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 (α = 1.71, Rs = 5.47) in polar organic solvent chromatography, while Chiralpak AS column exhibited remarkable separations (α = 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 × 20 mm i.d.; 10 µm) 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.

中文翻译：

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极性有机溶剂色谱和超临界流体色谱中基于多糖的固定相上6-（4-氨基苯基）-5-甲基-4、5-二氢-3（2H）-哒嗪酮对映异构体的高效制备分离

6-（4-氨基苯基）-5-甲基-4,5-二氢-3（2H）-哒嗪酮是强心剂左西孟旦的关键合成中间体。很少有研究涉及手性固定相在色谱中用于该中间体的对映体分离的用途。这项研究提出了两种在极性有机溶剂色谱和超临界流体中分离（R）（-）-6-（4-氨基苯基）-5-甲基-4,5-二氢-3（2H）-哒嗪酮的有效制备方法等度模式下使用无添加剂的基于多糖的手性固定相和挥发性有机流动相进行色谱分离 在最佳条件下，Chiralcel OJ色谱柱表现出最佳性能（α  = 1.71，Rs 在极性有机溶剂色谱中为5.47），而Chiralpak AS色谱柱在对映体洗脱顺序相反的超临界流体色谱中显示出显着的分离度（α  = 1.81和Rs  = 6.51）。考虑到样品的溶解度，运行时间和溶剂成本，制备方法是在Chiralcel OJ柱和Chiralpak AS柱（250×20 mm内径； 10 µm）上以极性有机模式和超临界流体色谱模式进行的，其中甲醇和CO ₂ /甲醇为流动相。通过利用色谱技术和基于多糖的手性固定相的优势，这项工作为快速经济地制备（R）（−）‐ 6-（4-氨基苯基）‐5‐甲基‐4,5‐二氢‐3（2H）‐哒嗪酮，适用于制药行业。