(S)-3-(((R)-1-phenylethyl)amino)-1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butan-1-one | 1456704-47-4

• 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: (S)-3-(((R)-1-phenylethyl)amino)-1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butan-1-one
• 英文别名: (3S)-3-[[(1R)-1-phenylethyl]amino]-1-[3-(trifluoromethyl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-4-(2,4,5-trifluorophenyl)butan-1-one
• CAS: 1456704-47-4
• 化学式: C₂₄H₂₃F₆N₅O
• 分子量: 511.47
• InChiKey: SSZKHYNLDAUWPS-PBHICJAKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  63
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  (2Z)-4-氧代-4-[3-(三氟甲基)-5,6-二氢-[1,2,4]三唑并[4,3-a]吡嗪-7-(8H)-基]-1-(2,4,5-三氟苯基)丁-2-酮 在 palladium on activated charcoal 、 氢气 、 乙酸酐 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 24.0h， 生成 (S)-3-(((R)-1-phenylethyl)amino)-1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butan-1-one
  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

• EXPEDIENT SYNTHESIS OF SITAGLIPTIN
  申请人：STEREOKEM, INC.

  公开号：US20170183351A1

  公开（公告）日：2017-06-29

  Novel intermediates are disclosed as intermediates for preparation of a Sitagliptin. A novel synthetic method to prepare Sitagliptin using the said intermediates is also disclosed.

  本发明揭示了用于制备西格列汀的新型中间体。还揭示了使用所述中间体制备西格列汀的新型合成方法。
• Practical, Asymmetric Route to Sitagliptin and Derivatives: Development and Origin of Diastereoselectivity
  作者：Osvaldo Gutierrez、Dattatray Metil、Namrata Dwivedi、Nagaraju Gudimalla、E. R. R. Chandrashekar、Vilas H. Dahanukar、Apurba Bhattacharya、Rakeshwar Bandichhor、Marisa C. Kozlowski

  DOI：10.1021/acs.orglett.5b00520

  日期：2015.4.3

  The development of a practical and scalable process for the asymmetric synthesis of sitagliptin is reported. Density functional theory calculations reveal that two noncovalent interactions are responsible for the high diastereoselection. The first is an intramolecular hydrogen bond between the enamide NH and the boryl mesylate S=O, consistent with MsOH being crucial for high selectivity. The second is a novel C-H center dot center dot center dot F interaction between the aryl C5-fluoride and the methyl of the mesylate ligand.
• [EN] EXPEDIENT SYNTHESIS OF SITAGLIPTIN<br/>[FR] SYNTHÈSE PRATIQUE DE SITAGLIPTINE
  申请人：STEREOKEM INC USA

  公开号：WO2015120111A3

  公开（公告）日：2015-11-05
• US9938282B2
  申请人：——

  公开号：US9938282B2

  公开（公告）日：2018-04-10
• 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.]