N-[(2R)-1,2,3,4-四氢-5-甲氧基-2-萘基]丙酰胺 | 244239-68-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 中文名称: N-[(2R)-1,2,3,4-四氢-5-甲氧基-2-萘基]丙酰胺
• 英文名称: (R)-N-(5-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)propionamide
• 英文别名: (R)-5-methoxy-2-propionamidotetralin；N-[(2R)-1,2,3,4-Tetrahydro-5-methoxy-2-naphthalenyl]propanamide；N-[(2R)-5-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl]propanamide
• CAS: 244239-68-7
• 化学式: C₁₄H₁₉NO₂
• 分子量: 233.31
• InChiKey: SAEUBVASPHMFGN-LLVKDONJSA-N

物化性质

• 沸点：
  447.8±45.0 °C(Predicted)
• 密度：
  1.09±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-[(2R)-1,2,3,4-四氢-5-甲氧基-2-萘基]丙酰胺 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 42.0h， 以91%的产率得到(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：

  N-(3,4-二氢-5-甲氧基-2-萘基)丙酰胺 在 氢气 、 C₃₄H₃₆Cl₂CoP₂ 作用下， 以 甲醇 为溶剂， 60.0 ℃ 、6.0 MPa 条件下， 以91 %的产率得到N-[(2R)-1,2,3,4-四氢-5-甲氧基-2-萘基]丙酰胺
  参考文献：
  名称：

  钴催化的三取代碳环烯烃的对映选择性氢化：获得手性环酰胺

  摘要：

  手性环酰胺的合成是通过钴催化的相应烯酰胺的不对称氢化反应实现的，具有高度的对映选择性。该方法扩展了地球丰富的金属催化在不对称合成中的利用。

  DOI：

  10.1002/anie.202301329

文献信息

• Novel Process for the Preparation of Nitrogen Substituted Aminotetralins Derivatives
  申请人：Vasselin David

  公开号：US20120302790A1

  公开（公告）日：2012-11-29

  The present invention provides an alternative synthesis of N-substituted aminotetralines which synthesis comprises catalytic asymmetric hydrogenation of compounds of general formula (A).

  本发明提供了N-取代氨基四氢萘的替代合成方法，该合成包括对一般式(A)化合物进行催化不对称加氢。
• New catalytic route for the synthesis of an optically active tetralone-derived amine for rotigotine
  作者：Christopher J. Cobley、George Evans、Tamara Fanjul、Shaun Simmonds、Amy Woods

  DOI：10.1016/j.tetlet.2016.01.060

  日期：2016.3

  Rotigotine is a launched drug for the treatment of Parkinson’s disease and restless legs syndrome. The key steps of an alternative route for the synthesis of rotigotine have been demonstrated. Formation of a prochiral enamide, asymmetric hydrogenation of the enamide with high enantioselectivity, and reduction of the resulting amide to an amine have been proved to work successfully. The best conditions

  罗替戈汀是一种用于治疗帕金森氏病和腿部躁动综合征的新药。已经证明了罗替戈汀合成的替代途径的关键步骤。已证明前手性酰胺的形成，具有高对映选择性的烯酰胺的不对称氢化以及将所得酰胺还原为胺的方法是成功的。迄今为止筛选出的将酰胺9不对称氢化为酰胺10的最佳条件是在25 bar H 2下用[[RuCl（（R）-T-BINAP））2（μ-Cl）3 ] [NH 2 Me 2 ]和30°C（500：1 S / C比率，99％转化率，91％ee S）。用Red-Al最佳地将酰胺10还原为胺5，得到95％的转化率。