摘要
目的:合成抗肿瘤药物呋喹替尼的关键中间体。方法:以4-(苄氧基)-2-羟基苯甲醛和2-溴丙酸乙酯为起始原料,经过亲核取代、水解、溴代、插碳和脱苄基等有机化学反应,成功合成了抗肿瘤药物呋喹替尼的关键中间体,并通过^(13)C NMR、1H NMR等方法对目标化合物及中间体结构进行了表征和确认。结果与结论:此合成路线中,我们与已报道的方法相比优化了反应条件,提高了收率,操作上更加安全环保。该中间体的合成不仅为呋喹替尼的后续合成提供了重要的原料保障,也为相关药物的研究和开发提供了有力支持。新合成路线的各步骤产物多以沉淀或萃取的方式纯化,操作简便、收率高、绿色环保,总收率为53.2%。该合成路线简单易行,适合工业化生产。
Objective:To synthesize the key intermediate of the anti-tumor drug Fruquintinib.Methods:Using 4-(benzyloxy)-2-hydroxybenzaldehyde and ethyl 2-bromopropionate as starting materials,the key intermediate of the anti-tumor drug Fruquintinib was successfully synthesized via organic chemical reactions including nucleophilic substitution,hydrolysis,bromination,carbon insertion,and debenzylation.The structures of the target compound and intermediates were characterized and confirmed by techniques such as ^(13)C NMR and ^(1)H NMR.Results and Conclusions:Compared with previously reported methods,the reaction conditions in this synthetic route were optimized,which improved the yield and enhanced operational safety and environmental friendliness.The synthesis of this intermediate not only provides an important raw material guarantee for the subsequent synthesis of Fruquintinib but also offers strong support for the research and development of related drugs.The products of each step in the new synthetic route are mostly purified by precipitation or extraction,which is characterized by simple operation,high yield,and environmental friendliness,with an overall yield of 53.2%.This synthetic route is simple and feasible,making it suitable for industrial production.
作者
季家乐
夏明涛
李帅
苗光新
JI Jiale;XIA Mingtao;LI Shuai;MIAO Guangxin(Institute of Traditional Chinese Medicine,Chengde Medical University,Chengde Hebei 067000)
出处
《天津化工》
2026年第1期33-36,共4页
Tianjin Chemical Industry
关键词
呋喹替尼
合成
抑制剂
工艺优化
fruquintinib
synthesis
VEGFR inhibitor
process optimization
