文献类型：期刊文献

英文题名：Efficient preparative separation of 6-(4-aminophenyl)-5-methyl-4, 5-dihydro-3(2H)-pyridazinone enantiomers on polysaccharide-based stationary phases in polar organic solvent chromatography and supercritical fluid chromatography

作者：Cheng, Lingping[1];Cai, Jianfeng[1];Fu, Qing[1];Ke, Yanxiong[1]

机构：[1]East China Univ Sci & Technol, Engn Res Ctr Pharmaceut Proc Chem, Shanghai 200237, Peoples R China

年份：2019

卷号：42

期号：15

起止页码：2482

外文期刊名：JOURNAL OF SEPARATION SCIENCE

收录：;EI(收录号：20192607094293);WOS:【SCI-EXPANDED(收录号:WOS:000478080800002)】；

基金：This work was supported by the National Natural Science Foundation of China (Grant No. 21375038).

语种：英文

外文关键词：chiral separation; enantiomers; levosimendan; polar organic solvent chromatography; supercritical fluid chromatography

摘要：6-(4-Aminophenyl)-5-methyl-4,5-dihydro-3(2H)-pyridazinone is a key synthetic intermediate for cardiotonic agent levosimendan. Very few studies address the use of chiral stationary phases in chromatography for the enantioseparation of this intermediate. This study presents two efficient preparative methods for the isolation of (R)(-)-6-(4-aminophenyl)-5-methyl-4,5-dihydro-3(2H)-pyridazinone in polar organic solvent chromatography and supercritical fluid chromatography using polysaccharide-based chiral stationary phases and volatile organic mobile phases without additives in isocratic mode. Under optimum conditions, Chiralcel OJ column showed the best performance (alpha = 1.71, Rs = 5.47) in polar organic solvent chromatography, while Chiralpak AS column exhibited remarkable separations (alpha = 1.81 and Rs = 6.51) in supercritical fluid chromatography with an opposite enantiomer elution order. Considering the sample solubility, runtime and solvent cost, the preparations were carried out on Chiralcel OJ column and Chiralpak AS column (250 x 20 mm i.d.; 10 mu m) in polar organic mode and supercritical fluid chromatography mode with methanol and CO2/methanol as mobile phases, respectively. By utilizing the advantages of chromatographic techniques and polysaccharide-based chiral stationary phases, this work provides two methods for the fast and economic preparation of (R)(-)-6-(4-aminophenyl)-5-methyl-4,5-dihydro-3(2H)-pyridazinone, which are suitable for the pharmaceutical industry.