(R)-5-甲氧基-2-氨基四氢萘 | 105086-92-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 中文名称: (R)-5-甲氧基-2-氨基四氢萘
• 中文别名: (R)-2-(N-苄氨基)-5-甲氧基四氢萘；(R)-(+)-5-甲氧基-2-氨基四啉
• 英文名称: (R)-5-methoxy-2-aminotetralin
• 英文别名: (R)-2-amino-5-methoxytetralin；(R)-5-Methoxy-1,2,3,4-tetrahydronaphthalen-2-amine；(2R)-5-methoxy-1,2,3,4-tetrahydronaphthalen-2-amine
• CAS: 105086-92-8
• 化学式: C₁₁H₁₅NO
• 分子量: 177.246
• InChiKey: SIHPGAYIYYGOIP-SECBINFHSA-N

物化性质

• 沸点：
  309.1±42.0 °C(Predicted)
• 密度：
  1.056

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (R)-5-甲氧基-2-氨基四氢萘 在 sodium hydroxide 、 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 60.0h， 生成 (2R)-1,2,3,4-四氢-5-甲氧基-N-丙基-2-萘胺
  参考文献：
  名称：

  Synthesis and pharmacology of the enantiomers of the potential atypical antipsychotic agents 5-OMe-BPAT and 5-OMe-(2,6-di-OMe)-BPAT

  摘要：

  The optically pure enantiomers of the potential atypical antipsychotic agents 5-methoxy-2-[N-(2-benzamidoethyl)-N-n-propylamino]tetralin (5-OMe-BPAT, 5) and 5-methoxy-2-{N-[2-(2,6-dimethoxy)benzamidoethyl]-N-n-propylamino}tetralin [5-OMe-(2,6-di-OMe)-BPAT, 6] were synthesized and evaluated for their in vitro binding affinities at alpha(1)-, alpha(2)-, and beta-adrenergic, muscarinic, dopamine D-1, D-2A,D- and D-3, and serotonin 5-HT1A and 5-HT2 receptors. In addition, their intrinsic efficacies at serotonin 5-HT1A receptors were established in vitro. (S)- and (R)-5 had high affinities for dopamine D2A, D3, and serotonin 5-HT1A receptors: moderate affinities for alpha(1)-adrenergic and serotonin 5-HT2 receptors, and no affinity (K-i > 1000 nM) for the other receptor subtypes. (S)- and (R)-6 had lower affinities for the dopamine D-2A and the serotonin 5-HT1A receptor, compared to (S)- and (R)-5, and hence showed some selectivity for the dopamine D3 receptor. The interactions with the receptors were stereospecific, since the serotonin 5-HT1A receptor preferred the (S)-enantiomers, while the dopamine D-2A and D-2 receptors preferred the (R)-enantiomers of 5 and 6. The intrinsic efficacies at the serotonin 5-HT1A receptor were established by measuring their ability to inhibit VIP-induced cAMP production in GH(4)ZD10 cells expressing serotonin 5-HT1A receptors. Both enantiomers of 5 behaved as full serotonin 5-HT1A receptor agonists in this assay, while both enantiomers of 6 behaved as weak partial agonists. The potential antipsychotic properties of (S)- and (R)-5 were evaluated by establishing their ability to inhibit d-amphetamine-induced locomotor activity in rats, while their propensity to induce extrapyramidal side-effects (EPS) in man was evaluated by determining their ability to induce catalepsy in rats. Whereas (R)-5 was capable of blocking d-amphetamine-induced locomotor activity, indicative of dopamine D-2 receptor antagonism, (S)-5 even enhanced the effect of d-amphetamine, suggesting that this compound has dopamine D-2 receptor-stimulating properties. Since both enantiomers also were devoid of cataleptogenic activity, they are interesting candidates for further exploring the dopamine D-2/serotonin 5-HT1A hypothesis of atypical antipsychotic drug action. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00073-5
• 作为产物：
  描述：

  在 高碘酸 、 甲胺 作用下， 以 甲醇 、 水 为溶剂， 反应 18.0h， 以85%的产率得到
  参考文献：
  名称：

  带有手性 N-(2-吡啶甲基) 磺酰胺配体的 Cp*Ir(III) 配合物催化苯甲基酮的不对称转移氢化胺化

  摘要：

  开发了一种由新设计的带有手性N- (2-吡啶甲基) 磺胺基配体的 Cp*Ir 配合物催化的方便的苯甲基酮（α-芳基化酮）的不对称还原胺化。使用容易获得的 β-氨基醇作为手性胺化剂，一系列苯并稠合和无环酮在 40°C 的甲醇溶液中成功地用甲酸还原，得到具有良好化学和非对映选择性的胺。氨基醇衍生的手性助剂很容易被温和的周期性氧化剂去除，从而产生具有光学活性的伯 β-芳胺，而不会影响光学纯度（高达 97% ee）。即使将催化剂的用量与底物/催化剂 (S/C) 的比值降低 20,000，仍能保持优异的催化性能，并且可以在超过 100 g 的大规模上进行胺化。对可分离的氢化铱配合物和模型中间体（如N、O-缩醛、烯胺和亚胺化合物）的化学计量反应的机理研究表明，从酮底物和手性胺对应物产生的精确氢化物转移到亚胺物种。

  DOI：

  10.1021/acs.joc.2c00580

文献信息

• Method of Preparing (S)-2-amino-5-Methoxytetralin Hydrochloride
  申请人：HUANG Qingyun

  公开号：US20140046095A1

  公开（公告）日：2014-02-13

  A method of preparing (S)-2-amino-5-methoxytetralin hydrochloride[(S)-2-amino-5-methoxyl-1,2,3,4-tetrahydronaphthalene hydrochloride], comprising the steps of: (1) producing a compound (I) by addition-elimination reaction of 5-methoxy-2-tetralone and R-(+)-a-phenylethylamine; (2) producing a compound (II) by reduction reaction of the compound (I) with a reducing agent; and (3) producing a compound (II) hydrochloride by reacting the compound (II) with a salt-forming agent, then carrying out reduction reaction with a palladium-carbon catalyst to produce (S)-2-amino-5-methoxytetralin hydrochloride. The method can significantly increase the yield of (S)-2-amino-5-methoxytetralin hydrochloride with short synthetic path, low preparation cost and less pollution, which is environmentally friendly and is suitable for medical industrialized production. The structural formulae of the compound (I) and the compound (II) are: resepectively.

  一种制备(S)-2-氨基-5-甲氧基四氢萘盐酸盐[(S)-2-氨基-5-甲氧基-1,2,3,4-四氢萘盐酸盐]的方法，包括以下步骤：(1)通过5-甲氧基-2-四氢萘酮和R-(+)-α-苯乙胺的加成-消除反应制备化合物(I)；(2)通过还原剂对化合物(I)进行还原反应制备化合物(II)；(3)将化合物(II)与盐类生成剂反应，然后使用钯碳催化剂进行还原反应制备化合物(II)盐酸盐。该方法可以显著提高(S)-2-氨基-5-甲氧基四氢萘盐酸盐的产率，具有合成路径短、制备成本低、污染少的特点，环保且适合医药工业化生产。化合物(I)和化合物(II)的结构式如下：（分别列出结构式）。
• [EN] ENZYMATIC TRANSAMINATION OF CYCLOPAMINE ANALOGS<br/>[FR] TRANSAMINATION ENZYMATIQUE D'ANALOGUES DE CYCLOPAMINE
  申请人：INFINITY PHARMACEUTICALS INC

  公开号：WO2011017551A1

  公开（公告）日：2011-02-10

  Provided are processes for the synthesis of amino analogues from ketone starting materials

  提供从酮起始材料合成氨基类似物的过程。
• HETEROCYCLYL-SUBSTITUTED-TETRAHYDRO-NAPHTHALEN-AMINE DERIVATIVES, THEIR PREPARATION AND USE AS MEDICAMENTS
  申请人：Garcia-Lopez Monica

  公开号：US20100105684A1

  公开（公告）日：2010-04-29

  The present invention relates to heterocyclyl-substituted-tetrahydro-naphthalen-amine compounds of general formula (I) and compositions thereof, methods for their preparation, and the use of said compounds for the treatment or prophylaxis of various disorders of humans or animals.

  本发明涉及一般式(I)的杂环取代四氢萘胺化合物及其组合物，其制备方法以及利用该化合物治疗或预防人或动物的各种疾病。
• Derivatives of (R)-2-amino-5-methoxytetralin: Antagonists and inverse agonists at the dopamine D2a receptor
  作者：Berit Backlund Höök、Cecilia Brege、Tero Linnanen、Åsa Mikaels、Åsa Malmberg、Anette M. Johansson

  DOI：10.1016/s0960-894x(99)00345-5

  日期：1999.8

  A series of N-arylmethyl substituted (R)-5-methoxy-2-(propylamino)tetralins has been prepared and evaluated for affinity and efficacy at dopamine (DA) D-2A receptors. The novel compounds appeared to be antagonists or inverse agonists. (R)-2-[(Benzyl)propylamino]-5-methoxytetralin (7) was characterized as a potent inverse agonists at DA D-2A receptors in a [S-35]GTP gamma S binding assay. (C) 1999 Elsevier Science Ltd. All rights reserved.
• Conformationally Selective 2-Aminotetralin Ligands Targeting the alpha2A- and alpha2C-Adrenergic Receptors
  作者：Nicholas R. Fragola、Brittany M. Brems、Munmun Mukherjee、Meng Cui、Raymond G. Booth

  DOI：10.1021/acschemneuro.3c00148

  日期：2023.5.17