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

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 se-quential continuous flow synthesis combined with a multistage in-line purification process of calcium dibutyryladenosine cyclophosphate was developed. The acylation reaction was completed in a continu-ous coil reactor at 160 degrees C 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. (c) 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.