3-propyl-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester | 457657-69-1

• 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: 3-propyl-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester
• 英文别名: 1-(1,1-Dimethylethyl) 3-methyl 3-propyl-1,3-pyrrolidinedicarboxylate；1-O-tert-butyl 3-O-methyl 3-propylpyrrolidine-1,3-dicarboxylate
• CAS: 457657-69-1
• 化学式: C₁₄H₂₅NO₄
• 分子量: 271.357
• InChiKey: FBLZCOZFOATJEQ-UHFFFAOYSA-N

物化性质

• 沸点：
  328.2±35.0 °C(Predicted)
• 密度：
  1.055±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-propyl-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 生成 3-formyl-3-propyl-pyrrolidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of new monoamine reuptake inhibitors with potential therapeutic utility in depression and pain

  摘要：

  Two new series of monoamine triple reuptake inhibitors (TRIs) have been discovered through scaffold homologation of our recently reported series of 3,3-disubstituted pyrrolidine TRIs. The regioisomeric 2- and 3-ketopyrrolidines demonstrated high levels of potency against all three monoamine transporters as well as good human in vitro stability, low drug-drug interaction potential and a decreased propensity for hERG channel binding. Representative compounds from these series displayed good in vivo pharmacokinetics and high monoamine receptor occupancies which are indicators of good brain penetration. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.07.020
• 作为产物：
  描述：

  N-苄基吡咯烷-3-甲酸甲酯 在 正丁基锂 、 palladium 10% on activated carbon 、 氢气 、 二异丙胺 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 为溶剂， 反应 6.0h， 生成 3-propyl-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester
  参考文献：
  名称：

  [EN] (3,4-DICHLORO-PHENYL)-((S)-3-PROPYL-PYRROLIDIN-3-YL)-METHANONE HYDROCHLORIDE AND MANUFACTURING PROCESSES
  [FR] CHLORHYDRATE DE (3,4-DICHLORO-PHÉNYL)-((S)-3-PROPYL-PYRROLIDIN-3-YL)-MÉTHANONE ET PROCÉDÉS DE FABRICATION

  摘要：

  本发明涉及一种新型制备化合物I及其水合物的方法，以及其晶体多型。化合物I的化学式和相应的水合物是具有药用活性的物质。

  公开号：

  WO2013160273A1

文献信息

• [EN] (3,4-DICHLORO-PHENYL)-((S)-3-PROPYL-PYRROLIDIN-3-YL)-METHANONE HYDROCHLORIDE AND MANUFACTURING PROCESSES<br/>[FR] CHLORHYDRATE DE (3,4-DICHLORO-PHÉNYL)-((S)-3-PROPYL-PYRROLIDIN-3-YL)-MÉTHANONE ET PROCÉDÉS DE FABRICATION
  申请人：HOFFMANN LA ROCHE

  公开号：WO2013160273A1

  公开（公告）日：2013-10-31

  The present invention is concerned with a novel process for the preparation of a compound of formula I and its hydrates, as well as with a crystall polymorph thereof. The compounds of formula (I) and the corresponding hydrates are pharmaceutically active substances.

  本发明涉及一种新型制备化合物I及其水合物的方法，以及其晶体多型。化合物I的化学式和相应的水合物是具有药用活性的物质。
• Preparation of Cyclic and Bicyclic β-Amino Acids Derivatives from Methyl 6-Ethoxy-5,6-dihydro-4H-1,2-oxazine-4-carboxylate
  作者：Alexander A. Tishkov、Hans-Ulrich Reissig、Sema L. Ioffe

  DOI：10.1055/s-2002-31908

  日期：——

  The readily available methyl 6-ethoxy-5,6-dihydro-4H-1,2-oxazine-4-carboxylate (1) was alkylated at C-4 and acylated at the nitrogen atom. 1,2-Oxazine 1 and the resulting new substituted 1,2-oxazines 2 and 3 were suitableprecursors for the preparation of derivatives of β-proline, nipecotic acid, as well as indolizine-6- and quinolizine-3-carboxylic acids.

  容易获得的 6-乙氧基-5,6-二氢-4H-1,2-恶嗪-4-羧酸甲酯 (1) 在 C-4 处被烷基化并在氮原子处被酰化。1,2-恶嗪 1 和所得的新取代的 1,2-恶嗪 2 和 3 是制备 β-脯氨酸、尼泊克酸以及 indolizine-6- 和 quinolizine-3- 羧酸衍生物的合适前体。
• US9527810B2
  申请人：——

  公开号：US9527810B2

  公开（公告）日：2016-12-27
• (3,4-DICHLORO-PHENYL)-((S)-3-PROPYL-PYRROLIDIN-3-YL)-METHANONE HYDROCHLORIDE AND MANUFACTURING PROCESSES
  申请人：Hoffmann-La Roche Inc.

  公开号：US20150045408A1

  公开（公告）日：2015-02-12

  The present invention is concerned with a novel process for the preparation of a compound of formula I and its hydrates The compounds of formula I and the corresponding hydrates are pharmaceutically active substances.

  本发明涉及一种制备化合物I及其水合物的新颖方法。化合物I的公式及相应的水合物是药用活性物质。
• Design, synthesis, and biological evaluation of new monoamine reuptake inhibitors with potential therapeutic utility in depression and pain
  作者：Matthew C. Lucas、Robert J. Weikert、David S. Carter、Hai-Ying Cai、Robert Greenhouse、Pravin S. Iyer、Clara J. Lin、Eun Kyung Lee、Ann Marie Madera、Amy Moore、Kerem Ozboya、Ryan C. Schoenfeld、Sandra Steiner、Yansheng Zhai、Stephen M. Lynch

  DOI：10.1016/j.bmcl.2010.07.020

  日期：2010.9

  Two new series of monoamine triple reuptake inhibitors (TRIs) have been discovered through scaffold homologation of our recently reported series of 3,3-disubstituted pyrrolidine TRIs. The regioisomeric 2- and 3-ketopyrrolidines demonstrated high levels of potency against all three monoamine transporters as well as good human in vitro stability, low drug-drug interaction potential and a decreased propensity for hERG channel binding. Representative compounds from these series displayed good in vivo pharmacokinetics and high monoamine receptor occupancies which are indicators of good brain penetration. (C) 2010 Elsevier Ltd. All rights reserved.