(1S,4R,6S,7Z,14S,18R)-14-cyclopentyloxycarbonylamino-18-[2-(2-isopropylamino-thiazol-4-yl)-7-methoxy-quinolin-4-yloxy]-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.0^4,6]nonadec-7-ene-4-carboxylic acid methyl ester | 681145-22-2

• 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: (1S,4R,6S,7Z,14S,18R)-14-cyclopentyloxycarbonylamino-18-[2-(2-isopropylamino-thiazol-4-yl)-7-methoxy-quinolin-4-yloxy]-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.0^4,6]nonadec-7-ene-4-carboxylic acid methyl ester
• 英文别名: methyl (1S,4R,6S,7Z,14S,18R)-14-(cyclopentyloxycarbonylamino)-18-[7-methoxy-2-[2-(propan-2-ylamino)-1,3-thiazol-4-yl]quinolin-4-yl]oxy-2,15-dioxo-3,16-diazatricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylate
• CAS: 681145-22-2
• 化学式: C₄₁H₅₂N₆O₈S
• 分子量: 788.965
• InChiKey: NINFPJNSLCHSQA-LFXJPFRNSA-N

物化性质

• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  56
• 可旋转键数：
  11
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  199
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  (1S,4R,6S,7Z,14S,18R)-14-cyclopentyloxycarbonylamino-18-[2-(2-isopropylamino-thiazol-4-yl)-7-methoxy-quinolin-4-yloxy]-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.0^4,6]nonadec-7-ene-4-carboxylic acid methyl ester 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 15.0h， 以99%的产率得到西鲁瑞韦
  参考文献：
  名称：

  Synthesis of BILN 2061, an HCV NS3 Protease Inhibitor with Proven Antiviral Effect in Humans

  摘要：

  The synthesis of BILN 2061, an NS3 protease inhibitor with proven antiviral effect in humans, was accomplished in a convergent manner from four building blocks. The procedure described here was suitable for the preparation of multigram quantities of BILN 2061 for preclinical pharmacological evaluation.

  DOI：

  10.1021/ol0489907
• 作为产物：
  描述：

  (Z)-(1S,4R,6S,14S,18R)-14-Cyclopentyloxycarbonylamino-18-(7-methoxy-2-methoxycarbonyl-quinolin-4-yloxy)-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.0^4,6]nonadec-7-ene-4-carboxylic acid methyl ester 在 sodium hydroxide 、 氢溴酸 、 三乙胺 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 甲醇 、 水 、 异丙醇 为溶剂， 反应 4.75h， 生成 (1S,4R,6S,7Z,14S,18R)-14-cyclopentyloxycarbonylamino-18-[2-(2-isopropylamino-thiazol-4-yl)-7-methoxy-quinolin-4-yloxy]-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.0^4,6]nonadec-7-ene-4-carboxylic acid methyl ester
  参考文献：
  名称：

  Synthesis of BILN 2061, an HCV NS3 Protease Inhibitor with Proven Antiviral Effect in Humans

  摘要：

  The synthesis of BILN 2061, an NS3 protease inhibitor with proven antiviral effect in humans, was accomplished in a convergent manner from four building blocks. The procedure described here was suitable for the preparation of multigram quantities of BILN 2061 for preclinical pharmacological evaluation.

  DOI：

  10.1021/ol0489907

文献信息

• Process for continuous ruthenium-catalysed metathesis
  申请人：Herweck Thomas

  公开号：US20060009667A1

  公开（公告）日：2006-01-12

  The invention relates to a process for carrying out metathesis reactions, wherein the process is carried out continuously and a ruthenium-containing catalyst is used.

  该发明涉及一种进行交换反应的方法，其中该方法是连续进行的并且使用含钌催化剂。
• US7268211B2
  申请人：——

  公开号：US7268211B2

  公开（公告）日：2007-09-11
• US7504378B2
  申请人：——

  公开号：US7504378B2

  公开（公告）日：2009-03-17
• Synthesis of BILN 2061, an HCV NS3 Protease Inhibitor with Proven Antiviral Effect in Humans
  作者：Anne-Marie Faucher、Murray D. Bailey、Pierre L. Beaulieu、Christian Brochu、Jean-Simon Duceppe、Jean-Marie Ferland、Elise Ghiro、Vida Gorys、Ted Halmos、Stephen H. Kawai、Martin Poirier、Bruno Simoneau、Youla S. Tsantrizos、Montse Llinàs-Brunet

  DOI：10.1021/ol0489907

  日期：2004.8.1

  The synthesis of BILN 2061, an NS3 protease inhibitor with proven antiviral effect in humans, was accomplished in a convergent manner from four building blocks. The procedure described here was suitable for the preparation of multigram quantities of BILN 2061 for preclinical pharmacological evaluation.
• Efficient Large-Scale Synthesis of BILN 2061, a Potent HCV Protease Inhibitor, by a Convergent Approach Based on Ring-Closing Metathesis
  作者：Nathan K. Yee、Vittorio Farina、Ioannis N. Houpis、Nizar Haddad、Rogelio P. Frutos、Fabrice Gallou、Xiao-jun Wang、Xudong Wei、Robert D. Simpson、Xuwu Feng、Victor Fuchs、Yibo Xu、Jonathan Tan、Li Zhang、Jinghua Xu、Lana L. Smith-Keenan、Jana Vitous、Michael D. Ridges、Earl M. Spinelli、Michael Johnson、Kai Donsbach、Thomas Nicola、Michael Brenner、Eric Winter、Paul Kreye、Wendelin Samstag

  DOI：10.1021/jo060285j

  日期：2006.9.1

  A multistep scalable synthesis of the clinically important hepatitis C virus (HCV) protease inhibitor BILN 2061 (1) is described. The synthesis is highly convergent and consists of two amide bond formations, one etherification, and one ring-closing metathesis (RCM) step, using readily available building blocks 2-5. The optimization of each step is described at length. The main focus of the paper is the study of the RCM step and the description of the main problems faced when scaling up to pilot scale this highly powerful but very challenging synthetic operation. Eventually, the RCM reaction was smoothly scaled up to produce > 400 kg of cyclized product.