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    • 9. 发明公开
    • SITAGLIPTIN INTERMEDIATE COMPOUNDS, PREPARATION METHODS AND USES THEREOF
    • SITAGLIPTIN-ZWISCHENPRODUKTVERBINDUNGEN SOWIE HERSTELLUNGSVERFAHREN UND VERWENDUNGENDAFÜR
    • EP2551259A1
    • 2013-01-30
    • EP11758796.4
    • 2011-03-22
    • Zhejiang Jiuzhou Pharmaceutical Co., Ltd.
    • GAO, HongjunLI, Min
    • C07C229/34C07C227/00C07C59/90C07D487/04
    • C07C68/06C07C68/065C07C69/96C07C227/18C07C229/24C07C229/34C07C269/04C07D487/04Y02P20/55C07C271/22
    • The invention relates to Sitagliptin intermediate compounds of formula (f), preparation methods and uses thereof. The compound of formula (f) are prepared by the following steps: compounds of formula (a) are subjected to electrophilic reaction with benzyl halides to form compounds of formula (b), which then react with compounds of formula (i) to form novel compounds of formula (e); Gignard agents formed from 2,4,5-trifluoro bromobenzene and magnesium metal react with compounds of formula (e) to afford compounds of formula (f), which are novel intermediate compounds for the preparation of Sitagliptin intermediates of formula (g). The compound of formula (f) was subjected to reduction by Pd/C, debenzylation, substitution of protecting group to form the compounds of formula (g). The mentioned compounds have the following structures, wherein, R is the protecting group of carboxyl, R 2 is (substituted) hydrocarbyl.
    • 本发明涉及式(f)的西他列汀中间体化合物,其制备方法和用途。 通过以下步骤制备式(f)化合物:将式(a)化合物与苄基卤进行亲电子反应,形成式(b)化合物,然后与式(ⅰ)化合物反应形成新颖的 式(e)化合物; 由2,4,5-三氟溴苯和镁金属形成的Gignard试剂与式(e)化合物反应,得到式(f)化合物,其为制备式(g)的西格列汀中间体的新型中间体化合物。 式(f)的化合物通过Pd / C进行还原,脱苄基,保护基的取代形成式(g)的化合物。 所述化合物具有以下结构,其中R为羧基的保护基,R 2为(取代的)烃基。