Palbociclib有关物质的分析及合成

Analysis and synthesis of the related substances of palbociclib

摘要: 为控制palbociclib药品质量，从palbociclib原料药中分离并鉴定了3个有关物质:8-环戊基-5-甲基-2-(5-哌嗪-1-基-吡啶-2-基氨基)-8H-吡啶并［2，3-d］嘧啶-7-酮( A )、8-环戊基-5-甲基-6-乙烯基-2-(5-哌嗪-1-基-吡啶-2-基氨基)-8H-吡啶并［2，3-d］嘧啶-7-酮( B )和4-［6-(6-乙酰基-8-环戊基-5-甲基-7-氧代-7，8-二氢吡啶并［2，3-d］嘧啶-2-基氨基)-吡啶-3-基］-哌嗪-1-羧酸叔丁酯( C )。分析了这些有关物质产生的原因并进行了设计合成，其结构经质谱、核磁共振氢谱确证。

Abstract: To strengthen the quality control of palbociclib, three related substances were separated from the bulk drug. These substances were identified as 8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido ［2, 3-d］ pyrimidin-7(8H)-one( A ), 8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridine-2-yl)amino)-6-vinylpyrido ［2, 3-d］ pyrimidin-7(8H)-one( B ), tert-butyl4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7, 8-dihydropyrido ［2, 3-d］ pyrimidin-2-yl)amino)pyridin-3-yl)piperazi-ne-1-carboxylate( C ). Based on the structures of the impurities, the possible routes to them were discussed, and their structures were elucidated by ¹H NMR and MS.