tert-butyl 4-(4-amino-5-fluoropyrimidin-2-yloxy)piperidine-1-carboxylate | 1033840-03-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl 4-(4-amino-5-fluoropyrimidin-2-yloxy)piperidine-1-carboxylate
• 英文别名: Tert-butyl 4-(4-amino-5-fluoropyrimidin-2-yl)oxypiperidine-1-carboxylate
• CAS: 1033840-03-7
• 化学式: C₁₄H₂₁FN₄O₃
• 分子量: 312.344
• InChiKey: BKFGBWYWDIMIOB-UHFFFAOYSA-N

物化性质

• 熔点：
  166 °C
• 沸点：
  459.8±55.0 °C(Predicted)
• 密度：
  1.263±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  90.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(4-amino-5-fluoropyrimidin-2-yloxy)piperidine-1-carboxylate 在 盐酸 作用下， 以 异丙醇 为溶剂， 反应 1.0h， 以92%的产率得到5-fluoro-2-(piperidin-4-yloxy)pyrimidin-4-amine hydrochloride
  参考文献：
  名称：

  Practical Synthesis of 5-Fluoro-2-(piperidin-4-yloxy)pyrimidin-4-amine, a Key Intermediate in the Preparation of Potent Deoxycytidine Kinase Inhibitors

  摘要：

  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.

  DOI：

  10.1021/op900060u
• 作为产物：
  描述：

  tert-butyl 4-((4-(di(prop-1-en-1-yl)amino)-5-fluoropyrimidin-2-yl)oxy)piperidine-1-carboxylate 在 盐酸 、 水 作用下， 以 二甲基亚砜 、 叔丁醇 为溶剂， 反应 12.0h， 以138 g的产率得到tert-butyl 4-(4-amino-5-fluoropyrimidin-2-yloxy)piperidine-1-carboxylate
  参考文献：
  名称：

  Practical Synthesis of 5-Fluoro-2-(piperidin-4-yloxy)pyrimidin-4-amine, a Key Intermediate in the Preparation of Potent Deoxycytidine Kinase Inhibitors

  摘要：

  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.

  DOI：

  10.1021/op900060u

文献信息

• O-LINKED PYRIMIDIN-4-AMINE-BASED COMPOUNDS, COMPOSITIONS COMPRISING THEM, AND METHODS OF THEIR USE TO TREAT CANCER
  申请人：Augeri David J.

  公开号：US20080146571A1

  公开（公告）日：2008-06-19

  O-linked pyrimidin-4-amine-based compounds, pharmaceutical compositions comprising them, and methods of their use are described. Particular compounds of the invention are of formula I:

  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：
• US8093246B2
  申请人：——

  公开号：US8093246B2

  公开（公告）日：2012-01-10
• 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.