2-Methyl-4-[5-((S)-1-methyl-pyrrolidin-2-yl)-pyridin-3-yl]-but-3-yn-2-ol | 179120-91-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-Methyl-4-[5-((S)-1-methyl-pyrrolidin-2-yl)-pyridin-3-yl]-but-3-yn-2-ol
• 英文别名: 2-methyl-4-[5-[(2S)-1-methylpyrrolidin-2-yl]pyridin-3-yl]but-3-yn-2-ol
• CAS: 179120-91-3
• 化学式: C₁₅H₂₀N₂O
• 分子量: 244.337
• InChiKey: IFPUJRNUSSIRNX-AWEZNQCLSA-N

物化性质

• 沸点：
  378.5±42.0 °C(Predicted)
• 密度：
  1.13±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  36.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-Methyl-4-[5-((S)-1-methyl-pyrrolidin-2-yl)-pyridin-3-yl]-but-3-yn-2-ol 在 sodium hydride 作用下， 以 甲苯 为溶剂， 反应 2.0h， 以92%的产率得到5-乙炔基尼古丁
  参考文献：
  名称：

  The first enantioselective synthesis of (S)-5-bromo-3-(1-methyl-2-pyrrolidinyl)pyridine: a key intermediate for the preparation of SIB-1508Y

  摘要：

  The first enantioselective synthesis of (S)-5-bromo-3-(1-methyl-2-pyrrodidinyl)pyridine is described via intramolecular hydroboration-cycloalkylation of an azido-olefin intermediate. The chiral homoallylic alcohol was efficiently synthesized by enantioselective reduction of the corresponding ketone using (+)-diisopinocamphenylchloroborane as the key reaction. The total synthesis of (S)-SIB-1508Y was achieved with an enantiomeric excess (e.e.) of 94% in ten steps and in 18% overall yield from the commercially available 5-bromo-3-pyridinecarboxylic acid. (C) 2001 Elsevier Science Ltd. Ali rights reserved.

  DOI：

  10.1016/s0957-4166(01)00204-x
• 作为产物：
  描述：

  5-溴吡啶-3-甲醛 在 palladium on activated charcoal copper(l) iodide 、 甲酸 、 sodium azide 、 bis(cyclohexanyl)borane 、 potassium carbonate 、 戴斯-马丁氧化剂 、 三乙胺 、 三苯基膦 、 (+)-二异松蒎基氯硼烷 、 锌 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 44.33h， 生成 2-Methyl-4-[5-((S)-1-methyl-pyrrolidin-2-yl)-pyridin-3-yl]-but-3-yn-2-ol
  参考文献：
  名称：

  The first enantioselective synthesis of (S)-5-bromo-3-(1-methyl-2-pyrrolidinyl)pyridine: a key intermediate for the preparation of SIB-1508Y

  摘要：

  The first enantioselective synthesis of (S)-5-bromo-3-(1-methyl-2-pyrrodidinyl)pyridine is described via intramolecular hydroboration-cycloalkylation of an azido-olefin intermediate. The chiral homoallylic alcohol was efficiently synthesized by enantioselective reduction of the corresponding ketone using (+)-diisopinocamphenylchloroborane as the key reaction. The total synthesis of (S)-SIB-1508Y was achieved with an enantiomeric excess (e.e.) of 94% in ten steps and in 18% overall yield from the commercially available 5-bromo-3-pyridinecarboxylic acid. (C) 2001 Elsevier Science Ltd. Ali rights reserved.

  DOI：

  10.1016/s0957-4166(01)00204-x

文献信息

• A Practical and Efficient Synthesis of the Selective Neuronal Acetylcholine-Gated Ion Channel Agonist (<i>S</i>)-(−)-5-Ethynyl-3-(1-methyl-2-pyrrolidinyl)pyridine Maleate (SIB-1508Y)
  作者：Leo S. Bleicher、Nicholas D. P. Cosford、Audrey Herbaut、J. Stuart McCallum、Ian A. McDonald

  DOI：10.1021/jo971572d

  日期：1998.2.1

  An efficient, high-yielding synthetic procedure for the preparation of the novel neuronal acetylcholine-gated ion channel agonist (S)-(-)-5-ethynyl-3-(1-methyl-2-pyrrolidinyl)pyridine maleate [(S)-2, SIB-1508Y] is described. The key steps in the process include the lithium bis(trimethylsilyl)amide-mediated acylation of N-vinylpyrrolidinone with ethyl 5-bromonicotinate, a high-yielding sodium borohydride reduction of imine 5, and a new heteroaryl-alkyne cross-coupling protocol for the introduction of the ethyne moiety in (S)-2. The preparation of enantiomerically pure (S)-2 was accomplished via a combination of enantioselective reduction of imine 5 and crystallization of enantiomerically enriched 5-bromo-3-(1-methyl-2-pyrrolidinyl)pyridine (7) as the dibenzoyl-L-tartaric acid salt.
• (<i>S</i>)-(−)-5-Ethynyl-3-(1-methyl-2-pyrroli- dinyl)pyridine Maleate (SIB-1508Y):  A Novel Anti-Parkinsonian Agent with Selectivity for Neuronal Nicotinic Acetylcholine Receptors
  作者：Nicholas D. P. Cosford、Leo Bleicher、Audrey Herbaut、J. Stuart McCallum、Jean-Michel Vernier、Heather Dawson、Jeffrey P. Whitten、Pamala Adams、Laura Chavez-Noriega、Lucia D. Correa、James H. Crona、Lorrence S. Mahaffy、Frederique Menzaghi、Tadimeti S. Rao、Richard Reid、Aida I. Sacaan、Emily Santori、Kenneth A. Stauderman、Kevin Whelan、G. Kenneth Lloyd、Ian A. McDonald

  DOI：10.1021/jm960328w

  日期：1996.1.1
• J. Med. Chem. 1996, 39, 3235-3237
  作者：

  DOI：——

  日期：——
• The first enantioselective synthesis of (S)-5-bromo-3-(1-methyl-2-pyrrolidinyl)pyridine: a key intermediate for the preparation of SIB-1508Y
  作者：François-Xavier Felpin、Giang Vo-Thanh、Jean Villiéras、Jacques Lebreton

  DOI：10.1016/s0957-4166(01)00204-x

  日期：2001.5

  The first enantioselective synthesis of (S)-5-bromo-3-(1-methyl-2-pyrrodidinyl)pyridine is described via intramolecular hydroboration-cycloalkylation of an azido-olefin intermediate. The chiral homoallylic alcohol was efficiently synthesized by enantioselective reduction of the corresponding ketone using (+)-diisopinocamphenylchloroborane as the key reaction. The total synthesis of (S)-SIB-1508Y was achieved with an enantiomeric excess (e.e.) of 94% in ten steps and in 18% overall yield from the commercially available 5-bromo-3-pyridinecarboxylic acid. (C) 2001 Elsevier Science Ltd. Ali rights reserved.