(S)-N-methyl-N-phenylpyrrolidine-2-carboxamide | 1173169-85-1

• 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-methyl-N-phenylpyrrolidine-2-carboxamide
• 英文别名: (2S)-N-methyl-N-phenylpyrrolidine-2-carboxamide
• CAS: 1173169-85-1
• 化学式: C₁₂H₁₆N₂O
• 分子量: 204.272
• InChiKey: PQJCHFZXCWAHMV-NSHDSACASA-N

物化性质

• 熔点：
  96-98 °C
• 沸点：
  329.1±35.0 °C(Predicted)
• 密度：
  1.123±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-N-methyl-N-phenylpyrrolidine-2-carboxamide 在 N-甲基吗啉 、 N-甲基吡咯烷酮 、 4-二甲氨基吡啶 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  Targeting the Src Homology 2 (SH2) Domain of Signal Transducer and Activator of Transcription 6 (STAT6) with Cell-Permeable, Phosphatase-Stable Phosphopeptide Mimics Potently Inhibits Tyr641 Phosphorylation and Transcriptional Activity

  摘要：

  Signal transducer and activator of transcription 6 (STAT6) transmits signals from cytokines IL-4 and IL-13 and is activated in allergic airway disease. We are developing phosphopeptide mimetics targeting the SH2 domain of STAT6 to block recruitment to phosphotyrosine residues on IL-4 or IL-13 receptors and subsequent Tyr641 phosphorylation to inhibit the expression of genes contributing to asthma. Structure-affinity relationship studies showed that phosphopeptides based on Tyr631 from IL-4R alpha bind with weak affinity to STAT6, whereas replacing the pY+3 residue with simple aryl and alkyl amides resulted in affinities in the mid to low nM range. A set of phosphatase-stable, cell-permeable prodrug analogues inhibited cytokine-stimulated STAT6 phosphorylation in both Beas-2B human airway cells and primary mouse T-lymphocytes at concentrations as low as 100 nM. IL-13-stimulated expression of CCL26 (eotaxin-3) was inhibited in a dose-dependent manner, demonstrating that targeting the SH2 domain blocks both phosphorylation and transcriptional activity of STAT6.

  DOI：

  10.1021/acs.jmedchem.5b01321
• 作为产物：
  描述：

  (S)-N-methyl-N^α-(benzyloxycarbonyl)prolinanilide 生成 (S)-N-methyl-N-phenylpyrrolidine-2-carboxamide
  参考文献：
  名称：

  ASAMI, MASATOSHI, BULL. CHEM. SOC. JAP., 63,(1990) N, C. 721-727

  摘要：

  DOI：
• 作为试剂：
  描述：

  靛红 、 丙酮 在 (S)-N-methyl-N-phenylpyrrolidine-2-carboxamide 、 溶剂黄146 作用下， 反应 12.0h， 生成 (R)-3-hydroxy-3-(2'-oxopropyl)indolin-2-one 、 (S)-3-(2-oxopropyl)-3-hydroxyindolin-2-one
  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

• Rational Design of 2-Substituted DMAP-<i>N</i>-oxides as Acyl Transfer Catalysts: Dynamic Kinetic Resolution of Azlactones
  作者：Ming-Sheng Xie、Bin Huang、Ning Li、Yin Tian、Xiao-Xia Wu、Yun Deng、Gui-Rong Qu、Hai-Ming Guo

  DOI：10.1021/jacs.0c09075

  日期：2020.11.11

  A novel concept that conversion of chiral 2-substituted DMAP into its DMAP-N-oxide could significantly enhance the catalytic activity and still be used as an acyl transfer catalyst is presented. A new type of chiral 2-substituted DMAP-N-oxides, derived from l-prolinamides, has been rationally designed, facilely synthesized, and applied in the dynamic kinetic resolution of azlactones. Using simple MeOH

  提出了一种新概念，即手性 2-取代 DMAP 转化为其 DMAP-N-氧化物可以显着提高催化活性，并且仍可用作酰基转移催化剂。一种由l-脯氨酰胺衍生的新型手性2-取代DMAP-N-氧化物被合理设计、简便合成并应用于吖内酯的动态动力学拆分。使用简单的甲醇作为亲核试剂，可以高产率（高达 98% 的产率）和对映选择性（高达 96% ee）生产各种 L-氨基酸衍生物。此外，还获得了α-氘标记的l-苯丙氨酸衍生物。实验和 DFT 计算表明，在 2-取代的 DMAP-N-氧化物中，氧原子充当亲核位点，NH 键充当 H 键供体。反应的高对映选择性受空间因素的控制，苯甲酸的加入通过参与氢键的构建降低了活化能。理论化学研究表明，只有充分考虑手性催化剂的攻击方向，才能得到正确的计算结果。这项工作为利用吡啶环的 C2 位置和开发手性 2-取代 DMAP-N-氧化物作为有效的酰基转移催化剂铺平了道路。
• Organocatalytic asymmetric Michael reaction with acylsilane donors
  作者：Lei Wu、Guangxun Li、Qingquan Fu、Luoting Yu、Zhuo Tang

  DOI：10.1039/c2ob26950c

  日期：——

  We have developed an organocatalytic asymmetric Michael reaction of acylsilane through the selection of acylsilane substrates and organocatalysts, thus creating a rare example of acylsilane α-alkylation with a chiral guanidine catalyst, which afforded products in good yields and high stereoselectivity. The corresponding adducts described here have also been demonstrated to be useful in the synthesis

  通过选择酰基硅烷底物和有机催化剂，我们开发了酰基硅烷的有机催化不对称迈克尔反应，从而创造了一个罕见的手性胍催化剂进行酰基硅烷α-烷基化的例子，该产物能够提供高收率和高立体选择性。还已经证明，在此描述的相应的加合物可用于合成非天然氨基酸和生物活性化合物。
• Proline imidazolidinones and enamines in Hajos–Wiechert and Wieland–Miescher ketone synthesis
  作者：Ángel L. Fuentes de Arriba、Luis Simón、César Raposo、Victoria Alcázar、Joaquín R. Morán

  DOI：10.1016/j.tet.2009.04.050

  日期：2009.6

  from the acid chloride of proline hydrochloride and anilines induce large enantiomeric excesses in intramolecular aldol condensations. Imidazolidinones derived from the reaction of the catalyst and enamines have been found as intermediates in these reactions.

  从脯氨酸盐酸盐的酰氯和苯胺获得的现成的芳香族脯氨酰胺在分子内羟醛缩合中引起大量的对映体过量。已经发现衍生自催化剂和烯胺的反应的咪唑烷酮是这些反应的中间体。
• Chiral DMAP‐ <i>N</i> ‐oxides as Acyl Transfer Catalysts: Design, Synthesis, and Application in Asymmetric Steglich Rearrangement
  作者：Ming‐Sheng Xie、Ye‐Fei Zhang、Meng Shan、Xiao‐Xia Wu、Gui‐Rong Qu、Hai‐Ming Guo

  DOI：10.1002/anie.201812864

  日期：2019.2.25

  pyridine nitrogen, which serves as the nucleophilic site in the asymmetric acyl transfer reaction, we discovered that chiral DMAP‐N‐oxides, in which the oxygen now acts as the nucleophilic site, are efficient acyl transfer catalysts. Our finding might open a new door for the development of chiral DMAP‐N‐oxides for asymmetric acyl transfer reactions.

  开发，合成并以非对称Steglich重排为特征的DMAP‐ N-氧化物（以α-氨基酸为手性来源）。一系列O-酰化的内酯提供了高收率（高达97％的收率）和出色的对映体选择性（EE高达97％）的四级立体中心的C-酰化的内酯 。与在不对称酰基转移反应中用作亲核位点的吡啶氮的广泛使用相比，我们发现手性DMAP- N-氧化物（其中的氧气现在充当亲核位点）是有效的酰基转移催化剂。我们的发现可能为开发用于不对称酰基转移反应的手性DMAP‐ N-氧化物打开了新的大门。