2-methylpropyl glycine, p-toluenesulfonic acid salt

• 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: 2-methylpropyl glycine, p-toluenesulfonic acid salt
• 英文别名: sec-butyl 2-aminoacetate p-tosylate；Isobutyl glycine, p-toluenesulfonic acid salt；4-Methylbenzenesulfonate;[2-(2-methylpropoxy)-2-oxoethyl]azanium；4-methylbenzenesulfonate;[2-(2-methylpropoxy)-2-oxoethyl]azanium
• 化学式: C₆H₁₃NO₂*C₇H₈O₃S
• 分子量: 303.379
• InChiKey: YAFUQQOZKSYAGA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.39
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-methylpropyl glycine, p-toluenesulfonic acid salt 、 (R)-2-苄基-3-[(3R,4R)-4-(3-羟基苯基)-3,4-二甲基哌啶-1-基]丙酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以100%的产率得到(+)-<<2'(S)-<<4(R)-3-(hydroxyphenyl)-3(R),4-dimethyl-1-piperidinyl>methyl>-1-oxo-3-phenylpropyl>amino>acetic acid 2-methylpropyl ester
  参考文献：
  名称：

  爱维莫潘中间体的制备方法

  摘要：

  本发明公开了一种如式VI所示的爱维莫潘中间体的制备方法，其包括如下步骤：30℃～160℃条件下，有机溶剂中，将如式III所示的化合物进行如下所示的消旋化反应；其中R是氢或C1～6烷基。本发明还公开了一种如式III所示的化合物的制备方法，其包含如下步骤：溶剂中，pH＝7～14的条件下，将如式II所示的化合物进行如下所示的中和反应；其中，Z是氯、溴、琥珀酸的酸根或(+)‑二苯甲酰酒石酸的酸根。本发明的爱维莫潘中间体的制备工艺，操作简单、反应条件温和、三废少、更环保、原料利用率高、收率高、利于工业化生产。

  公开号：

  CN105820106B
• 作为产物：
  描述：

  异丁醇 、 聚甘氨酸 在 对甲苯磺酸一水合物 作用下， 以 正己烷 、 乙酸乙酯 、 甲苯 为溶剂， 生成 2-methylpropyl glycine, p-toluenesulfonic acid salt
  参考文献：
  名称：

  Preparation of 3,4,4-trisubstituted-piperidinyl-N-alkylcarboxylates and

  摘要：

  本发明涉及一种制备特定的3,4,4-三取代哌啶基-N-烷基羧酸酯、中间体和类似物的过程。最终，该发明提供了新的3,4,4-三取代哌啶基-N-烷基羧酸酯的配方和使用该化合物的方法。

  公开号：

  US05434171A1

文献信息

• Novel trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines as μ opioid receptor antagonists with improved opioid receptor selectivity profiles
  作者：Bertrand Le Bourdonnec、William M. Barker、Serge Belanger、Daniel D. Wiant、Nathalie C. Conway-James、Joel A. Cassel、Timothy J. O’Neill、Patrick J. Little、Robert N. DeHaven、Diane L. DeHaven-Hudkins、Roland E. Dolle

  DOI：10.1016/j.bmcl.2008.01.106

  日期：2008.3

  A series of N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl) piperidines, mu opioid receptor antagonists, analogs of alvimopan, were prepared using solid phase methodology. This study led to the identification of a highly selective l opioid receptor antagonist, which interacts selectively with l peripheral receptors. (C) 2008 Elsevier Ltd. All rights reserved.
• Synthesis of <i>trans</i>-3,4-Dimethyl-4-(3-hydroxyphenyl)piperidine Opioid Antagonists:  Application of the <i>Cis</i>-Thermal Elimination of Carbonates to Alkaloid Synthesis
  作者：John A. Werner、Louis R. Cerbone、Scott A. Frank、Jeffrey A. Ward、Parviz Labib、Roger W. Tharp-Taylor、C. W. Ryan

  DOI：10.1021/jo951403y

  日期：1996.1.1

  Improved syntheses of two trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine opioid antagonists from 1,3-dimethyl-4-piperidinone are described. The 1,3 dimethyl-4-arylpiperidinol 23 was selectively dehydrated in a two step process to the 1,3-dimethyl-4-aryl-1,2,3,6-tetrahydropyrodome 26 by the cis-thermal elimination of the corresponding alkyl carbonate derivative at 190 degrees C. In the presence of a basic nitrogen, the success of the elimination was found to be critically dependent upon the nature of the carbonate alkyl group, with Et, i-Bu, and i-Pr being preferred (90% yield). Alkylation of the metalloenamine, formed by deprotonation of 26 with n-BuLi, proceeded regio- and stereospecifically to give the trans-3,4-dimethyl-4-aryl-1,2,3,4-tetrahydrpyridine 27, which was converted in three steps to the common intermediate, (3R,4R)-3,4-dimethyl-4-(3-hydroxyphenyl)-piperidine. LY255582, a centrally-active opioid antagonist, and LY246736-dihydrate, a peripherally-active opioid antagonist, were prepared from 1,3-dimethyl-4-piperidinone in 11.8% yield (8 steps) and 6.2% yield (12 steps), respectively.
• Discovery of a Potent, Peripherally Selective trans-3,4-Dimethyl-4-(3-hydroxyphenyl)piperidine Opioid Antagonist for the Treatment of Gastrointestinal Motility Disorders
  作者：Dennis M. Zimmerman、Jaswant S. Gidda、Buddy E. Cantrell、Darryle D. Schoepp、Bryan G. Johnson、J. David Leander

  DOI：10.1021/jm00041a003

  日期：1994.7

  Structure-activity relationship studies were pursued within N-substituted-trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines in an effort to discover a peripherally selective opioid antagonist with high activity following systemic administration. Altering the size and the polarity of the N-substituent led to the discovery of 3 (LY246736). Compound 3 has high affinity for opioid receptors (K-i = 0.77, 40, and 4.4 nM for mu, kappa, and delta receptors, respectively). It is a potent mu receptor antagonist following parenteral and oral administration and distributes selectively (>200-fold selectivity) to peripheral receptors. Thus, 3 has properties suitable for the clinical investigation of mu opioid receptor involvement in GI motility disorders.
• [EN] PROCESS FOR ALVIMOPAN<br/>[FR] PROCÉDÉ DE PURIFICATION D'ALVIMOPAN
  申请人：HETERO RESEARCH FOUNDATION

  公开号：WO2013080221A2

  公开（公告）日：2013-06-06

  The present invention provides a novel process for the purification of alvimopan. In accordance with the present invention alvimopan was dissolved in dimethylformamide and heated to 120 to 125 deg C, and then added n-butanol at room temperature, the contents were stirred for 15 hours, filtered and then dried to obtain pure alvimopan.
• 爱维莫潘中间体的制备方法
  申请人：上海医药工业研究院

  公开号：CN105820106B

  公开（公告）日：2018-11-09

  本发明公开了一种如式VI所示的爱维莫潘中间体的制备方法，其包括如下步骤：30℃～160℃条件下，有机溶剂中，将如式III所示的化合物进行如下所示的消旋化反应；其中R是氢或C1～6烷基。本发明还公开了一种如式III所示的化合物的制备方法，其包含如下步骤：溶剂中，pH＝7～14的条件下，将如式II所示的化合物进行如下所示的中和反应；其中，Z是氯、溴、琥珀酸的酸根或(+)‑二苯甲酰酒石酸的酸根。本发明的爱维莫潘中间体的制备工艺，操作简单、反应条件温和、三废少、更环保、原料利用率高、收率高、利于工业化生产。