(1R)-1-[1-(4-氯苯基)环丁基]-3-甲基丁烷-1-胺 | 229639-56-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (1R)-1-[1-(4-氯苯基)环丁基]-3-甲基丁烷-1-胺
• 英文名称: (R)-didesmethylsibutramine
• 英文别名: (R)-N,N-didesmethylsibutramine；(R)-mono-dimethylsibutramine；(R)-N-{1-[1-(4-Chlorophenyl)cyclobutyl]-3-methylbutyl}amine；(+)-Didesmethylsibutramine；(R)-1-[1-(4-chlorophenyl) cyclobutyl]-3-methylbutylamine；(R)-didesmethylsibutramne；(R)-DDMS；Didesmethylsibutramine, (+)-；(1R)-1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutan-1-amine
• CAS: 229639-56-9
• 化学式: C₁₅H₂₂ClN
• 分子量: 251.799
• InChiKey: WQSACWZKKZPCHN-CQSZACIVSA-N

物化性质

• 沸点：
  337.9±25.0 °C(Predicted)
• 密度：
  1.072±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  26
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (1R)-1-[1-(4-氯苯基)环丁基]-3-甲基丁烷-1-胺 生成 (R)-(+)-N-{1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutyl}-N,N-dimethylamine
  参考文献：
  名称：

  WO2006/67060

  摘要：

  公开号：
• 作为产物：
  描述：

  1-(4-氯苯基)环丁烷羧醛 在 titanium(IV) tetraethanolate 、 三氟化硼乙醚 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 3.0h， 生成 (1R)-1-[1-(4-氯苯基)环丁基]-3-甲基丁烷-1-胺
  参考文献：
  名称：

  可调节的烷基或芳基亚磺酰胺在手性胺的立体选择性合成中的首次应用：使用（R）-三乙基甲基亚磺酰胺（（R）-TESA）不对称合成（R）-二甲基甲基异丁胺（（R）-DDMS）。

  摘要：

  将i-BuLi高度非对映选择性地添加到三乙基甲基亚磺酰胺衍生的Aldimine中，作为（R）-didesmethylsibutramine的首个不对称合成的关键步骤。[反应：看文字]

  DOI：

  10.1021/ol026699q

文献信息

• アミン立体異性体の製造方法
  申请人：アプシンターム・リミテッド・ライアビリティ・カンパニー

  公开号：JP2005522525A

  公开（公告）日：2005-07-28

  According to the present invention, a sulfinyl imine having an alcohol, thiol or amine residue on a sulfinyl group is stereoselectively reduced, or a sulfinyl imine stereoisomer having an alcohol, thiol or amine residue on a sulfinyl group is nucleophilic. Reacting with an atomic source to provide a sulfinylamine stereoisomer, and then contacting the sulfinylamine stereoisomer with a reagent suitable for cleavage of a sulfur-nitrogen bond to provide the amine stereoisomer. A method for producing amine stereoisomers is provided. The present invention also provides methods for using some of the above intermediates in the preparation of novel intermediates, sulfoxide and sulfinylamine stereoisomers useful in the above methods.

  根据本发明，对具有醇基、硫醇基或胺基残基的亚砜亚胺进行立体选择性还原，或者对具有醇基、硫醇基或胺基残基的亚砜亚胺立体异构体进行亲核反应。与原子源反应，提供亚砜胺立体异构体，然后将亚砜胺立体异构体与适用于裂解硫-氮键的试剂接触，以提供胺立体异构体。提供一种生产胺立体异构体的方法。本发明还提供了使用上述一些中间体在制备新型中间体、对上述方法有用的亚砜和亚砜胺立体异构体的方法。
• Highly Enantioselective Catalytic Asymmetric Synthesis of a (R)-Sibutramin Precursor
  作者：Ulrich Berens、Andreas Hafner、Oliver Dosenbach、Tanja Tritschler、Franz Schwarzenbach、Hans-Jörg Kirner、Christophe Malan、Oanh Mai-Huynh

  DOI：10.2533/chimia.2010.59

  日期：——

  The first highly enantioselective, catalytic asymmetric synthesis of di-des-methylsibutramine 3 is described. Dienamide 10, prepared by acetic acid anhydride quenching of the condensation product of nitrile 4 with a methallyl magnesium chloride, proved to be an excellent substrate for ruthenium-catalyzed asymmetric hydrogenation with atropisomeric diphosphine ligands. Hydrogenation with a ruthenium/(R)- MeOBiPheP catalyst at S/C = 500, gave the chiral amide (R)-9 in 98.5% ee in almost quantitative yield. After acidic amide hydrolysis the desired amine (R)-3 was obtained without erosion of enantioselectivity. It is anticipated that the overall process will be amenable to large-scale production.

  描述了对二去甲基西布曲明3进行高度对映选择性的催化不对称合成的首次尝试。通过乙酸酐灭活腈4与甲丙基镁氯化物缩合产物得到的二烯酰胺10，被证明是一种优良的底物，可用于铑催化的不对称氢化反应，使用对映异构的二膦配体。在S/C = 500条件下，使用铑/(R)- MeOBiPheP 催化剂进行氢化反应，得到98.5% ee几乎定量产率的手性酰胺 (R)-9。在酸性酰胺水解后，所需胺类产物 (R)-3 获得，而对映选择性未受影响。预计整个过程适用于大规模生产。
• A New and Direct Asymmetric Synthesis of a Hindered Chiral Amine via a Novel Sulfinate Ketimine Derived from <i>N</i>-Tosyl-1,2,3-oxathiazolidine-2-oxide:  Practical Asymmetric Synthesis of (<i>R</i>)-Sibutramine
  作者：Zhengxu Han、Dhileepkumar Krishnamurthy、Chris H. Senanayake

  DOI：10.1021/op050182n

  日期：2006.3.1

  A novel and direct approach for the asymmetric synthesis of (R)-sibutramine via chiral amine 5 using N-tosyl-1,2,3-oxathiazolidine-2-oxide (13) as a recyclable chiral auxiliary is described. Chiral sulfinate imine 16e was obtained by treatment of 13e with the imine intermediate formed from the reaction of a nitrile 1 and iBuMgCl that, upon reduction, provides an optically active amine 5 with high enantiopurity

  描述了一种新颖且直接的方法，其使用N-甲苯磺酰基-1,2,3-氧代噻唑烷-2-氧化物（13）作为可循环的手性助剂，通过手性胺5不对称合成（R）-西布曲明。手性亚磺酸亚胺16e是通过用腈1和i的反应形成的亚胺中间体处理13e而获得的还原后可提供具有高对映体纯度的旋光胺5的BuMgCl。
• Therapeutic agents
  申请人：——

  公开号：US20030130355A1

  公开（公告）日：2003-07-10

  The present invention provides a method of treating and preventing obesity and related co-morbid conditions comprising the administration of a therapeutically effective amount of one or more monoamine reuptake inhibitors which are serotonin reuptake inhibitors and/or noradrenaline reuptake inhibitors and a 5-HT 1A agonist to a patient in need thereof.

  本发明提供了一种治疗和预防肥胖及相关共病症的方法，包括向需要此类治疗的患者给予一种或多种单胺再摄取抑制剂，这些抑制剂是选择性5-羟色胺再摄取抑制剂和/或去甲肾上腺素再摄取抑制剂，以及一种5-HT1A受体激动剂的治疗有效量。
• PHENYLCYCLOBUTYLAMIDE DERIVATIVES AND THEIR STEREOISOMERS, THE PREPARATION PROCESSES AND USES THEREOF
  申请人：Zhao Shuqiang

  公开号：US20110224305A1

  公开（公告）日：2011-09-15

  Phenylcyclobutylamide derivatives and their optical isomers, the preparing processes and the uses thereof, which includes the compounds of formula (I), their pure stereoisomers and their pharmaceutically acceptable salts. In formula (I), R is H, formacyl, acetyl, haloacetyl, benzoyl, benzyloxy carbonyl (Cbz), t-butoxy carbonyl (Boc), or 9-fluorenyl methoxyl carbonyl (Fmoc). The present novel compounds have pharmaceutical activity and are prepared by condensation reaction of racemic, levo- or dextro-demethyl Sibutramine and racemic or D/L isoleucine under a mild condition. It is demonstrated that the present compounds have effect of losing weight to obese mode rats in different level and the effect is better than Sibutramine by the animal experiments. So the medicaments prepared by the present compounds or the medicaments prepared by the compositions of the present compounds and other pharmaceutical activity compounds may be used for treating obesity.

  苯基环丁酰胺衍生物及其光学异构体，其制备方法和用途，包括式(I)化合物，其纯立体异构体和其药学可接受的盐。在式(I)中，R为H，甲酰基，乙酰基，卤代乙酰基，苯甲酰基，苄氧羰基（Cbz），叔丁氧羰基（Boc）或9-芴甲氧羰基（Fmoc）。这些新型化合物具有药理活性，是通过在温和条件下将外消旋、左旋或右旋去甲基西布曲明和外消旋或D/L异亮氨酸进行缩合反应制备的。动物实验表明，这些化合物对不同程度的肥胖模式大鼠有减肥作用，且效果优于西布曲明。因此，通过这些化合物制备的药物或通过这些化合物和其他药理活性化合物组成的药物可以用于治疗肥胖症。