双氯芬酸杂质D | 123790-84-1

• 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: 双氯芬酸杂质D
• 英文名称: (2-Bromo-6-chloro-phenyl)-phenyl-amine
• 英文别名: 2-bromo-6-chloro-N-phenylaniline
• CAS: 123790-84-1
• 化学式: C₁₂H₉BrClN
• 分子量: 282.567
• InChiKey: JFCSJFULARWPIQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  双氯芬酸杂质D 在 sodium hydroxide 、 三氯化铝 作用下， 以 乙醇 、 水 为溶剂， 反应 22.0h， 生成 双氯芬酸单溴钠盐
  参考文献：
  名称：

  Synthesis and quantitative structure-activity relationships of diclofenac analogs

  摘要：

  The synthesis of a series of 2-anilinophenylacetic acids, close analogues of diclofenac, is described. These compounds were tested in two models used for evaluating the activity of nonsteroidal antiinflammatory drugs (NSAID's), inhibition of cyclooxygenase enzyme activity in vitro, and adjuvant-induced arthritis (AdA) in rats. Statistically significant correlations were found between the inhibitory activities of the compounds in these two models, indicating that cyclooxygenase inhibition seems to be the underlying mechanism for the antiinflammatory activity of these compounds. Quantitative structure-activity relationship (QSAR) analysis revealed that the crucial parameters for activity in both models were the lipophilicity and the angle of twist between the two phenyl rings. Optimal activities were associated with halogen or alkyl substituents in both ortho positions of the anilino ring. Compounds with OH groups in addition to two ortho substituents or compounds with only one or no ortho substituents were less active.

  DOI：

  10.1021/jm00171a008
• 作为产物：
  描述：

  溴苯 、 2,6-二氯乙酰苯胺 生成 双氯芬酸杂质D
  参考文献：
  名称：

  KEJHA, JIRI;BRUNOVA, BOHUMILA;SLUKOVA, DARIA;NOVACEK, ALOIS;GREF, JAN

  摘要：

  DOI：

文献信息

• N-phenyl-2,2,6,6-tetrahalocyclohexaneimine and processes for preparing 2,2,6,6-tetrahalocyclohexaneimine derivative and 2,6-dihaloaniline derivative
  申请人：OSAKA YUKI KAGAKU KOGYO KABUSHIKI KAISHA

  公开号：EP0313740A2

  公开（公告）日：1989-05-03

  A process for preparing a 2,2,6,6-tetrahalo­cyclohexaneimine derivative (I) which comprises reacting a 2,2,6,6-tetrahalocyclohexanone with a primary amine or ammonia in the presence of a Lewis acid, a process for preparing a 2,6-dihaloaniline derivative (II) which comprises subjecting the 2,2,6,6-tetrahalocyclo­hexaneimine derivative (I) to dehydrohalogenation in the presence or absence of a catalyst, and an N-phenyl-­2,2,6,6-tetrahalocyclohexaneimine. According to the process of the present invention, the 2,2,6,6-tetrahalo­cyclohexaneimine derivative (I) can be prepared from inexpensive starting materials in high yield through a few steps. Also, the 2,6-dihaloaniline derivative (II) can be prepared from inexpensive starting materials in high yield and high purity through a few steps. Further, the N-phenyl-2,2,6,6-tetrahalocyclohexaneimine is very useful in the preparation of N-phenyl-2,6-dihaloaniline.

  一种制备 2,2,6,6-四卤环己烷亚胺衍生物 (I) 的工艺，包括在路易斯酸存在下，使 2,2,6,6-四卤环己酮与伯胺或氨反应；一种制备 2、2,2,6,6-四氰基环己烷亚胺衍生物(I)在催化剂存在或不存在的情况下进行脱氢卤化的工艺，以及N-苯基-2,2,6,6-四氰基环己烷亚胺的制备工艺。根据本发明的工艺，2,2,6,6-四卤环己烷亚胺衍生物（I）可由廉价的起始原料通过几个步骤高产制备。此外，2,6-二卤苯胺衍生物（II）也可以由廉价的起始原料通过几个步骤高产率、高纯度地制备出来。此外，N-苯基-2,2,6,6-四环己烷亚胺对制备 N-苯基-2,6-二卤苯胺非常有用。
• Method of synthesizing diclofenac sodium
  申请人：FUDAN UNIVERSITY

  公开号：US10662145B2

  公开（公告）日：2020-05-26

  The invention relates to the chemical synthesis of pharmaceutical API, and specifically to a method of synthesizing diclofenac sodium, which is a kind of nonsteroidal anti-inflammatory drug for relieving pain. The method includes: nitrating phenylacetate to prepare o-nitrophenylacetate (2); hydrogenating o-nitrophenylacetate (2) to prepare o-aminophenylacetate (3); amidating an amino group of o-aminophenylacetate (3) to obtain 2-(2-benzoylaminophenyl) acetate (4); 2-(2-benzoylaminophenyl) acetate (4) reacting with thionyl chloride to prepare a chloroimine intermediate, and then condensing the intermediate of chloroimine with 2,6-dichlorophenol using an inorganic base to prepare (E)-methyl-2-(2-((2,6-dichlorophenoxy)(phenyl)methyleneamino) phenyl ester (5); subjecting (E)-methyl-2-(2-((2,6-dichlorophenoxy)(phenyl)methyleneamino) phenyl ester (5) to Chapman rearrangement to afford methyl 2-(2-(N-(2,6-dichlorophenyl)benzoylamino)phenyl) ester (6); and hydrolyzing methyl 2-(2-(N-(2,6-dichlorophenyl)benzoylamino)phenyl) ester (6) to provide the target compound as of diclofenac sodium API. The overall yield is up to 67% based on methyl phenylacetate.

  本发明涉及药物原料药的化学合成，具体涉及一种合成双氯芬酸钠的方法，双氯芬酸钠是一种用于缓解疼痛的非甾体类消炎药。该方法包括硝化苯乙酸，制备邻硝基苯乙酸酯（2）；氢化邻硝基苯乙酸酯（2），制备邻氨基苯乙酸酯（3）；酰胺化邻氨基苯乙酸酯（3）的氨基，得到 2-（2-苯甲酰基氨基苯基）乙酸酯（4）；2-(2-苯甲酰基氨基苯基)乙酸酯(4)与亚硫酰氯反应，制备氯亚胺中间体，然后用无机碱将氯亚胺中间体与 2,6-二氯苯酚缩合，制备(E)-甲基-2-(2-((2,6-二氯苯氧基)(苯基)亚甲基氨基)苯基酯(5)将(E)-甲基-2-(2-((2,6-二氯苯氧基)(苯基)亚甲基氨基)苯基酯(5)进行查普曼重排，得到甲基-2-(2-(N-(2,6-二氯苯基)苯甲酰氨基)苯基)酯(6)并水解 2-(2-(N-(2,6-二氯苯基)苯甲酰氨基)苯基)甲基酯 (6)，得到双氯芬酸钠原料药的目标化合物。以苯乙酸甲酯为基准，总产率高达 67%。
• METHOD OF SYNTHESIZING DICLOFENAC SODIUM
  申请人：FUDAN UNIVERSITY

  公开号：US20200055811A1

  公开（公告）日：2020-02-20

  The invention relates to the chemical synthesis of pharmaceutical API, and specifically to a method of synthesizing diclofenac sodium, which is a kind of nonsteroidal anti-inflammatory drug for relieving pain. The method includes: nitrating phenylacetate to prepare o-nitrophenylacetate (2); hydrogenating o-nitrophenylacetate (2) to prepare o-aminophenylacetate (3); amidating an amino group of o-aminophenylacetate (3) to obtain 2-(2-benzoylaminophenyl) acetate (4); 2-(2-benzoylaminophenyl) acetate (4) reacting with thionyl chloride to prepare a chloroimine intermediate, and then condensing the intermediate of chloroimine with 2,6-dichlorophenol using an inorganic base to prepare (E)-methyl-2-(2-((2,6-dichlorophenoxy)(phenyl)methyleneamino) phenyl ester (5); subjecting (E)-methyl-2-(2-((2,6-dichlorophenoxy)(phenyl)methyleneamino) phenyl ester (5) to Chapman rearrangement to afford methyl 2-(2-(N-(2,6-dichlorophenyl)benzoylamino)phenyl) ester (6); and hydrolyzing methyl 2-(2-(N-(2,6-dichlorophenyl)benzoylamino)phenyl) ester (6) to provide the target compound as of diclofenac sodium API. The overall yield is up to 67% based on methyl phenylacetate.
• US4908479A
  申请人：——

  公开号：US4908479A

  公开（公告）日：1990-03-13
• US5001264A
  申请人：——

  公开号：US5001264A

  公开（公告）日：1991-03-19