methyl-2-(2-(5-methyl-1,3,4-oxadiazole-2-carboxamido)propan-2-yl)-1,6-dihydro-5-hydroxy-6-oxopyrimidine-4-carboxylate | 1391918-15-2

• 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: methyl-2-(2-(5-methyl-1,3,4-oxadiazole-2-carboxamido)propan-2-yl)-1,6-dihydro-5-hydroxy-6-oxopyrimidine-4-carboxylate
• 英文别名: Methyl 2-(2-(5-methyl-1,3,4-oxadiazole-2-carboxamido)propan-2-yl)-1,6-dihydro-5-hydroxy-6-oxopyrimidine-4-carboxylate；methyl 5-hydroxy-2-[2-[(5-methyl-1,3,4-oxadiazole-2-carbonyl)amino]propan-2-yl]-6-oxo-1H-pyrimidine-4-carboxylate
• CAS: 1391918-15-2
• 化学式: C₁₃H₁₅N₅O₆
• 分子量: 337.292
• InChiKey: LBVLPWFXXSJTDR-UHFFFAOYSA-N

物化性质

• 密度：
  1.58±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  156
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  methyl-2-(2-(5-methyl-1,3,4-oxadiazole-2-carboxamido)propan-2-yl)-1,6-dihydro-5-hydroxy-6-oxopyrimidine-4-carboxylate 在 magnesium hydroxide 作用下， 以 水 、 异丙醇 为溶剂， 反应 7.0h， 生成 雷特格韦
  参考文献：
  名称：

  SYNTHESIS OF RALTEGRAVIR

  摘要：

  本发明涉及一种用于制备拉替格韦及药用可接受盐的新型合成路线，从2-氨基-2-甲基丙腈和噁二唑羰氯开始，通过形成式（V）的嘧啶酮中间体。

  公开号：

  US20150045554A1
• 作为产物：
  描述：

  N-(2-cyanopropan-2-yl)-5-methyl-1,3,4-oxadiazole-2-carboxamide 在 羟胺 作用下， 以 甲醇 、 水 、 异丙醇 为溶剂， 反应 0.92h， 生成 methyl-2-(2-(5-methyl-1,3,4-oxadiazole-2-carboxamido)propan-2-yl)-1,6-dihydro-5-hydroxy-6-oxopyrimidine-4-carboxylate
  参考文献：
  名称：

  Identification, Synthesis, and Strategy For Minimization of Potential Impurities Observed In Raltegravir Potassium Drug Substance

  摘要：

  Multiple sources of anticipated degradation and process impurities of raltegravir potassium drug substance observed during the laboratory optimization and later during its bulk synthesis are described in this article. The impurities were monitored by UPLC, and their structures are tentatively assigned on the basis of fragmentation patterns in LC-MS and NMR spectroscopy. Most of the impurities are synthesized, and their assigned constitutions were confirmed by co-injection in UPLC. In addition to the formation, synthesis, and characterization, strategy for minimizing these impurities to the level accepted by ICH is also described. We feel that our study will be helpful to the generic industry for obtaining chemically pure raltegravir potassium.

  DOI：

  10.1021/op300077m

文献信息

• Synthesis of raltegravir
  申请人：Emcure Pharmaceuticals Limited

  公开号：US09403809B2

  公开（公告）日：2016-08-02

  The present invention relates to a novel synthetic route for the preparation of raltegravir and pharmaceutically acceptable salts, starting from 2-amino-2-methylpropanenitrile and oxadiazole carbonyl chloride, through the formation of a pyrimidinone intermediate of formula (V).

  本发明涉及一种新型合成路线，用于制备拉替尼韦及其药学上可接受的盐。该路线以2-氨基-2-甲基丙烯腈和噁二唑羰基氯为起始原料，通过形成公式（V）的嘧啶酮中间体来完成。
• US9403809B2
  申请人：——

  公开号：US9403809B2

  公开（公告）日：2016-08-02
• US9475799B1
  申请人：——

  公开号：US9475799B1

  公开（公告）日：2016-10-25
• [EN] SYNTHESIS OF RALTEGRAVIR<br/>[FR] SYNTHÈSE DE RALTÉGRAVIR
  申请人：EMCURE PHARMACEUTICALS LTD

  公开号：WO2013098854A2

  公开（公告）日：2013-07-04

  The present invention relates to a novel synthetic route for the preparation of raltegravir and pharmaceutically acceptable salts, starting from 2-amino-2- methylpropanenitrile and oxadiazole carbonyl chloride, through the formation of a pyrimidinone intermediate of formula (V).
• Identification, Synthesis, and Strategy For Minimization of Potential Impurities Observed In Raltegravir Potassium Drug Substance
  作者：Gulabrao D. Patil、Siddheshwar W. Kshirsagar、Shivnath B. Shinde、Pankaj S. Patil、Mangesh S. Deshpande、Ashok T. Chaudhari、Swapnil P. Sonawane、Golak C. Maikap、Mukund K. Gurjar

  DOI：10.1021/op300077m

  日期：2012.8.17

  Multiple sources of anticipated degradation and process impurities of raltegravir potassium drug substance observed during the laboratory optimization and later during its bulk synthesis are described in this article. The impurities were monitored by UPLC, and their structures are tentatively assigned on the basis of fragmentation patterns in LC-MS and NMR spectroscopy. Most of the impurities are synthesized, and their assigned constitutions were confirmed by co-injection in UPLC. In addition to the formation, synthesis, and characterization, strategy for minimizing these impurities to the level accepted by ICH is also described. We feel that our study will be helpful to the generic industry for obtaining chemically pure raltegravir potassium.