phosphoric acid 5-(4-bromobenzyl)-7-(3,5-dichlorophenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazol-3-yl ester diethyl ester | 397329-89-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: phosphoric acid 5-(4-bromobenzyl)-7-(3,5-dichlorophenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazol-3-yl ester diethyl ester
• 英文别名: [(5R)-5-[(4-bromophenyl)methyl]-7-(3,5-dichlorophenyl)-5-methyl-6-oxoimidazo[1,2-a]imidazol-3-yl] diethyl phosphate
• CAS: 397329-89-4
• 化学式: C₂₃H₂₃BrCl₂N₃O₅P
• 分子量: 603.236
• InChiKey: ULXGJZQAMAXHQX-HSZRJFAPSA-N

物化性质

• 沸点：
  657.7±65.0 °C(Predicted)
• 密度：
  1.57±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  82.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  phosphoric acid 5-(4-bromobenzyl)-7-(3,5-dichlorophenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazol-3-yl ester diethyl ester 在 三甲基氯硅烷 、 sodium iodide 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 0.33h， 生成 (R)-3-(4-Bromo-benzyl)-1-(3,5-dichloro-phenyl)-3-methyl-5-(piperazine-1-sulfonyl)-1H-imidazo[1,2-a]imidazol-2-one
  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：

  (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 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 、 乙腈 为溶剂， 反应 0.5h， 生成 phosphoric acid 5-(4-bromobenzyl)-7-(3,5-dichlorophenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazol-3-yl ester diethyl ester
  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

• 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.
• 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