threo-(4S,5S)-5-methyl-4-phenylpyrrolidin-2-one | 33654-16-9

• 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: threo-(4S,5S)-5-methyl-4-phenylpyrrolidin-2-one
• 英文别名: (4S,5S)-5-methyl-4-phenylpyrrolidin-2-one
• CAS: 33654-16-9
• 化学式: C₁₁H₁₃NO
• 分子量: 175.23
• InChiKey: ZIZRQVWVGIHEIC-WCBMZHEXSA-N

物化性质

• 熔点：
  118 °C(Solv: ethyl acetate (141-78-6))
• 沸点：
  359.3±31.0 °C(Predicted)
• 密度：
  1.059±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  threo-(4S,5S)-5-methyl-4-phenylpyrrolidin-2-one 、 溴乙酸乙酯 在 sodium hydride 作用下， 以 甲苯 为溶剂， 反应 6.5h， 以72%的产率得到ethyl threo-(4S,5S)-2-(5-methyl-4-phenylpyrrolidin-1-yl)acetate
  参考文献：
  名称：

  Synthesis and biological evaluation of 2-(5-methyl-4-phenyl-2-oxopyrrolidin-1-yl)-acetamide stereoisomers as novel positive allosteric modulators of sigma-1 receptor

  摘要：

  Novel positive allosteric modulators of sigma-1 receptor represented by 2-(5-methyl-4-phenyl-2-oxopyrrolidin-l-yl)-acetamide enantiomers were synthesised using an asymmetric Michael addition of 2-nitroprop-1-enylbenzene to diethyl malonate. Following the chromatographic separation of the methyl erythro- and threo-4-nitro-3R- and 3S-phenylpentanoate diastereoisomers, target compounds were obtained by their reductive cyclisation into 5-methyl-4-phenylpyrrolidin-2-one enantiomers and the attachment of the acetamide group to the heterocyclic nitrogen. Experiments with electrically stimulated rat vas deference contractions induced by the PRE-084, an agonist of sigma-1 receptor, showed that (4R,5S)- and (4R,5R)-2-(5-methyl-4-phenyl-2-oxopyrrolidin-l-yl)-acetamides with an R-configuration at the C-4 chiral centre in the 2-pyrrolidone ring were more effective positive allosteric modulators of sigma-1 receptor than were their optical antipodes. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.03.016
• 作为产物：
  描述：

  methyl threo-(3S,4S)-4-nitro-3-phenylpentanoate 在 Ni Raney 作用下， 以 乙醇 、 水 为溶剂， 50.0 ℃ 、5.07 MPa 条件下， 反应 18.0h， 以84%的产率得到threo-(4S,5S)-5-methyl-4-phenylpyrrolidin-2-one
  参考文献：
  名称：

  Synthesis and biological evaluation of 2-(5-methyl-4-phenyl-2-oxopyrrolidin-1-yl)-acetamide stereoisomers as novel positive allosteric modulators of sigma-1 receptor

  摘要：

  Novel positive allosteric modulators of sigma-1 receptor represented by 2-(5-methyl-4-phenyl-2-oxopyrrolidin-l-yl)-acetamide enantiomers were synthesised using an asymmetric Michael addition of 2-nitroprop-1-enylbenzene to diethyl malonate. Following the chromatographic separation of the methyl erythro- and threo-4-nitro-3R- and 3S-phenylpentanoate diastereoisomers, target compounds were obtained by their reductive cyclisation into 5-methyl-4-phenylpyrrolidin-2-one enantiomers and the attachment of the acetamide group to the heterocyclic nitrogen. Experiments with electrically stimulated rat vas deference contractions induced by the PRE-084, an agonist of sigma-1 receptor, showed that (4R,5S)- and (4R,5R)-2-(5-methyl-4-phenyl-2-oxopyrrolidin-l-yl)-acetamides with an R-configuration at the C-4 chiral centre in the 2-pyrrolidone ring were more effective positive allosteric modulators of sigma-1 receptor than were their optical antipodes. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.03.016

文献信息

• Conjugate addition of organocopper reagents to n-tosylated α, β-unsaturated amides
  作者：Hideo Nagashima、Nobuyasu Ozaki、Masayoshi Washiyama、Kenji ltoh

  DOI：10.1016/s0040-4039(00)89172-8

  日期：1985.1

  N-Tosylated α, β-unsaturated amides and lactams undergo facile conjugate addition with R2CuLi or RMgX/CuI (cat.). Stereoselective synthesis of trans-β,γ-dialkyl-γ-lactams can be achieved by this procedure. The resulting N-tosylamide moiety is further transformed to alcohol and several carbonyl compounds by way of reduction or nucleophillic displacement.

  N-甲苯磺酸化的α，β-不饱和酰胺和内酰胺与R 2 CuLi或RMgX / CuI（目录）轻松偶联。通过该方法可以实现反式-β，γ-二烷基-γ-内酰胺的立体选择性合成。通过还原或亲核取代，将所得的N-甲苯磺酰胺部分进一步转化为醇和几种羰基化合物。
• Catalytic Asymmetric Conjugate Addition of Nitroalkanes to 4-Nitro-5-styrylisoxazoles
  作者：Andrea Baschieri、Luca Bernardi、Alfredo Ricci、Surisetti Suresh、Mauro F. A. Adamo

  DOI：10.1002/anie.200905018

  日期：2009.11.23

  Nitro versus nitro: 4‐Nitro‐5‐styrylisoxazoles were used as masked α,β‐unsaturated carboxylic acids in the titled catalytic asymmetric transformation. The 4‐nitroisoxazole core acts as an activator of the conjugated alkene and a latent carboxylate functionality. The reaction proceeded with 5 mol % of a readily prepared phase‐transfer catalyst at room temperature with remarkable diastereo‐ and enantioselectivity

  硝基与硝基：在标题为催化不对称转化中，使用4‐Nitro‐5‐styrylisoxazoles作为掩蔽的α，β‐不饱和羧酸。4-硝基异恶唑核心充当共轭烯烃的活化剂和潜在的羧酸盐官能团。反应在室温下以5摩尔％的现成相转移催化剂进行，反应具有非对映选择性和对映选择性（参见方案）。
• Cyclisation at very high temperature. Thermal transformations of N-alkyl and N, N-dialkyl amides of α,β-unsaturated acids into mono- and bicyclic heterocycles under FVT conditions
  作者：Stanisław Leśniak、Ryszard B. Nazarski、Beata Pasternak

  DOI：10.1016/j.tet.2009.06.011

  日期：2009.8

  Cyclisations of N-alkyl and N,N-dialkyl cinnamic amides to the corresponding pyrrolidin-2-ones under the conditions of flash vacuum thermolysis (FVT), are described. It was found that these reactions proceed at 950-1000 degrees C affording in various yields the mixtures of isomeric mono and bicyclic gamma-lactams, which were separated chromatographically and analysed by means of NMR spectroscopy. Two alternative mechanisms for the title process are proposed. (C) 2009 Elsevier Ltd. All rights reserved.
• Synthesis and biological evaluation of 2-(5-methyl-4-phenyl-2-oxopyrrolidin-1-yl)-acetamide stereoisomers as novel positive allosteric modulators of sigma-1 receptor
  作者：Grigory Veinberg、Maxim Vorona、Liga Zvejniece、Reinis Vilskersts、Edijs Vavers、Edvards Liepinsh、Helena Kazoka、Sergey Belyakov、Anatoly Mishnev、Jevgenijs Kuznecovs、Sergejs Vikainis、Natalja Orlova、Anton Lebedev、Yuri Ponomaryov、Maija Dambrova

  DOI：10.1016/j.bmc.2013.03.016

  日期：2013.5

  Novel positive allosteric modulators of sigma-1 receptor represented by 2-(5-methyl-4-phenyl-2-oxopyrrolidin-l-yl)-acetamide enantiomers were synthesised using an asymmetric Michael addition of 2-nitroprop-1-enylbenzene to diethyl malonate. Following the chromatographic separation of the methyl erythro- and threo-4-nitro-3R- and 3S-phenylpentanoate diastereoisomers, target compounds were obtained by their reductive cyclisation into 5-methyl-4-phenylpyrrolidin-2-one enantiomers and the attachment of the acetamide group to the heterocyclic nitrogen. Experiments with electrically stimulated rat vas deference contractions induced by the PRE-084, an agonist of sigma-1 receptor, showed that (4R,5S)- and (4R,5R)-2-(5-methyl-4-phenyl-2-oxopyrrolidin-l-yl)-acetamides with an R-configuration at the C-4 chiral centre in the 2-pyrrolidone ring were more effective positive allosteric modulators of sigma-1 receptor than were their optical antipodes. (C) 2013 Elsevier Ltd. All rights reserved.