(-)-(S)-2-(2-chloroethyl)-1-methylpyrrolidine

• 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: (-)-(S)-2-(2-chloroethyl)-1-methylpyrrolidine
• 英文别名: (S)-2-(2-chloroethyl)-1-methylpyrrolidine；(-)-(S)-2-(2-chloroethyl)pyrrolidine；(2S)-2-(2-chloroethyl)-1-methylpyrrolidine
• 化学式: C₇H₁₄ClN
• 分子量: 147.648
• InChiKey: CLVNTYZKUHNUEF-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  9
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (-)-(S)-2-(2-chloroethyl)-1-methylpyrrolidine 生成 1-Methyl-1-azoniabicyclo<3.2.0>heptane chloride
  参考文献：
  名称：

  N→C芳基在锂化氨基甲酸酯中的逆迁移合成（-）-（S，S）-clemastine

  摘要：

  通过在脯氨酸衍生的氯乙基吡咯烷与对映异构体富集的叔醇之间形成醚，实现了抗组胺剂clemastine作为其（S，S）-立体异构体的首次对映选择性合成。叔醇由α-甲基-对氯苄基醇的氨基甲酸酯衍生物通过锂化时的芳基反型迁移而形成。产品的（S，S）立体化学证实了重排的反相性质。

  DOI：

  10.1021/ol100627c
• 作为产物：
  描述：

  2-(2-氯乙基)-1-甲基吡咯烷 生成 (-)-(S)-2-(2-chloroethyl)-1-methylpyrrolidine
  参考文献：
  名称：

  4-[[[2-（1-甲基-2-吡咯烷基）乙基]硫]苯酚盐酸盐（SIB-1553A）：一种新型的认知增强剂，对神经元烟碱乙酰胆碱受体具有选择性。

  摘要：

  DOI：

  10.1021/jm990035d

文献信息

• 1,5-Disubstituted indole derivatives as selective human neuronal nitric oxide synthase inhibitors
  作者：Paul Renton、Joanne Speed、Shawn Maddaford、Subhash C. Annedi、Jailall Ramnauth、Suman Rakhit、John Andrews

  DOI：10.1016/j.bmcl.2011.07.022

  日期：2011.9

  A series of 1,5-disubstituted indole derivatives was designed, synthesized and evaluated as inhibitors of human nitric oxide synthase. A variety of flexible and restricted basic amine side chain substitutions was explored at the 1-position of the indole ring, while keeping the amidine group fixed at the 5-position. Compounds having N-(1-(2-(1-methylpyrrolidin-2-yl) ethyl)- (12, (R)-12, (S)-12 and 13) and N-(1-(1-methylazepan-4-yl)-side chains (14, 15, (-)-15 and (+)-15) showed increased inhibitory activity for the human nNOS isoform and selectivity over eNOS and iNOS isoforms. The most potent compound of the series for human nNOS (IC(50) = 0.02 mu M) (S)-12 showed very good selectivity over the eNOS (eNOS/nNOS = 96-fold) and iNOS (iNOS/nNOS = 850-fold) isoforms. (C) 2011 Elsevier Ltd. All rights reserved.
• 1,6-Disubstituted indole derivatives as selective human neuronal nitric oxide synthase inhibitors
  作者：Shawn Maddaford、Paul Renton、Joanne Speed、Subhash C. Annedi、Jailall Ramnauth、Suman Rakhit、John Andrews、Gabriela Mladenova、Lisa Majuta、Frank Porreca

  DOI：10.1016/j.bmcl.2011.07.042

  日期：2011.9

  A series of 1,6-disubstituted indole derivatives was designed, synthesized and evaluated as inhibitors of human nitric oxide synthase (NOS). By varying the basic amine side chain at the 1-position of the indole ring, several potent and selective inhibitors of human neuronal NOS were identified. In general compounds with bulkier side chains displayed increased selectivity for nNOS over eNOS and iNOS isoforms. One of the compounds, (R)-8 was shown to reduce tactile hyperesthesia (allodynia) after oral administration (30 mg/kg) in an in vivo rat model of dural inflammation relevant to migraine pain. (C) 2011 Elsevier Ltd. All rights reserved.
• Synthesis of (−)-(<i>S</i>,<i>S</i>)-clemastine by Invertive N → C Aryl Migration in a Lithiated Carbamate
  作者：Anne M. Fournier、Robert A. Brown、William Farnaby、Hideki Miyatake-Ondozabal、Jonathan Clayden

  DOI：10.1021/ol100627c

  日期：2010.5.21

  The first enantioselective synthesis of the antihistamine agent clemastine, as its (S,S)-stereoisomer, has been achieved by ether formation between a proline-derived chloroethylpyrrolidine and an enantiomerically enriched tertiary alcohol. The tertiary alcohol was formed from the carbamate derivative of α-methyl-p-chlorobenzyl alcohol by invertive aryl migration on lithiation. The (S,S)-stereochemistry

  通过在脯氨酸衍生的氯乙基吡咯烷与对映异构体富集的叔醇之间形成醚，实现了抗组胺剂clemastine作为其（S，S）-立体异构体的首次对映选择性合成。叔醇由α-甲基-对氯苄基醇的氨基甲酸酯衍生物通过锂化时的芳基反型迁移而形成。产品的（S，S）立体化学证实了重排的反相性质。
• 4-[[2-(1-Methyl-2-pyrrolidinyl)ethyl]thio]- phenol Hydrochloride (SIB-1553A):  A Novel Cognitive Enhancer with Selectivity for Neuronal Nicotinic Acetylcholine Receptors
  作者：Jean-Michel Vernier、Hassan El-Abdellaoui、Heather Holsenback、Nicholas D. P. Cosford、Leo Bleicher、Geoffrey Barker、Bruno Bontempi、Laura Chavez-Noriega、Frederique Menzaghi、Tadimeti S. Rao、Richard Reid、Aida I. Sacaan、Carla Suto、Mark Washburn、G. Kenneth Lloyd、Ian A. McDonald

  DOI：10.1021/jm990035d

  日期：1999.5.1