3-(4-bromobenzyl)-1-(3,5-dichlorophenyl)-3-methyl-1,6-dehydroimidazo[1,2-a]imidazole-2,5-dione | 397329-88-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 3-(4-bromobenzyl)-1-(3,5-dichlorophenyl)-3-methyl-1,6-dehydroimidazo[1,2-a]imidazole-2,5-dione
• 英文别名: (5R)-5-[(4-bromophenyl)methyl]-7-(3,5-dichlorophenyl)-5-methyl-2H-imidazo[1,2-a]imidazole-3,6-dione
• CAS: 397329-88-3
• 化学式: C₁₉H₁₄BrCl₂N₃O₂
• 分子量: 467.149
• InChiKey: IPUSXBRIHIMPOO-LJQANCHMSA-N

物化性质

• 熔点：
  82-84 °C(Solv: toluene (108-88-3))
• 沸点：
  554.4±60.0 °C(Predicted)
• 密度：
  1.66±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  53
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(4-bromobenzyl)-1-(3,5-dichlorophenyl)-3-methyl-1,6-dehydroimidazo[1,2-a]imidazole-2,5-dione 在 三甲基氯硅烷 、 双(三甲基硅烷基)氨基钾 、 sodium iodide 作用下， 以 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 1.33h， 生成 (R)-3-(4-bromobenzyl)-1-(3,5-dichlorophenyl)-5-iodo-3-methyl-1H-imidazo[1,2-α]imidazol-2-one
  参考文献：
  名称：

  Development of a Scalable Process for 1-(3,5-Dichlorophenyl)-5-iodo-3-methyl- (4-methylbenzyl)-1H-imidazo[1,2-a]imidazol-2-one:  A Key Intermediate for the Synthesis of LFA-1 Inhibitors

  摘要：

  A safe, robust, chromatography-free and reproducible process for the multi-kilogram synthesis of vinyl iodide 2, a key intermediate for the synthesis of LFA-1 inhibitors, was developed and implemented at the pilot plant. Execution of the above process allowed us to support preclinical activities in the LFA-1 program.

  DOI：

  10.1021/op049813o
• 作为产物：
  描述：

  (2R)-2-amino-3-(4-bromophenyl)-N-(3,5-dichlorophenyl)-2-methyl-propionamide 在 Celite 、 三甲基乙酰氯 、 对甲苯磺酸 、 N,N-二异丙基乙胺 、 copper(l) chloride 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 、 乙腈 为溶剂， 反应 0.5h， 生成 3-(4-bromobenzyl)-1-(3,5-dichlorophenyl)-3-methyl-1,6-dehydroimidazo[1,2-a]imidazole-2,5-dione
  参考文献：
  名称：

  A practical synthesis of LFA-1 inhibitors utilizing CuCl-promoted intramolecular cyclization of thiohydantoins

  摘要：

  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

  DOI：

  10.1016/j.tetlet.2004.11.065

文献信息

• A Practical Synthesis of Highly Functionalized Fused 1,6-Dihydroimidazo-[1,2-<i>a</i>]imidazole-2,5-diones, Key Intermediates for LFA-1 Inhibitors
  作者：Xiao-jun Wang、Yibo Xu、Li Zhang、Dhileepkumar Krishnamurthy、Laurence Nummy、Vittorio Farina、Chris Senanayake

  DOI：10.1055/s-2004-835638

  日期：——

  An alternative and chromatography-free approach for synthesis of a new class of LFA-1 inhibitors was developed. A key feature of this process involved a transformation of thioureas 14 to acyclic guanidine derivatives 9 followed by intramolecular cyclization to highly functionalized bicyclic guanidines 1, that were sub­sequently converted to 1H-imidazo[1,2-a]imidazol-2-one LFA-1 inhibitors.

  我们开发了一种无色谱法合成新型 LFA-1 抑制剂的替代方法。该方法的一个主要特点是将硫脲类化合物 14 转化为无环胍衍生物 9，然后进行分子内环化，生成高官能度的双环胍类化合物 1，随后转化为 1H-咪唑并[1,2-a]咪唑-2-酮 LFA-1 抑制剂。
• Synthesis of (R)-3-(4-Bromobenzyl)-1-(3,5-dichlorophenyl)-5-iodo-3-methyl-1-H-imidazo[1,2-a]imidazol-2-one
  申请人：——

  公开号：US20020028949A1

  公开（公告）日：2002-03-07

  A novel process for the preparation of (R)-3-(4-Bromobenzyl)-1-(3,5-dichlorophenyl)-5-iodo-3-methyl-1-H-imidazo[1,2-&agr;]imidazol-2-one (1): 1 This compound is useful as an intermediate in the preparation of certain small molecules that are useful in the treatment of prevention of inflammatory and immune cell-mediated diseases. The present invention also relates to certain intermediates used in this novel process.

  一种新的制备(R)-3-(4-溴苯基)-1-(3,5-二氯苯基)-5-碘-3-甲基-1H-咪唑[1,2-a]咪唑-2-酮(1)的方法：该化合物在制备某些小分子用于治疗和预防炎症和免疫细胞介导疾病的过程中作为中间体有用。本发明还涉及在这种新的过程中使用的某些中间体。
• (R)-3-(4-bromobenzyl)-1-(3,5-dichlorophenyl)-3-methyl-1,6-dihydroimidazo&lsqb;1,2-a&rsqb;imidazole-2,5-dione
  申请人：Boehringer Ingelheim Pharmaceuticals, Inc.

  公开号：US06433183B1

  公开（公告）日：2002-08-13

  A novel process for the preparation of (R)-3-(4-Bromobenzyl)-1-(3,5-dichlorophenyl)-5-iodo-3-methyl-1-H-imidazo[1,2-&agr;]imidazol-2-one (1): This compound is useful as an intermediate in the preparation of certain small molecules that are useful in the treatment or prevention of inflammatory and immune cell-mediated diseases. The present invention also relates to certain intermediates used in this novel process.

  一种制备(R)-3-(4-溴苯基)-1-(3,5-二氯苯基)-5-碘-3-甲基-1H-咪唑[1,2-a]咪唑-2-酮（1）的新工艺：该化合物可作为某些小分子的中间体，这些小分子对治疗或预防炎症和免疫细胞介导的疾病有用。本发明还涉及用于该新工艺的某些中间体。
• INTERMEDIATE FOR (R)-3-(4-BROMOBENZYL)-1-(3,5-DICHLOROPHENYL)-5-IODO-3-METHYL-1-H-IMIDAZO[1,2-A]IMIDAZOL-2-ONE
  申请人：——

  公开号：US20020082441A1

  公开（公告）日：2002-06-27

  A novel process for the preparation of (R)-3-(4-Bromobenzyl)-1-(3,5-dichlorophenyl)-5-iodo-3-methyl-1-H-imidazo[1,2-a]imidazol-2-one (1): 1 This compound is useful as an intermediate in the preparation of certain small molecules that are useful in the treatment or prevention of inflammatory and immune cell-mediated diseases. The present invention also relates to certain intermediates used in this novel process.

  制备(R)-3-(4-溴苄基)-1-(3,5-二氯苯基)-5-碘-3-甲基-1-H-咪唑[1,2-a]咪唑-2-酮(1)的新工艺： 1 该化合物可用作制备某些小分子化合物的中间体，这些小分子化合物可用于治疗或预防炎症和免疫细胞介导的疾病。本发明还涉及用于这种新工艺的某些中间体。
• INTERMEDIATES FOR (R)-3(4-BROMOBENZYL)-1-(3,5-DICHLOROPHENYL)-5-IODO-3-METHYL-1-H-IMIDAZO[1,2-A] IMIDAZOL-2-ONE
  申请人：——

  公开号：US20020087009A1

  公开（公告）日：2002-07-04

  A novel process for the preparation of (R)-3-(4-Bromobenzyl)-1-(3,5-dichlorophenyl)-5-iodo-3-methyl-1-H-imidazo[1 ,2-a]imidazol-2-one (1): 1 This compound is useful as an intermediate in the preparation of certain small molecules that are useful in the treatment or prevention of inflammatory and immune cell-mediated diseases. The present invention also relates to certain intermediates used in this novel process.

  一种制备(R)-3-(4-溴苄基)-1-(3,5-二氯苯基)-5-碘-3-甲基-1-H-咪唑[1,2-a]咪唑-2-酮(1)的新工艺： 1 该化合物可用作制备某些小分子化合物的中间体，这些小分子化合物可用于治疗或预防炎症和免疫细胞介导的疾病。本发明还涉及用于这种新工艺的某些中间体。