhong Sun、James R. Corte、Tianan Fang、Pancras C. Wong、Alan R. Rendina、Frank A. Barbera、Jeffrey M. Bozarth、Joseph M. Luettgen、Carol A. Watson、Ge Zhang、Anzhi Wei、Vidhyashankar Ramamurthy、Paul E. Morin、Gregory S. Bisacchi、Srinath Subramaniam、Piramanayagam Arunachalam、Arvind Mathur、Dietmar A. Seiffert、Ruth R. Wexler、Mimi L. Quan

  DOI：10.1021/jm5010607

  日期：2014.12.11

  Novel inhibitors of FXIa containing an (S)-2-phenyl-1-(4-phenyl-1H-imidazol-2-yl)ethanamine core have been optimized to provide compound 16b, a potent, reversible inhibitor of FXIa (K-i = 0.3 nM) having in vivo antithrombotic efficacy in the rabbit AV-shunt thrombosis model (ID50 = 0.6 mg/kg + 1 mg kg(-1) h(-1)). Initial analog selection was informed by molecular modeling using compounds 11a and 11h overlaid onto the X-ray crystal structure of tetrahydroquinoline 3 complexed to FXIa. Further optimization was achieved by specific modifications derived from careful analysis of the X-ray crystal structure of the FXIa/11h complex. Compound 16b was well tolerated and enabled extensive pharmacologic evaluation of the FXIa mechanism up to the ID90 for thrombus inhibition.
• Chiral imidazole derivatives synthesis from enantiopure N-protected α-amino acids
  作者：Filip Bureš、Jiří Kulhánek

  DOI：10.1016/j.tetasy.2005.01.049

  日期：2005.4

  A route to the preparation of enantiopure ligands based on a 2-phenylimidazol ring is described. The stereogenic centre is placed into the chain bonded to the fourth carbon of the imidazole ring. The synthesis starts from inexpensive and readily available N-protected alpha-amino acids, as the source of chirality, which are converted into appropriate alpha-diazoketones and, consequently, into alpha-bromoketones. These alpha-bromoketones are good precursors for reactions with amidines to provide the imidazole ring. The deprotection into the final products was carried out using hydrogen. (c) 2005 Elsevier Ltd. All rights reserved.