[(3-aminophenyl)methyl] carbamic acid [(3S)-tetrahydro-3-furanyl] ester | 267406-34-8

• 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: [(3-aminophenyl)methyl] carbamic acid [(3S)-tetrahydro-3-furanyl] ester
• 英文别名: carbamic acid [(3-nitrophenyl)methyl]-(3S)-tetrahydro-3-furanyl ester；(S)-tetrahydrofuran-3-yl 3-aminobenzylcarbamate；(S)-Tetrahydrofuran-3-yl (3-aminobenzyl)carbamate；[(3S)-oxolan-3-yl] N-[(3-aminophenyl)methyl]carbamate
• CAS: 267406-34-8
• 化学式: C₁₂H₁₆N₂O₃
• 分子量: 236.271
• InChiKey: IFWYTYQAUPOOCM-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  73.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [(3-aminophenyl)methyl] carbamic acid [(3S)-tetrahydro-3-furanyl] ester 在 N,N-二异丙基乙胺 作用下， 以 水 、 乙酸乙酯 为溶剂， 反应 18.0h， 生成 carbamic acid,N-[[3-[[[[3-methoxy-4-(5-oxazolyl)phenyl]amino]carbonyl]amino]phenyl]methyl]-(3S)-tetrahydro-3-furanyl ester
  参考文献：
  名称：

  Development and Manufacture of the Inosine Monophosphate Dehydrogenase Inhibitor Merimepodib, VX-497

  摘要：

  A process for the manufacture of merimepodib (VX-497), an inosine monophosphate dehydrogenase (IMPDH) inhibitor, has been developed and efficiently scaled to produce clinical supply. The process comprises five steps, incorporating simple and robust chemistry that ultimately yielded 96.5 kg with a purity of 100% (by HPLC analysis) and 99.7% w/w assay. Highlights of the process are the effective use of production-scale phosgene, manipulation of Schotten-Baumann reaction conditions to give a low pH procedure that avoids a critical impurity, and the use of online tools to better identify parameters of the API purification.

  DOI：

  10.1021/op800060h
• 作为产物：
  描述：

  (S)-tetrahydrofuran-3-yl carbonochloridate 在 5%-palladium/activated carbon 、 氢气 、 sodium carbonate 作用下， 以 水 、 乙酸乙酯 、 甲苯 为溶剂， 25.0~50.0 ℃ 、600.01 kPa 条件下， 反应 8.0h， 生成 [(3-aminophenyl)methyl] carbamic acid [(3S)-tetrahydro-3-furanyl] ester
  参考文献：
  名称：

  Development and Manufacture of the Inosine Monophosphate Dehydrogenase Inhibitor Merimepodib, VX-497

  摘要：

  A process for the manufacture of merimepodib (VX-497), an inosine monophosphate dehydrogenase (IMPDH) inhibitor, has been developed and efficiently scaled to produce clinical supply. The process comprises five steps, incorporating simple and robust chemistry that ultimately yielded 96.5 kg with a purity of 100% (by HPLC analysis) and 99.7% w/w assay. Highlights of the process are the effective use of production-scale phosgene, manipulation of Schotten-Baumann reaction conditions to give a low pH procedure that avoids a critical impurity, and the use of online tools to better identify parameters of the API purification.

  DOI：

  10.1021/op800060h

文献信息

• PROCESSES FOR PREPARING BIARYL UREAS AND ANALOGS THEREOF
  申请人：Ansell Graham

  公开号：US20090221835A1

  公开（公告）日：2009-09-03

  The present invention relates to processes for preparing biaryl ureas derivatives and analogs thereof. The invention also provides compounds useful as intermediates in the processes of the present invention. The process is useful for preparing compounds that inhibit IMPDH.

  本发明涉及制备联苯基脲类衍生物及其类似物的过程。本发明还提供了在本发明过程中作为中间体有用的化合物。该过程用于制备抑制IMPDH的化合物。
• Processes for preparing biaryl ureas and analogs thereof
  申请人：Ansell Graham

  公开号：US20080021222A1

  公开（公告）日：2008-01-24

  The present invention relates to processes for preparing biaryl ureas derivatives and analogs thereof. The invention also provides compounds useful as intermediates in the processes of the present invention. The process is useful for preparing compounds that inhibit IMPDH.

  本发明涉及制备联苯基脲类衍生物及其类似物的过程。本发明还提供了在本发明过程中用作中间体的化合物。该过程用于制备抑制IMPDH的化合物。
• Novel diamide-Based inhibitors of IMPDH
  作者：Henry H. Gu、Edwin J. Iwanowicz、Junqing Guo、Scott H. Watterson、Zhongqi Shen、William J. Pitts、T.G.Murali Dhar、Catherine A. Fleener、Katherine Rouleau、N.Z. Sherbina、Mark Witmer、Jeffrey Tredup、Diane Hollenbaugh

  DOI：10.1016/s0960-894x(02)00132-4

  日期：2002.5

  A series of novel amide-based small molecule inhibitors of inosine monophosphate dehydrogenase is described. The synthesis and the structure-activity relationships (SARs) derived front in vitro studies are presented. (C). 2002 Elsevier Science Ltd. All rights reserved.
• WO2006/122072
  申请人：——

  公开号：——

  公开（公告）日：——
• Novel guanidine-Based inhibitors of inosine monophosphate dehydrogenase
  作者：Edwin J. Iwanowicz、Scott H. Watterson、Chunjian Liu、Henry H. Gu、Toomas Mitt、Katerina Leftheris、Joel C. Barrish、Catherine A. Fleener、Katherine Rouleau、N.Z. Sherbina、Diane L. Hollenbaugh

  DOI：10.1016/s0960-894x(02)00600-5

  日期：2002.10

  A series of novel guanidine-based small molecule inhibitors of inosine monophosphate dehydrogenase (IMPDH) was explored. IMPDH catalyzes the rate determining step in guanine nucleotide biosynthesis and is a target for anticancer, immunosuppressive and antiviral therapy. The synthesis and the structure-activity relationships (SARs), derived from in vitro studies, for this new series of inhibitors is given. (C) 2002 Elsevier Science Ltd. All rights reserved.