(2S)-2({(1S)-3-oxo-1-(2,4,5-trifluorobenzyl)-3-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-α]pyrazin-7(8H)-yl]propyl}amino)-2-phenylethanamide | 1456704-50-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S)-2({(1S)-3-oxo-1-(2,4,5-trifluorobenzyl)-3-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-α]pyrazin-7(8H)-yl]propyl}amino)-2-phenylethanamide
• CAS: 1456704-50-9
• 化学式: C₂₄H₂₂F₆N₆O₂
• 分子量: 540.468
• InChiKey: DQIPFFHYFVHRIT-BTYIYWSLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.87
• 重原子数：
  38.0
• 可旋转键数：
  8.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  106.14
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  西他列汀杂质10 在 sodium acetate 、 乙酸酐 、 溶剂黄146 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 30.0h， 生成 (2S)-2({(1S)-3-oxo-1-(2,4,5-trifluorobenzyl)-3-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-α]pyrazin-7(8H)-yl]propyl}amino)-2-phenylethanamide
  参考文献：
  名称：

  [EN] EXPEDIENT SYNTHESIS OF SITAGLIPTIN
  [FR] SYNTHÈSE PRATIQUE DE SITAGLIPTINE

  摘要：

  公开号：

  WO2015120111A3

文献信息

• Synthesis of Sitagliptin Phosphate by a NaBH₄/ZnCl₂-catalyzed Diastereoselective Reduction
  作者：Xianhua Pan、Kun Wang、Wansheng Yu、Ruimin Zhang、Lu Xu、Feng Liu

  DOI：10.1246/cl.150390

  日期：2015.9.5

  A practical asymmetric synthesis of sitagliptin phosphate, from 1-3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo-[4,3-a]pyrazin-7(8H)-yl}-4-(2,4,5-trifluorophenyl)butane-1,3-dione, in overall 65.3% yield has been reported. The target compound was synthesized via eneamination, diastereoselective reduction, amine-deprotection, and phosphatization. The key diastereoselective reduction was performed with NaBH4 and ZnCl2, and it gave the product with almost quantitative yield and 68.5% d.e. value after simple work-up and recrystallization with IPA/PE; a high enantiopurity (d.e.% = 99.3%) can also be obtained in 57.1% yield.

  本研究以 1-3-(三氟甲基)-5,6-二氢-[1,2,4]三唑并-[4,3-a]吡嗪-7(8H)-基}-4-(2,4,5-三氟苯基)丁烷-1,3-二酮为原料，不对称合成了磷酸西他列汀，总收率为 65.3%。目标化合物是通过烯化、非对映选择性还原、胺脱保护和磷酸化合成的。关键的非对映选择性还原是用 NaBH4 和 ZnCl2 进行的，经过简单的加工和用 IPA/PE 重结晶后，产物的收率几乎达到定量，d.e.值为 68.5%；还可以获得高对映体纯度（d.e.% = 99.3%），收率为 57.1%。
• Practical and Economical Approach to Synthesize Sitagliptin
  作者：Kuaile Lin、Zhengyan Cai、Weicheng Zhou

  DOI：10.1080/00397911.2013.773353

  日期：2013.12.17

  Economic syntheses of sitagliptin phosphate monohydrate, acknowledged as the first dipeptidyl peptidase 4 (DPP-4) inhibitor, have been achieved in an overall yield of 42.4% in four steps from 1-3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl}-4-(2,4,5-trifluorophenyl)butane-1,3-dione. The key stereoselective reduction of this process was carried out by NaBH4/HCOOH instead of expensive and toxic catalysts or ligands. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications (R) for the following free supplemental resource(s): Full experimental and spectral details.]