恩他卡彭杂质72 | 893419-47-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 中文名称: 恩他卡彭杂质72
• 英文名称: (2E)-2-cyano-3-(3-methoxy-4-hydroxy-phenyl)-N,N-diethylprop-2-enamide
• 英文别名: (E)-2-cyano-N,N-diethyl-3-(4-hydroxy-3-methoxyphenyl)-acrylamide；(E)-N,N-diethyl-2-cyano-3-(3-methoxy-4-hydroxyphenyl)acrylamide；(E)-N,N-diethyl-2-cyano-3-(3-methoxy-4-hydroxy-phenyl)-acryl-amide；2-cyano-N,N-diethyl-3-(4-hydroxy-3-methoxyphenyl)acrylamide；(E)-2-cyano-N,N-diethyl-3-(4-hydroxy-3-methoxyphenyl)prop-2-enamide
• CAS: 893419-47-1
• 化学式: C₁₅H₁₈N₂O₃
• 分子量: 274.32
• InChiKey: DBTGDJLRURNRLD-XYOKQWHBSA-N

物化性质

• 沸点：
  481.4±45.0 °C(Predicted)
• 密度：
  1.177±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  73.6
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P305+P351+P338,P330,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  恩他卡彭杂质72 在 aluminum (III) chloride 、 硝酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 恩他卡朋
  参考文献：
  名称：

  Efficient Approach to Pure Entacapone and Related Compounds

  摘要：

  A new and efficient process through a new intermediate, (2E)-2-cyano-3(3,4-dihydroxy-5-nirtrophenyl)prop-2-enoic acid 15, has been described for preparing substantially pure entacapone 1. This new intermediate 15 was prepared by Knoevenagel condensation of 3,4-dihydroxy-5-nitrobenzaldehyde 2 with 2-cyanoacetic acid 14 and was further condensed with diethylamine to get pure entacapone 1. Some of the important process-related impurities of entacapone (17, 18, 19, and 20) were also prepared easily from this intermediate 15.

  DOI：

  10.1080/00397911.2010.539894
• 作为产物：
  描述：

  2-氰基-N,N-二乙基乙酰胺 、 香草醛 在 溶剂黄146 、 二乙胺 作用下， 以 环己烷 为溶剂， 以92%的产率得到恩他卡彭杂质72
  参考文献：
  名称：

  [EN] PROCESS FOR THE PREPARATION OF ENTACAPONE AND ITS INTERMEDIATE THEREOF
  [FR] PROCÉDÉ DE PRÉPARATION D'ENTOCAPONE ET DE SON INTERMÉDIAIRE

  摘要：

  本文提供了制备化合物（V）的方法，包括在催化剂存在下，用硝化剂对化合物（IV）进行硝化。

  公开号：

  WO2013149566A1

文献信息

• Process for the preparation of entacapone and intermediates thereof
  申请人：ESTEVE QUIMICA, S.A.

  公开号：EP1978014A1

  公开（公告）日：2008-10-08

  New preparation process for the preparation of entacapone which comprises converting the 3,4-dimethoxy-5-nitrobenzoic acid into an activated derivative which is reacted with 2-cyano-N,N-diethylacetamide in the presence of a base to give 2-cyano-3-(3,4-dimethoxy-5-nitrophenyl)-N,N-diethyl-3-hydroxyacrylamide; reacting the resulting compound with MHB(OCOR)3 where R is (C1-C4)-alkyl, phenyl, or CF3; and M is a sodium, potassium or ((C1-C4)-alkyl)4N, in the presence of an appropriate solvent to give E-2-cyano-3-3,4-dimethoxy-5-nitrophenyl)-N,N-diethylacrylamide; and finally submitting the compound obtained to a demethylation reaction to yield entacapone. Both 2-cyano-3-(3,4-dimethoxy-5-nitrophenyl)-N,N-diethyl-3-hydroxyacrylamide and E-2-cyano-3-3,4-dimethoxy-5-nitrophenyl)-N,N-diethylacrylamide are new. Entacapone has industrial applicability as antiparkinson's agent.

  新的恩他卡朋制备工艺包括将3,4-二甲氧基-5-硝基苯甲酸转化为活化衍生物，与2-氰基-N,N-二乙基乙酰胺在碱存在下反应，得到2-氰基-3-(3,4-二甲氧基-5-硝基苯基)-N,N-二乙基-3-羟基丙烯酰胺；将所得化合物与MHB(OCOR)3反应，其中R为(C1-C4)-烷基、苯基或CF3；M为钠、钾或((C1-C4)-烷基)4N，在适当溶剂存在下，得到E-2-氰基-3-(3,4-二甲氧基-5-硝基苯基)-N,N-二乙基丙烯酰胺；最后将所得化合物进行去甲基化反应，得到恩他卡朋。2-氰基-3-(3,4-二甲氧基-5-硝基苯基)-N,N-二乙基-3-羟基丙烯酰胺和E-2-氰基-3-(3,4-二甲氧基-5-硝基苯基)-N,N-二乙基丙烯酰胺均为新化合物。恩他卡朋作为抗帕金森病药物具有工业适用性。
• WO2006/64296
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthesis of Entacapone by Pd-Catalyzed Heck Coupling Reaction
  作者：Arava Veerareddy、Gogireddy Surendra Reddy

  DOI：10.1080/00397911.2013.853190

  日期：2014.5.3

  Synthesis of entacapone from 4-iodo-2-methoxy-phenol with 2-cyano-N,N-diethylacrylamide by palladium-catalyzed Heck reaction, as a key step, is described.
• Synthetic Commun. 2014, 44, 1274-1278
  作者：

  DOI：——

  日期：——
• [EN] PROCESS FOR THE PREPARATION OF (E)-N,N-DIETHYL-2-CYANO-3(3,4-DIHYDROXY-5-NITRO-PHENYL)-ACRYLAMIDE IN STABLE POLYMORPHIC FORM AND INTERMEDIATES OF THE PROCESS<br/>[FR] PROCEDE DE PREPARATION DU (E)-N1N- DIETHYL-2-CYANO-3-(3,4-DIHYDROXY-T5-NITRO-PHENYL)-ACRYLAMIDE SOUS UNE FORME POLYMORPHE STABLE ET DES INTERMEDIAIRES DU PROCEDE
  申请人：ALKALOIDA KUTATO ES FEJLESZTOE

  公开号：WO2006064296A1

  公开（公告）日：2006-06-22

  [EN] The invention relates to a process for the preparation of pure E isomer of N1N- diethyl-2-cyano-3-(3,4-dihydrÌxy-t5-nitro-phenyl)-acryIamide of formula (1 ) ( D in stable polymorphic form. According to the invention _ (a) (E)-N, N-diethyl-2-cyano-3-(3-methoxy-4-hydroxy-5-nitro-phenyl)-acryl- amide is demethylated; or (b) (E)-N, N-diethyl-2-cyano-3-(3-methoxy-4-hydroxy-phenyl)-acrylamide is nitrated, and the. resulting (E)-N-, N-diethyl-2-cyano-3-(3-methoxy-4-hydroxy-5-nitro- phenyl)-acrylamide is demethylated; or - (c) vanillin is reacted with N.N-diethyl-cy.anoacetamide in the presence of a weak organic acid and of an amine compound used as catalysts, the resulting (E)- N,N-diethyl-2-cyano-3-(3-methoxy-4-hydroxy-phenyl)-acrylamide is nitrated, and the resulting (E)-N, N-diethyl-2-cyano-3-(3-methoxy-4-hydroxy-5-nitro-phenyl)-acrylamide is demethylated. The invention also relates to (E)-N, N-diethyl-2-cyano-3-(3-methoxy-4-hydroxy- phenyl)-acrylamide and (E)-N, N-diethyl-2-cyano-3-(3-rhethoxy-4-hydroxy-5-nitro- phenyl)-acrylamide and to their preparation.
  [FR] L'invention porte sur un procédé de préparation d'un isomère E pur de N1N- diéthyl-2-cyano-3-(3,4-dihydroxy-t5-nitro-phényl)-acryIamide de formule (I) sous une forme polymorphe stable, comportant les étapes suivantes: (a) déméthylation du (E)-N, N-diéthyl-2-cyano-3-(3-méthoxy-4-hydroxy-5-nitro-phényl)-acrylamide; ou (b) nitration du (E)-N, N-diéthyl-2-cyano-3-(3-méthoxy-4-hydroxy-phényl)-acrylamide, et déméthylation du (E)-N-, N-diéthyl-2-cyano-3-(3-méthoxy-4-hydroxy-5-nitro- phényl)-acrylamide résultant; ou (c) réaction de vanilline avec du N.N-diéthyl-cyanoacétamide en présence d'un acide organique faible et d'un composé aminé servant de catalyseur, et nitration du (E)- N,N-diéthyl-2-cyano-3-(3-méthoxy-4-hydroxy-phényl)-acrylamide, et déméthylation du (E)-N, N-diéthyl-2-cyano-3-(3-méthoxy-4-hydroxy-5-nitro-phényl)-acrylamide résultant. L'invention porte également sur le (E)-N, N-diéthyl-2-cyano-3-(3-méthoxy-4-hydroxy- phényl)-acrylamide et le (E)-N, N-diéthyl-2-cyano-3-(3-rhéthoxy-4-hydroxy-5-nitro- phényl)-acrylamide et leur préparation.