N-[(2S,3R)-2-(2,5-二氟苯基)四氢-5-氧代-2H-吡喃-3-基]氨基甲酸叔丁酯 | 1456616-42-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-[(2S,3R)-2-(2,5-二氟苯基)四氢-5-氧代-2H-吡喃-3-基]氨基甲酸叔丁酯
• 中文别名: 奥格列汀杂质4；奥格列汀中间体杂质
• 英文名称: tert-butyl [(2S,3R)-5-oxo-2-(2,5-difluorophenyl)tetrahydro-2H-pyran-3-yl]carbamate
• 英文别名: Tert-butyl ((2S,3R)-2-(2,5-difluorophenyl)-5-oxotetrahydro-2H-pyran-3-yl)carbamate；tert-butyl N-[(2S,3R)-2-(2,5-difluorophenyl)-5-oxooxan-3-yl]carbamate
• CAS: 1456616-42-4
• 化学式: C₁₆H₁₉F₂NO₄
• 分子量: 327.328
• InChiKey: OTCULXVRRSCLLI-KGLIPLIRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-[(2S,3R)-2-(2,5-二氟苯基)四氢-5-氧代-2H-吡喃-3-基]氨基甲酸叔丁酯 在 盐酸 、 癸硼烷 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 生成 (2S,3R,5S)-2-(2,5-difluorophenyl)-5-(4,6-dihydro-1H-pyrrolo[3,4-c]pyrazol-5-yl)oxan-3-amine
  参考文献：
  名称：

  Novel tetrahydropyran analogs as dipeptidyl peptidase IV inhibitors: Profile of clinical candidate (2R,3S,5R)-2-(2,5-difluorophenyl)-5-[2-(methylsulfonyl)-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]tetrahydro-2H-pyran-3-amine (23)

  摘要：

  A series of novel tri-2,3,5-substituted tetrahydropyran analogs were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4) for the treatment of type 2 diabetes. Optimization of the series provided inhibitors with good DPP-4 potency and selectivity over other peptidases (QPP, DPP8, and FAP). Compound 23, which is very potent, selective, efficacious in the diabetes PD model, and has an excellent pharmacokinetic profile, is selected as a clinical candidate. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.07.061
• 作为产物：
  描述：

  2,5-二氟苯甲酰氯 在 盐酸 、 sodium tetrahydroborate 、 sodium periodate 、 rhodium(III) chloride 、 sodium hydride 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二异丙基乙胺 、 锌 作用下， 以 甲醇 、 乙醇 、 正己烷 、 水 为溶剂， 生成 N-[(2S,3R)-2-(2,5-二氟苯基)四氢-5-氧代-2H-吡喃-3-基]氨基甲酸叔丁酯
  参考文献：
  名称：

  Novel tetrahydropyran analogs as dipeptidyl peptidase IV inhibitors: Profile of clinical candidate (2R,3S,5R)-2-(2,5-difluorophenyl)-5-[2-(methylsulfonyl)-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]tetrahydro-2H-pyran-3-amine (23)

  摘要：

  A series of novel tri-2,3,5-substituted tetrahydropyran analogs were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4) for the treatment of type 2 diabetes. Optimization of the series provided inhibitors with good DPP-4 potency and selectivity over other peptidases (QPP, DPP8, and FAP). Compound 23, which is very potent, selective, efficacious in the diabetes PD model, and has an excellent pharmacokinetic profile, is selected as a clinical candidate. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.07.061

文献信息

• 一种化合物的制备方法
  申请人：四川凯科医药科技有限公司

  公开号：CN105198847B

  公开（公告）日：2017-05-17

  本发明公开了一种化合物的制备方法，包括将化合物3 5‑氨基‑6‑（2,5‑二氟苯基）‑四氢‑2H‑吡喃‑3‑醇进行化学拆分，并获得该化合物3与拆分剂形成的盐；将化合物3与拆分剂形成的盐在碱液中与二碳酸二叔丁酯化合得到化合物4；将化合物4的羟基氧化得到式1所示化合物N‑[(2R,3S)‑2‑(2,5‑二氟苯基)四氢‑5‑氧‑2H‑吡喃‑3‑基]‑氨基甲酸 1,1‑二甲基乙基酯。本发明的制备方法，通过选择价格低廉的原料，缩短合成路线，省略不对称氢化反应步骤，进而大大降低了生产成本，而且显著的提高了产率。
• Process for preparing aminotetrahydropyrans
  申请人：F.I.S.—Fabbrica Italiana Sintetici S.p.A.

  公开号：US10377732B2

  公开（公告）日：2019-08-13

  The present invention relates to a process for preparing 3-amino tetrahydropyrans and, more particularly, to an improved method for synthesizing a 2,3,5-substituted tetrahydropyran derivative, intermediate being used in the preparation of dipeptidyl peptidase-IV enzyme inhibitors (DPP-4 inhibitors).

  本发明涉及一种制备3-氨基四氢吡喃的工艺，更具体地说，涉及一种合成2,3,5-取代的四氢吡喃衍生物的改进方法，该衍生物中间体可用于制备二肽基肽酶-IV酶抑制剂（DPP-4抑制剂）。
• Omarigliptin (MK-3102): A Novel Long-Acting DPP-4 Inhibitor for Once-Weekly Treatment of Type 2 Diabetes
  作者：Tesfaye Biftu、Ranabir Sinha-Roy、Ping Chen、Xiaoxia Qian、Dennis Feng、Jeffrey T. Kuethe、Giovanna Scapin、Ying Duo Gao、Youwei Yan、Davida Krueger、Annette Bak、George Eiermann、Jiafang He、Jason Cox、Jacqueline Hicks、Kathy Lyons、Huaibing He、Gino Salituro、Sharon Tong、Sangita Patel、George Doss、Aleksandr Petrov、Joseph Wu、Shiyao Sherrie Xu、Charles Sewall、Xiaoping Zhang、Bei Zhang、Nancy A. Thornberry、Ann E. Weber

  DOI：10.1021/jm401992e

  日期：2014.4.24

  In our effort to discover DPP-4 inhibitors with added benefits over currently commercially available DPP-4 inhibitors, MK-3102 (omarigliptin), was identified as a potent and selective dipeptidyl peptidase 4 (DPP-4) inhibitor with an excellent pharmacokinetic profile amenable for once-weekly human dosing and selected as a clinical development candidate. This manuscript summarizes the mechanism of action, scientific rationale, medicinal chemistry, pharmacokinetic properties, and human efficacy data for omarigliptin, which is currently in phase 3 clinical development.