3-(2-bromo-4,5-dimethoxyphenyl)pentan-2-one | 546104-93-2

• 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: 3-(2-bromo-4,5-dimethoxyphenyl)pentan-2-one
• 英文别名: 3-(2-bromo-4,5-dimethoxy-phenyl)-pentan-2-one
• CAS: 546104-93-2
• 化学式: C₁₃H₁₇BrO₃
• 分子量: 301.18
• InChiKey: BLWGLUGFLOPVHX-UHFFFAOYSA-N

物化性质

• 沸点：
  353.3±42.0 °C(Predicted)
• 密度：
  1.288±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(2-bromo-4,5-dimethoxyphenyl)pentan-2-one 在 盐酸 、 正己基锂 、 对甲苯磺酸 、 溶剂黄146 作用下， 以 正己烷 、 水 、 甲苯 为溶剂， 反应 29.0h， 生成 托非索泮
  参考文献：
  名称：

  New, Lithiation-Based Synthesis of Tofisopam, a 2,3-Benzodiazepine Type Anxiolytic Drug

  摘要：

  The classical, widely-used synthesis of the anxiolytic drug tofisopam applies chromium(VI) oxide reagent for the synthesis of the diketone key intermediate. The chromium salts formed in the course of the reaction are strongly toxic compounds. In order to reduce the reagents contributing to the pollution of the environment, an alternative manufacturing process has been elaborated at our laboratory. Starting compound (3,4-dimethoxyphenyl)acetone was transformed to the ethylene ketal of (2-bromo-4,5-dimethoxyphenyl)acetone. Bromine-lithium exchange and introduction of a 3,4-dimethoxybenzoyl moiety resulted in the new key intermediate. Removal of the ketal protecting group and ring closure with hydrazine was carried out in one pot affording drug substance tofisopam.

  DOI：

  10.3987/com-13-s(s)15
• 作为产物：
  描述：

  3,4-二甲氧基苯丙酮 在 N-溴代丁二酰亚胺(NBS) 、 苄基三甲基氢氧化铵 、 sodium hydroxide 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 9.25h， 生成 3-(2-bromo-4,5-dimethoxyphenyl)pentan-2-one
  参考文献：
  名称：

  New, Lithiation-Based Synthesis of Tofisopam, a 2,3-Benzodiazepine Type Anxiolytic Drug

  摘要：

  The classical, widely-used synthesis of the anxiolytic drug tofisopam applies chromium(VI) oxide reagent for the synthesis of the diketone key intermediate. The chromium salts formed in the course of the reaction are strongly toxic compounds. In order to reduce the reagents contributing to the pollution of the environment, an alternative manufacturing process has been elaborated at our laboratory. Starting compound (3,4-dimethoxyphenyl)acetone was transformed to the ethylene ketal of (2-bromo-4,5-dimethoxyphenyl)acetone. Bromine-lithium exchange and introduction of a 3,4-dimethoxybenzoyl moiety resulted in the new key intermediate. Removal of the ketal protecting group and ring closure with hydrazine was carried out in one pot affording drug substance tofisopam.

  DOI：

  10.3987/com-13-s(s)15

文献信息

• [EN] PROCESS FOR THE PREPARATION OF 3-[2-(3,4-DIMETHOXY-BENZOYL)-4,5-DIMETHOXY-PHENYL]-PENTAN-2-ONE<br/>[FR] PROCEDE DE PREPARATION DE 3-[2-(3,4-DIMETHOXY-BENZOYL)-4,5-DIMETHOXY-PHENYL]-PENTAN-2-ONE
  申请人：EGYT GYOGYSZERVEGYESZETI GYAR

  公开号：WO2004054951A1

  公开（公告）日：2004-07-01

  The invention relates to a process for the preparation of 3-[2-(3,4-dimethoxy-benzoyl)-4,5-dimethoxy-phenyl]-pentan-2-one of the Formula (I) starting from a compound of the general Formula (II) (wherein R1 and R2 each stands for C1-4-alkyl or together form C2-6-alkylene).

  该发明涉及一种从一般式（II）化合物（其中R1和R2分别代表C1-4-烷基或一起形成C2-6-烷基）出发制备式（I）的3-[2-(3,4-二甲氧基苯甲酰基)-4,5-二甲氧基苯基]-戊-2-酮的过程。
• [EN] PROCESS FOR THE PREPARATION OF 3-[2-(3,4-DIMETHOXYBENZOYL)-4,5- DIMETHOXYPHENYL] -PENTAN-2-ONE<br/>[FR] PROCEDE DE PREPARATION DE 3-[2-(3,4-DIMETHOXYBENZOYL)-4,5- DIMETHOXYPHENYL] -PENTAN-2-ONE
  申请人：EGYT GYOGYSZERVEGYESZETI GYAR

  公开号：WO2004054952A1

  公开（公告）日：2004-07-01

  The invention relates to a new process for the preparation of 3-[2-(3,4-dimethoxybenzoyl)-4,5- dimethoxyphenyl]-pentan-2-one of the formula (I), starting from a compound of the general formula (II) and subjecting the thus-obtained compound of the general formula (IV) to hydrolysis. The compound of the formula (I) is a pharmaceutical intermediate, which can be used for the preparation of an anxiolytic, namely tofisopam (INN).

  本发明涉及一种制备3-[2-(3,4-二甲氧基苯甲酰)-4,5-二甲氧基苯基]-戊酮(I)的新工艺，其从一般式(II)的化合物开始，将得到的一般式(IV)的化合物进行水解。式(I)的化合物是一种药物中间体，可用于制备一种抗焦虑药物，即托吡酮（INN）。
• PROCESS FOR THE PREPARATION OF TOFISOPAM AND NEW INTERMEDIATES
  申请人：EGIS GYOGYSZERGYAR RT.

  公开号：EP1465879A2

  公开（公告）日：2004-10-13
• PROCESS FOR THE PREPARATION OF 3- 2-(3,4-DIMETHOXY-BENZOYL)- 4,5-DIMETHOXY-PHENYL -PENTAN-2-ONE
  申请人：EGIS GYOGYSZERGYAR RT.

  公开号：EP1575890A1

  公开（公告）日：2005-09-21
• [EN] PROCESS FOR THE PREPARATION OF TOFISOPAM AND NEW INTERMEDIATES<br/>[FR] PROCESSUS DE PREPARATION DE TOFISOPAM ET DE NOUVEAUX INTERMEDIAIRES
  申请人：EGYT GYOGYSZERVEGYESZETI GYAR

  公开号：WO2003050092A2

  公开（公告）日：2003-06-19

  The invention relates to a new process for the preparation of 1-(3,4-dimethoxy-phenyl)-4-methyl-5-ethyl-7,8-dimethoxy-5H-2,3-benzodizepine of Formula (I) which comprises reacting a compound of general Formula (II) (wherein R1 and R2 independently each stands for C1-4-alkyl or together form C2-6-alkylene) with hydrazine or a hydrate or salt thereof formed with an inorganic or organic acid. 1-(3,4-dimethoxy-phenyl)-4-methyl-5-ethyl-7,8-dimethoxy-5H-2,3-benzodiazepine of the Formula I is a known anxiolytic agent. The invention also relates to new intermediates and a process for the preparation thereof.