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

• 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: 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: 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
• 化学式: C₂₄H₂₃F₆N₅O
• 分子量: 511.47
• InChiKey: SSZKHYNLDAUWPS-XPCCGILXSA-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

• 作为反应物：
  描述：

  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 在 isopropanol hydrochloride 、 palladium 10% on activated carbon 、 氢气 作用下， 以 乙二醇二甲醚 、 水 、 异丙醇 、 甲苯 为溶剂， 70.0 ℃ 、723.97 kPa 条件下， 反应 10.0h， 生成 西他列汀
  参考文献：
  名称：

  Practical, Asymmetric Route to Sitagliptin and Derivatives: Development and Origin of Diastereoselectivity

  摘要：

  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.

  DOI：

  10.1021/acs.orglett.5b00520

文献信息

• Processes for the preparation of sitagliptin and pharmaceutically acceptable salts thereof
  申请人：Dr. Reddy's Laboratories Ltd.

  公开号：EP2599781A1

  公开（公告）日：2013-06-05

  There is provided salts and polymorphs of sitagliptin, processes for the preparation thereof, and pharmaceutical compositions comprising the same.

  提供了西格列汀的盐和多晶形式，其制备方法以及包含它们的制药组合物。
• PROCESSES FOR THE PREPARATION OF SITAGLIPTIN AND PHARMACEUTICLLY ACCEPTABLE SALTS THEREOF
  申请人：Padi Pratap Reddy

  公开号：US20100274017A1

  公开（公告）日：2010-10-28

  There is provided salts and polymorphs of sitagliptin, processes for the preparation thereof, and pharmaceutical compositions comprising the same.

  提供了西格列汀的盐和多晶形态，以及其制备方法和包含其的药物组合物。
• PROCESSES FOR THE PREPARATION OF SITAGLIPTIN AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
  申请人：DR. REDDY'S LABORATORIES LIMITED

  公开号：US20130035486A1

  公开（公告）日：2013-02-07

  There is provided salts and polymorphs of sitagliptin, processes for the preparation thereof, and pharmaceutical composition comprising the same.

  提供了西格列汀的盐和多晶形态，其制备方法以及包含其的药物组合物。
• 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。
• US8309724B2
  申请人：——

  公开号：US8309724B2

  公开（公告）日：2012-11-13