5-[(R)-2-(5,6-diethylindan-2-ylamino)-1-hydroxyethyl]-8-hydroxy-1H-quinolin-2-one benzoate | 753498-41-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 5-[(R)-2-(5,6-diethylindan-2-ylamino)-1-hydroxyethyl]-8-hydroxy-1H-quinolin-2-one benzoate
• 英文别名: (5,6-diethyl-2,3-dihydro-1H-inden-2-yl)-[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]azanium;benzoate
• CAS: 753498-41-8
• 化学式: C₇H₆O₂*C₂₄H₂₈N₂O₃
• 分子量: 514.621
• InChiKey: PCUKZDXOSUEHIU-FTBISJDPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.53
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  119
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-[(R)-2-(5,6-diethylindan-2-ylamino)-1-hydroxyethyl]-8-hydroxy-1H-quinolin-2-one benzoate 、 顺丁烯二酸 以 乙醇 为溶剂， 生成 马来酸茚达特罗
  参考文献：
  名称：

  [EN] PROCESS FOR PREPARING 5-'(R)-2-(5,6-DIETHYL-INDIAN-2-YLAMINO)-1-HYDROXY-ETHYL!-8-HYDROXY-(1H)-QUINOLIN-2-ONE SALT, USEFUL AS AN ADRENOCEPTOR AGONIST
  [FR] PROCEDE DE PREPARATION D'UN SEL DE 5-[(R)-2-(5,6-DIETHYL-INDIAN-2-YLAMINO)-1-HYDROXY-ETHYL]-8-HYDROXY-(1H)-QUINOLIN-2-ONE, UTILISE EN TANT QU'AGONISTE D'UN ADRENO-RECEPTEUR

  摘要：

  一种制备5-[(R)-2-(5,6-二乙基-2-基-茚烷基氨基)-1-羟基乙基]-8-羟基-(1H)-喹啉-2-酮盐的方法。该方法包括形成5-[(R)-2-(5,6-二乙基-2-基-茚烷基氨基)-1-羟基乙基]-8-取代氧基-(1H)-喹啉-2-酮（V）的酸盐，然后在不分离5-[(R)-2-(5,6-二乙基-2-基-茚烷基氨基)-1-羟基乙基]-8-羟基-(1H)-喹啉-2-酮自由碱的情况下将酸盐转化为5-[(R)-2-(5,6-二乙基-2-基-茚烷基氨基)-1-羟基乙基]-8-羟基-(1H)-喹啉-2-酮（VI）的盐。公式（A）；（V）：R = 保护基，（VI）：R = H。

  公开号：

  WO2004076422A1
• 作为产物：
  描述：

  8-(phenylmethoxy)-5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-(1H)-quinolin-2-one benzoate 在 5%-palladium/activated carbon 氢气 作用下， 以 溶剂黄146 为溶剂， 反应 8.0h， 生成 5-[(R)-2-(5,6-diethylindan-2-ylamino)-1-hydroxyethyl]-8-hydroxy-1H-quinolin-2-one benzoate
  参考文献：
  名称：

  [EN] PROCESS FOR PREPARING 5-'(R)-2-(5,6-DIETHYL-INDIAN-2-YLAMINO)-1-HYDROXY-ETHYL!-8-HYDROXY-(1H)-QUINOLIN-2-ONE SALT, USEFUL AS AN ADRENOCEPTOR AGONIST
  [FR] PROCEDE DE PREPARATION D'UN SEL DE 5-[(R)-2-(5,6-DIETHYL-INDIAN-2-YLAMINO)-1-HYDROXY-ETHYL]-8-HYDROXY-(1H)-QUINOLIN-2-ONE, UTILISE EN TANT QU'AGONISTE D'UN ADRENO-RECEPTEUR

  摘要：

  一种制备5-[(R)-2-(5,6-二乙基-2-基-茚烷基氨基)-1-羟基乙基]-8-羟基-(1H)-喹啉-2-酮盐的方法。该方法包括形成5-[(R)-2-(5,6-二乙基-2-基-茚烷基氨基)-1-羟基乙基]-8-取代氧基-(1H)-喹啉-2-酮（V）的酸盐，然后在不分离5-[(R)-2-(5,6-二乙基-2-基-茚烷基氨基)-1-羟基乙基]-8-羟基-(1H)-喹啉-2-酮自由碱的情况下将酸盐转化为5-[(R)-2-(5,6-二乙基-2-基-茚烷基氨基)-1-羟基乙基]-8-羟基-(1H)-喹啉-2-酮（VI）的盐。公式（A）；（V）：R = 保护基，（VI）：R = H。

  公开号：

  WO2004076422A1

文献信息

• Process for the preparation of 5-(halocetyl)-8-(substituted oxy)-(1h)-quinolin-2-ones
  申请人：Lohse Olivier

  公开号：US20060189653A1

  公开（公告）日：2006-08-24

  The invention relates to a process for preparing 5-(α-haloacetyl)-8-substituted oxy-(1H)-quinolin-2-ones. The process involves (i) reacting (a) 8-hydroxy-(1H)-quinolin-2-one with an acylating agent and a Lewis acid to form 5-acetyl-8-hydroxy-(1H)-quinolin-2-one; or (b) 8-hydroxy-(1H)-quinolin-2-one with an acylating agent to form 8-acetoxy-(1H)-quinolin-2-one, and treating, in-situ, the 8-acetoxy-(1H)-quinolin-2-one with a Lewis acid to form 5-acetyl-8-hydroxy-(1H)-quinolin-2-one; or (c) 8-acetoxy-(1H)-quinolin-2-one with a Lewis acid to form 5-acetyl-8-hydroxy-(1H)-quinolin-2-one; (ii) reacting the 5-acetyl-8-hydroxy-(1H)-quinolin-2-one prepared in Step (i) with a compound having the Formula RL in the presence of a base and a solvent to form 5-acetyl-8-substituted oxy-(1H)-quinolin-2-one, wherein R is a protecting group and L is a leaving group; and (iii) reacting the 5-acetyl-8-substituted oxy-(1H)-quinolin-2-one with a halogenating agent in the presence of a solvent to form a 5-(α-haloacetyl)-8-substituted oxy-(1H)-quinolin-2-one.

  本发明涉及一种制备5-(α-卤代乙酰基)-8-取代氧基-(1H)-喹啉-2-酮的过程。该过程包括：(i)将8-羟基-(1H)-喹啉-2-酮与酰化剂和Lewis酸反应，形成5-乙酰基-8-羟基-(1H)-喹啉-2-酮；或将8-羟基-(1H)-喹啉-2-酮与酰化剂反应，形成8-乙酰氧基-(1H)-喹啉-2-酮，然后在原位处理8-乙酰氧基-(1H)-喹啉-2-酮与Lewis酸反应，形成5-乙酰基-8-羟基-(1H)-喹啉-2-酮；或将8-乙酰氧基-(1H)-喹啉-2-酮与Lewis酸反应，形成5-乙酰基-8-羟基-(1H)-喹啉-2-酮；(ii)将步骤(i)中制备的5-乙酰基-8-羟基-(1H)-喹啉-2-酮与具有RL式的化合物在碱和溶剂的存在下反应，形成5-乙酰基-8-取代氧基-(1H)-喹啉-2-酮，其中R是保护基，L是离去基；(iii)将5-乙酰基-8-取代氧基-(1H)-喹啉-2-酮与卤代试剂在溶剂的存在下反应，形成5-(α-卤代乙酰基)-8-取代氧基-(1H)-喹啉-2-酮。
• Process for preparing 5-'(r)-2-(5,6-diethyl-indian-2-ylamino)-1-hydroxy-ethyl!-8-hydroxy-(1h)-quinolin-2-one salt, useful as an andrenoceptor agonist
  申请人：Lohse Olivier

  公开号：US20060252794A1

  公开（公告）日：2006-11-09

  A process for preparing 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-(1H)-quinolin-2-one salt. The process involves forming an acid salt of 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-substituted oxy-(1H)-quinolin-2-one; and converting the acid salt to a salt of 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-(1H)-quinolin-2-one without isolating the free base of 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-(1H)-quinolin-2-one.

  一种制备5-[(R)-2-(5,6-二乙基-2-基-茚-2-基氨基)-1-羟乙基]-8-羟基-(1H)-喹啉-2-酮盐的方法。该方法涉及形成5-[(R)-2-(5,6-二乙基-2-基-茚-2-基氨基)-1-羟乙基]-8-取代氧基-(1H)-喹啉-2-酮的酸盐；并将酸盐转化为5-[(R)-2-(5,6-二乙基-2-基-茚-2-基氨基)-1-羟乙基]-8-羟基-(1H)-喹啉-2-酮的盐，而无需分离5-[(R)-2-(5,6-二乙基-2-基-茚-2-基氨基)-1-羟乙基]-8-羟基-(1H)-喹啉-2-酮的自由碱。
• ENANTIOSELEKTIVE PREPARATION OF QUINOLINE DERIVATIVE
  申请人：Lohse Olivier

  公开号：US20090054653A1

  公开（公告）日：2009-02-26

  A process for preparing 8-substituted oxy-5-((R)-2-halo-1-hydroxy-ethyl)-(1H)-quinolin-2-ones or acceptable solvates thereof. The process involves reacting a 5-(α-haloacetyl)-8-substituted oxy-(1H)-quinolin-2-one with a reducing agent in the presence of a chiral agent and a base to form a 8-(substituted oxy)-5-((R)-2-halo-1-hydroxy-ethyl)-(1H)-quinolin-2-one, said chiral agent having a formula I or II wherein M, L, X, R 1 , R 2 and R 3 have the meanings as indicated in the specification.

  一种制备8-取代氧基-5-((R)-2-卤代-1-羟基-乙基)-(1H)-喹啉-2-酮或其可接受的溶剂化物的方法。该方法涉及将5-(α-卤代乙酰基)-8-取代氧基-(1H)-喹啉-2-酮与还原剂在手性试剂和碱的存在下反应，以形成8-(取代氧基)-5-((R)-2-卤代-1-羟基-乙基)-(1H)-喹啉-2-酮，所述手性试剂具有公式I或II，其中M、L、X、R1、R2和R3如说明书所示。
• ENANTIOSELECTIVE PREPARATION OF QUINOLINE DERIVATIVES
  申请人：Lohse Olivier

  公开号：US20120220775A1

  公开（公告）日：2012-08-30

  A process for preparing 8-substituted oxy-5-((R)-2-halo-1-hydroxy-ethyl)-(1H)-quinolin-2-ones or acceptable solvates thereof. The process involves reacting a 5-(α-haloacetyl)-8-substituted oxy-(1H)-quinolin-2-one with a reducing agent in the presence of a chiral agent and a base to form a 8-(substituted oxy)-5-((R)-2-halo-1-hydroxy-ethyl)-(1H)-quinolin-2-one, said chiral agent having a formula I or II wherein M, L, X, R 1 , R 2 and R 3 have the meanings as indicated in the specification.

  一种制备8-取代氧基-5-((R)-2-卤代-1-羟基-乙基)-(1H)-喹啉-2-酮或其可接受的溶剂化物的方法。该方法涉及将5-(α-卤代酰基)-8-取代氧基-(1H)-喹啉-2-酮与还原剂在手性剂和碱的存在下反应，以形成8-(取代氧基)-5-((R)-2-卤代-1-羟基-乙基)-(1H)-喹啉-2-酮，所述手性剂具有I或II式，其中M，L，X，R1，R2和R3的含义如说明书中所示。
• PROCESS FOR PREPARING 5-[(R)-2-(5,6-DIETHYL-INDAN-2-YLAMINO)-1-HYDROXY-ETHYL]-8-HYDROXY-(1H)-QUINOLIN-2-ONE SALTS, USEFUL AS ADRENOCEPTOR AGONISTS
  申请人：NOVARTIS AG

  公开号：EP1599450B1

  公开（公告）日：2009-06-24