(+)-[(2R)-1-benzyl-4-butylpiperazin-2-yl]methanol | 366003-68-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (+)-[(2R)-1-benzyl-4-butylpiperazin-2-yl]methanol
• 英文别名: [(2R)-1-benzyl-4-butylpiperazin-2-yl]methanol
• CAS: 366003-68-1
• 化学式: C₁₆H₂₆N₂O
• 分子量: 262.395
• InChiKey: VSLNOMIVVIQWLF-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  26.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (+)-[(2R)-1-benzyl-4-butylpiperazin-2-yl]methanol 在 草酰氯 、 二甲基亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 17.25h， 生成 (-)-(6S)-4-butyl-1,4-diazabicyclo[4.3.0]nonan-9-one
  参考文献：
  名称：

  （1-苄基哌嗪-2-基）甲醇：从（S）-丝氨酸合成新的EPC，并转化为中枢神经系统受体的配体

  摘要：

  4-取代的- （1-苄基-2-基）基甲醇的一种新颖的三步合成5A - 5c中描述从蛋白质氨基酸（甲酯起始小号） -丝氨酸，它涉及非对映体衍生物恶唑11A - 11c作为关键中间体。通过Swern氧化，随后的Wittig反应和随后的氢化，将5b和5c转化为手性，非外消旋的双环内酰胺14b和14c。在筛选用于中枢神经系统受体亲和力丁基衍生物14b中被发现具有与σ有为相互作用1-受体（K i = 345 nM）。

  DOI：

  10.1016/s0957-4166(01)00208-7
• 作为产物：
  描述：

  (S)-7-Butyl-3-phenyl-tetrahydro-oxazolo[3,4-a]pyrazine-5,8-dione 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 以74%的产率得到(+)-[(2R)-1-benzyl-4-butylpiperazin-2-yl]methanol
  参考文献：
  名称：

  Chiral, nonracemic (piperazin-2-yl)methanol derivatives with σ-receptor affinity

  摘要：

  Starting with the proteinogenic amino acid (S)-serine a series of chiral nonracemic (piperazin-2-yl)methanols 3 with various N-4 substituents is described. The key step in the synthesis of 3 is the reaction of the chloroacetamide 5 with various primary amines to yield the diastereomeric bicyclic piperazinediones cis-6 and traps-6. The scope and limitation of this transformation is thoroughly investigated. The sigma(1)- and sigma(2)-receptor affinities of the piperazines 3 are determined in receptor binding studies with guinea pig brain and rat liver membrane preparations using [H-3]-labeled (+)-pentazocine and ditolylguanidine, respectively. It was found, that an additional phenyl residue in the N-4 substituent is favorable to high sigma(1)-receptor affinity. In this series the p-methoxybenzyl substituted piperazine 3d reveals the highest sigma(1)-receptor affinity (K-i = 12.4 nM) with selectivity toward sigma(2)-, NMDA-, kappa-opioid, and mu-opioid receptors. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.03.059

文献信息

• (1-Benzylpiperazin-2-yl)methanols: novel EPC synthesis from (S)-serine and transformation into ligands for central nervous system receptors
  作者：Stephan Bedürftig、Manuela Weigl、Bernhard Wünsch

  DOI：10.1016/s0957-4166(01)00208-7

  日期：2001.6

  A novel three-step synthesis of 4-substituted-(1-benzylpiperazin-2-yl)methanols 5a–5c is described starting from the methyl ester of the proteinogenic amino acid (S)-serine, which involves the diastereomeric oxazolidine derivatives 11a–11c as key intermediates. 5b and 5c were transformed into the chiral, non-racemic bicyclic lactams 14b and 14c via Swern oxidation followed by Wittig reaction and subsequent

  4-取代的- （1-苄基-2-基）基甲醇的一种新颖的三步合成5A - 5c中描述从蛋白质氨基酸（甲酯起始小号） -丝氨酸，它涉及非对映体衍生物恶唑11A - 11c作为关键中间体。通过Swern氧化，随后的Wittig反应和随后的氢化，将5b和5c转化为手性，非外消旋的双环内酰胺14b和14c。在筛选用于中枢神经系统受体亲和力丁基衍生物14b中被发现具有与σ有为相互作用1-受体（K i = 345 nM）。
• Chiral, nonracemic (piperazin-2-yl)methanol derivatives with σ-receptor affinity
  作者：Stephan Bedürftig、Bernhard Wünsch

  DOI：10.1016/j.bmc.2004.03.059

  日期：2004.6

  Starting with the proteinogenic amino acid (S)-serine a series of chiral nonracemic (piperazin-2-yl)methanols 3 with various N-4 substituents is described. The key step in the synthesis of 3 is the reaction of the chloroacetamide 5 with various primary amines to yield the diastereomeric bicyclic piperazinediones cis-6 and traps-6. The scope and limitation of this transformation is thoroughly investigated. The sigma(1)- and sigma(2)-receptor affinities of the piperazines 3 are determined in receptor binding studies with guinea pig brain and rat liver membrane preparations using [H-3]-labeled (+)-pentazocine and ditolylguanidine, respectively. It was found, that an additional phenyl residue in the N-4 substituent is favorable to high sigma(1)-receptor affinity. In this series the p-methoxybenzyl substituted piperazine 3d reveals the highest sigma(1)-receptor affinity (K-i = 12.4 nM) with selectivity toward sigma(2)-, NMDA-, kappa-opioid, and mu-opioid receptors. (C) 2004 Elsevier Ltd. All rights reserved.