(1R)-1-[8-(benzyloxy)-2-oxo-1,2-dihydroquinolin-5-yl]-2-[(5,6-diethyl-2,3-dihydro-1H-inden-2-yl)amino]ethyl benzoate | 753498-24-7

• 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: (1R)-1-[8-(benzyloxy)-2-oxo-1,2-dihydroquinolin-5-yl]-2-[(5,6-diethyl-2,3-dihydro-1H-inden-2-yl)amino]ethyl benzoate
• 英文别名: [(1R)-2-[(5,6-diethyl-2,3-dihydro-1H-inden-2-yl)amino]-1-(2-oxo-8-phenylmethoxy-1H-quinolin-5-yl)ethyl] benzoate
• CAS: 753498-24-7
• 化学式: C₃₈H₃₈N₂O₄
• 分子量: 586.7
• InChiKey: SRPUDSTYMYHTLE-DHUJRADRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  44
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  76.7
• 氢给体数：
  2
• 氢受体数：
  5

文献信息

• [EN] METHODS FOR THE PREPARATION OF INDACATEROL AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF<br/>[FR] PROCÉDÉS DE PRÉPARATION D'INDACATÉROL ET DE SELS PHARMACEUTIQUEMENT ACCEPTABLES DE CELUI-CI
  申请人：CRYSTAL PHARMA SAU

  公开号：WO2014044566A1

  公开（公告）日：2014-03-27

  The invention relates to new and improved processes for the preparation of Indacaterol and pharmaceutically acceptable salts thereof as well as intermediates for the preparation of Indacaterol. The new process avoids the use of the epoxide compound known in the art and the impurities associated therewith and results in a higher yield.

  该发明涉及一种新的改进工艺，用于制备Indacaterol及其药用可接受的盐，以及用于制备Indacaterol的中间体。这种新工艺避免了在现有技术中已知的环氧化合物的使用以及相关的杂质，并且产率更高。
• [EN] A PROCESS FOR THE PREPARATION OF 5-(HALOACETYL)-8-(SUBSTITUTED OXY)-(1H)-QUINOLIN-2-ONES<br/>[FR] PROCEDE DE PREPARATION DE 5-(HALOACETYL)-8-(SUBSTITUE OXY)-(1H)-QUINOLIN-2-ONES
  申请人：NOVARTIS AG

  公开号：WO2004087668A1

  公开（公告）日：2004-10-14

  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-(lH)-quinolin-2-one with an acylating agent to form 8-acetoxy-(lH)-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-(lH)-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.

  该发明涉及一种制备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) 与酰化试剂和Lewis酸反应，将（a）8-羟基-(1H)-喹啉-2-酮形成5-乙酰基-8-羟基-(1H)-喹啉-2-酮；或（b）8-羟基-(1H)-喹啉-2-酮与酰化试剂反应形成8-乙酰氧基-(1H)-喹啉-2-酮，并在原位处理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（c）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) 在碱和溶剂的存在下，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) 在溶剂的存在下，将5-乙酰基-8-取代氧基-(1H)-喹啉-2-酮与卤代试剂反应，形成5-(α-卤代乙酰基)-8-取代氧基-(1H)-喹啉-2-酮。
• [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<br/>[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
  申请人：NOVARTIS AG

  公开号：WO2004076422A1

  公开（公告）日：2004-09-10

  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-(1 H)-quinolin-2-one (V); 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 (VI) without isolating the free base of 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-(1H)-quinolin-2-one. Formula (A); (V): R = a protecting group, (VI): R = H.

  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。
• 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。