[(R)-6-oxo-4-(2,4,5-trifluorophenyl)piperidin-3-yl]carbamic acid tert-butyl ester | 888321-35-5

• 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: [(R)-6-oxo-4-(2,4,5-trifluorophenyl)piperidin-3-yl]carbamic acid tert-butyl ester
• 英文别名: tert-butyl [(3R,4R)-6-oxo-4-(2,4,5-trifluorophenyl)piperidin-3-yl]carbamate；tert-butyl [(3R,4R)-6-oxo-4-(2,4,5-trifluoropheny)piperidin-3-yl]carbamate；tert-butyl N-[(3R,4R)-6-oxo-4-(2,4,5-trifluorophenyl)piperidin-3-yl]carbamate
• CAS: 888321-35-5
• 化学式: C₁₆H₁₉F₃N₂O₃
• 分子量: 344.334
• InChiKey: XVLZNAHLOCVRAW-RNCFNFMXSA-N

物化性质

• 沸点：
  470.9±45.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [(R)-6-oxo-4-(2,4,5-trifluorophenyl)piperidin-3-yl]carbamic acid tert-butyl ester 、 2,4-二氯-6-甲基-吡啶-3-胺 在 copper(l) iodide 、 potassium carbonate 、 N,N'-二甲基乙二胺 作用下， 以 甲苯 为溶剂， 反应 24.0h， 生成 tert-butyl [(7R,8R)-4-chloro-2-methyl-7-(2,4,5-trifluorophenyl)-6,7,8,9-tetrahydropyrido[3',2':4,5]imidazo[1,2-α]pyridine-8-yl]carbamate
  参考文献：
  名称：

  WO2007/70434

  摘要：

  公开号：
• 作为产物：
  描述：

  tert-butyl [(3R,4R)-1-(4-methoxybenzyl)-6-oxo-4-(2,4,5-trifluorophenyl)piperidin-3-yl]carbamate 在 ammonium cerium (IV) nitrate 作用下， 以 水 、 乙腈 为溶剂， 以75%的产率得到[(R)-6-oxo-4-(2,4,5-trifluorophenyl)piperidin-3-yl]carbamic acid tert-butyl ester
  参考文献：
  名称：

  强力的氨基哌啶融合的咪唑并吡啶二肽基肽酶IV抑制剂的不对称合成

  摘要：

  已经开发了实用的不对称合成新型氨基哌啶融合的咪唑并吡啶二肽基肽酶IV（DPP-4）抑制剂1。独特的三组分级联偶合与手性硝基二酯7的结合可轻松实现，该手性可通过将高丙二酸二甲酯向硝基苯乙烯的高对映选择性迈克尔加成反应而实现，从而可以在一个罐中组装官能化的哌啶酮骨架。通过碱催化的，动态结晶驱动的过程，将顺式-哌啶酮16a差向异构化为所需的反式异构体16b，其以高收率和纯度直接从粗反应物流中结晶。烯丙基酰胺的异构化在存在RhCl 3的条件下获得16b时，与哌啶酮环上的硝基相邻的酸/碱不稳定的立体异构中心没有任何差向异构化，而通过利用痕量HCl生成的少量HCl将不需要的烯胺中间体消耗到<0.5％ RhCl 3。通过氢化和水解获得的氨基内酰胺4作为结晶的pTSA盐直接从反应溶液中分离出来，因为这种分子内转酰胺作用已通过动力学控制得到了显着抑制。最后，Cu（I）催化的偶联环化作用可形成有效的DPP-4

  DOI：

  10.1021/jo902573q

文献信息

• Fused Aminopiperidines as Dipeptidyl Peptidase-4 Inhibitors for the Treatment or Prevention of Diabetes
  申请人：Cox Jason M.

  公开号：US20090233936A1

  公开（公告）日：2009-09-17

  The present invention is directed to novel substituted fused aminopiperidines of structural formula (I) which are inhibitors of the dipeptidyl peptidase-4 enzyme and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-4 enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-4 enzyme is involved.

  本发明涉及一种新颖的结构式（I）的取代融合氨基哌啶，其是二肽基肽酶-4酶的抑制剂，并且在治疗或预防二肽基肽酶-4酶参与的疾病中，例如糖尿病和特别是2型糖尿病中有用。本发明还涉及包含这些化合物的制药组合物以及这些化合物和组合物在预防或治疗二肽基肽酶-4酶参与的这些疾病中的使用。
• Fused aminopiperidines as dipeptidyl peptidase-4 inhibitors for the treatment or prevention of diabetes
  申请人：Merck Sharp & Dohme Corp.

  公开号：US07943615B2

  公开（公告）日：2011-05-17

  The present invention is directed to novel substituted fused aminopiperidines of structural formula (I) which are inhibitors of the dipeptidyl peptidase-4 enzyme and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-4 enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-4 enzyme is involved.

  本发明涉及结构式（I）的新型取代融合氨基哌啶，它们是二肽基肽酶-4酶的抑制剂，并可用于治疗或预防二肽基肽酶-4酶参与的疾病，如糖尿病，特别是2型糖尿病。本发明还涉及包含这些化合物的制药组合物以及在预防或治疗二肽基肽酶-4酶参与的这种疾病中使用这些化合物和组合物。
• Fused aminopiperidines as dipeptidyl peptidase-IV inhibitors for the treatment or prevention of diabetes
  申请人：Merck Sharp & Dohme Corp.

  公开号：US07718667B2

  公开（公告）日：2010-05-18

  The present invention is directed to novel substituted fused aminopiperidines which are inhibitors of the dipeptidyl peptidase-IV enzyme (“DPP-IV inhibitors”) and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

  本发明涉及新型的取代融合氨基哌啶，其为二肽基肽酶-IV酶（“DPP-IV抑制剂”）的抑制剂，并且在治疗或预防与二肽基肽酶-IV酶有关的疾病，如糖尿病和特别是2型糖尿病方面具有用途。本发明还涉及包括这些化合物的制药组合物以及这些化合物和组合物在预防或治疗与二肽基肽酶-IV酶有关的这些疾病中的使用。
• WO2006/58064
  申请人：——

  公开号：——

  公开（公告）日：——
• WO2007/24993
  申请人：——

  公开号：——

  公开（公告）日：——