摘要
为了提高抗肿瘤药阿帕鲁胺(Apalutamide)的中间体Boc-1-氨基环丁烷羧酸的合成效率,设计了一条合成路线。以氰基乙酸乙酯和1,3-二溴丙烷为起始原料,经过关环、双水解和霍夫曼重排,最后经Boc酸酐保护氨基,高效合成了Boc-1-氨基环丁烷羧酸(5)。产物与中间体结构经MS(ESI)和^(1)H NMR确证。该合成路线经优化后,具有可控性强、产率高和操作简单等特点,总产率可达46%,适合工业化大规模生产,且有利于其作为中间体在阿帕鲁胺药物研发中的应用,同时对三元、四元和五元环化合物的合成提供了思路借鉴。
To improve the synthesis efficiency of the intermediate Boc-1-aminocyclobutanecarboxylic acid of the anti-tumor drug apalutamide,we designed a synthesis route.With ethyl cyanoacetate and 1,3-dibromopropane as the starting materials,Boc-1-aminocyclobutanecarboxylic acid was efficiently synthesized through four steps including ring closure substitution,double hydrolysis,Hoffman rearrangement and N-protection with Boc.The results of LCMS and 1H NMR analysis indicate the successful synthesis of Boc-1-aminocyclobutanecarboxylic acid(5).This synthesis route has many advantages,such as strong controllability,high yield and simple operation,which is conducive to the scale-up production of Boc-1-aminocyclobutanecarboxylic acid and its application as an intermediate in apalutamide drugs search and development.It has reference significance for the synthesis of ternary,quaternary,and pentacyclic compounds.
作者
游奇璋
曹小冬
YOU Qizhang;CAO Xiaodong(College of Chemistry and Chemical Engineering,Zhejiang Sci-Tech University,Hangzhou 310018,China)
出处
《合成化学》
2025年第3期205-210,共6页
Chinese Journal of Synthetic Chemistry
关键词
阿帕鲁胺
Boc-1-氨基环丁烷羧酸
关环取代
霍夫曼重排
合成优化
apalutamide
boc-1-aminocyclobutanecarboxylic acid
ring-closure reaction
hofmann rearrangement
synthesis optimization
