本文選題：咔噠唑胺　切入點(diǎn)：艱難梭菌感染　出處：《中國(guó)醫(yī)藥工業(yè)雜志》2017年03期 　論文類(lèi)型：期刊論文

【摘要】：1,2-二氟-4-硝基苯與苯甲醇反應(yīng)后,經(jīng)三氯化鐵與水合肼還原硝基得4-芐氧基-3-氟苯胺,經(jīng)酰胺化后,以二(三甲基硅基)氨基鋰為堿經(jīng)環(huán)合反應(yīng)得(5R)-3-(4-芐氧基-3-氟苯基)-5-羥甲基VA唑烷-2-酮,經(jīng)脫保護(hù)、與1-氧-6-氮雜螺[2.5]辛烷-6-羧酸芐酯發(fā)生親核取代反應(yīng)、再經(jīng)催化氫化脫保護(hù)得(5R)-3-[3-氟-4-[(4-羥基哌啶-4-基)甲氧基]-苯基]-5-羥甲基VA唑烷-2-酮,與7-氯-1-環(huán)丙基-6-氟-1,4-二氫-4-氧代-3-喹啉甲酸硼二乙酸鹽復(fù)合物反應(yīng)后經(jīng)酸解制得咔噠唑胺,總收率18.4%(以1,2-二氟-4-硝基苯計(jì))。
[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).

【作者單位】： 中國(guó)醫(yī)藥工業(yè)研究總院上海醫(yī)藥工業(yè)研究院化學(xué)制藥新技術(shù)中心;上海藥物合成工藝過(guò)程工程技術(shù)研究中心;
【分類(lèi)號(hào)】：R914.5
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本文編號(hào)：1617979