(2S) tert-butyl N-(tert-butoxycabonyl)-3-[(dimethylamino)methylidene]-4-oxoprolinate | 166410-06-6

• 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: (2S) tert-butyl N-(tert-butoxycabonyl)-3-[(dimethylamino)methylidene]-4-oxoprolinate
• 英文别名: tert-butyl (2S)-N-tert-butoxycarbonyl-3-dimethylaminomethylene-4-oxoprolinate；1,2-Pyrrolidinedicarboxylic acid, 3-[(dimethylamino)methylene]-4-oxo-, bis(1,1-dimethylethyl) ester, [S-(E)]-；ditert-butyl (2S,3E)-3-(dimethylaminomethylidene)-4-oxopyrrolidine-1,2-dicarboxylate
• CAS: 166410-06-6
• 化学式: C₁₇H₂₈N₂O₅
• 分子量: 340.42
• InChiKey: PPZKPPCVXOWYLX-FUWURINLSA-N

物化性质

• LogP：
  2.62

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  76.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S) tert-butyl N-(tert-butoxycabonyl)-3-[(dimethylamino)methylidene]-4-oxoprolinate 在 三乙基硼氢化锂 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 0.25h， 生成 (2S,4S) tert-butyl N-(tert-butoxycabonyl)-3-ethylidene-4-hydroxyprolinate
  参考文献：
  名称：

  Stereoselective synthesis of (3S,4S)-tert-butyl-N-Boc-3-ethyl-4-hydroxy-l-prolinate and (3S,4R)-tert-butyl-N-Boc-3-ethyl-4-hydroxy-l-prolinate

  摘要：

  Diastereomers of tert-butyl-N-Boc-3-ethyl-4-hydroxy-L-prolinate 1 and 2 have been synthesized in six steps starting from readily available Boc-protected trans-4-hydroxy-L-proline. The key reactions in the synthesis are asymmetric reductions, firstly on the 4-ketoproline intermediate 6 and secondly on the 3-exocyclic olefin bond of the resulting allylic alcohol 7 or 8. Reaction conditions were optimized in order to control the stereochemistry of the three chiral centers. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2005.02.006
• 作为产物：
  描述：

  (2S,4R)-双-叔丁基4-羟基吡咯烷-1,2-二甲酸酯 在 甲基三辛基氯化铵 、 碳酸氢钠 2,2,6,6-tetramethyl-piperidine-N-oxyl 、 亚硝酰氯 、 potassium bromide 作用下， 以 乙二醇二甲醚 、 二氯甲烷 、 水 为溶剂， 反应 4.0h， 生成 (2S) tert-butyl N-(tert-butoxycabonyl)-3-[(dimethylamino)methylidene]-4-oxoprolinate
  参考文献：
  名称：

  Stereoselective synthesis of (3S,4S)-tert-butyl-N-Boc-3-ethyl-4-hydroxy-l-prolinate and (3S,4R)-tert-butyl-N-Boc-3-ethyl-4-hydroxy-l-prolinate

  摘要：

  Diastereomers of tert-butyl-N-Boc-3-ethyl-4-hydroxy-L-prolinate 1 and 2 have been synthesized in six steps starting from readily available Boc-protected trans-4-hydroxy-L-proline. The key reactions in the synthesis are asymmetric reductions, firstly on the 4-ketoproline intermediate 6 and secondly on the 3-exocyclic olefin bond of the resulting allylic alcohol 7 or 8. Reaction conditions were optimized in order to control the stereochemistry of the three chiral centers. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2005.02.006

文献信息

• [EN] SUBSTITUTED PROLINE INHIBITORS OF HEPATITIS C VIRUS REPLICATION<br/>[FR] INHIBITEURS PROLINE SUBSTITUÉE DE RÉPLICATION DU VIRUS DE L'HÉPATITE C
  申请人：INTERMUNE INC

  公开号：WO2012040242A1

  公开（公告）日：2012-03-29

  The embodiments provide compounds of the general Formulae I, la, II,IIa,III, IIIa, Illb, IV, IVa, IVb, V, Va, Vb, VI, VIa, VIb, and VIc, as well as compositions, including pharmaceutical compositions, comprising a subject compound. The embodiments further provide treatment methods, including methods of treating a hepatitis C virus infection and methods of treating liver fibrosis, the methods generally involving administering to an individual in need thereof an effective amount of a subject compound or composition. The embodiments also provide methods for the synthesis of subject compounds and intermediates in the synthetic methods.

  该实施例提供了一般式I、Ia、II、IIa、III、IIIa、IIIb、IV、IVa、IVb、V、Va、Vb、VI、VIa、VIb和VIc的化合物，以及包括药物化合物的组合物，包括制药组合物。该实施例还提供了治疗方法，包括治疗丙型肝炎病毒感染和治疗肝纤维化的方法，这些方法通常涉及向需要的个体施用所述化合物或组合物的有效量。该实施例还提供了用于合成所述化合物和合成方法中间体的方法。
• Synthesis of kainoid analogues
  作者：Paul Barraclough、Piétrick Hudhomme、Caroline A. Spray、Douglas W. Young

  DOI：10.1016/0040-4020(95)00135-u

  日期：1995.4

  4-oxoproline has been used as a chiral template in a synthesis of kainoid analogues which are epimeric with the parent compound at C-3.

  4-氧代脯氨酸已被用作手性模板，用于合成与母体化合物在C-3上游离的类红素类似物。
• SUBSTITUTED PROLINE INHIBITORS OF HEPATITIS C VIRUS REPLICATION
  申请人：Buckman Brad

  公开号：US20120095211A1

  公开（公告）日：2012-04-19

  The embodiments provide compounds of the general Formulae I, Ia, II, IIa, III, IIIa, IIIb, IV, IVa, IVb, V, Va, Vb, VI, VIa, VIb, and VIc, as well as compositions, including pharmaceutical compositions, comprising a subject compound. The embodiments further provide treatment methods, including methods of treating a hepatitis C virus infection and methods of treating liver fibrosis, the methods generally involving administering to an individual in need thereof an effective amount of a subject compound or composition. The embodiments also provide methods for the synthesis of subject compounds and intermediates in the synthetic methods.

  本实施例提供了通式I、Ia、II、IIa、III、IIIa、IIIb、IV、IVa、IVb、V、Va、Vb、VI、VIa、VIb和VIc的化合物，以及包括药物组成物在内的组合物，其中包括一种主体化合物。本实施例还提供了治疗方法，包括治疗丙型肝炎病毒感染和治疗肝纤维化的方法，通常涉及向需要治疗的个体投与有效量的主体化合物或组合物。本实施例还提供了主体化合物的合成方法和合成方法中的中间体。
• Alternative Approach to the Large-Scale Synthesis of the Densely Functionalized Pyrrolidone BMT-415200
  作者：Souvik Rakshit、Shunmugaraj Sathasivam、Raghurami Reddy、Saladi V. Rao、Vijaykumar Shekarappa、Moorthy Kandasamy、Mohamed Jaleel、Saravanan Murugan、Anuradha Bhat、Tamilarasan Subramani、Thirumalai Lakshminarasimhan、Aravind Gangu、Steven R. Wisniewski、Nathaniel Kopp、Ian Hale、Jason M. Stevens、Victor W. Rosso、Martin D. Eastgate、Rajappa Vaidyanathan

  DOI：10.1021/acs.oprd.3c00007

  日期：——

  -5-oxopyrrolidin-2-yl)methyl methanesulfonate (BMT-415200) 1 is described in this work. In this sequence, a safe and robust process of nine linear steps with four isolations was implemented. The synthesis features highly diastereoselective hydrogenation of enones 12, diastereoselective reduction of ketone 13, and deoxyfluorination of the corresponding secondary alcohol 8 followed by C–H oxidation of

  对映体纯 ((2 S ,3 S ,4 S )-3-ethyl-4-fluoro-5-oxopyrrolidin-2-yl)methyl methanesulfonate (BMT-415200) 1 的多千克规模合成路线的开发在这项工作中进行了描述。在这个序列中，实施了一个安全可靠的过程，该过程由九个线性步骤和四个隔离组成。该合成的特点是烯酮12的高度非对映选择性氢化、酮13的非对映选择性还原以及相应仲醇8的脱氧氟化，然后9被 C-H 氧化为内酰胺10。目标化合物1由市售二叔丁基 (S)-4-氧代吡咯烷-1,2-二羧酸酯 7 制备，总收率为 19% ，纯度> 99 %。
• INHIBITORS OF HEPATITIS C VIRUS
  申请人：Gilead Sciences, Inc.

  公开号：US20140017198A1

  公开（公告）日：2014-01-16

  Compounds of Formula I are disclosed As well as pharmaceutically acceptable salts thereof. Methods of using said compounds and pharmaceutical compositions containing said compounds are also disclosed.