(2Z)-1-[5,6-二氢-3-(三氟甲基)-1,2,4-三唑并[4,3-a]吡嗪-7(8H)-基]-3-[[(1R)-1-苯乙基]氨基]-4-(2,4,5-三氟苯基)-2-丁烯-1-酮 | 1169707-29-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并吡嗪类
• 中文名称: (2Z)-1-[5,6-二氢-3-(三氟甲基)-1,2,4-三唑并[4,3-a]吡嗪-7(8H)-基]-3-[[(1R)-1-苯乙基]氨基]-4-(2,4,5-三氟苯基)-2-丁烯-1-酮
• 英文名称: (R,Z)-3-[(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)but-2-en-1-one
• 英文别名: (Z)-7-(1-oxo-3((R)-1-phenylethylamino)-4-(2,4,5-trifluorophenyl)but-2-enyl)-3-trifluoromethyl-5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyrazine；(Z)-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)but-2-en-1-one
• CAS: 1169707-29-2
• 化学式: C₂₄H₂₁F₆N₅O
• 分子量: 509.454
• InChiKey: ARABQUBUKONQTQ-RQNDZEIBSA-N

物化性质

• 密度：
  1.41

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 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：

  (2Z)-1-[5,6-二氢-3-(三氟甲基)-1,2,4-三唑并[4,3-a]吡嗪-7(8H)-基]-3-[[(1R)-1-苯乙基]氨基]-4-(2,4,5-三氟苯基)-2-丁烯-1-酮 在 sodium tetrahydroborate 、 磷酸 、 20% palladium hydroxide-activated charcoal 、 水 、 氢气 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 水 、 异丙醇 为溶剂， 20.0~75.0 ℃ 、1.0 MPa 条件下， 反应 17.0h， 生成 磷酸西他列汀一水合物
  参考文献：
  名称：

  Practical and Economical Approach to Synthesize Sitagliptin

  摘要：

  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.]

  DOI：

  10.1080/00397911.2013.773353
• 作为产物：
  描述：

  3-三氟甲基-5,6,7,8-四氢-1,2,4-三唑并[4,3-a]吡嗪盐酸盐 在 N-甲基吗啉 、 溶剂黄146 作用下， 以 乙酸乙酯 为溶剂， 反应 11.0h， 生成 (2Z)-1-[5,6-二氢-3-(三氟甲基)-1,2,4-三唑并[4,3-a]吡嗪-7(8H)-基]-3-[[(1R)-1-苯乙基]氨基]-4-(2,4,5-三氟苯基)-2-丁烯-1-酮
  参考文献：
  名称：

  [EN] PREPARATION OF SITAGLIPTIN AND SALTS THEREOF
  [FR] PRÉPARATION DE LA SITAGLIPTINE ET DE SES SELS

  摘要：

  公开号：

  WO2011025932A3

文献信息

• METHOD FOR PREPARING INTERMEDIATE COMPOUND OF SITAGLIPTIN
  申请人：ZHEJIANG MEDICINE CO., LTD. XIANCHANG PHARMAUCEUTICAL FACTORY

  公开号：US20160229859A1

  公开（公告）日：2016-08-11

  The present invention provides a method for preparing an intermediate compound of sitagliptin represented by formula I. The preparation method comprises: dissolving a compound represented by formula II into an organic solvent; and under the catalysis of fatty acid and effect of chlorosilane, performing a reduction reaction of carbon-carbon double bonds, so as to obtain the intermediate compound of sitagliptin represented by formula I, R being methyl or formoxyl. The preparation method of the present invention avoids precious metal as a catalyst, and accordingly, the cost is low, the post-treatment is simple, the product has a high yield, chemical purity and optical purity, and de % is greater than 99.6%, and the preparation method can be used in synthesis of sitagliptin and is suitable for industrial production.

  本发明提供了一种制备西他列汀中间体化合物的方法，其表示为式I。制备方法包括：将式II表示的化合物溶解于有机溶剂中；在脂肪酸的催化作用和氯硅烷的影响下，进行碳-碳双键的还原反应，从而获得西他列汀中间体化合物，其表示为式I，其中R为甲基或甲氧基。本发明的制备方法避免了贵金属作为催化剂，因此成本低廉，后处理简单，产品产率高，化学纯度和光学纯度高，de%大于99.6%，该制备方法可用于西他列汀的合成，并适用于工业生产。
• 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。
• [EN] PROCESSES FOR THE PREPARATION OF SITAGLIPTIN AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF<br/>[FR] PROCÉDÉS DE PRÉPARATION DE SITAGLIPTINE ET SELS PHARMACEUTIQUEMENT ACCEPTABLES DE CELLE-CI
  申请人：REDDYS LAB LTD DR

  公开号：WO2009085990A3

  公开（公告）日：2009-09-03