咔哒唑胺的合成

发布时间：2018-03-16 02:33

  本文选题：咔哒唑胺　切入点：艰难梭菌感染　出处：《中国医药工业杂志》2017年03期 　论文类型：期刊论文

【摘要】：1,2-二氟-4-硝基苯与苯甲醇反应后,经三氯化铁与水合肼还原硝基得4-苄氧基-3-氟苯胺,经酰胺化后,以二(三甲基硅基)氨基锂为碱经环合反应得(5R)-3-(4-苄氧基-3-氟苯基)-5-羟甲基VA唑烷-2-酮,经脱保护、与1-氧-6-氮杂螺[2.5]辛烷-6-羧酸苄酯发生亲核取代反应、再经催化氢化脱保护得(5R)-3-[3-氟-4-[(4-羟基哌啶-4-基)甲氧基]-苯基]-5-羟甲基VA唑烷-2-酮,与7-氯-1-环丙基-6-氟-1,4-二氢-4-氧代-3-喹啉甲酸硼二乙酸盐复合物反应后经酸解制得咔哒唑胺,总收率18.4%(以1,2-二氟-4-硝基苯计)。
[Abstract]:The reaction of 1,2- two fluoro -4- nitrobenzene and benzoic alcohol by ferric chloride, and hydrazine hydrate reduction of nitro 4- benzyloxyl -3- Fluoroaniline, via amidation, with two (three trimethylsilyl amino) lithium as alkali by cyclization reaction to (5R) -3- (4- benzyloxyl -3- difluorophenyl) -5- hydroxymethyl VA oxazolidine -2- ketone, after deprotection, nucleophilic substitution and 1- oxygen -6- aza spiro [2.5] octane -6- carboxylic acid benzyl ester by catalytic hydrogenation of protection (5R) -3-[3- fluoro -4-[(4- hydroxy piperidine based -4- methoxy phenyl) -]-5- hydroxymethyl VA oxazolidine -2- ketone, and 7- chloro -1- cyclopropyl -6- fluoro -1,4- two -4- hydrogen oxygen generation -3- quinoline acid boron two acetic acid salt complex reaction after acid hydrolysis to prepare temozolomide cracking, the total yield is 18.4% (based on 1,2- two -4- fluoride nitrobenzene meter).

【作者单位】： 中国医药工业研究总院上海医药工业研究院化学制药新技术中心;上海药物合成工艺过程工程技术研究中心;
【分类号】：R914.5
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本文编号：1617979