(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。
• Process for preparing (2R)-methyl-4,4,4-trifluorobutylamine
  申请人：Imperial Chemical Industries PLC

  公开号：US05274118A1

  公开（公告）日：1993-12-28

  A process for the preparation of (2R)-methyl-4,4,4-trifluorobutylamine, or an acid addition salt thereof which comprises a) acylating an optically active amine with 2-methyl-4,4,4-trifluorobutanoic acid or a reactive derivative thereof to afford a butyramide; b) separating (R)-diastereomeric butyramide from (S)-diastereomeric butyramide; and c) converting the (R)-diastereomeric butyramide into the desired (2R)-methyl-4,4,4-trifluorobutylamine, or an acid addition salt thereof. The product may be acylated with a carboxylic acid of formula III ##STR1## wherein U is carboxy, or a reactive derivative thereof to afford (R)-4-[5-(N-[4,4,4-trifluoro-2-methylbutyl]carbamoyl)-1-methylindol-3-yl-m ethyl]-3-methoxy-N-o-tolylsulphonylbenzamide. The indole is useful as a leukotriene antagonist, for example in the treatment of asthma or allergic rhinitis.

  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。
• 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