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).
引文
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