N-benzyloxy-4-(2,4,5-trifluorophenyl)-3(S)-hydroxybutanamide | 1256815-04-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-benzyloxy-4-(2,4,5-trifluorophenyl)-3(S)-hydroxybutanamide
• 英文别名: (S)-N-(benzyloxy)-3-hydroxy-4-(2,4,5-trifluorophenyl)butanamide；(3S)-N-benzyloxy-3-hydroxy-4-(2,4,5-trifluorophenyl) butanamide；(3S)-3-hydroxy-N-phenylmethoxy-4-(2,4,5-trifluorophenyl)butanamide
• CAS: 1256815-04-9
• 化学式: C₁₇H₁₆F₃NO₃
• 分子量: 339.314
• InChiKey: GAARSSHFSQQEGX-ZDUSSCGKSA-N

物化性质

• 熔点：
  99-105 °C(Solv: dichloromethane (75-09-2); hexane (110-54-3))
• 密度：
  1.329±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-benzyloxy-4-(2,4,5-trifluorophenyl)-3(S)-hydroxybutanamide 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以72%的产率得到(4R)-1-苯甲氧基-4-[(2,4,5-三氟苯基)甲基]-2-氮杂环丁酮
  参考文献：
  名称：

  Synthesis, biological assay in vitro and molecular docking studies of new imidazopyrazinone derivatives as potential dipeptidyl peptidase IV inhibitors

  摘要：

  A series of novel imidazopyrazinone derivatives were synthesized and evaluated with regard to their ability to inhibit dipeptidyl peptidase IV (DPP-IV) in vitro. Of these compounds (2R)-4-oxo-4-[2-(3-carbamoylbenzyl)-hexahydro-3-oxoimidazo [1,5-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine fumaric acid (17h, IC50 = 78 nM) was shown to effectively inhibit the activity of the dipeptidyl peptidase IV enzyme. Molecular docking studies were also performed to illustrate the binding mode of compounds 15c and 17h. Favorable interactions were identified from the binding of inhibitor 15c with DPP-IV. By analogy to the binding mode of compound 15c, it seems that the introduction of a substituted benzyl moiety onto the imidazopyrazinone could remarkably improve the inhibitory activity of compound 17h. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.08.002
• 作为产物：
  描述：

  3(S)-4-(2,4,5-trifluorophenyl)-3-hydroxybenzenebutanoic acid methyl ester 在 水 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 N-benzyloxy-4-(2,4,5-trifluorophenyl)-3(S)-hydroxybutanamide
  参考文献：
  名称：

  [EN] PREPARATION OF R-SITAGLIPTIN AND INTERMEDIATES THEREOF
  [FR] PROCÉDÉS DE PRÉPARATION DE R-SITAGLIPTINE ET DE SES INTERMÉDIAIRES

  摘要：

  公开号：

  WO2012042534A3

文献信息

• INTERMEDIATES OF SITAGLIPTIN AND PREPARATION PROCESS THEREOF
  申请人：Pan Xianhua

  公开号：US20130281695A1

  公开（公告）日：2013-10-24

  Disclosed are intermediates of Sitagliptin, a preparation process thereof, and a process for synthesizing Sitagliptin using these intermediates. Sitagliptin is synthesized by using chiral amino compounds as a raw material, without having to build a chiral center with a chiral asymmetric catalytic hydrogenation, and high-pressure hydrogenation is avoided.

  揭示了西他列汀的中间体、其制备过程以及利用这些中间体合成西他列汀的方法。西他列汀是通过使用手性氨基化合物作为原料合成的，无需通过手性不对称催化氢化建立手性中心，并且避免了高压氢化反应。
• [EN] A NOVEL PROCESS FOR THE PREPARATION OF SITAGLIPTIN<br/>[FR] NOUVEAU PROCÉDÉ DE PRÉPARATION DE SITAGLIPTINE
  申请人：SMILAX LAB LTD

  公开号：WO2013114173A1

  公开（公告）日：2013-08-08

  The present invention is directed to a process for the preparation of enantiomerically enriched β-amino acid derivatives which are important chiral building blocks and intermediates in pharmaceuticals. More specifically, the invention pertains to a novel process for practically convenient and economically producing enantiomerically enriched β-amino acid derivatives which are useful for the synthesis of amide inhibitors of dipeptidyl peptidase IV like Sitagliptin, which have been used to treat type 2 diabetes.

  本发明涉及一种制备对映富集的β-氨基酸衍生物的方法，这些衍生物是重要的手性构建块和药物中间体。更具体地，该发明涉及一种新颖的方法，用于方便实用和经济地生产对映富集的β-氨基酸衍生物，这些衍生物对于合成类似西他列汀的二肽基肽酶IV抑制剂的酰胺具有用处，这些抑制剂已被用于治疗2型糖尿病。
• [EN] NOVEL PROCESS FOR THE PREPARATION OF DIPEPTIDYL PEPTIDASE-4 (DPP-4) ENZYME INHIBITOR<br/>[FR] NOUVEAU PROCÉDÉ POUR LA PRÉPARATION D'INHIBITEUR DE L'ENZYME DIPEPTIDYL PEPTIDASE-4 (DPP-4)
  申请人：LEE PHARMA LTD

  公开号：WO2016110750A1

  公开（公告）日：2016-07-14

  The present invention relates to a novel and improved process for the preparation of Sitagliptin of Formula (I) and its pharmaceutically acceptable salts. The present invention also relates to novel intermediates and process for the preparation of intermediates used in the preparation of Sitagliptin.

  本发明涉及一种用于制备化学式（I）的西他列汀及其药用可接受盐的新型改进工艺。本发明还涉及用于制备西他列汀中所用的新型中间体和制备中间体的工艺。
• Process for the synthesis of beta-amino acids and derivatives thereof
  申请人：LEK Pharmaceuticals d.d.

  公开号：EP2397141A1

  公开（公告）日：2011-12-21

  The present invention relates to a process for the preparation of β-amino acids and derivatives thereof, which is especially suited for gliptins and particularly sitagliptin. A key step makes use of suitably derivatized epoxides or aziridines, which owing to a chirality provides a source of chirality for intermediates which are suitable for building up β-amino acids and similar compounds, in particular in the construction of the sitagliptin molecule.

  本发明涉及一种制备β-氨基酸及其衍生物的方法，该方法特别适用于格列酮类药物，尤其是西他列汀。关键步骤利用适当衍生的环氧化物或氮杂环丙烷，由于手性而为中间体提供手性来源，适用于构建β-氨基酸和类似化合物，特别是在构建西他列汀分子时。
• METHOD FOR MANUFACTURING DIPEPTIDYL PEPTIDASE-IV INHIBITOR AND INTERMEDIATE
  申请人：Kwak Woo Young

  公开号：US20120016126A1

  公开（公告）日：2012-01-19

  The present invention relates to an improved method for manufacturing dipeptidyl peptidase-IV inhibitor and intermediate. The present invention allows reduction of production costs by reacting low cost reagents, improves yield and is adaptable for mass production.

  本发明涉及一种改进的二肽基胰岛素释放肽酶-IV抑制剂及中间体制备方法。本发明通过使用低成本试剂反应，降低生产成本，提高产量，并适用于大规模生产。