1,1'-(4,4'-(propane-1,3-diylbis(oxy))bis(3-methoxy-4,1-phenylene))diethanone | 19417-90-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1,1'-(4,4'-(propane-1,3-diylbis(oxy))bis(3-methoxy-4,1-phenylene))diethanone
• 英文别名: 1,1'-((Propane-1,3-diylbis(oxy))bis(3-methoxy-4,1-phenylene))diethanone；1-[4-[3-(4-acetyl-2-methoxyphenoxy)propoxy]-3-methoxyphenyl]ethanone
• CAS: 19417-90-4
• 化学式: C₂₁H₂₄O₆
• 分子量: 372.418
• InChiKey: JNWAMMFTNOZAIM-UHFFFAOYSA-N

物化性质

• 熔点：
  121-122 °C(Solv: acetone (67-64-1))
• 沸点：
  527.7±45.0 °C(Predicted)
• 密度：
  1.142±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  香草乙酮 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 1,1'-(4,4'-(propane-1,3-diylbis(oxy))bis(3-methoxy-4,1-phenylene))diethanone
  参考文献：
  名称：

  Improved and Efficient Process for the Production of Highly Pure Iloperidone: A Psychotropic Agent

  摘要：

  The present work describes an improved and highly efficient process for the synthesis of iloperidone (1), an antipsychotic agent, which is free from potential impurities. The synthesis comprises N-alkylation of 1-(4-(3-chloropropoxy)-3-methoxyphenyl)ethanone (4) with 6-fluoro-3-piperidin-4-yl-1,2-benzisoxazole hydrochloride (5) in a mixture of water and heptane as solvent and sodium hydroxide as a base in the presence of tetrabutylammonium bromide as a phase transfer catalyst to yield iloperidone (1) with a yield of around 95% and a purity of 99.80% by HPLC. The present work also describes the optimization details performed to achieve the process attributes responsible for high yield and purity.

  DOI：

  10.1021/op400335p

文献信息

• [EN] AN IMPROVED PROCESS FOR THE PREPARATION OF ILOPERIDONE<br/>[FR] AMÉLIORATION DE PROCÉDÉ D'ÉLABORATION D'ILOPÉRIDONE
  申请人：ORCHID CHEMICALS & PHARM LTD

  公开号：WO2011055188A1

  公开（公告）日：2011-05-12

  The present invention relates to an improved process for the preparation of Iloperidone of formula (I). Further the present invention also provides a novel polymorph of acid addition salts of Iloperidone of formula (I). (I)

  本发明涉及一种改进的制备公式（I）的依洛噻酮的方法。此外，本发明还提供了一种新型的依洛噻酮盐酸盐多晶形式。
• Isolation and Characterization of Process Related Substances of an Antipsychotic Drug: Iloperidone
  作者：Ravendra Babu Kilaru、Chandra Sekhar Kuruva、Venkata Ramana Katla、Naga Raju Chamarthi

  DOI：10.14233/ajchem.2013.14169

  日期：——

  Seven unknown recurring impurities were isolated during the synthesis of Iloperidone process. All six impurities were subsequently synthesized and characterized by FTIR, MS and NMR spectral data. The structures of impurities were confirmed as 1-[4-(3-chloropropoxy)-3-methoxyphenyl]ethanone (4), 1-[4-(3-hydroxypropoxy)-3-methoxy phenyl]ethanone (7), 1-[4-(3-bromopropoxy)-3-methoxyphenyl] ethanone (9), 1,1-[4,4-(propane-1,3- diylbis(oxy))bis(3-methoxy-4,1-phenylene)]diethanone (10), 1-[3-(4-acetyl-2-methoxyphenoxy)-propyl]-4-(6-fluorobenzo[d]isoxazol-3-yl)piperidine-1-oxide (11) and in final other two impurities 1-(4-hydroxy-3-methoxyphenyl)-ethanone (2) and 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole (5). The present work describes the formation, synthesis and characterization of these impurities.

  在伊洛哌酮的合成过程中分离出了七种未知的重复出现的杂质。随后，对所有六种杂质进行了合成，并通过傅立叶变换红外光谱、质谱和核磁共振光谱数据对其进行了表征。杂质的结构被确认为 1-[4-（3-氯丙氧基）-3-甲氧基苯基]乙酮 (4)、1-[4-（3-羟基丙氧基）-3-甲氧基苯基]乙酮 (7)、1-[4-（3-溴丙氧基）-3-甲氧基苯基]乙酮 (9)、1,1-[4,4-（丙烷-1,3-二基双（氧））双（3-甲氧基-4、1-苯基)]二乙酮 (10)、1-[3-(4-乙酰基-2-甲氧基苯氧基)-丙基]-4-(6-氟苯并[d]异恶唑-3-基)哌啶-1-氧化物 (11)，以及最后的另外两种杂质 1-(4-羟基-3-甲氧基苯基)-乙酮 (2) 和 6-氟-3-(哌啶-4-基)苯并[d]异恶唑 (5)。本研究描述了这些杂质的形成、合成和表征。
• [EN] AN IMPROVED PROCESS FOR PREPARING ILOPERIDONE<br/>[FR] PROCÉDÉ AMÉLIORÉ POUR LA PRÉPARATION DE L'ILOPÉRIDONE
  申请人：ALEMBIC PHARMACEUTICALS LTD

  公开号：WO2011154860A1

  公开（公告）日：2011-12-15

  The present invention relates to an improved process for preparing Iloperidone of formula (I).

  本发明涉及一种改进的制备化合物I的伊洛必利的方法。其中化合物I的结构式为：(I)。
• [EN] A PROCESS FOR PREPARATION OF ILOPERIDONE AND AMORPHOUS CO- PRECIPITATE OF ILOPERIDONE WITH PHARMACEUTICALLY ACCEPTABLE EXCIPIENT<br/>[FR] PROCÉDÉ POUR LA PRÉPARATION D'ILOPÉRIDONE ET DE COPRÉCIPITÉ AMORPHE D'ILOPÉRIDONE AVEC UN EXCIPIENT PHARMACEUTIQUEMENT ACCEPTABLE
  申请人：MEGAFINE PHARMA P LTD

  公开号：WO2012123963A2

  公开（公告）日：2012-09-20

  A process for preparation of iloperidone wherein 1-(4-(3-chloropropoxy-3- methoxyphenyl)ethanone is reacted with 6-fluoro-3-piperidin-4-yl-1,2 benzisoxazole hydrochloride in a biphasic solvent system in presence of an inorganic base and a phase transfer catalyst. Further, process for preparation of an amorphous co-precipitate of iloperidone or its acid addition salt along with pharmaceutically acceptable excipient is proposed. Further, the present invention also relates to a co-precipitate of amorphous form of iloperidone along with pharmaceutically acceptable excipients.
• Improved and Efficient Process for the Production of Highly Pure Iloperidone: A Psychotropic Agent
  作者：Pavankumar V. Solanki、Sekhar Babu Uppelli、Bhushan S. Pandit、Vijayavitthal T. Mathad

  DOI：10.1021/op400335p

  日期：2014.2.21

  The present work describes an improved and highly efficient process for the synthesis of iloperidone (1), an antipsychotic agent, which is free from potential impurities. The synthesis comprises N-alkylation of 1-(4-(3-chloropropoxy)-3-methoxyphenyl)ethanone (4) with 6-fluoro-3-piperidin-4-yl-1,2-benzisoxazole hydrochloride (5) in a mixture of water and heptane as solvent and sodium hydroxide as a base in the presence of tetrabutylammonium bromide as a phase transfer catalyst to yield iloperidone (1) with a yield of around 95% and a purity of 99.80% by HPLC. The present work also describes the optimization details performed to achieve the process attributes responsible for high yield and purity.