6-(4-chlorobutoxy)indan-1-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 6-(4-chlorobutoxy)indan-1-one
• 英文别名: 6-(4-chloro butoxy)-indan-1-one；6-(4-chlorobutoxy)-indan-1-one；6-(4-chlorobutoxy)-2,3-dihydro-1H-inden-1-one；6-(4-chlorobutoxy)-2,3-dihydroinden-1-one
• 化学式: C₁₃H₁₅ClO₂
• 分子量: 238.714
• InChiKey: IXYSVHVGZZIRNC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-(4-chlorobutoxy)indan-1-one 、 4-[(benzylmethylamino)methyl]benzaldehyde 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以60%的产率得到2-{4-[(benzylmethylamino)methyl]benzylidene}-6-(4-chlorobutoxy)indan-1-one
  参考文献：
  名称：

  Targeting Alzheimer’s disease: Novel indanone hybrids bearing a pharmacophoric fragment of AP2238

  摘要：

  We report on a series of hybrid compounds structurally derived from donepezil and AP2238. This study was aimed at improving the activities of the reference compounds, donepezil and AP2238, and at broadening the range of activities of new derivatives as, due to the multifactorial nature of AD, molecules that modulate the activity of a single protein target are unable to significantly modify the progression of the disease. In particular, the indanone core from donepezil was linked to the phenyl-N-methylbenzylamino moiety from AP2238, through a double bond that was kept to evaluate the role of a lower flexibility in the biological activities. Moreover, SAR studies were performed to evaluate the role of different substituents in position 5 or 6 of the indanone ring in the interaction with the PAS, introducing also alkyl chains of different lengths carrying different amines at one end. Derivatives 21 and 22 proved to be the most active within the series and their potencies against AChE were in the same order of magnitude of the reference compounds. Compounds 15, 21-22, with a 5-carbon alkyl chain bearing an amino moiety at one end, better contacting the PAS, remarkably improved the inhibition of AChE-induced A beta aggregation with respect to the reference compounds. They also showed activity against self-aggregation of A beta(42) peptide, the most amyloidogenic form of amyloid produced in AD brains, while the reference compounds resulted completely ineffective. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.01.071
• 作为产物：
  描述：

  6-羟基-1-茚酮 、 1,4-二氯丁烷 生成 6-(4-chlorobutoxy)indan-1-one
  参考文献：
  名称：

  Intermediates useful for the preparation of aripiprazole and methods for the preparation of the novel intermediates and aripiprazole

  摘要：

  一种改进的阿立哌唑（1）制备工艺，包括（i）在碱和溶剂的存在下，将6-羟基-1-茚酮（11）与1,4-二卤丁烷（12）在90至110℃的温度范围内反应，形成新的中间体6-（4-卤丁氧基）-茚-1-酮（3），（ii）将新的中间体与1-（2,3-二氯苯基）-哌嗪（9）反应，得到另一个新的中间体6-[4-[4-（2,3-二氯苯基）-1-哌嗪基]丁氧基]-茚-1-酮（2），以及（iii）将所得的新化合物与叠氮化钠反应。本发明还涉及式（2）和（3）的新中间体及其制备工艺。本发明还包括用于制备阿立哌唑的中间化合物。

  公开号：

  US07872132B2
• 作为试剂：
  描述：

  6-羟基-1-茚酮 、 、 potassium carbonate 、 1,4-二氯丁烷 在 四丁基溴化铵 1,4-二氯丁烷 、 水 、 乙酸乙酯 、 6-(4-chlorobutoxy)indan-1-one 作用下， 反应 3.0h， 以gave 29.5 gm of novel 6-(4-CHLORO BUTOXY)-INDAN-1-ONE of the formula (3)的产率得到6-(4-chlorobutoxy)indan-1-one
  参考文献：
  名称：

  Intermediates useful for the preparation of aripiprazole and methods for the preparation of the novel intermediates and aripiprazole

  摘要：

  一种改进的阿立哌唑（1）制备工艺，包括（i）在碱和溶剂存在下，将6-羟基-1-茚酮（11）与1,4-二卤丁烷（12）在90至110℃的温度范围内反应，形成新的中间体6-（4-卤丁氧基）-茚-1-酮（3），（ii）将新的中间体与1-（2,3-二氯苯基）-哌嗪（9）反应，得到另一个新的中间体6- [4- [4-（2,3-二氯苯基）-1-哌嗪基]丁氧基]茚-1-酮（2），以及（iii）将所得的新化合物与偏氮化钠反应。本发明还涉及公式（2）和（3）的新中间体及其制备工艺。本发明还包括用于制备阿立哌唑的中间化合物。

  公开号：

  US07872132B2

文献信息

• [EN] NOVEL INTERMEDIATES USEFUL FOR THE PREPARATION OF ARIPIPRAZOLE AND METHODS FOR THE PREPARATION OF THE NOVEL INTERMEDIATES AND ARIPIPRAZOLE<br/>[FR] NOUVEAUX INTERMEDIAIRES UTILES POUR LA PREPARATION DE L'ARIPIPRAZOLE ET PROCEDES DE PREPARATION DE CES NOUVEAUX INTERMEDIAIRES ET DE L'ARIPIPRAZOLE
  申请人：SUVEN LIFESCIENCES LTD

  公开号：WO2006038220A1

  公开（公告）日：2006-04-13

  The invention disclosed in this application relates to an improved process for the preparation of aripiprazole (1) which comprises (i) Reacting 6-hydroxy-l-indanone (11) with 1,4-dihalobutane (12) in the presence of a base and a solvent at a temperature in the range of 90 to 110 deg C to form the novel intermediate 6-(4-halo butoxy)-indan-l-one (3), (ii) reacting the novel intermediate with 1-(2,3-clichlorophenyl)-piperazine (9) to get another novel intermediate 6-[4-[4-(2,3-dichlorophenyl)-l-piperazinyl] butoxy]-indan-l-one (2) and (iii) Reacting the resulting novel compound with sodium azide. The invention also relates to the novel intermediates of the formulae (2) & (3) and processes for their preparation.

  该申请公开的发明涉及一种改进的阿立哌唑（1）制备工艺，包括（i）在存在碱和溶剂的条件下，将6-羟基-1-茚酮（11）与1,4-二卤丁烷（12）在90至110摄氏度范围内反应，形成新的中间体6-(4-卤丁氧基)-茚-1-酮（3），（ii）将新的中间体与1-(2,3-二氯苯基)-哌嗪（9）反应，得到另一个新的中间体6-[4-[4-(2,3-二氯苯基)-1-哌嗪基]氧基]-茚-1-酮（2），以及（iii）将所得的新化合物与偶氮氮化钠反应。该发明还涉及公式（2）和（3）的新中间体以及其制备工艺。
• METHOD FOR THE PREPARATION OF ARIPIPRAZOLE, AND CORRESPONDING INTERMEDIATES AND THEIR PREPARATION
  申请人：Suven Life Sciences Limited

  公开号：EP1812395B1

  公开（公告）日：2008-05-21
• US7872132B2
  申请人：——

  公开号：US7872132B2

  公开（公告）日：2011-01-18
• Novel intermediates useful for the preparation of aripiprazole and methods for the preparation of the novel intermediates and aripiprazole
  申请人：Chinnapillai Rajendiran

  公开号：US20090203907A1

  公开（公告）日：2009-08-13

  An improved process for the preparation of aripiprazole (1) which comprises (i) reacting 6-hydroxy-l-indanone (11) with 1,4-dihalobutane (12) in the presence of a base and a solvent at a temperature in the range of 90 to 110 deg C. to form the novel intermediate 6-(4-halo butoxy)-indan-1-one (3), (ii) reacting the novel intermediate with 1-(2,3-clichlorophenyl)-piperazine (9) to get another novel intermediate 6-[4-[4-(2,3-dichlorophenyl)-l-piperazinyl]butoxy]-indan-l-one (2) and (iii) reacting the resulting novel compound with sodium azide. The invention also relates to the novel intermediates of the formulae (2) & (3) and processes for their preparation. The invention also includes intermediate compounds useful for the preparation of aripiprazole.

  一种改进的阿立哌唑制备方法，包括（i）在存在碱和溶剂的条件下，将6-羟基-1-茚酮（11）与1,4-二卤丁烷（12）在90至110摄氏度范围内反应，形成新的中间体6-(4-卤丁氧基)-1-茚酮（3），（ii）将新的中间体与1-(2,3-二氯苯基)-哌嗪（9）反应，得到另一个新的中间体6-[4-[4-(2,3-二氯苯基)-1-哌嗪基]氧基]-1-茚酮（2），以及（iii）将所得的新化合物与叠氮化钠反应。该发明还涉及公式（2）和（3）的新中间体及其制备方法。该发明还包括用于阿立哌唑制备的中间体化合物。
• Targeting Alzheimer’s disease: Novel indanone hybrids bearing a pharmacophoric fragment of AP2238
  作者：Stefano Rizzo、Manuela Bartolini、Luisa Ceccarini、Lorna Piazzi、Silvia Gobbi、Andrea Cavalli、Maurizio Recanatini、Vincenza Andrisano、Angela Rampa

  DOI：10.1016/j.bmc.2010.01.071

  日期：2010.3

  We report on a series of hybrid compounds structurally derived from donepezil and AP2238. This study was aimed at improving the activities of the reference compounds, donepezil and AP2238, and at broadening the range of activities of new derivatives as, due to the multifactorial nature of AD, molecules that modulate the activity of a single protein target are unable to significantly modify the progression of the disease. In particular, the indanone core from donepezil was linked to the phenyl-N-methylbenzylamino moiety from AP2238, through a double bond that was kept to evaluate the role of a lower flexibility in the biological activities. Moreover, SAR studies were performed to evaluate the role of different substituents in position 5 or 6 of the indanone ring in the interaction with the PAS, introducing also alkyl chains of different lengths carrying different amines at one end. Derivatives 21 and 22 proved to be the most active within the series and their potencies against AChE were in the same order of magnitude of the reference compounds. Compounds 15, 21-22, with a 5-carbon alkyl chain bearing an amino moiety at one end, better contacting the PAS, remarkably improved the inhibition of AChE-induced A beta aggregation with respect to the reference compounds. They also showed activity against self-aggregation of A beta(42) peptide, the most amyloidogenic form of amyloid produced in AD brains, while the reference compounds resulted completely ineffective. (C) 2010 Elsevier Ltd. All rights reserved.