摘要
目的改进吡贝地尔的合成工艺。方法以邻苯二酚和二氯甲烷为原料经环和反应合成胡椒环,胡椒环与多聚甲醛经Blanc氯甲基化反应合成重要中间体胡椒基氯(3);以哌嗪和二氯嘧啶为原料经氮烷基化反应合成重要中间体1-(2-嘧啶基)哌嗪(4);3和4经氮烷基化反应得到目标化合物。结果与结论目标化合物的结构经1H-NMR、GC-MS谱确证,总收率为44.2%,改进后的工艺操作简便,成本低廉,有利于工业化生产。
Aim To improve the procedure of piribedil.Methods The intermediate piperonyl chloride(3) was obtained through cyclization and Blanc reaction by using o-dihydroxybenzene and dichloromethane as starting material.Another intermediate 1-(2-pyrimidyl)piperazine(4) was obtained through N-alkylation by using 2-chloropyrimidine and piperazine as starting material.After N-alkylation between intermediates(3) and(4),piribedil could be obtained.Results and conclusion The structure of piribedil was confirmed by 1H-NMR,GC-MS.The overall yield is 44.2%.The improved process has the advantage of low cost and it is also suitable for industrial production.
出处
《中国药物化学杂志》
CAS
CSCD
2010年第4期285-286,297,共3页
Chinese Journal of Medicinal Chemistry
关键词
吡贝地尔
多巴胺能激动剂
帕金森病
工艺改进
piribedil
dopaminergic agonist
Parkinson′s disease
process improvement