(2R)-2-amino-3-(4-bromophenyl)-N-(3,5-dichlorophenyl)-2-methyl-propionamide | 302840-67-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2R)-2-amino-3-(4-bromophenyl)-N-(3,5-dichlorophenyl)-2-methyl-propionamide
• 英文别名: (R)-2-amino-3-(4-bromophenyl)-N-(3,5-dichlorophenyl)-2-methylpropionamide；(R)-2-amino-2-(4-bromobenzyl)-N-(3,5-dichlorophenyl)propionamide；(2R)-2-amino-3-(4-bromophenyl)-N-(3,5-dichlorophenyl)-2-methylpropanamide
• CAS: 302840-67-1
• 化学式: C₁₆H₁₅BrCl₂N₂O
• 分子量: 402.118
• InChiKey: JXUNUTPDCRASLK-MRXNPFEDSA-N

物化性质

• 沸点：
  551.0±50.0 °C(Predicted)
• 密度：
  1.546±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  3,5-二氯苯胺 在 N-甲基吗啉 、 sodium hydroxide 、 苄基三甲基氢氧化铵 、 三乙胺 、 三氟乙酸 、 lithium hexamethyldisilazane 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 正戊烷 为溶剂， 生成 (2R)-2-amino-3-(4-bromophenyl)-N-(3,5-dichlorophenyl)-2-methyl-propionamide
  参考文献：
  名称：

  立体中心的自我再生：LFA-1拮抗剂BIRT-377的实用对映体合成。

  摘要：

  [反应：见正文]通过8个步骤，LFA-1拮抗剂BIRT-377的有效对映体合成达到了43％的总收率。关键的转化包括反式咪唑烷酮7的立体定向形成，随后的烷基化以及二取代的咪唑烷酮9的有效水解。该方法实用，可靠且具有成本效益。它已在中试工厂成功实施，可生产多千克量的BIRT-377药物。

  DOI：

  10.1021/ol000147v

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。
• 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。
• Regiocontrolled synthesis of highly-functionalized fused imidazoles: a novel synthesis of second generation LFA-1 inhibitors
  作者：Rogelio P. Frutos、Michael Johnson

  DOI：10.1016/s0040-4039(03)01535-1

  日期：2003.8

  A new and reliable route to a new class of LFA-1 inhibitors such as (2) has been developed. A key aspect of this route is the transformation of amino amide 5 into iodide 3 in four steps. Iodide 3 is a key advanced intermediate used in the synthesis of all second-generation 1H-imidazo[1,2-alpha]imidazol-2-one LFA-1 inhibitors. (C) 2003 Elsevier Ltd. All rights reserved.
• Development of a Scalable Process for 1-(3,5-Dichlorophenyl)-5-iodo-3-methyl- (4-methylbenzyl)-1<i>H</i>-imidazo[1,2-<i>a</i>]imidazol-2-one:  A Key Intermediate for the Synthesis of LFA-1 Inhibitors
  作者：Rogelio P. Frutos、Magnus Eriksson、Xiao-Jun Wang、Denis Byrne、Richard Varsolona、Michael D. Johnson、Lawrence Nummy、Dhileepkumar Krishnamurthy、Chris H. Senanayake

  DOI：10.1021/op049813o

  日期：2005.3.1

  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.