5-fluoro-2-(piperidin-4-yloxy)pyrimidin-4-amine hydrochloride | 1202005-99-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 5-fluoro-2-(piperidin-4-yloxy)pyrimidin-4-amine hydrochloride
• CAS: 1202005-99-9
• 化学式: C₉H₁₃FN₄O*ClH
• 分子量: 248.688
• InChiKey: UTUBFVDGMPDYJU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.75
• 重原子数：
  16.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  73.06
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  4,5,6-三氟嘧啶 、 5-fluoro-2-(piperidin-4-yloxy)pyrimidin-4-amine hydrochloride 在 N,N-二异丙基乙胺 作用下， 以 正丁醇 为溶剂， 反应 1.0h， 以83%的产率得到2-[1-(5,6-Difluoropyrimidin-4-yl)piperidin-4-yl]oxy-5-fluoropyrimidin-4-amine
  参考文献：
  名称：

  O-LINKED PYRIMIDIN-4-AMINE-BASED COMPOUNDS, COMPOSITIONS COMPRISING THEM, AND METHODS OF THEIR USE TO TREAT CANCER

  摘要：

  O-连接的嘧啶-4-胺基化合物，包括它们的药物组合物以及它们的使用方法。本发明的特定化合物为公式I：

  公开号：

  US20080146571A1
• 作为产物：
  描述：

  1-butyl-3-methylimidazolium Tetrafluoroborate 在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 18.0h， 生成 5-fluoro-2-(piperidin-4-yloxy)pyrimidin-4-amine hydrochloride
  参考文献：
  名称：

  O-LINKED PYRIMIDIN-4-AMINE-BASED COMPOUNDS, COMPOSITIONS COMPRISING THEM, AND METHODS OF THEIR USE TO TREAT CANCER

  摘要：

  O-连接的嘧啶-4-胺基化合物，包括它们的药物组合物以及它们的使用方法。本发明的特定化合物为公式I：

  公开号：

  US20080146571A1

文献信息

• Practical Synthesis of 5-Fluoro-2-(piperidin-4-yloxy)pyrimidin-4-amine, a Key Intermediate in the Preparation of Potent Deoxycytidine Kinase Inhibitors
  作者：Haiming Zhang、Jie Yan、Ramanaiah C. Kanamarlapudi、Wenxue Wu、Philip Keyes

  DOI：10.1021/op900060u

  日期：2009.7.17

  A practical synthesis of 5-fluoro-2-(piperidin-4-yloxy)pyrimidin-4-amine, a key intermediate in the preparation of a new class of potent deoxycytidine kinase (dCK) inhibitors, is described. The commercially available 2,4-dichloro-5-fluoropyrimidine (12) is converted in four telescoped steps to tert-butyl 4-(4-amino-5- fluoropyrimidin-2-yloxy)piperidine-1-carboxylate (6a) which upon deprotection gives 5-fluoro-2-(piperidin-4-yloxy)pyrimidin-4-amine dihydrochloride (1a) in about 68% overall yield. This process proved to be an economical alternative to a Mitsunobu-based synthesis.
• 5-Fluorocytosine derivatives as inhibitors of deoxycytidine kinase
  作者：James E. Tarver、Theodore C. Jessop、Marianne Carlsen、David J. Augeri、Qinghong Fu、Jason P. Healy、Alexander Heim-Riether、Amy Xu、Jerry A. Taylor、Min Shen、Philip E. Keyes、S. David Kimball、Xuan-Chuan Yu、Maricar Miranda、Qingyun Liu、Jonathan C. Swaffield、Amr Nouraldeen、Alan G.E. Wilson、Rick Finch、Kanchan Jhaver、Ann Marie DiGeorge Foushee、Steve Anderson、Tamas Oravecz、Kenneth G. Carson

  DOI：10.1016/j.bmcl.2009.09.082

  日期：2009.12

  A series of potent piperidine-linked cytosine derivatives were prepared as inhibitors of deoxycytidine kinase (dCK). Compound 9h was discovered to be a potent inhibitor of dCK and shows a good combination of cellular potency and pharmacokinetic parameters. Compound 9h blocks the incorporation of radiolabeled cytosine into mouse T-cells in vitro, as well as in vivo in mice following a T-cell challenge. (C) 2009 Published by Elsevier Ltd.