5-Ethoxy-3-oxo-4-pentensaeure-ethylester | 115933-33-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: 5-Ethoxy-3-oxo-4-pentensaeure-ethylester
• 英文别名: (E)-ethyl 5-ethoxy-3-oxo-4-pentenoate；ethyl (E)-5-ethoxy-3-oxo-4-pentenoate；ethyl (4E)-5-ethoxy-3-oxopent-4-noate；ethyl (4E)-5-ethoxy-3-oxopent-4-enoate；ethyl (E)-5-ethoxy-3-oxopent-4-enoate
• CAS: 115933-33-0
• 化学式: C₉H₁₄O₄
• 分子量: 186.208
• InChiKey: XDHWYQRLMSOZOP-AATRIKPKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  13
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-氨基-4-氰基吡唑 、 5-Ethoxy-3-oxo-4-pentensaeure-ethylester 以94%的产率得到
  参考文献：
  名称：

  SUNTHANKAR S. V.; VAIDYA S. D., INDIAN J. CHEM. , 1977, B 15, NO 4, 349-351

  摘要：

  DOI：
• 作为产物：
  描述：

  ethyl 5,5-diethoxy-3-oxopentanoate 在 硫酸 作用下， 反应 0.25h， 以9%的产率得到5-Ethoxy-3-oxo-4-pentensaeure-ethylester
  参考文献：
  名称：

  Effenberger, Franz; Ziegler, Thomas; Schoenwaelder, Karl-Heinz, Chemische Berichte, 1985, vol. 118, # 2, p. 741 - 752

  摘要：

  DOI：

文献信息

• Bicyclic aromatic substituted pyridone derivative
  申请人：Sakuraba Shunji

  公开号：US20090264426A1

  公开（公告）日：2009-10-22

  Disclosed is a compound represented by the formula (I): Wherein R 1 and R 2 independently represent a hydrogen atom, a lower alkyl group or the like; X 1 , X 2 and X 3 independently represent a methine group or a nitrogen atom; Y 1 and Y 3 independently represent a single bond, —O— or the like; Y 2 represents a lower alkylene group or the like; W1 to W4 independently represent a single bond, a methylene group or the like; L represents a single bond, a methylene group or the like; Z 1 and Z 2 independently represent a single bond, a C 1-4 alkylene group or the like; Ar 1 represents an aromatic carbocyclic ring or the like; and Ar 2 represents a bicyclic aromatic carbocyclic ring or the like. The compound is useful as a pharmaceutical for a central disease, a cardiovascular disease or a metabolic disease.

  本发明揭示了一种化合物，其化学式为（I）：其中R1和R2分别代表氢原子、低碳烷基或类似物；X1、X2和X3分别代表亚甲基基团或氮原子；Y1和Y3分别代表单键、—O—或类似物；Y2代表低碳烷基基团或类似物；W1至W4独立地代表单键、亚甲基基团或类似物；L代表单键、亚甲基基团或类似物；Z1和Z2独立地代表单键、C1-4烷基基团或类似物；Ar1代表芳香环烷基环或类似物；Ar2代表双环芳香环烷基环或类似物。该化合物可用作治疗中枢疾病、心血管疾病或代谢性疾病的药物。
• Process for preparing 5-methylisoxazole-4-carboxylic- (4'-trifluoromethyl)-anilide
  申请人：——

  公开号：US20030139606A1

  公开（公告）日：2003-07-24

  A process for preparing 5-methylisoxazole-4-carboxylic-(4′-trifluoromethyl)-anilide comprising: (a) reacting ethylacetoacetate, triethylorthoformate, and acetic anhydride at a temperature of from about 75° C. to about 150° C., to form ethyl ethoxymethyleneacetoacetic ester; (b) combining the ethyl ethoxymethyleneacetoacetic ester with sodium acetate or a salt of trifluoroacetic acid in the presence of hydroxylamine sulfate at a temperature of from about −20° C. to 10° C., to form ethyl-5-methylisoxazole-4-carboxylate; (c) reacting the ethyl-5-methylisoxazole-4-carboxylate with a strong acid to form 5-methylisoxazole-4-carboxylic acid; (d) reacting the crystallized 5-methylisoxazole-4-carboxylic acid with thionyl chloride to form 5-methylisoxazole-4-carbonyl chloride; and (e) reacting the 5-methylisoxazole-4-carbonyl chloride with trifluoromethyl aniline and an amine base at a temperature of from about 0° C. to about 50° C. to form 5-methylisoxazole-4-carboxylic-(4′-trifluoromethyl)-anilide. The process of the invention is especially advantageous for preparing 5-methylisoxazole-4-carboxylic-(4′-trifluoromethyl)-anilide, since the process: (1) eliminates or reduces the formation of the by-product 2-cyanoacetoacetic-1-(4′-trifluoromethyl)-anilide (CATA), generally as low as 0.0006%; (2) eliminates or reduces the formation of isomeric impurity ethyl-3-methyisoxazole-4-carboxylate and its corresponding acid as low as 0.1%, (3) produces a high quality of 5-methylisoxazole-4-carboxylic-(4′-trifluoromethyl)-anilide generally having 99.8-100% HPLC potency; and (4) does not require distillation of the isoxazole ester.

  制备5-甲基异噁唑-4-羧酸-(4'-三氟甲基)-苯胺的过程包括：(a)在约75°C至约150°C的温度下，将乙酰乙酸乙酯、三乙基正甲酸酯和乙酸酐反应，形成乙酸乙酯亚甲基乙酮乙酸酯；(b)将乙酸乙酯亚甲基乙酮乙酸酯与乙酸钠或三氟乙酸盐在氢氧胺硫酸存在下，在约-20°C至10°C的温度下反应，形成乙酸-5-甲基异噁唑-4-羧酸酯；(c)将乙酸-5-甲基异噁唑-4-羧酸酯与强酸反应，形成5-甲基异噁唑-4-羧酸；(d)将结晶的5-甲基异噁唑-4-羧酸与氯化亚硫酸形成5-甲基异噁唑-4-羰基氯化物；(e)将5-甲基异噁唑-4-羰基氯化物与三氟甲基苯胺和胺碱在约0°C至约50°C的温度下反应，形成5-甲基异噁唑-4-羧酸-(4'-三氟甲基)-苯胺。该发明的过程特别有利于制备5-甲基异噁唑-4-羧酸-(4'-三氟甲基)-苯胺，因为该过程：(1)消除或减少了副产物2-氰基乙酮乙酸-1-(4'-三氟甲基)-苯胺（CATA）的生成，通常低至0.0006%；(2)消除或减少了异构杂质乙酸-3-甲基异噁唑-4-羧酸酯及其对应酸的生成至0.1%；(3)产生高品质的5-甲基异噁唑-4-羧酸-(4'-三氟甲基)-苯胺，通常具有99.8-100%的HPLC纯度；(4)不需要对异噁唑酯进行蒸馏。
• 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。
• AMIDE DERIVATIVE AND USE THEREOF
  申请人：Ushio Hiroyuki

  公开号：US20130211075A1

  公开（公告）日：2013-08-15

  The present invention relates to a novel amide derivative. More specifically, the present invention provides a medicinal agent useful as a prophylactic or therapeutic agent for diseases, which relies on the production of cytokines from T cells, and which comprises an amide derivative or a pharmacologically acceptable salt thereof or a solvate of the derivative or the pharmacologically acceptable salt as an active ingredient. Provided is an amide derivative represented by general formula (I) [wherein each symbol is as defined in the description] or a pharmacologically acceptable salt thereof, or a solvate of the derivative or the pharmacologically acceptable salt.

  本发明涉及一种新型酰胺衍生物。更具体地说，本发明提供了一种药用剂，可用作依赖于T细胞产生细胞因子的疾病的预防或治疗剂，该药用剂包括酰胺衍生物或其药理学上可接受的盐或该衍生物或药理学上可接受的盐的溶剂的溶剂作为活性成分。提供的是由通式(I)所表示的酰胺衍生物[其中每个符号如描述中所定义]或其药理学上可接受的盐，或该衍生物或药理学上可接受的盐的溶剂。
• [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。