methyl 1-(4-chlorobenzyl)-5-oxopyrrolidine-3-carboxylate | 133748-56-8

• 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: methyl 1-(4-chlorobenzyl)-5-oxopyrrolidine-3-carboxylate
• 英文别名: methyl 1-(4-chlorobenzyl)-5-oxo-3-pyrrolidinecarboxylate；Methyl 1-[(4-chlorophenyl)methyl]-5-oxopyrrolidine-3-carboxylate
• CAS: 133748-56-8
• 化学式: C₁₃H₁₄ClNO₃
• 分子量: 267.712
• InChiKey: TYSKCDVEMVHWPO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 1-(4-chlorobenzyl)-5-oxopyrrolidine-3-carboxylate 在 三乙基硅烷 、 C₂₅H₂₆IrN₂⁽¹⁺⁾*C₃₂H₁₂BF₂₄^(1-) 作用下， 以 1,2-二氯乙烷 为溶剂， 以98%的产率得到methyl 1-(4-chlorobenzyl)pyrrolidine-3-carboxylate
  参考文献：
  名称：

  Et3SiH 化学选择性铱 (III) 金属环催化取代 γ-内酰胺还原的联合实验/理论研究

  摘要：

  本研究探讨了由苯并[ h ]喹啉衍生的五甲基环戊二烯基环乙腈盐介导的 Et 3 SiH 催化还原一系列不同取代的 γ-内酰胺的化学选择性。在 γ-内酰胺 5 元环内引入不饱和度会消除酰胺官能团相对于硅阳离子捕获的优先性，从而导致较低的化学选择性。通过1 H NMR 光谱随时间监测带有羧酸酯附加物的 γ-内酰胺的催化还原，揭示了内酰胺酰胺先前氢化硅烷化的伪零级动力学。在该初级氢化硅烷化反应之后，所形成的中间体按照伪一级速率定律完全转化为吡咯烷。在无水条件下，当γ-内酰胺的酰胺官能团完全还原羰基官能团时，侧酯官能团的氢化硅烷化仅发生在后期。 DFT 研究表明，化学选择性受 (1) 有机底物对三乙基硅鎓阳离子（通过 Ir(III) 催化剂亲电活化 Et 3 SiH 产生）的亲和力和 (2)原位形成的能力的影响。氢化铱(III)中间体将氢化物转移到活化的底物上。

  DOI：

  10.1021/acs.organomet.4c00044
• 作为产物：
  描述：

  衣康酸二甲酯 、 对氯苄胺 生成 methyl 1-(4-chlorobenzyl)-5-oxopyrrolidine-3-carboxylate
  参考文献：
  名称：

  Discovery of an orally efficaceous 4-phenoxypyrrolidine-based BACE-1 inhibitor

  摘要：

  Based on a lead compound identified from the patent literature, we developed patentably novel BACE-1 inhibitors by introducing a cyclic amine scaffold as embodied by la and 1b. Extensive SAR studies assessed a variety of isophthalamide replacements including substituted pyrrolidinones and ultimately led to the identification of 11. Due to its favorable overall profile, 11 has been extensively profiled in various in vivo settings. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.10.053

文献信息

• Lp(a)-LOWERING AGENTS AND APOPROTEIN (a) PRODUCTION INHIBTORS
  申请人：TAIHO PHARMACEUTICAL COMPANY, LIMITED

  公开号：EP1000620A1

  公开（公告）日：2000-05-17

  Lp(a)-lowering agents or apo(a) production inhibitors containing as the active ingredient phenylcarboxylic acid derivatives represented by general formula (1) or salts thereof, wherein R1 represents optionally substituted phenyl; A represents lower alkylene or lower alkyleneoxy; B represents methylene or carbonyl; D represents lower alkylene; E represents lower alkylene or lower alkenylene; R2 represents hydrogen or lower alkyl; and l, m and n are each 0 or 1. These drugs can significantly lower Lp(a) while scarcely showing any side effects.

  Lp(a)降低剂或apo(a)生成抑制剂，其活性成分为通式(1)代表的苯基羧酸衍生物或其盐类，其中R1代表任选取代的苯基；A代表低级亚烷基或低级亚烷氧基；B代表亚甲基或羰基；D代表低级亚烷基；E代表低级亚烷基或低级亚烯基；R2代表氢或低级亚烷基；l、m和n均为0或1。这些药物可以大大降低脂蛋白（a），同时几乎没有任何副作用。
• Phenylcarboxylic acid derivatives having a hetero ring
  申请人：OTSUKA PHARMACEUTICAL CO., LTD.

  公开号：EP0393607B1

  公开（公告）日：1996-02-21
• Lp(a)-LOWERING AGENTS AND APOPROTEIN (a) PRODUCTION INHIBITORS
  申请人：TAIHO PHARMACEUTICAL COMPANY, LIMITED

  公开号：EP1000620B1

  公开（公告）日：2005-12-07
• US6166036A
  申请人：——

  公开号：US6166036A

  公开（公告）日：2000-12-26
• Discovery of an orally efficaceous 4-phenoxypyrrolidine-based BACE-1 inhibitor
  作者：U. Iserloh、J. Pan、A.W. Stamford、M.E. Kennedy、Q. Zhang、L. Zhang、E.M. Parker、N.A. McHugh、L. Favreau、C. Strickland、J. Voigt

  DOI：10.1016/j.bmcl.2007.10.053

  日期：2008.1

  Based on a lead compound identified from the patent literature, we developed patentably novel BACE-1 inhibitors by introducing a cyclic amine scaffold as embodied by la and 1b. Extensive SAR studies assessed a variety of isophthalamide replacements including substituted pyrrolidinones and ultimately led to the identification of 11. Due to its favorable overall profile, 11 has been extensively profiled in various in vivo settings. (c) 2007 Elsevier Ltd. All rights reserved.