tert-butyl (2S,5R)-2-cyano-5-ethynylpyrrolidine-1-carboxylate | 1003021-82-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: tert-butyl (2S,5R)-2-cyano-5-ethynylpyrrolidine-1-carboxylate
• CAS: 1003021-82-6
• 化学式: C₁₂H₁₆N₂O₂
• 分子量: 220.271
• InChiKey: IFGDWYKMKLNOJR-UWVGGRQHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  53.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl (2S,5R)-2-cyano-5-ethynylpyrrolidine-1-carboxylate 在 对甲苯磺酸 作用下， 以 乙腈 为溶剂， 生成 (2S,5R)-5-ethynylpyrrolidine-2-carbonitrile
  参考文献：
  名称：

  WO2008/11499

  摘要：

  公开号：
• 作为产物：
  描述：

  tert-butyl (2S,5R)-2-carbamoyl-5-ethynylpyrrolidine-1-carboxylate 在 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 醋酸异丙酯 为溶剂， 生成 tert-butyl (2S,5R)-2-cyano-5-ethynylpyrrolidine-1-carboxylate
  参考文献：
  名称：

  Development of a Scalable Synthesis of Dipeptidyl Peptidase-4 Inhibitor ABT-279

  摘要：

  A convergent, scalable Synthesis of dipeptidyl peptidase-4 inhibitor, ABT-279, has been developed and demonstrated on multikilogram scale. The cis-2,5-disubstituted pyrrolidine is generated by cyclization of a Boc-amine onto an alkynyl ketone followed by stereospecific reduction of the resulting acyliminium intermediate. The amine coupling partner was prepared by a novel Hofmann rearrangement promoted by 1,3-dibromo-5,5-dimethylhydantoin. The final product was isolated as the L-malic acid salt. The scale-up campaign consisted of 15 steps and delivered 42 kg of ABT-279 in 14% overall yield. A second-generation Synthesis that addresses some of the issues encountered during scale-up was developed and demonstrated on kilogram scale.

  DOI：

  10.1021/op900197r

文献信息

• SYNTHESIS OF (2S,5R)-5-ETHYNYL-1-PYRROLIDINE-2-CARBONITRILE
  申请人：AbbVie Inc.

  公开号：US20160152600A1

  公开（公告）日：2016-06-02

  A process for making (2S,5R)-5-ethynyl-1-N-(4-methyl-1-(4-carboxy-pyridin-2-yl)piperidin-4-yl)glycyl}pyrrolidine-2-carbonitrile and salts thereof, and intermediates used in the process are disclosed.

  本发明公开了一种制备(2S,5R)-5-乙炔基-1-N-(4-甲基-1-(4-羧基-吡啶-2-基)哌啶-4-基)甘氨酰}吡咯烷-2-羧腈及其盐的方法，以及所使用的中间体。
• Development of a Scalable Synthesis of Dipeptidyl Peptidase-4 Inhibitor ABT-279
  作者：Todd S. McDermott、Lakshmi Bhagavatula、Thomas B. Borchardt、Kenneth M. Engstrom、Jorge Gandarilla、Brian J. Kotecki、Albert W. Kruger、Michael J. Rozema、Ahmad Y. Sheikh、Seble H. Wagaw、Steven J. Wittenberger

  DOI：10.1021/op900197r

  日期：2009.11.20

  A convergent, scalable Synthesis of dipeptidyl peptidase-4 inhibitor, ABT-279, has been developed and demonstrated on multikilogram scale. The cis-2,5-disubstituted pyrrolidine is generated by cyclization of a Boc-amine onto an alkynyl ketone followed by stereospecific reduction of the resulting acyliminium intermediate. The amine coupling partner was prepared by a novel Hofmann rearrangement promoted by 1,3-dibromo-5,5-dimethylhydantoin. The final product was isolated as the L-malic acid salt. The scale-up campaign consisted of 15 steps and delivered 42 kg of ABT-279 in 14% overall yield. A second-generation Synthesis that addresses some of the issues encountered during scale-up was developed and demonstrated on kilogram scale.
• WO2008/11499
  申请人：——

  公开号：——

  公开（公告）日：——