Study on Synthetic Process of Vandetanib
Abstract: Objective: To develop a new synthetic route for Vandetanib. Methods: 4-(2-fluoro-4-bromo-ami- no)-6-methoxy-7-hydroxy-quinazoline (10) was prepared from vanillin (2) via phenolic hydroxyl protection, oxidation, nitration, reduction, cyclization and chlorination to afford 7-benzyloxy-4- chloro-6-methoxy-quinazoline (7), and then (7) coupled with 2-fluoro-4-bromoaniline, followed by debenzylation, yield 33.1%. (1-methylpiperidin-4-yl)methyl 4-methylbenzenesulfonate (14) was prepared from ethyl piperidine-4-carboxylate(11) by Leuckart reaction, reduction and then reacted with p-toluenesulfonyl chloride, yielding 35.1%. In addition, 10 was reacted with 14 to yield the antitumor drug vandetanib (1) with an overall yield of 11.6% (based on compound 2 and 11). Results: The structure of all products was confirmed by IR, 1H-NMR and HR-MS. Conclusion: The improved process has several advantages over those reported procedures, such as brief reac-tion steps, mild conditions, and simple operations.
文章引用: 张志鹏 , 周艳红 , 李冬冬 , 石 伟 , 王亚楼 (2015) 凡德他尼的合成工艺研究。 合成化学研究， 3， 28-34. doi: 10.12677/SSC.2015.32005
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