(4R,5S)-3-((2R)-2-methyl-1-oxo-4,4,4-trifluorobutyl)-4-methyl-5-phenyl-2-oxazolidinone | 136564-81-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (4R,5S)-3-((2R)-2-methyl-1-oxo-4,4,4-trifluorobutyl)-4-methyl-5-phenyl-2-oxazolidinone
• 英文别名: (4R,5S)-4-methyl-3-((2R)-2-methyl-4,4,4-trifluorobutyryl)-5-phenyl-2-oxazolidinone；(4R,5S)-4-methyl-5-phenyl-3-[(2R)-4,4,4-trifluoro-2-methylbutanoyl]-1,3-oxazolidin-2-one
• CAS: 136564-81-3
• 化学式: C₁₅H₁₆F₃NO₃
• 分子量: 315.292
• InChiKey: SJESKRZTAGTNBP-CKYFFXLPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (4R,5S)-3-((2R)-2-methyl-1-oxo-4,4,4-trifluorobutyl)-4-methyl-5-phenyl-2-oxazolidinone 在 sodium hydroxide 作用下， 以 乙醚 、 水 为溶剂， 生成 (4R,5S)-(+)-4-甲基-5-苯基-2-恶唑啉酮
  参考文献：
  名称：

  Chemical process for the preparation of 3-alkylated indole

  摘要：

  制备3-烷基吲哚的方法包括：a) 将N-(2-硝基苯乙烯基)烯胺与烷基化试剂反应，形成亚胺盐，b) 可选地将亚胺盐与水反应，形成(2-硝基苯基)乙醛，以及c) 将亚胺盐或(2-硝基苯基)乙醛与能够选择性还原硝基的还原剂反应，形成所需的3-烷基吲哚。

  公开号：

  US05280125A1
• 作为产物：
  描述：

  (4R,5S)-3-(1-oxo-4,4,4-trifluorobutyl)-4-methyl-5-phenyl-2-oxazolidinone 以55的产率得到(4R,5S)-3-((2R)-2-methyl-1-oxo-4,4,4-trifluorobutyl)-4-methyl-5-phenyl-2-oxazolidinone
  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

• 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.

  制备3-烷基吲哚的方法包括：a) 将N-(2-硝基苯乙烯基)烯胺与烷基化试剂反应，形成亚胺盐，b) 可选地将亚胺盐与水反应，形成(2-硝基苯基)乙醛，以及c) 将亚胺盐或(2-硝基苯基)乙醛与能够选择性还原硝基的还原剂反应，形成所需的3-烷基吲哚。
• 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.

  制备（2R）-甲基-4,4,4-三氟丁基胺或其酸加成盐的过程包括：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)将（R）-对映异构体丁酰胺与（S）-对映异构体丁酰胺分离；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。该产品可与公式III的羧酸进行酰化反应，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-邻甲苯磺酰苯甲酰胺。该吲哚化合物可用作白三烯拮抗剂，例如用于治疗哮喘或过敏性鼻炎。
• 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
  作者：Robert T. Jacobs、Peter R. Bernstein、Laura A. Cronk、Edward P. Vacek、Lisa F. Newcomb、David Aharony、Carl K. Buckner、Edward J. Kusner

  DOI：10.1021/jm00035a008

  日期：1994.4

  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.
• A process for the preparation of 2(R)-methyl-4,4,4-trifluorobutylamine, intermediates, and a process for the preparation of a derivative thereof
  申请人：ZENECA LIMITED

  公开号：EP0489548B1

  公开（公告）日：1994-12-14
• 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