来氟米特杂质 | 208401-20-1

• 物质功能分类: 有机原料 - 氨基化合物
• 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: 来氟米特杂质
• 中文别名: 5-去甲基-3-甲基来氟米特
• 英文名称: 3-Methyl-4-[4-(trifluoromethyl)phenyl-aminocarbonyl]isoxazole
• 英文别名: N-(4-trifluoromethylphenyl)-3-methyl-isoxazole-4-carboxamide；3-Methyl-N-(4-(trifluoromethyl)phenyl)isoxazole-4-carboxamide；3-methyl-N-[4-(trifluoromethyl)phenyl]-1,2-oxazole-4-carboxamide
• CAS: 208401-20-1
• 化学式: C₁₂H₉F₃N₂O₂
• 分子量: 270.211
• InChiKey: SNUBGILHVSSQAY-UHFFFAOYSA-N

物化性质

• 熔点：
  140-145°C
• 沸点：
  287.2±40.0 °C(Predicted)
• 密度：
  1.392±0.06 g/cm3(Predicted)
• 溶解度：
  氯仿（微溶）、乙酸乙酯（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-[4-(trifluoromethyl)phenyl]-2-(ethoxymethylene)acetoacetamide 在 sodium hydroxide 、 盐酸羟胺 作用下， 以 乙醇 、 水 为溶剂， 生成 来氟米特杂质
  参考文献：
  名称：

  Isoxazole-4-carboxamide compounds active against protein tryosine kinase related disorders

  摘要：

  本发明涉及一种新型异噁唑-4-羧酰胺，其调节蛋白酪氨酸激酶活性，因此预计可用于治疗包括癌症在内的异常蛋白酪氨酸激酶活性驱动的疾病。

  公开号：

  US06316479B1

文献信息

• Method for systhesizing leflunomide
  申请人：——

  公开号：US20020022646A1

  公开（公告）日：2002-02-21

  A process for synthesizing leflunomide from 5-methylisoxazole-4-carboxylic acid and 4-trifluoromethylaniline is provided. Further provided is the leflunomide prepared by the inventive process, which is substantially free of difficult-to-separate impurities often found in leflunomide prepared by known methods, including N-(4-trifluoromethylphenyl)-2-cyano-3-hydroxycrotonamide, 5-methyl-N-(4-methylphenyl)-isoxazole-4-carboxamide and N-(4-trifluoromethylphenyl)-3-methyl-isoxazole-4-carboxamide. The invention further provides pharmaceutical compositions and dosage forms containing highly pure leflunomide and methods of treating disease using the leflunomide.

  提供一种从5-甲基异噁唑-4-羧酸和4-三氟甲基苯胺合成来氟米特的方法。进一步提供了通过创新方法制备的来氟米特，该方法基本上不含常见方法制备的来氟米特中难以分离的杂质，包括N-(4-三氟甲基苯基)-2-氰基-3-羟基丙烯酰胺、5-甲基-N-(4-甲基苯基)-异噁唑-4-羧酰胺和N-(4-三氟甲基苯基)-3-甲基异噁唑-4-羧酰胺。该发明还提供含有高纯度来氟米特的药物组合物和剂型，以及使用来氟米特治疗疾病的方法。
• [EN] A METHOD FOR SYNTHESIZING LEFLUNOMIDE<br/>[FR] PROCEDE PERMETTANT D'EFFECTUER LA SYNTHESE DU LEFLUNOMIDE
  申请人：TEVA PHARMA

  公开号：WO2001060363A1

  公开（公告）日：2001-08-23

  A process for synthesizing leflunomide from 5-methylisoxazole-4-carboxylic acid and 4-trifluoromethylaniline is provided. Further provided is the leflunomide prepared by the inventive process, which is substantially free of difficult-to-separate impurities often found in leflunomide prepared by known methods, including N-(4-trifluoromethylphenyl)-2-cyano-3-hydroxycrotonamide, 5-methyl-N-(4-methylphenyl)-isoxazole-4-carboxamide and N-(4-trifluoromethylphenyl)-3-methyl-isoxazole-4-carboxamide. The invention further provides pharmaceutical compositions and dosage forms containing highly pure leflunomide and methods of treating disease using the leflunomide.

  提供了一种从5-甲基异噁唑-4-羧酸和4-三氟甲基苯胺合成来氟米特的方法。此外，该创新方法制备的来氟米特基本上没有难以分离的杂质，这些杂质通常存在于已知方法制备的来氟米特中，包括N-(4-三氟甲基苯基)-2-氰基-3-羟基巴豆酰胺，5-甲基-N-(4-甲基苯基)-异噁唑-4-羧酰胺和N-(4-三氟甲基苯基)-3-甲基异噁唑-4-羧酰胺。该发明还提供了含有高纯度来氟米特的药物组合物和剂型，并提供了使用来氟米特治疗疾病的方法。
• Heteroarylcarboxamide compounds active against protein tyrosine kinase related disorders
  申请人：Sugen, Inc.

  公开号：US20040102489A1

  公开（公告）日：2004-05-27

  The present invention relates to novel heteroaryl-carboxamides which modulate the activity of protein tyrosine kinases and therefore are expected to be useful in the treatment of abnormal protein tyrosine kinase activity driven disorders including cancer.

  本发明涉及一种新型杂环基-羧酰胺，其可以调节蛋白酪氨酸激酶的活性，因此被期望在治疗异常的蛋白酪氨酸激酶活性驱动的疾病，包括癌症中有用。
• Method for synthesizing leflunomide
  申请人：——

  公开号：US20040127532A1

  公开（公告）日：2004-07-01

  A process for synthesizing leflunomide from 5-methylisoxazole-4-carboxylic acid and 4-trifluoromethylaniline is provided. Further provided is the leflunomide prepared by the inventive process, which is substantially free of difficult-to-separate impurities often found in leflunomide prepared by known methods, including N-(4-trifluoromethylphenyl)-2-cyano-3-hydroxycrotonamide, 5-methyl-N-(4-methylphenyl)-isoxazole-4-carboxamide and N-(4-trifluoromethylphenyl)-3-methyl-isoxazole-4-carboxamide. The invention further provides pharmaceutical compositions and dosage forms containing highly pure leflunomide and methods of treating disease using the leflunomide.

  本发明提供一种从5-甲基异噁唑-4-羧酸和4-三氟甲基苯胺合成左氟氮酰胺的方法。本发明还提供了通过本发明方法制备的左氟氮酰胺，其基本上不含左氟氮酰胺已知方法中常见的难以分离的杂质，包括N-(4-三氟甲基苯基)-2-氰基-3-羟基巴豆酰胺，5-甲基-N-(4-甲基苯基)-异噁唑-4-羧酰胺和N-(4-三氟甲基苯基)-3-甲基异噁唑-4-羧酰胺。本发明还提供了含有高纯度左氟氮酰胺的药物组合物和剂型，以及使用左氟氮酰胺治疗疾病的方法。
• Leflunomide of high purity
  申请人：TEVA PHARMACEUTICAL INDUSTRIES LTD.

  公开号：EP1473035A1

  公开（公告）日：2004-11-03

  Leflunomide prepared from 5-methylisoxazole-4-carboxylic acid and 4-trifluoromethylaniline is provided which is substantially free of difficult-to-separate impurities found in leflunomide prepared by known methods, including N-(4-trifluoromethylphenyl)-2-cyano-3-hydroxycrotonamide, 5-methyl-N-(4-methylphenyl)-isoxazole-4-carboxamide and N-(4-trifluoromethylphenyl)-3-methyl-isoxazole-4-carboxamide. The invention further provides pharmaceutical compositions and dosage forms containing highly pure leflunomide and methods of treating disease using the leflunomide.

  由 5-甲基异恶唑-4-羧酸和 4-三氟甲基苯胺制备的来氟米特基本上不含已知方法制备的来氟米特中难以分离的杂质、包括 N-(4-三氟甲基苯基)-2-氰基-3-羟基巴豆酰胺、5-甲基-N-(4-甲基苯基)-异恶唑-4-甲酰胺和 N-(4-三氟甲基苯基)-3-甲基-异恶唑-4-甲酰胺。本发明进一步提供了含有高纯度来氟米特的药物组合物和剂型，以及使用来氟米特治疗疾病的方法。