tert-butyl (S)-2-(3-fluorophenyl)-1-((2S,4R)-tetrahydro-4-(3-methylbut-2-enyl)-5-oxofuran-2-yl)ethylcarbamate | 379216-93-0

• 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: tert-butyl (S)-2-(3-fluorophenyl)-1-((2S,4R)-tetrahydro-4-(3-methylbut-2-enyl)-5-oxofuran-2-yl)ethylcarbamate
• 英文别名: {2-(3-fluorophenyl)-1-[4-(3-methyl-but-2-enyl)-5-oxo-tetrahydrofuran-2-yl]-ethyl}-t-butoxycarbonyl-protected amine；tert-butyl N-[(1S)-2-(3-fluorophenyl)-1-[(2S,4R)-4-(3-methylbut-2-enyl)-5-oxooxolan-2-yl]ethyl]carbamate
• CAS: 379216-93-0
• 化学式: C₂₂H₃₀FNO₄
• 分子量: 391.483
• InChiKey: ZNMKIXKXNZWKDL-NEWSRXKRSA-N

物化性质

• 沸点：
  534.4±30.0 °C(Predicted)
• 密度：
  1.111±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (S)-2-(3-fluorophenyl)-1-((2S,4R)-tetrahydro-4-(3-methylbut-2-enyl)-5-oxofuran-2-yl)ethylcarbamate 在 磷酸 、 N,N'-羰基二咪唑 作用下， 以 乙酸乙酯 、 甲苯 为溶剂， 反应 25.0h， 生成 CP 481715
  参考文献：
  名称：

  Process Development of CP-481715, a Novel CCR1 Antagonist

  摘要：

  Process development for the synthesis of 2-quinoxalinecarboxamide, N-[(1S,2S,4R)-4-(aminocarbonyl)-1-[(3-fluorophenyl)methyl]-2,7-dihydroxy-7-methyloctyl] is described. An optimized,and streamlined process starting from lactone 2 was developed: Lactone 2 was alkylated diastereoselectively with prenyl bromide, followed by deprotection of the N-Boc group and concomitant hydration of the olefin. Aminolysis of the lactone in methanolic ammonia afforded the titled compound.

  DOI：

  10.1021/op050059w
• 作为产物：
  描述：

  1-溴-3-甲基-2-丁烯 、 5-[(1S)-N-Boc-amino-(2S)-(3-fluorophenyl)ethyl]dihydrofuran-2-one 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 生成 tert-butyl (S)-2-(3-fluorophenyl)-1-((2S,4R)-tetrahydro-4-(3-methylbut-2-enyl)-5-oxofuran-2-yl)ethylcarbamate
  参考文献：
  名称：

  [EN] CRYSTAL FORMS OF QUINOXALINE-2-CARBOXYLIC ACID [4-CARBAMOYL-1-(3-FLUOROBENZYL)-2,7-DIHYDROXY-7-METHYL-OCTYL]-AMIDE
  [FR] FORMES CRISTALLINES D'ACIDE QUINOXALINE-2-CARBOXYLIQUE [4-CARBAMOYL-1-(3-FLUOROBENZYL)-2,7-DIHYDROXY-7-METHYL-OCTYL]-AMIDE

  摘要：

  该发明涉及喹喔啉-2-羧酸[4-氨基甲酰基-1-(3-氟苯基)-2,7-二羟基-7-甲基辛基]-酰胺的晶型，用于通过拮抗CCR1受体来治疗或预防某种疾病或状况，以及其制备和使用方法。

  公开号：

  WO2004014875A1

文献信息

• Aqueous Phosphoric Acid as a Mild Reagent for Deprotection of <i>tert</i>-Butyl Carbamates, Esters, and Ethers
  作者：Bryan Li、Martin Berliner、Richard Buzon、Charles K.-F. Chiu、Stephen T. Colgan、Takushi Kaneko、Nandell Keene、William Kissel、Tung Le、Kyle R. Leeman、Brian Marquez、Ronald Morris、Lisa Newell、Silke Wunderwald、Michael Witt、John Weaver、Zhijun Zhang、Zhongli Zhang

  DOI：10.1021/jo061377b

  日期：2006.11.1

  an effective, environmentally benign reagent for the deprotection of tert-butyl carbamates, tert-butyl esters, and tert-butyl ethers. The reaction conditions are mild and offer good selectivity in the presence of other acid-sensitive groups, including CBZ carbamates, azetidine, benzyl and methyl esters, TBDMS, and methyl phenyl ethers. The mildness of the reaction is further demonstrated in the synthesis

  磷酸水溶液（85重量％）是用于脱保护的有效，环境友好的试剂叔丁基氨基甲酸酯，叔丁基酯，和叔-丁基醚。反应条件温和，在其他酸敏感基团（包括氨基甲酸CBZ，氮杂环丁烷，苄基和甲基酯，TBDMS和甲基苯基醚）存在下，具有良好的选择性。反应的温和性在克拉霉素衍生物4的合成中得到了进一步证明，其中叔酸在环状氨基甲酸酯，内酯，缩酮，乙酸酯和可差向异构的甲基酮官能团存在下，除去丁酯。该反应保留了底物的立体化学完整性。反应产率高，后处理方便。
• Novel CCR1 antagonists with improved metabolic stability
  作者：Matthew F Brown、Mike Avery、William H Brissette、J.H Chang、Kevin Colizza、Maryrose Conklyn、Amy P DiRico、Ronald P Gladue、John C Kath、Suzanne S Krueger、Paul D Lira、Brett M Lillie、Greg D Lundquist、Erin N Mairs、Eric B McElroy、Molly A McGlynn、Timothy J Paradis、Christopher S Poss、Michelle I Rossulek、Richard M Shepard、Jeff Sims、Timothy J Strelevitz、Susan Truesdell、Laurie A Tylaska、Kwansik Yoon、Deye Zheng

  DOI：10.1016/j.bmcl.2004.02.022

  日期：2004.5

  The synthesis, biological activity, and pharmacokinetic profile of novel CCR1 antagonists are described. (C) 2004 Elsevier Ltd. All rights reserved.
• Case Study of a γ-Butyrolactone Alkylation with 1,3-Dimethyl-2-imidazolidinone as a Promoter
  作者：Bryan Li、Richard A. Buzon、Michael J. Castaldi

  DOI：10.1021/op010224h

  日期：2001.11.1

  1,3-Dimethyl 2-imidazolidinone (DMI) is of lower toxicological risk than 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU), hexamethyl-phosphorus triamide (HMPT), and hexamethylphosphoramide (HMPA). Formation of dialkylation byproducts is a common problem in lactone alkylation. DMI, used in stoichiometric amount, increases the rate of alkylation of gamma -butyrolactone 1 by >30-fold, therefore minimizing the dialkylation in multi-kilogram preparations. The isolated yield of the monoalkylated product 2 is >90%. The reaction protocol is also demonstrated to work on other lactone substrates and alkylating agents.
• Org. Process Res. Dev. 2005, 9, 466-471
  作者：

  DOI：——

  日期：——
• [EN] CRYSTAL FORMS OF QUINOXALINE-2-CARBOXYLIC ACID [4-CARBAMOYL-1-(3-FLUOROBENZYL)-2,7-DIHYDROXY-7-METHYL-OCTYL]-AMIDE<br/>[FR] FORMES CRISTALLINES D'ACIDE QUINOXALINE-2-CARBOXYLIQUE [4-CARBAMOYL-1-(3-FLUOROBENZYL)-2,7-DIHYDROXY-7-METHYL-OCTYL]-AMIDE
  申请人：PFIZER PROD INC

  公开号：WO2004014875A1

  公开（公告）日：2004-02-19

  The invention relates to crystal forms of quinoxaline-2-carboxylic acid [4-carbamoyl-1-(3-fluorobenzyl)-2,7-dihydroxy-7-methyl-octyl]-amide, useful in treating or preventing a disorder or condition by antogonizing the CCR1 receptor, and to their methods of preparation and use.

  该发明涉及喹喔啉-2-羧酸[4-氨基甲酰基-1-(3-氟苯基)-2,7-二羟基-7-甲基辛基]-酰胺的晶型，用于通过拮抗CCR1受体来治疗或预防某种疾病或状况，以及其制备和使用方法。