• 中国中文核心期刊
  • 中国科学引文数据库核心期刊
  • 中国科技核心期刊
  • 中国高校百佳科技期刊
高级检索

Palbociclib有关物质的分析及合成

袁铎, 朱雄, 张仕金, 王铎, 李志裕, 孙丽萍

袁铎, 朱雄, 张仕金, 王铎, 李志裕, 孙丽萍. Palbociclib有关物质的分析及合成[J]. 中国药科大学学报, 2015, 46(6): 696-699. DOI: 10.11665/j.issn.1000-5048.20150610
引用本文: 袁铎, 朱雄, 张仕金, 王铎, 李志裕, 孙丽萍. Palbociclib有关物质的分析及合成[J]. 中国药科大学学报, 2015, 46(6): 696-699. DOI: 10.11665/j.issn.1000-5048.20150610
YUAN Duo, ZHU Xiong, ZHANG Shijin, WANG Duo, LI Zhiyu, SUN Liping. Analysis and synthesis of the related substances of palbociclib[J]. Journal of China Pharmaceutical University, 2015, 46(6): 696-699. DOI: 10.11665/j.issn.1000-5048.20150610
Citation: YUAN Duo, ZHU Xiong, ZHANG Shijin, WANG Duo, LI Zhiyu, SUN Liping. Analysis and synthesis of the related substances of palbociclib[J]. Journal of China Pharmaceutical University, 2015, 46(6): 696-699. DOI: 10.11665/j.issn.1000-5048.20150610

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.
  • [1] Toogood PL,Harvey PJ,Repine JT,et al.Discovery of a potent and selective inhibitor of cyclin-dependent kinase 4/6[J].J Med Chem,2005,48(7):2388-2406.
    [2] Mayer EL.Targeting breast cancer with CDK inhibitors[J].Curr Oncol Rep,2015,17(5):1-5.
    [3] Erdman DT,Flamme CM,Nelson JD,et al.Preparation of 2-(pyridin-2-ylamino)-pyrido-[2,3-d]pyrimidin-7-ones:WO,2008032157[P].2007-08-27.
    [4] Moon J,Lee S.Palladium catalyzed-dehalogenation of aryl chlorides and bromides using phosphite ligands[J].J Organomet Chem,2009,694(3):473-477.
    [5] Murray PM,Bower JF,Cox DK,et al.A robust first-pass protocol for the Heck-Mizoroki reaction[J].Org Process Res Dev,2013,17(3):397-405.
计量
  • 文章访问数:  2076
  • HTML全文浏览量:  3
  • PDF下载量:  2012
  • 被引次数: 0
出版历程
  • 刊出日期:  2015-12-24

目录

    /

    返回文章
    返回
    x 关闭 永久关闭