Process for the preparation of high-purity 1-[3'-(chloro)-phenyl]-4-[methyl]-7,8-di-[methoxy]-5H-2,3-benzo diazepine
    2.
    发明公开
    Process for the preparation of high-purity 1-[3'-(chloro)-phenyl]-4-[methyl]-7,8-di-[methoxy]-5H-2,3-benzo diazepine 失效
    Verfahren zur Herstellung von 1- [3' - (氯) - 苯基] -4- [甲基] -7,8-二 - [甲氧基] -5H-2,3-苯并二氮杂环庚烷。

    公开(公告)号:EP0512419A1

    公开(公告)日:1992-11-11

    申请号:EP92107402.7

    申请日:1992-05-04

    IPC分类号: C07D243/02

    CPC分类号: C07D243/02

    摘要: According to an aspect of the invention there is provided for a process for the preparation of 1-[3'-(chloro)-phenyl]-4-[methyl[-7,8-di-[methoxy]-5 H -2,3-benzodiazepine of formula

    in high purity and in a quality suitable for pharmaceutical purposes by reacting 1 mole of 2-(acetonyl)-3'-(chloro)-4,5-di-(methoxy)-benzophenone of formula

    with 3 to 7 moles of hydrazine hydrate in an organic solvent or in a mixture of organic solvents, at a temperature from 15°C to 85°C, and subsequently recrystallizing the crude product from an aliphatic alcohol containing 1 to 5 carbon atom(s), which is carried out in the absence of air oxygen.
    According to another aspect of the invention there is provided for a process for preparing purified 1-[3'-(chloro)-phenyl]-4-[methyl]-7,8-di-[methoxy]-5 H -2,3-benzodiazepine of formula I from such containing contamination(s) of formula

    and/or particularly formula

    in which first the contaminated 1-[3'-(chloro)-phenyl]-4-[methyl]-7,8-di-[methoxy]-5 H -2,3-benzodiazepine of formula I is treated with a solvent and an alkali hydroxide, alkali carbonate or alkali alcoholate and thereafter the compound 1-[3'-(chloro)-phenyl]-4-[methyl]-7,8-di-[methoxy]-5 H -2,3-benzodiazepine of formula I is crystallized from the obtained solution.

    摘要翻译: 根据本发明的一个方面,提供了制备1- [3' - (氯) - 苯基] -4- [甲基[-7,8-二 - [甲氧基] -5H- 具有高纯度和适合于药物目的的式的3-苯并二氮杂,其通过使1摩尔式(I)的2-(丙酮基)-3' - (氯)-4,5-二(甲氧基) - 二苯甲酮 < CHEM>在有机溶剂或有机溶剂的混合物中,在15℃〜85℃的温度下,使用3〜7摩尔水合肼,然后从含有1〜5个碳原子的脂肪醇中重结晶粗产物 原子,其在不存在空气氧的情况下进行。 根据本发明的另一方面,提供了制备纯化的1- [3' - (氯) - 苯基] -4- [甲基] -7,8-二 - [甲氧基] -5H- 苯并二氮杂从这样的含有式CHEM的污染物和/或特别是式CHEM>中首先将被污染的1- [3' - (氯) - 苯基] -4- [甲基] -7 ,式I的8-二 - [甲氧基] -5H-2,3-苯并二氮杂用溶剂和碱金属氢氧化物,碱金属碳酸盐或碱性醇化物处理,然后将化合物1- [3' - (氯) - 苯基] 从所得溶液中结晶式I的4- [甲基] -7,8-二 - [甲氧基] -5H-2,3-苯并二氮杂。