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    • 8. 发明公开
    • New intermediates of voriconazole and preparation of voriconazole using the same
    • 新戊酰唑的新中间体及其使用的五唑酮的制备
    • KR20100135349A
    • 2010-12-27
    • KR20090053670
    • 2009-06-17
    • BORYUNG PHARM
    • CHOI OK KYOUNGPARK YONGLEE JOON KWANGKIM JI HANTAN HYUN KWANG
    • C07D401/06A61K31/4196A61K31/506A61K47/40
    • C07D403/10C07D239/38C07D403/06
    • PURPOSE: A novel intermediate of voriconazole and a method for preparing voriconazole using the same are provided to remove irritative and unpleasant smell and to obtain environmentally-friendly voriconazole of high purity and yield. CONSTITUTION: A novel intermediate compound of voriconazole is denoted by chemical formula 2. In chemical formula 2, R is alkyl of C1-C6 or cyclo alkyl of C3-C6. The compound of chemical formula 2 is methyl 2-[6-(1-bromoethyl)-5-fluoropyrimidine-4-yl-sulfanyl]benzoate. A compound of chemical formula 4 is prepared by reacting a compound of chemical formula 2 with 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazole-1-yl)ethanone by Reformatsky reaction. A method for preparing the voriconazole comprises: a step of removing thiol group from thiol derivative under the presence of (2R,3S/2S,3R)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidine-4-yl)-1- (1H-1,2,4-triazole-1-yl)butane-2-orin racemic voriconazole; and a step of performing optical resolution of the racemic voriconaole by R-(-)-camphorsulfonic acid.
    • 目的:提供伏立康唑的新型中间体和使用其的伏立康唑制备方法,以消除刺激性和令人不快的气味,并获得高纯度和高产量的环保型伏立康唑。 构成:化学式2表示伏立康唑的新型中间体化合物。在化学式2中,R为C 1 -C 6烷基或C 3 -C 6环烷基。 化学式2的化合物是2- [6-(1-溴乙基)-5-氟嘧啶-4-基 - 硫基]苯甲酸甲酯。 通过Reformatsky反应使化学式2的化合物与1-(2,4-二氟苯基)-2-(1H-1,2,4-三唑-1-基)乙酮反应制备化学式4的化合物。 一种制备伏立康唑的方法包括:在(2R,3S / 2S,3R)-2-(2,4-二氟苯基)-3-(5-氟嘧啶-4-甲酸)存在下,从硫醇衍生物中除去硫醇基的步骤, (1H-1,2,4-三唑-1-基)丁烷-2-醛,外消旋的伏立康唑; 和通过R - ( - ) - 樟脑磺酸进行外消旋伏立康唑的光学拆分的步骤。