(R)-N-(2-[4-((R)-2-hydroxy-2-phenylethylamino)phenyl]ethyl)-2-hydroxy-2-(3-formamido-4-benzyloxyphenyl)ethylamine monohydrochloride | 804518-04-5

• 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: (R)-N-(2-[4-((R)-2-hydroxy-2-phenylethylamino)phenyl]ethyl)-2-hydroxy-2-(3-formamido-4-benzyloxyphenyl)ethylamine monohydrochloride
• 英文别名: N-{2-[4-((R)-2-hydroxy-2-phenylethylamino)phenyl]ethyl}-(R)-2-hydroxy-2-(3-formamido-4-benzyloxyphenyl)ethylamine monohydrochloride；N-{2-[4-((R)-2-hydroxy-2-phenylethylamino)phenyl]ethyl}-(R)-2-hydroxy-2-(3-formamido-4-benzyloxyphenyl) ethylamine monohydrochloride；N-[5-[(1R)-1-hydroxy-2-[2-[4-[[(2R)-2-hydroxy-2-phenylethyl]amino]phenyl]ethylamino]ethyl]-2-phenylmethoxyphenyl]formamide;hydrochloride
• CAS: 804518-04-5
• 化学式: C₃₂H₃₅N₃O₄*ClH
• 分子量: 562.109
• InChiKey: BYHNQETZBTVRPX-PNXDLZEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.27
• 重原子数：
  40
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  103
• 氢给体数：
  6
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (R)-N-(2-[4-((R)-2-hydroxy-2-phenylethylamino)phenyl]ethyl)-2-hydroxy-2-(3-formamido-4-benzyloxyphenyl)ethylamine monohydrochloride 在 5%-palladium/activated carbon 氢气 作用下， 以 N-甲基吡咯烷酮 、 水 、 异丙醇 为溶剂， 反应 23.25h， 以88%的产率得到GSK159797
  参考文献：
  名称：

  Crystalline form of beta2 adrenergic receptor agonist

  摘要：

  该发明提供了一种新型的β2肾上腺素能受体激动剂的结晶盐形式。该发明还提供了包含该新型β2肾上腺素能受体激动剂的结晶盐形式的药物组合物，含有该药物组合物的配方，使用该结晶盐治疗与β2肾上腺素能受体活性相关的疾病的方法，以及用于制备这种结晶化合物的有用过程。

  公开号：

  US20040248985A1
• 作为产物：
  描述：

  (R)-2-bromo-1-tert-butyldimethylsilyloxy-1-(3-formamido-4-benzyloxyphenyl)ethane 在 sodium acetate 、 溶剂黄146 、 sodium hydroxide 作用下， 以 醋酸异丙酯 、 水 、 丁酮 为溶剂， 反应 32.5h， 生成 (R)-N-(2-[4-((R)-2-hydroxy-2-phenylethylamino)phenyl]ethyl)-2-hydroxy-2-(3-formamido-4-benzyloxyphenyl)ethylamine monohydrochloride
  参考文献：
  名称：

  Sequential Acetic Acid–Sodium Chloride Treatment to Control Salt Stoichiometry of a Hydrochloride Salt

  摘要：

  The sequential treatment of an intermediate in the synthesis of GSK159797 with a protic acid and sodium chloride was developed to control the stoichiometry of the hydrochloric acid salt of the API. This offered significant advantages over addition of hydrochloric acid, thus avoiding decomposition of an acid-sensitive formamide group. A range of acids were investigated to determine the optimum pK(a) range in which to use the acid. The optimum process, using acetic acid, was performed on >100 kg input scale.

  DOI：

  10.1021/op2003375

文献信息

• [EN] CHEMICAL PROCESS AND NEW CRYSTALLINE FORM<br/>[FR] PROCESSUS CHIMIQUE ET NOUVELLE FORME CRISTALLINE
  申请人：GLAXO GROUP LTD

  公开号：WO2005095328A1

  公开（公告）日：2005-10-13

  The present invention relates to the preparation of a ?2 adrenergic agonist in crystalline salt form. In particular the invention relates to preparation of a crystalline salt of compound (I): in particular a crystalline monohydrochloride salt. The invention also relates to a new crystalline form (polymorph) of the monohydrochloride salt of compound (Ia) and a process for preparing it.

  本发明涉及以结晶盐形式制备β2肾上腺素受体激动剂。具体而言，本发明涉及制备化合物(I)的结晶盐，特别是结晶单盐酸盐。该发明还涉及化合物(Ia)的单盐酸盐的新结晶形式（多形态）以及其制备方法。
• CHEMICAL PROCESS AND NEW CRYSTALLINE FORM
  申请人：CAINE Darren Michael

  公开号：US20100063157A1

  公开（公告）日：2010-03-11

  The present invention relates to the preparation of a β 2 adrenergic agonist in crystalline salt form. In particular the invention relates to preparation of a crystalline salt of compound (I) in particular a crystalline monohydrochloride salt. The invention also relates to a new crystalline form (polymorph) of the monohydrochloride salt of compound (Ia) and a process for preparing it.

  本发明涉及制备β2肾上腺素受体激动剂的晶体盐形式。特别地，本发明涉及制备化合物(I)的晶体盐，特别是晶体单盐酸盐。本发明还涉及化合物(Ia)的单盐酸盐的一种新的晶体形态（多晶形式）及其制备方法。
• CRYSTALLINE FORM OF A BETA2 ADRENERGIC RECEPTOR AGONIST
  申请人：Stergiades Ioanna

  公开号：US20100125150A1

  公开（公告）日：2010-05-20

  The invention provides a novel β 2 adrenergic receptor agonist in crystalline salt form. The invention also provides pharmaceutical compositions comprising the novel β 2 adrenergic receptor agonist in crystalline salt form, formulations containing the pharmaceutical compositions, methods of using the crystalline salt to treat diseases associated with β 2 adrenergic receptor activity, and processes useful for preparing such crystalline compounds.

  本发明提供了一种新型β2肾上腺素能受体激动剂的晶体盐形式。本发明还提供了包含该新型β2肾上腺素能受体激动剂晶体盐的制药组合物、含有该制药组合物的配方、使用晶体盐治疗与β2肾上腺素能受体活性相关的疾病的方法，以及用于制备这种晶体化合物的有用过程。
• Crystalline form of a β2 adrenergic receptor agonist
  申请人：Theravance, Inc.

  公开号：US07772434B2

  公开（公告）日：2010-08-10

  The invention provides a novel β2 adrenergic receptor agonist in crystalline salt form. The invention also provides pharmaceutical compositions comprising the novel β2 adrenergic receptor agonist in crystalline salt form, formulations containing the pharmaceutical compositions, methods of using the crystalline salt to treat diseases associated with β2 adrenergic receptor activity, and processes useful for preparing such crystalline compounds.

  本发明提供了一种新型的β2肾上腺素能受体激动剂晶体盐形式。本发明还提供了包含该新型β2肾上腺素能受体激动剂晶体盐形式的药物组合物、含有药物组合物的制剂、使用晶体盐治疗与β2肾上腺素能受体活性相关的疾病的方法，以及用于制备这种晶体化合物的有用工艺。
• Crystalline form of β2 adrenergic receptor agonist
  申请人：Theravance, Inc.

  公开号：US07557247B2

  公开（公告）日：2009-07-07

  The invention provides a novel β2 adrenergic receptor agonist in crystalline salt form. The invention also provides pharmaceutical compositions comprising the novel β2 adrenergic receptor agonist in crystalline salt form, formulations containing the pharmaceutical compositions, methods of using the crystalline salt to treat diseases associated with β2 adrenergic receptor activity, and processes useful for preparing such crystalline compounds.

  本发明提供了一种新型的β2肾上腺素受体激动剂的结晶盐形式。本发明还提供了包含该新型β2肾上腺素受体激动剂的结晶盐形式的制药组合物，包含该制药组合物的配方，使用该结晶盐治疗与β2肾上腺素受体活性相关的疾病的方法以及用于制备这种结晶化合物的有用工艺。