Palbociclib有关物质的分析及合成

Analysis and synthesis of the related substances of palbociclib

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。

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 were l H NMR and MS.