Methyl-[(S)-1-((S)-methyl-pyrrolidin-3-yl-carbamoyl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester | 762285-87-0

• 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-[(S)-1-((S)-methyl-pyrrolidin-3-yl-carbamoyl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester
• CAS: 762285-87-0
• 化学式: C₁₆H₃₀N₄O₃
• 分子量: 326.439
• InChiKey: YIUKASWFPUCKRT-STQMWFEESA-N

物化性质

• 沸点：
  453.1±45.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.34
• 重原子数：
  23.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  65.12
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  Methyl-[(S)-1-((S)-methyl-pyrrolidin-3-yl-carbamoyl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester 在 四(三苯基膦)钯 、 TEA 、 三乙酰氧基硼氢化钠 、 sodium carbonate 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 37.0h， 生成 (3S)-N-methyl-N-[(3S)-1-methylpyrrolidin-3-yl]-3-[methyl-[5-[4-(trifluoromethyl)phenyl]thiophene-2-carbonyl]amino]pyrrolidine-1-carboxamide
  参考文献：
  名称：

  Synthesis and structure–activity relationships of biarylcarboxamide bis-aminopyrrolidine urea derived small-molecule antagonists of the melanin-concentrating hormone receptor-1 (MCH-R1)

  摘要：

  A novel series of bis-aminopyrrolidine ureas containing either a 4-biphenylcarboxmide or 5-phenyl-2-thiophenecarboxamide group have been identified as potent and functional antagonists of the melanin-concentrating hormone receptor-1. Syntheses and SAR are described, which led to the discovery of compounds with high binding affinity (K-i = 1 nM) for the receptor. Preliminary in vitro metabolic stability data are also reported for key compounds. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.015
• 作为产物：
  描述：

  {(S)-1-[((S)-1-Benzyl-pyrrolidin-3-yl)-methyl-carbamoyl]-pyrrolidin-3-yl}-methyl-carbamic acid tert-butyl ester 在 palladium dihydroxide 氢气 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、275.79 kPa 条件下， 反应 17.0h， 生成 Methyl-[(S)-1-((S)-methyl-pyrrolidin-3-yl-carbamoyl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis and structure–activity relationships of biarylcarboxamide bis-aminopyrrolidine urea derived small-molecule antagonists of the melanin-concentrating hormone receptor-1 (MCH-R1)

  摘要：

  A novel series of bis-aminopyrrolidine ureas containing either a 4-biphenylcarboxmide or 5-phenyl-2-thiophenecarboxamide group have been identified as potent and functional antagonists of the melanin-concentrating hormone receptor-1. Syntheses and SAR are described, which led to the discovery of compounds with high binding affinity (K-i = 1 nM) for the receptor. Preliminary in vitro metabolic stability data are also reported for key compounds. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.015

文献信息

• Bis(aminopyrrolidine)-derived ureas (APUs) as potent MCH1 receptor antagonists
  作者：Jonathan Grey、Brian Dyck、Martin W. Rowbottom、Junko Tamiya、Troy D. Vickers、Mingzhu Zhang、Liren Zhao、Christopher E. Heise、David Schwarz、John Saunders、Val S. Goodfellow

  DOI：10.1016/j.bmcl.2004.12.036

  日期：2005.2

  Ureas derived from two substituted 3-aminopyrrolidine subunits were prepared as constrained analogs of a linear lead compound and tested as antagonists of the MCH1 receptor. The series was optimized for substitution and stereochemistry to generate a functional antagonist with a K-i of 3.3 nM and IC50 of 12 nM (GTPgammaS). (C) 2004 Elsevier Ltd. All rights reserved.