(2R,5R)-3-(3,5-二氯苯基)-2-异丙基-5-甲基-1-(2,2,2-三氯乙酰基)-咪唑烷-4-酮 | 341027-25-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 中文名称: (2R,5R)-3-(3,5-二氯苯基)-2-异丙基-5-甲基-1-(2,2,2-三氯乙酰基)-咪唑烷-4-酮
• 英文名称: (2R,5R)-3-(3,5-dichlorophenyl)-2-isopropyl-5-methyl-1-(2,2,2-trichloroacetyl)-imidazolidin-4-one
• 英文别名: (2S,5R)-3-(3,5-dichlorophenyl)-2-isopropyl-5-methyl-1-(2,2,2-trifluoroacetyl)imidazolidin-4-one；(2S,5R)-3-(3,5-dichloro-phenyl)-2-isopropyl-5-methyl-1-(2,2,2-trifluoroacetyl)-imidazolidin-4-one；(2S,5R)-3-(3,5-dichlorophenyl)-5-methyl-2-propan-2-yl-1-(2,2,2-trifluoroacetyl)imidazolidin-4-one
• CAS: 341027-25-6
• 化学式: C₁₅H₁₅Cl₂F₃N₂O₂
• 分子量: 383.198
• InChiKey: QEGGHVPQKVXLHC-PELKAZGASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  40.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R,5R)-3-(3,5-二氯苯基)-2-异丙基-5-甲基-1-(2,2,2-三氯乙酰基)-咪唑烷-4-酮 在 硫酸 、 potassium tert-butylate 、 水 、 sodium methylate 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 1.0h， 生成 (R)-5-(4-bromobenzyl)-3-(3,5-dichlorophenyl)-5-methylimidazolidine-2,4-dione
  参考文献：
  名称：

  An improved synthesis of N-aryl-hydantoin LFA-1 antagonists via the enantiospecific alkylation of an isobutyraldehyde-derived imidazolidinone template

  摘要：

  An improved and cost-effective process for the synthesis of N-aryl-hydantoin LFA-1 antagonists is described. Key transformations include the synthesis and stereospecific alkylation of the trans-isobutyraldehyde-derived template 4, and the one-pot hydrolysis of intermediate 6. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(01)00009-x
• 作为产物：
  描述：

  (2R)-2-amino-N-(3,5-dichlorophenyl)-propionamide 在 三乙胺 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 13.5h， 生成 (2R,5R)-3-(3,5-二氯苯基)-2-异丙基-5-甲基-1-(2,2,2-三氯乙酰基)-咪唑烷-4-酮
  参考文献：
  名称：

  An improved synthesis of N-aryl-hydantoin LFA-1 antagonists via the enantiospecific alkylation of an isobutyraldehyde-derived imidazolidinone template

  摘要：

  An improved and cost-effective process for the synthesis of N-aryl-hydantoin LFA-1 antagonists is described. Key transformations include the synthesis and stereospecific alkylation of the trans-isobutyraldehyde-derived template 4, and the one-pot hydrolysis of intermediate 6. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(01)00009-x

文献信息

• Synthesis of 6,7-Dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonic acid amides
  申请人：WIRTH Thomas

  公开号：US20070173517A1

  公开（公告）日：2007-07-26

  Disclosed is an improved multi-step process for preparing a compound of Formula I: wherein R 1 to R 3 are as defined herein. The compounds of formula I inhibit the binding of human intercellular adhesion molecules to the Leukointegrins. As a result, these compounds are useful in the treatment of inflammatory and immune cell-mediated diseases.

  公开了一种改进的多步骤制备Formula I化合物的方法：其中R1到R3如本文所定义。 Formula I化合物抑制人类细胞间粘附分子与白细胞整合素的结合。因此，这些化合物在治疗炎症和免疫介导的细胞疾病方面是有用的。
• Synthesis of 6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonic acid amides
  申请人：Wang Xiao-Jun

  公开号：US20060025447A1

  公开（公告）日：2006-02-02

  Disclosed is a multi-step process for preparing a compound of Formula I: wherein R 1 to R 3 are as defined herein. The compounds of formula I inhibit the binding of human intercellular adhesion molecules to the Leukointegrins. As a result, these compounds are useful in the treatment of inflammatory and immune cell-mediated diseases.

  公开了一种制备化合物I的多步过程：其中R1至R3如本文所定义。化合物I的公式抑制人体细胞间粘附分子与白细胞整合素的结合。因此，这些化合物在治疗炎症和免疫细胞介导的疾病中是有用的。
• Asymmetric Synthesis of LFA-1 Inhibitor BIRT2584 on Metric Ton Scale
  作者：Xiao-Jun Wang、Rogelio P. Frutos、Li Zhang、Xiufeng Sun、Yibo Xu、Thomas Wirth、Thomas Nicola、Lawrence J. Nummy、Dhileep Krishnamurthy、Carl A. Busacca、Nathan Yee、Chris H. Senanayake

  DOI：10.1021/op200175t

  日期：2011.9.16

  The synthesis of LFA-1 inhibitor BIRT2584 on metric-ton scale was accomplished by means of a safe and robust process. Highlights of the process include the asymmetric synthesis of the key advanced intermediate by implementation of Seebach’s self-regeneration of stereocenters principle, and a Ph3PCl2-induced dehydration of a critical urea followed by a regioselective bromination to give the elaborated

  LFA-1抑制剂BIRT2584的合成以公吨为单位，是通过安全，可靠的方法完成的。该方法的亮点包括通过实施Seebach立体中心原理的自我再生来不对称合成关键高级中间体，以及Ph 3 PCl 2诱导的关键尿素脱水，然后进行区域选择性溴化，得到了精细的1 H-咪唑[1,2 - a ]咪唑-2-one。通过碘代咪唑的Br / Mg交换，然后在THF中添加至SO 2并随后进行氧化，可制得磺酰氯中间体。在一个单釜操作中，磺酰氯直接反应用升-在DMF / THF水溶液中使用NaOH作为碱的α-丙氨酰胺，得到BIRT2584。
• A practical synthesis of LFA-1 inhibitors utilizing CuCl-promoted intramolecular cyclization of thiohydantoins
  作者：Xiao-jun Wang、Li Zhang、Yibo Xu、Dhileepkumar Krishnamurthy、Richard Varsolona、Laurence Nummy、Sherry Shen、Rogelio P. Frutos、Denis Byrne、J.C. Chung、Vittorio Farina、Chris H. Senanayake

  DOI：10.1016/j.tetlet.2004.11.065

  日期：2005.1

  An efficient and chromatography-free approach for synthesis of a new class of LFA- I inhibitor was developed. A copper(I) chloride-promoted intramolecular cyclization of thiohydantoins 7a-b serves as a key step to highly functionalized bicyclic guanidines 5a-b, that were subsequently converted to H-imidazol[l,2-a]imidazol-2-one LFA-1 inhibitors. This process has been successfully implemented in the pilot plant to produce multikilogram quantities of LFA-1 inhibitors such as la-b. (C) 2004 Elsevier Ltd. All ri.-hts reserved
• Efficient Synthesis of a Small Molecule, Nonpeptide Inhibitor of LFA-1
  作者：Xiao-jun Wang、Yibo Xu、Li Zhang、Dhileepkumar Krishnamurthy、Thomas Wirth、Thomas Nicola、Chris H. Senanayake

  DOI：10.1021/ol101960x

  日期：2010.10.1

  A three-stage process for the synthesis of LFA-1 inhibitor 1 from amine 4 with an overall yield of 65% is described. The key stage involves a Ph(3)PCl(2)-induced dehydration/cyclization of urea 6 followed by a regioselective bromination to give (1)H-imidazo[1,2-a]imidazol-2-one 9. Br/Mg exchange of 9 followed by addition to SO(2) in THF and subsequent oxidation produces a sulfonyl chloride which is directly reacted with L-alaninamide using K(2)CO(3) as base in aqueous DMF/THF to give 1 in a one-pot operation. The process was implemented for the production of 1 on a metric ton scale.