PROCESS FOR THE SYNTHESIS OF BENZYLIDENE ROSIGLITAZONE BASE
    3.
    发明申请
    PROCESS FOR THE SYNTHESIS OF BENZYLIDENE ROSIGLITAZONE BASE 审中-公开
    苯并噻唑基合成方法

    公开(公告)号:US20090270630A1

    公开(公告)日:2009-10-29

    申请号:US12302127

    申请日:2007-06-21

    IPC分类号: C07D417/12

    CPC分类号: C07D417/12

    摘要: Process for the synthesis of 5-{4-[N-methyl-N-(2-pyridyl)-amino-ethoxy]-benzylidene}-thiazolidine-2,4-dione (INN name: benzylidene-rosiglitazone) of formula (I), which consist of the following steps: Step a) reaction of 2-chloro-pyridine and 2-(N-methylamino)-ethanol Step b) reaction of the obtained compound of formula (III) with 4-fluorobenzaldehyde Step c) reaction of the obtained compound of formula (IV) with thiazolidine-2,4-dione characterized by dissolving 4-{2-[N-methyl-N-(2-pyridyl)amino]-ethanol of formula (III) obtained in Step a) in toluene and using it in Step b) without isolation; reacting the solution of compound of formula (III) in toluene in Step b) with 4-fluorobenzaldehyde in the presence of aqueous alkali hydroxide solution and phase transfer catalyst at 25-50° C.; reacting the solution of the benzaldehyde derivative of formula (IV) obtained in Step b) in toluene in Step c) and isolating the desired product.

    摘要翻译: 合成式(I)的5- {4- [N-甲基-N-(2-吡啶基) - 氨基 - 乙氧基] - 亚苄基} - 噻唑烷-2,4-二酮(INN名称:亚苄基 - 罗格列酮) ),其步骤如下:步骤a)2-氯 - 吡啶和2-(N-甲基氨基) - 乙醇的反应步骤b)将所得到的式(III)化合物与4-氟苯甲醛反应步骤c)反应 所得到的式(Ⅳ)化合物与噻唑烷-2,4-二酮的特征在于将步骤a中获得的式(Ⅳ)的4- {2- [N-甲基-N-(2-吡啶基)氨基] - 乙醇 )并在步骤b)中使用它而不分离; 使步骤b)中式(III)化合物在甲苯中的溶液与4-氟苯甲醛在碱金属氢氧化物水溶液和相转移催化剂存在下,在25-50℃下反应。 使步骤b)中获得的式(IV)的苯甲醛衍生物在步骤c)中的甲苯中的溶液反应,并分离所需产物。