tert-butyl (S)-2-[((S)-2-hydroxy-1-phenylethyl)carbamoyl]pyrrolidine-1-carboxylate | 1042690-70-9

• 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: tert-butyl (S)-2-[((S)-2-hydroxy-1-phenylethyl)carbamoyl]pyrrolidine-1-carboxylate
• 英文别名: tert-butyl (2S)-2-[[(1S)-2-hydroxy-1-phenylethyl]carbamoyl]pyrrolidine-1-carboxylate
• CAS: 1042690-70-9
• 化学式: C₁₈H₂₆N₂O₄
• 分子量: 334.415
• InChiKey: USQYHWXXNKHCJW-CABCVRRESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (S)-2-[((S)-2-hydroxy-1-phenylethyl)carbamoyl]pyrrolidine-1-carboxylate 在 [双(2-甲氧基乙基)胺]三氟化硫 作用下， 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  The design of potent and selective inhibitors of DPP-4: Optimization of ADME properties by amide replacements

  摘要：

  For a series of beta-homophenylalanine based inhibitors of dipeptidyl peptidase IV ADME properties were improved by the incorporation of amide replacements. These efforts led to a novel series of potent and selective inhibitors of DPP-4 that exhibit an attractive pharmacokinetic profile and show excellent efficacy in an animal model of diabetes. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.09.078
• 作为产物：
  描述：

  BOC-L-脯氨酸 、 L-苯甘氨醇 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以78%的产率得到tert-butyl (S)-2-[((S)-2-hydroxy-1-phenylethyl)carbamoyl]pyrrolidine-1-carboxylate
  参考文献：
  名称：

  A bio-inspired approach to proline-derived 2,4-disubstituted oxazoles

  摘要：

  摘要：描述了一种从l-Boc-脯氨酸获得灵感的天然存在含有噁唑基肽类似物的合成(S)-4-烷基-2-(吡咯啉-2-基)噁唑的便捷四步法。关键步骤是在Appel反应条件下，将1-Boc-N-(1-氧代烷基)吡咯啉-2-羧酰胺-醛中间体（表现出低至中等稳定性）环化。该方法以98%以上的ee产率合成目标化合物，在17-51%的总产率下，可用于高达45克的规模。

  DOI：

  10.1515/hc-2017-0235

文献信息

• The design of potent and selective inhibitors of DPP-4: Optimization of ADME properties by amide replacements
  作者：Sonja Nordhoff、Stephan Bulat、Silvia Cerezo-Gálvez、Oliver Hill、Barbara Hoffmann-Enger、Meritxell López-Canet、Claudia Rosenbaum、Christian Rummey、Meinolf Thiemann、Victor G. Matassa、Paul J. Edwards、Achim Feurer

  DOI：10.1016/j.bmcl.2009.09.078

  日期：2009.11

  For a series of beta-homophenylalanine based inhibitors of dipeptidyl peptidase IV ADME properties were improved by the incorporation of amide replacements. These efforts led to a novel series of potent and selective inhibitors of DPP-4 that exhibit an attractive pharmacokinetic profile and show excellent efficacy in an animal model of diabetes. (C) 2009 Elsevier Ltd. All rights reserved.
• A bio-inspired approach to proline-derived 2,4-disubstituted oxazoles
  作者：Evgeniy Y. Slobodyanyuk、Oleksiy S. Artamonov、Irene B. Kulik、Eduard Rusanov、Dmitriy M. Volochnyuk、Oleksandr O. Grygorenko

  DOI：10.1515/hc-2017-0235

  日期：2018.2.23

  A convenient four-step approach to the synthesis of (S)-4-alkyl-2-(pyrrolidin-2-yl)oxazoles starting from l-Boc-proline inspired by naturally occurring oxazole-containing peptidomimetics is described. The key step is the cyclization of 1-Boc-N-(1-oxoalkan-2-yl)pyrrolidine-2-carboxamides – aldehyde intermediates which demonstrate low to moderate stability – under Appel reaction conditions. This method furnishes the target compounds with more than 98% ee and in a 17–51% overall yield and has been used at up to a 45-g scale.

  摘要：描述了一种从l-Boc-脯氨酸获得灵感的天然存在含有噁唑基肽类似物的合成(S)-4-烷基-2-(吡咯啉-2-基)噁唑的便捷四步法。关键步骤是在Appel反应条件下，将1-Boc-N-(1-氧代烷基)吡咯啉-2-羧酰胺-醛中间体（表现出低至中等稳定性）环化。该方法以98%以上的ee产率合成目标化合物，在17-51%的总产率下，可用于高达45克的规模。