(S)-N-(3,5-bis(trifluoromethyl)phenylsulfonyl)-pyrrolidine-2-carboxamide | 1338799-21-5

• 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: (S)-N-(3,5-bis(trifluoromethyl)phenylsulfonyl)-pyrrolidine-2-carboxamide
• 英文别名: N-[[3,5-Bis(trifluoromethyl)phenyl]sulfonyl]-L-prolinamide；(2S)-N-[3,5-bis(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide
• CAS: 1338799-21-5
• 化学式: C₁₃H₁₂F₆N₂O₃S
• 分子量: 390.306
• InChiKey: GWEGCBHUTZANOT-JTQLQIEISA-N

物化性质

• 熔点：
  222.3-223.1 °C
• 密度：
  1.492±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  83.6
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  在 三氟乙酸 、 sodium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 2.0h， 以200 mg的产率得到(S)-N-(3,5-bis(trifluoromethyl)phenylsulfonyl)-pyrrolidine-2-carboxamide
  参考文献：
  名称：

  Screening of simple N-aryl and N-heteroaryl pyrrolidine amide organocatalysts for the enantioselective aldol reaction of acetone with isatin

  摘要：

  We have screened a range of simple N-aryl and N-heteroaryl pyrrolidine amide organocatalysts incorporating N-pyridyl and N-quinolinyl groups in the synthetically useful aldol reaction of isatin with acetone. The 'reverse amide' N-pyridyl pyrrolidinylmethyl amide catalysts proved highly catalytically active but gave disappointing enantioselectivities. However, an N-3-pyridyl prolinamide catalyst gave the aldol adduct in high yields and high enantioselectivity with up to 72% ee of the (S)-isomer. Conditions were optimised for this catalyst and in particular an additive screen identified a link between the pK(a) of the acid additive and the yield and enantioselectivity. An N-arylsulfonamide prolinamide was also identified as a catalyst for this reaction giving the (R)-enantiomer in 68% ee. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2011.07.016

文献信息

• METHODS
  申请人：Sedelmeier Gottfried

  公开号：US20100130749A1

  公开（公告）日：2010-05-27

  The invention related to a novel process, novel process steps and novel intermediates useful in the synthesis of pharmaceutically active compounds, especially renin inhibitors, such as Aliskiren Inter alia the invention relates to a process for the manufacture of a compound of the formula I. or a salt thereof, wherein R1 as well as Act are as defined in the specification, and processes of manufacturing this compound as well as intermediates in this process.

  本发明涉及一种新的过程、新的过程步骤和新的中间体，适用于合成药物活性化合物，特别是肾素抑制剂，如阿利司他。此外，本发明还涉及一种制备式I化合物或其盐的方法，其中R1和Act如规范中定义，以及制备该化合物和该过程中的中间体的方法。
• US8338620B2
  申请人：——

  公开号：US8338620B2

  公开（公告）日：2012-12-25
• Screening of simple N-aryl and N-heteroaryl pyrrolidine amide organocatalysts for the enantioselective aldol reaction of acetone with isatin
  作者：Michael Kinsella、Patrick G. Duggan、Claire M. Lennon

  DOI：10.1016/j.tetasy.2011.07.016

  日期：2011.7

  We have screened a range of simple N-aryl and N-heteroaryl pyrrolidine amide organocatalysts incorporating N-pyridyl and N-quinolinyl groups in the synthetically useful aldol reaction of isatin with acetone. The 'reverse amide' N-pyridyl pyrrolidinylmethyl amide catalysts proved highly catalytically active but gave disappointing enantioselectivities. However, an N-3-pyridyl prolinamide catalyst gave the aldol adduct in high yields and high enantioselectivity with up to 72% ee of the (S)-isomer. Conditions were optimised for this catalyst and in particular an additive screen identified a link between the pK(a) of the acid additive and the yield and enantioselectivity. An N-arylsulfonamide prolinamide was also identified as a catalyst for this reaction giving the (R)-enantiomer in 68% ee. (C) 2011 Elsevier Ltd. All rights reserved.