利扎曲普坦EP杂质A | 887001-08-3

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 利扎曲普坦EP杂质A
• 英文名称: 3-[[3-[2-(N,N-dimethylamino)ethyl]-2-[[3-[2-(N,N-dimethylamino)ethyl]-1H-indol-5-yl]methyl]-1H-indol-5-yl]methyl]-1H-1,2,4-triazole
• 英文别名: 3-[2-(N,N-dimethylamino)ethyl-2-[[3-[2-(N,N-dimethylamino)ethyl]-1H-indol-5-yl]methyl]-1H-indol-5-yl]methyl-1H-1,2,4-triazole；3-[2-(dimethylamino)ethyl]-2-[[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]methyl]-5-(1H-1,2,4-triazol-1-ylmethyl)indole；Rizatriptan dimer；2-[5-[[3-[2-(dimethylamino)ethyl]-5-(1,2,4-triazol-1-ylmethyl)-1H-indol-2-yl]methyl]-1H-indol-3-yl]-N,N-dimethylethanamine
• CAS: 887001-08-3
• 化学式: C₂₈H₃₅N₇
• 分子量: 469.633
• InChiKey: WMKBUQPKAAJBHZ-UHFFFAOYSA-N

物化性质

• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  68.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  利扎曲坦 在 盐酸 作用下， 反应 4.0h， 以13.7%的产率得到利扎曲普坦EP杂质A
  参考文献：
  名称：

  Synthesis and Characterization of Potential Impurities of the Antimigraine Drug, Rizatriptan Benzoate

  摘要：

  Rizatriptan benzoate is a recently developed antimigraine drug used for the treatment of migraines and severe headaches. In the synthesis of rizatriptan benzoate in bulk,various impurities are formed. The present work details the development of a simple and novel process for the preparation of hydrazone impurity (6), rizatriptan N-oxide (7), rizatriptan dimer (9), desmethyl rizatriptan (13), 5-(1H-1,2,4-triazol-1-yl-methyl)-1H-indole-3-ethanamine hydrochloride (14), N-methyl rizatriptan oxalate (15), and impurities.

  DOI：

  10.1080/00397910701798051

文献信息

• NOVEL PROCESS
  申请人：Gore Vinayak G.

  公开号：US20100256208A1

  公开（公告）日：2010-10-07

  The present invention relates to a novel process for the preparation of rizatriptan and its pharmaceutically acceptable salts. It provides a novel process for the preparation of highly pure rizatriptan, which can be easily adopted for commercial production with a high degree of consistency in purity and yield. Subsequently the rizatriptan base prepared can be converted into any suitable pharmaceutically acceptable salt, such as the oxalate, succinate or benzoate salt, for dosage form preparation. The present invention also provides a composition comprising rizatriptan useful for the manufacture of a medicament for the treatment or prevention of migraine.

  本发明涉及一种制备瑞佐托品及其药用可接受盐类的新工艺。它提供了一种制备高纯度瑞佐托品的工艺，该工艺可以轻松地用于商业生产，且在纯度和收率方面具有高度一致性。随后，所制备的瑞佐托品碱可以转化为任何合适的药用可接受盐，例如草酸盐、琥珀酸盐或苯甲酸盐，用于制备剂型。本发明还提供了一种包含瑞佐托品的组合物，该组合物用于制造用于治疗或预防偏头痛的药物。
• Process for the Large Scale Production of Rizatriptan Benzoate
  申请人：Ray Purna Chandra

  公开号：US20090062550A1

  公开（公告）日：2009-03-05

  The present invention provides a method for preparing pure Rizatriptan benzoate having purity more than 99.5% and dimer impurity less than 0.1% comprises, i) Condensation of 1,2,4-Triazole with 4-Nitro benzyl bromide to yield 1-(4-nitrophenyl)methyl-1,2,4-triazole ii) Reducing the 1-(4-nitrophenyl)methyl-1,2,4-triazole to give 1-(4-aminophenyl)methyl-1,2,4-triazole iii) Converting 1-(4-aminophenyl)methyl-1,2,4-triazole to 1-(4-hydrazinophenyl)methyl-1,2,4-triazole hydrochloride iv) Condensing the hydrazine derivative with 4-(Dimethylamino) butanal diethylacetal to get Rizatriptan and v) Salification of Rizatriptan to Rizatriptan benzoate.

  本发明提供了一种制备纯度大于99.5％且二聚体杂质小于0.1％的纯利扎替普坦苯甲酸盐的方法，包括：i）将1,2,4-三唑与4-硝基苄基溴缩合，得到1-(4-硝基苯基)甲基-1,2,4-三唑；ii）还原1-(4-硝基苯基)甲基-1,2,4-三唑，得到1-(4-氨基苯基)甲基-1,2,4-三唑；iii）将1-(4-氨基苯基)甲基-1,2,4-三唑转化为1-(4-肼基苯基)甲基-1,2,4-三唑盐酸盐；iv）将肼衍生物与4-(二甲氨基)丁醛二乙基缩酮缩合，得到利扎替普坦；v）将利扎替普坦盐化为利扎替普坦苯甲酸盐。
• WO2006/53116
  申请人：——

  公开号：——

  公开（公告）日：——
• WO2006/137083
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] IMPROVED PROCESS FOR THE PREPARATION OF RIZATRIPTAN BENZOATE<br/>[FR] PROCEDE DE PREPARATION AMELIORE DE RIZATRIPTAN BENZOATE
  申请人：NATCO PHARMA LTD

  公开号：WO2006137083A1

  公开（公告）日：2006-12-28

  [EN] Present invention discloses an improved and commercially viable process for the preparation of rizatriptan benzoate of formula (I). According to the present process the hydrazone intermediate derived from the phenylhydrazine of formula- (III) and 4- dimethylaminobutyraldehyde diethyl acetal is gradually heated to 60-70 °C in aqueous sulfuric acid medium and maintained for 3-4hr to get rizatriptan with less dimeric impurity of formula (X). The resultant rizatriptan is isolated and converted into the pharmaceutically acceptable benzoate salt. Present process produces less percentage of dimeric (less than 3 %) or polymeric impurities compared to the prior art process and more yield of rizatriptan. Rizatriptan benzoate produced according to the present process has more than 99.5 % purity with less than 0.1% dimeric impurity of formula (X) by HPLC. Rizatriptan benzoate is useful for the treatment of migraine.
  [FR] La présente invention concerne un procédé de préparation, amélioré et viable d'un point de vue commercial, de rizatriptan benzoate représenté par la formule (I). Selon ledit procédé, l'intermédiaire d'hydrazone dérivé de la phénylhydrazine représentée par la formule (III) et 4-diméthylaminobutyraldéhyde diéthyl acétal est graduellement chauffé à 60-70 °C dans un milieu aqueux d'acide sulfurique et maintenu pendant 3-4 heures afin d'obtenir un rizatriptan avec moins d'impuretés dimériques de formule (X). Le rizatriptan obtenu est isolé et converti en un sel de benzoate acceptable d'un point de vue pharmaceutique. Le procédé de l'invention permet d'obtenir un pourcentage inférieur d'impuretés dimériques (moins de 3%) ou polymériques par rapport au procédé de l'état de la technique et un rendement supérieur de rizatriptan. Le rizatriptan benzoate obtenu selon la présente invention présente une pureté supérieure à 99,5 % avec moins de 0,1 % d'impuretés dimériques de formule (X) par HPLC. Le rizatriptan benzoate est utilisé dans le traitement de la migraine.