(R)-2-methyl-4,4,4-trifluorobutylamine hydrochloride

• 分子结构分类: 有机化合物 - 有机卤素化合物 - 有机氟化物
• 英文名称: (R)-2-methyl-4,4,4-trifluorobutylamine hydrochloride
• 英文别名: (2R)-4,4,4-trifluoro-2-methylbutan-1-amine;hydrochloride
• 化学式: C₅H₁₀F₃N*ClH
• 分子量: 177.597
• InChiKey: PKZZMNUWBBIRHO-PGMHMLKASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.96
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  26
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-2-methyl-4,4,4-trifluorobutylamine hydrochloride 在 4-二甲氨基吡啶 、 lithium hydroxide 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 84.0h， 生成 马鲁司特
  参考文献：
  名称：

  Synthesis, Structure-Activity Relationships, and Pharmacological Evaluation of a Series of Fluorinated 3-Benzyl-5-Indolecarboxamides: Identification of 4-[[5-[((2R)-2-Methyl-4,4,4-trifluorobutyl)carbamoyl]-1-methylindol-3-yl]methyl]-3methoxy-N-[(2-methylphenyl)sulfonyl]benzamide, a Potent, Orally Active Antagonist of Leukotrienes D4 and E4

  摘要：

  The continued exploration of a series of 3-(arylmethyl)-1H-indole-5-carboxamides by the introduction of fluorinated amide substituents has resulted in the discovery of 4-[[5-[((2R)-2-methyl-4,4,4-trifluorobutyl)carbamoyl]-1-methylindol-3-yl]methyl]-3-methoxy-N-[(2-methylphenyl)sulfonyl]benzamide (38p, ZENECA ZD 3523),which has been chosen for clinical evaluation. This compound exhibited a K-i of 0.42 nM for displacement of [H-3]LTD(4) on guinea pig lung membranes, a pK(B) Of 10.13 +/- 0.14 versus LTE(4) on guinea pig trachea, and an oral ED(50) Of 1.14 mu mol/kg opposite LTD(4)-induced bronchoconstriction in guinea pigs. The R enantiomer was found to be modestly more potent than the S enantiomer 38o. Modification of the amide substituent to afford achiral compounds was unsuccessful in achieving comparable levels of activity. Profiling of 38p opposite a variety of functional assays has demonstrated the selectivity of this compound as a leukotriene receptor antagonist. The enantioselective synthesis of 38p, which employed a diastereoselective alkylation of (4R,5S)-3-(1-oxo-4,4,4-trifluorobutyl)-4-methyl-5-phenyl-2-oxazolidinone (27) as the key step to establish the chirality of the amide substituent, provided an efficient route for generating 38p in >99% enantiomeric purity.

  DOI：

  10.1021/jm00035a008
• 作为产物：
  描述：

  一水合肼 、 (R)-2-(2-methyl-4,4,4-trifluorobutyl)-1H-isoindole-1,3-(2H)-dione 、 盐酸 以 乙醇 为溶剂， 170.0 ℃ 、879.93 Pa 条件下， 反应 3.0h， 以to yield (R)-2-methyl-4,4,4-trifluorobutylamine hydrochloride as a white solid (9.89 g, 88%)的产率得到(R)-2-methyl-4,4,4-trifluorobutylamine hydrochloride
  参考文献：
  名称：

  Process for preparing (2R)-methyl-4,4,4-trifluorobutylamine

  摘要：

  一种制备(2R)-甲基-4,4,4-三氟丁基胺或其酸加成盐的方法，包括a)用2-甲基-4,4,4-三氟丁酸或其反应衍生物酰化手性胺以得到丁酰胺；b)分离(R)-对映异构体丁酰胺和(S)-对映异构体丁酰胺；c)将(R)-对映异构体丁酰胺转化为所需的(2R)-甲基-4,4,4-三氟丁基胺或其酸加成盐。 该产品可用式III的羧酸进行酰化，其中U是羧基，或其反应衍生物，以得到(R)-4-[5-(N-[4,4,4-三氟-2-甲基丁基]氨基甲酰)-1-甲基吲哚-3-基甲基]-3-甲氧基-N-o-甲苯磺酰基苯甲酰胺。吲哚可用作白三烯受体拮抗剂，例如用于哮喘或过敏性鼻炎的治疗。

  公开号：

  US05274118A1
• 作为试剂：
  描述：

  4-(5-carboxy-1-methylindol-3-ylmethyl)-3-methoxy-N-(2-methylphenylsulfonyl)benzamide 、 (R)-2-methyl-4,4,4-trifluorobutylamine hydrochloride 在 (R)-2-methyl-4,4,4-trifluorobutylamine hydrochloride 作用下， 以65的产率得到马鲁司特
  参考文献：
  名称：

  A process for the preparation of 2(R)-methyl-4,4,4-trifluorobutylamine, intermediates, and a process for the preparation of a derivative thereof

  摘要：

  公开号：

  EP0489548B1

文献信息

• Process for preparing a physical form of pharmaceutical agent
  申请人：Imperial Chemical Industries, PLC

  公开号：US05466826A1

  公开（公告）日：1995-11-14

  A physical form of (R)-3-methoxy-4-[1-methyl-5-(2-methyl-4,4,4-trifluorobutylcarbamoyl)indol- 3-ylmethyl]-N-(2-methylphenylsulphonyl)benzamide substantially free of other physical forms, which form is crystalline and has an X-ray powder diffraction pattern with specific peaks at 2.THETA.=14.0.degree., 19.4.degree., 22.0.degree., 22.4.degree. and 24.7.degree., processes for preparing the form and pharmaceutical compositions containing it. The compound is a leukotriene antagonist useful in the treatment of diseases such as asthma.

  一种物理形式的(R)-3-甲氧基-4-[1-甲基-5-(2-甲基-4,4,4-三氟丁基氨基)吲哚-3-基甲基]-N-(2-甲基苯磺酰)苯甲酰胺，该物理形式基本上不含其他物理形式，其形式为结晶体，并具有X射线粉末衍射图谱，在2.THETA. = 14.0度，19.4度，22.0度，22.4度和24.7度具有特定峰，制备该形式的方法和含有该形式的药物组合物。该化合物是一种白三烯拮抗剂，可用于治疗哮喘等疾病。
• Carbamoyl derivatives
  申请人：Imperial Chemical Industries PLC

  公开号：US05286740A1

  公开（公告）日：1994-02-15

  The present invention concerns novel carbamoyl derivatives of formula I, set out herein, which antagonize the pharmacological actions of one or more of the arachidonic acid metabolites known as leukotrienes, making them useful whenever such antagonism is desired, such as in the treatment of those diseases in which leukotrienes are implicated, for example, in the treatment of allergic or inflammatory diseases, or of endotoxic or traumatic shock conditions. The invention also provides pharmaceutical compositions containing the novel derivatives for use in such treatments, methods for their use and processes and intermediates for the manufacture of the novel derivatives.

  本发明涉及一种新的卡巴莫基衍生物，其化学式为I，该衍生物可以拮抗被称为白三烯的花生四烯酸代谢产物的药理作用，使其在需要此种拮抗作用时变得有用，例如在治疗白三烯参与的疾病，如过敏或炎症性疾病，或内毒素性或创伤性休克症状的治疗中。本发明还提供了包含新衍生物的药物组合物，用于这种治疗，以及用于制造新衍生物的方法和中间体。
• Chemical process for the preparation of 3-alkylated indole
  申请人：Imperial Chemical Industries PLC

  公开号：US05280125A1

  公开（公告）日：1994-01-18

  A process for the preparation of a 3-alkylated indole, which comprises: a) reacting a N-(2-nitrostyryl) enamine with an alkylating agent to afford an imine salt, b) optionally reacting the imine salt with water to afford a (2-nitrophenyl)acetaldehyde, and c) reacting the imine salt or the (2-nitrophenyl)acetaldehyde with a reducing agent capable of selectively reducing the nitro group, to afford the desired 3-alkylated indole.

  一种制备3-烷基化吲哚的方法，包括：a）将N-(2-硝基苯乙烯基)恩酰与烷基化试剂反应，得到一种亚胺盐；b）可选择性地将亚胺盐与水反应，得到一种(2-硝基苯基)乙醛；c）将亚胺盐或(2-硝基苯基)乙醛与具有选择性还原硝基的还原剂反应，得到所需的3-烷基化吲哚。
• Pharmaceutical agents
  申请人：Imperial Chemical Industries PLC

  公开号：US05352694A1

  公开（公告）日：1994-10-04

  A physical form of (R)-3-methoxy-4-[1-methyl-5-(2-methyl-4,4,4-trifluorobutylcarbamoyl)indol -3-ylmethyl]-N-(2-methylphenylsulphonyl)benzamide substantially free of other physical forms, which form is crystalline and has an X-ray powder diffraction pattern with specific peaks at 2.theta.=14.0, 19.4, 22.0, 22.4 and 24.7.degree. , processes for preparing the form and pharmaceutical compositions containing it. The compound is a leukotriene antagonist useful in the treatment of diseases such as asthma.

  一种物理形式的(R)-3-甲氧基-4-[1-甲基-5-(2-甲基-4,4,4-三氟丁基氨基)吲哚-3-基甲基]-N-(2-甲基苯磺酰)苯甲酰，该物理形式基本上不含其他物理形式，其形态为结晶体，并具有X射线粉末衍射图谱，其在2.theta.=14.0、19.4、22.0、22.4和24.7度处具有特定峰，制备该物形式的方法以及含有该物形式的药物组合物。该化合物是一种白三烯受体拮抗剂，可用于治疗哮喘等疾病。
• A process for the preparation of a 3-alkylated indole, intermediates, and a process for the preparation of a derivative thereof
  申请人：ZENECA LIMITED

  公开号：EP0489547B1

  公开（公告）日：1998-07-29