4,4,4-三氟-3-甲基丁酰胺 | 155953-61-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: 4,4,4-三氟-3-甲基丁酰胺
• 英文名称: 4,4,4-trifluoro-3-methylbutanamide
• 英文别名: 3-(trifluoromethyl)butanamide；Butanamide, 4,4,4-trifluoro-3-methyl-
• CAS: 155953-61-0
• 化学式: C₅H₈F₃NO
• 分子量: 155.12
• InChiKey: RXWSANZGHLWOLA-UHFFFAOYSA-N

物化性质

• 沸点：
  148.0±35.0 °C(Predicted)
• 密度：
  1.205±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  43.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4,4,4-三氟-3-甲基丁酰胺 在 4-二甲氨基吡啶 、 lithium aluminium tetrahydride 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 30.0h， 生成 3-Methoxy-4-[1-methyl-5-(4,4,4-trifluoro-3-methyl-butylcarbamoyl)-1H-indol-3-ylmethyl]-benzoic acid methyl ester
  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：

  4,4,4-trifluoro-3-methylbutanoic acid 在 氨 、 N,N'-羰基二咪唑 作用下， 生成 4,4,4-三氟-3-甲基丁酰胺
  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

文献信息

• Csp³–H Trifluoromethylation of Unactivated Aliphatic Systems
  作者：Jiachen He、Truong N. Nguyen、Shuo Guo、Silas P. Cook

  DOI：10.1021/acs.orglett.0c03891

  日期：2021.2.5

  method for the undirected trifluoromethylation of unactivated methylene units was developed. The reaction proceeds in aqueous acetonitrile with Grushin’s reagent, bpyCu(CF3)3, under broad-spectrum white-light irradiation. The trifluoromethylation tolerates a wide range of functional groups including ketones, esters, nitriles, amides, alcohols, and carboxylic acids. The C–H cleavage step is performed

  开发了一种用于未活化亚甲基单元的非定向三氟甲基化的简单方法。该反应在乙腈水溶液中与 Grushin 试剂 bpyCu(CF 3 ) 3在广谱白光照射下进行。三氟甲基化可耐受多种官能团，包括酮、酯、腈、酰胺、醇和羧酸。C-H 裂解步骤是通过分子间 H 原子抽象进行的，并且报告了在一系列亚甲基单元上的选择性。机理研究为整体转化提供了一般反应坐标。