(1R,5S)-1-(2-萘基)-3-氮杂双环[3.1.0]己烷 | 924012-43-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: (1R,5S)-1-(2-萘基)-3-氮杂双环[3.1.0]己烷
• 英文名称: (1R,5S)-(+)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane
• 英文别名: centanafadine；(1R,5S)-1-naphthalen-2-yl-3-azabicyclo[3.1.0]hexane
• CAS: 924012-43-1
• 化学式: C₁₅H₁₅N
• 分子量: 209.291
• InChiKey: HKHCSWPSUSWGLI-CABCVRRESA-N

物化性质

• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  1

制备方法与用途

Centanafadine 是一种双抑制剂，能够抑制去甲肾上腺素（NE）/多巴胺（DA）转运，并且还能抑制5-羟色胺（serotonin）转运体。其对人NE、DA和5-羟色胺转运体的IC50值分别为6纳摩尔、38纳摩尔和83纳摩尔。

反应信息

• 作为产物：
  描述：

  在 1-氯乙基氯甲酸酯 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 (1R,5S)-1-(2-萘基)-3-氮杂双环[3.1.0]己烷
  参考文献：
  名称：

  Studies on the structure–activity relationship of bicifadine analogs as monoamine transporter inhibitors

  摘要：

  Compounds with various activities and selectivities were discovered through structure -activity relationship studies of bicifadine analogs as monoamine transporter inhibitors. The norepinephrine-selective 2-thienyl compound S-6j was efficacious in a rodent pain model. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.05.077

文献信息

• METHOD FOR MANUFACTURING AROMATIC NITRILE COMPOUND
  申请人：API CORPORATION

  公开号：US20210078940A1

  公开（公告）日：2021-03-18

  The present invention provides a method for industrially producing a highly pure aromatic nitrile compound and a highly pure aromatic carboxylic acid compound safely and highly efficiently at low costs. Compound (2) is subjected to Willgerodt reaction in the presence of an additive as necessary, and the obtained amide compound (3) is hydrolyzed and neutralized to give carboxylic acid compound (4). Carboxylic acid compound (4) is reacted with a halogenating agent in the presence of a catalyst as necessary in an organic solvent, and further reacted with an amidating agent, and the obtained amide compound (5) or (6) is reacted with a dehydrating agent to give nitrile compound (1). Alternatively, carboxylic acid compound (4) is reacted with a halogenating agent and a compound represented by the formula R 6 SO 2 R 7 in the presence of a catalyst as necessary in an organic solvent to give nitrile compound (1). Np is a naphthyl group optionally having substituent(s), R 5 is an alkylene group having 1-3 carbon atoms, and other symbols are as described in the DESCRIPTION.

  本发明提供了一种低成本、高纯度、安全高效地工业生产高纯度芳香基腈化合物和高纯度芳香基羧酸化合物的方法。化合物（2）在必要的添加剂存在下经过威尔格罗德反应，得到酰胺化合物（3），然后将酰胺化合物（3）水解并中和，得到羧酸化合物（4）。在有机溶剂中，羧酸化合物（4）在必要的催化剂存在下与卤代试剂反应，进一步与酰胺化试剂反应，得到酰胺化合物（5）或（6），然后与脱水试剂反应，得到腈化合物（1）。或者，羧酸化合物（4）在必要的催化剂存在下与卤代试剂和式为R6SO2R7的化合物反应，得到腈化合物（1）。其中，Np是一个萘基，可选地具有取代基，R5是一个具有1-3个碳原子的烷基，其他符号如描述中所述。
• HIGH PURITY 2-NAPHTHYLACETONITRILE AND METHOD FOR PRODUCING SAME
  申请人：API CORPORATION

  公开号：US20220009880A1

  公开（公告）日：2022-01-13

  High purity 2-naphthylacetonitrile with fewer impurities can be used as a starting material or intermediate for synthesizing various pharmaceutical products, agricultural chemicals, and chemical products, and a production method thereof. A high purity 2-naphthylacetonitrile having an HPLC purity of 2-naphthylacetonitrile of not less than 95 area %, and containing naphthalene compounds represented by the formulas (a)-(j) at a content of a predetermined area % or below. A method for producing high purity 2-naphthylacetonitrile, may include: subjecting 2′-acetonaphthone to a Willgerodt reaction in the presence of an additive where necessary, and hydrolyzing the obtained amide compound to give 2-naphthylacetic acid; and reacting the 2-naphthylacetic acid obtained in the subjecting, a halogenating agent and sulfamide in the presence of a catalyst as necessary in an organic solvent to give 2-naphthylacetonitrile.

  高纯度的2-萘乙腈含有较少的杂质，可用作合成各种药物产品、农药化学品和化工产品的起始物料或中间体，以及其生产方法。具有不低于95%面积百分比的2-萘乙腈的HPLC纯度，并且包含在预定面积百分比以下的由式(a)-(j)表示的萘化合物。生产高纯度2-萘乙腈的方法可能包括：在必要时在添加剂的存在下，将2'-乙酰基萘酮经Willgerodt反应，并水解得到酰胺化合物以得到2-萘乙酸；并在有机溶剂中，在必要时在催化剂的存在下，将通过上述步骤得到的2-萘乙酸、卤代试剂和磺胺酰胺反应以得到2-萘乙腈。
• [EN] CRYSTALLINE COMPOUNDS<br/>[FR] COMPOSÉS CRISTALLINS
  申请人：MCKINNEY ANTHONY ALEXANDER

  公开号：WO2016205762A1

  公开（公告）日：2016-12-22

  The present invention relates to crystalline forms of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride and compositions comprising the same and methods of making and using the same.

  本发明涉及(1R,5S)-1-(萘-2-基)-3-氮杂双环[3.1.0]己烷盐酸盐的晶体形式，以及包含其的组合物和制备和使用其的方法。
• [EN] USE OF (1R,5S)-(+)-1-(NAPHTHALEN-2-YL)-3-AZABICYCLO{3.1.0}HEXANE IN THE TREATMENT OF CONDITIONS AFFECTED BY MONOAMINE NEUROTRANSMITTERS<br/>[FR] UTILISATION DE (LR,5S)-(+)-L-(NAPHTHALÈN-2-YL)-3-AZABICYCLO[3.1.0]HEXANE DANS LE CADRE DU TRAITEMENT D'AFFECTIONS ASSOCIÉES AUX NEUROTRANSMETTEURS MONO-AMINE
  申请人：NEUROVANCE INC

  公开号：WO2013019271A1

  公开（公告）日：2013-02-07

  The present invention relates to (lR,5S)-(+)-l-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane and pharmaceutical compositions thereof, and methods employing their use in the treatment of conditions affected by monoamine neurotransmitters, including ADHD and substance abuse.

  本发明涉及（lR,5S）-（+）-1-（萘基）-3-氮杂双环[3.1.0]己烷及其制药组合物，以及使用它们治疗受单胺神经递质影响的疾病，包括注意力缺陷多动障碍和物质滥用的方法。
• METHODS AND COMPOSITIONS FOR PRODUCTION, FORMULATION AND USE OF 1 ARYL-3-AZABICYCLO[3.1.0]HEXANES
  申请人：Chen Zhengming

  公开号：US20080058535A1

  公开（公告）日：2008-03-06

  The invention provides novel compositions and methods of making (−)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane and other 1-aryl-3-azabicyclo[3.1.0]hexanes, including synthetic methods that form novel intermediate compounds of the invention for producing)-(−)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane and other 1-aryl-3-azabicyclo[3.1.0]hexanes and pharmaceutically acceptable salts thereof.

  本发明提供了制备(-)-1-(3,4-二氯苯基)-3-氮杂双环[3.1.0]己烷和其他1-芳基-3-氮杂双环[3.1.0]己烷的新型组合物和制备方法，包括形成本发明的新型中间化合物的合成方法，用于生产(-)-1-(3,4-二氯苯基)-3-氮杂双环[3.1.0]己烷和其他1-芳基-3-氮杂双环[3.1.0]己烷及其药学上可接受的盐。