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    • 9. 发明公开
    • METHOD FOR PRODUCING ZALTOPROFEN AND DERIVATIVE THEREOF
    • VERFAHREN ZUR HERSTELLUNG VON ZALTOPROFEN UND DERIVAT DAVON
    • EP2842952A1
    • 2015-03-04
    • EP13780982.8
    • 2013-04-24
    • Nippon Chemiphar Co., Ltd.
    • TENDO, Atsushi
    • C07D337/14A61K31/38A61P29/00
    • C07D337/14
    • The present invention relates to a method for preparing zaltoprofen or a zaltoprofen derivative by a Friedel-Crafts reaction type intramolecular cyclization reaction in an industrial scale at an industrially acceptable yield and a purity sufficient for use as an active ingredient of medicaments in a simple and economical manner, without generating a detectable amount of impurities such as dimmers, by using polyphosphoric acid in an amount of 6.5 times or less of amount of a starting material compound before cyclization. More specifically, the present invention relates to such a method for preparing zaltoprofen or a zaltoprofen derivative as mentioned above, which comprises cyclizing a starting material compound before cyclization by an intramolecular cyclization reaction thereof in the presence of one or more kinds of organic solvents selected from the group consisting of 1,1,2-trichloroethene, methylcyclohexane, cyclohexane, n-heptane and the like.
    • 本发明涉及一种以工业规模以工业上可接受的产率和纯度足以用作药物活性成分的纯粹和经济的方法,通过Friedel-Crafts反应型分子内环化反应制备扎洛芬或扎洛芬衍生物的方法 的方式,通过在环化前使用原料化合物的量的6.5倍以下的多磷酸,不产生可检测量的杂质如二聚体。 更具体地,本发明涉及如上所述的制备扎洛芬或扎洛芬衍生物的方法,其包括在环化前的原料化合物通过其分子内环化反应在选自以下的一种或多种有机溶剂存在下使原料化合物环化: 由1,1,2-三氯乙烯,甲基环己烷,环己烷,正庚烷等组成的组。