A sequential continuous flow synthesis and purification process of calcium dibutyryladenosine cyclophosphate  

作　　者：Liming Cao Maolin Sun Chaoming Liang Lei Yang Yueyue Ma Ruihua Cheng Yanxiong Ke Wei Yu Jinxing Ye 

机构地区：[1]Engineering Research Center of Pharmaceutical Process Chemistry,Ministry of Education,School of Pharmacy,East China University of Science and Technology,Shanghai 200237,China [2]School of Biomedical and Pharmaceutical Sciences,Guangdong University of Technology,Guangzhou 510006,China [3]Shanghai No.1 Biochemical& Pharmaceutical Co.,Ltd.,Shanghai 200080,China

出　　处：《Chinese Chemical Letters》2024年第2期402-406,共5页中国化学快报（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.22278087)。

摘　　要：Calcium dibutyryladenosine cyclophosphate is a widely used cardiovascular drug.The traditional batch synthesis process suffers from long reaction times,tedious operations,and unstable yields.Herein,a sequential continuous flow synthesis combined with a multistage in-line purification process of calcium dibutyryladenosine cyclophosphate was developed.The acylation reaction was completed in a continuous coil reactor at 160℃ in 20 min.And the high toxic solvent pyridine was replaced by acetonitrile.Furthermore,the multistage in-line purification process was integrated into the homemade 3D circular cyclone-type micromixer chip.Combining with the membrane phase separators,the residence time of the purification step was 30 s.The isolated yield of this sequential continuous process was 92%with 99%purity.

关 键 词：Flow chemistry Calcium dibutyryladenosine cyclophosphate Continuous flow synthesis In-line purification 3D circular cyclone-type micromixer chip 

分 类 号：TQ460.3[化学工程—制药化工]