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Cobimetinib消旋体的合成

Synthesis of Cobimetinib Racemate
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摘要 以3-羟基氮杂环丁烷盐酸盐为原料,经Cbz保护和氧化反应制得1-苄氧羰基氮杂环丁烷-3-酮(3);3与N-亚硝基哌啶发生亲核反应后与2,3-二氟-(2-氟-4-碘氨基)苯甲酸发生缩合反应,最后经氯化氢脱亚硝基和碱化合成了Cobimetinib消旋体,其结构经1H NMR和HR-MS(ESI)确证。 Benzyl 3-oxoazetidine-1-carboxylate（ 3） was obtained by Cbz protection and oxidation,using 3-hydroxyazetidine hydrochloride as raw material. Racemate of Cobimetinib was synthesized by nucleophilic reaction with N-nitrosopiperidine,then followed by a condensation reaction with 3,4-difluoro-2-[（ 2-fluoro-4-iodophenyl） amino]benzoic acid and finally deprotection with hydrochloric acid gas and alkalization. The structure was confirmed by1 H NMR and HR-MS（ ESI）.
作者 熊卫华 安然 曹东坡 马美 郭春 XIONG Wei-hua;AN Ran;CAO Dong-po;MA Mei;GUO Chun(College of Pharmaceutical Engineering,Shenyang Pharmaceutial University,Shenyang 110016,China)
机构地区 沈阳药科大学制药工程学院
出处 《合成化学》 CAS CSCD 北大核心 2018年第6期458-461,共4页 Chinese Journal of Synthetic Chemistry
基金 国家基础科学人才培养基金资助项目(J1103606)
关键词 卡比替尼 药物合成 N-亚硝基哌啶 消旋体 Cobimetinib drug synthesis （nitrosopiperidine racemate
分类号 R914.5 [医药卫生—药物化学] O626.3 [理学—有机化学]
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合成化学
2018年 第6期

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