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    • 8. 发明申请
    • NOVEL PROCESS FOR PRODUCTION OF 5--6-CHLORO-1,3-DIHYDRO-2H-INDOL-2-ONE (ZIPRASIDONE)
    • 生产5-6-氯-1,3-二氢-2H-吲哚-2-酮(ZIPRASIDONE)的新方法
    • US20090111988A1
    • 2009-04-30
    • US12298590
    • 2007-05-02
    • Jozsef NeuJozsef TorleySandor Garadnay
    • Jozsef NeuJozsef TorleySandor Garadnay
    • C07D417/14C07D209/34
    • C07D417/12
    • The present invention provides a novel, industrially easily realisable and economically preferable process for production of pure 5-{2-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]-ethyl}-6-chloro-1,3-dihydro-2H-indol-2-one i.e., ziprasidone hydrochloride shown in the reaction scheme (II), (III), (IV), (V) and (VI). According to the invention the intermediate compound 5-(2-bromoethyl)-6-chloro-1,3-dihydro-2H-indol-2-one of Formula (III) is produced from 5-(2-bromoacethyl)-6-chloro-1,3-dihydro-2H-indole-2-one of Formula (IV). The highly pure ziprasidone base of Formula (II) is obtained in the reaction of 3-piperazinyl-1,2-benzisothiazol of Formula (VI) with 5-(2-bromoethyl)-6-chloro-1,3-dihydro-2H-indol-2-one of Formula (III) in an organic solvent or organic solvent mixture.
    • 本发明提供了一种工业上容易实现的和经济上优选的纯5- {2- [4-(1,2-苯并异噻唑-3-基)-1-哌嗪基] - 乙基} -6-氯 - (II),(III),(IV),(V)和(VI)所示的齐拉昔酮盐酸盐,例如1,3-二氢-2H-吲哚-2-酮。 根据本发明,式(III)的中间体化合物5-(2-溴乙基)-6-氯-1,3-二氢-2H-吲哚-2-酮由5-(2-溴代乙基)-6- (IV)的3-氯-1,3-二氢-2H-吲哚-2-酮。 在式(Ⅵ)的3-哌嗪基-1,2-苯并异噻唑与5-(2-溴乙基)-6-氯-1,3-二氢-2H-哒嗪酮的反应中得到式(II)的高纯度齐拉西酮碱 (III)的吲哚-2-酮在有机溶剂或有机溶剂混合物中的溶液。