(6S)-N-(2-amino-4,5,6,7-tetrahydrobenzothiazole-6-yl)-2-nitro-N-propylbenzenesulfonamide | 1046124-81-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (6S)-N-(2-amino-4,5,6,7-tetrahydrobenzothiazole-6-yl)-2-nitro-N-propylbenzenesulfonamide
• 英文别名: (6S)-N-(2-amino-4,5,6,7-tetrahydrobenzo[d]thiazole-6-yl)-2-nitro-N-propylbenzenesulfonamide；N-[(6S)-2-Amino-4,5,6,7-tetrahydro-6-benzothiazolyl]-2-nitro-N-propylbenzenesulfonamide；N-[(6S)-2-amino-4,5,6,7-tetrahydro-1,3-benzothiazol-6-yl]-2-nitro-N-propylbenzenesulfonamide
• CAS: 1046124-81-5
• 化学式: C₁₆H₂₀N₄O₄S₂
• 分子量: 396.491
• InChiKey: IVXJQMOFZIWNHV-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  159
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (6S)-N-(2-amino-4,5,6,7-tetrahydrobenzothiazole-6-yl)-2-nitro-N-propylbenzenesulfonamide 、 巯基乙酸 在 lithium hydroxide 作用下， 以 乙醇 为溶剂， 反应 4.75h， 生成 (2-硝基苯基)硫代]乙酸 、 普拉克索
  参考文献：
  名称：

  A Novel Scalable Synthesis of Pramipexole

  摘要：

  Pramipexole is a dopamine D-2 subfamily receptor agonist that is used for the treatment of Parkinson's disease. We report here on the successful application of the Fukuyama alkylation protocol to the development of a novel and scalable process for synthesis of pramipexole and its pharmaceutically acceptable salts. The synthesis consists of converting the crucial intermediate (S)-2,6-diamino-4,5,6,7-tetrahydrobenzothiazole to (6S)-N-(2-amino-4,5,6,7-tetrahydrobenzothiazole-6-y1)-2-nitrobenzenesulfonamide, which is in turn monoalkylated to (6S)-N-(2-amino-4,5,6,7-tetrahydrobenzothiazole-6-y1)-2-nitro-N-propylbenzenesulfonamide. Deprotection of the latter yields pramipexole base, which is finally converted to a crude pramipexole dihydrochloride monohydrate with a yield of over 50% over four steps. The process allows for the telescoping of the final three steps, has high conversion rates of intermediates, offers ease of purification, and preserves high optical purity throughout all of the stages.

  DOI：

  10.1021/op1000989
• 作为产物：
  描述：

  (S)-2,6-二氨基-4,5,6,7-四氢苯并噻唑 在 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 12.0h， 生成 (6S)-N-(2-amino-4,5,6,7-tetrahydrobenzothiazole-6-yl)-2-nitro-N-propylbenzenesulfonamide
  参考文献：
  名称：

  A Novel Scalable Synthesis of Pramipexole

  摘要：

  Pramipexole is a dopamine D-2 subfamily receptor agonist that is used for the treatment of Parkinson's disease. We report here on the successful application of the Fukuyama alkylation protocol to the development of a novel and scalable process for synthesis of pramipexole and its pharmaceutically acceptable salts. The synthesis consists of converting the crucial intermediate (S)-2,6-diamino-4,5,6,7-tetrahydrobenzothiazole to (6S)-N-(2-amino-4,5,6,7-tetrahydrobenzothiazole-6-y1)-2-nitrobenzenesulfonamide, which is in turn monoalkylated to (6S)-N-(2-amino-4,5,6,7-tetrahydrobenzothiazole-6-y1)-2-nitro-N-propylbenzenesulfonamide. Deprotection of the latter yields pramipexole base, which is finally converted to a crude pramipexole dihydrochloride monohydrate with a yield of over 50% over four steps. The process allows for the telescoping of the final three steps, has high conversion rates of intermediates, offers ease of purification, and preserves high optical purity throughout all of the stages.

  DOI：

  10.1021/op1000989

文献信息

• WO2008/97203
  申请人：——

  公开号：——

  公开（公告）日：——
• NOVEL PROCESS FOR SYNTHESIS OF PRAMIPEXOLE AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS
  申请人：KRKA, tovarna zdravil, d.d., Novo mesto

  公开号：EP2125761B1

  公开（公告）日：2017-03-01
• [EN] NOVEL PROCESS FOR SYNTHESIS OF PRAMIPEXOLE AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS<br/>[FR] NOUVEAU PROCÉDÉ POUR UNE SYNTHÈSE DE PRAMIPEXOLE ET DE SES SELS ACCEPTABLES DU POINT DE VUE PHARMACEUTIQUE
  申请人：KRKA TOVARNA ZDRAVIL D D NOVO

  公开号：WO2008097203A1

  公开（公告）日：2008-08-14

  [EN] The present invention relates to a novel process for synthesis of pramipexole, shown in the synthesis scheme. Formulae (I), (II), (III), (IV), (V) and (VI).
  [FR] La présente invention concerne un nouveau procédé pour une synthèse de pramipexole, représenté dans le schéma de synthèse. Formules (I), (II), (III), (IV), (V) et (VI).
• A Novel Scalable Synthesis of Pramipexole
  作者：Matej Živec、Borut Anžič、Stanislav Gobec

  DOI：10.1021/op1000989

  日期：2010.9.17

  Pramipexole is a dopamine D-2 subfamily receptor agonist that is used for the treatment of Parkinson's disease. We report here on the successful application of the Fukuyama alkylation protocol to the development of a novel and scalable process for synthesis of pramipexole and its pharmaceutically acceptable salts. The synthesis consists of converting the crucial intermediate (S)-2,6-diamino-4,5,6,7-tetrahydrobenzothiazole to (6S)-N-(2-amino-4,5,6,7-tetrahydrobenzothiazole-6-y1)-2-nitrobenzenesulfonamide, which is in turn monoalkylated to (6S)-N-(2-amino-4,5,6,7-tetrahydrobenzothiazole-6-y1)-2-nitro-N-propylbenzenesulfonamide. Deprotection of the latter yields pramipexole base, which is finally converted to a crude pramipexole dihydrochloride monohydrate with a yield of over 50% over four steps. The process allows for the telescoping of the final three steps, has high conversion rates of intermediates, offers ease of purification, and preserves high optical purity throughout all of the stages.