4-chloro-7-(2-fluoro-4-methanesulfonylphenyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine | 1001397-19-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 4-chloro-7-(2-fluoro-4-methanesulfonylphenyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine
• 英文别名: 4-chloro-7-[2-fluoro-4-(methylsulfonyl)phenyl]-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine；4-Chloro-7-(2-fluoro-4-(methylsulfonyl)phenyl)-6,7-dihydro-5H-pyrrolo[2,3-D]pyrimidine；4-chloro-7-(2-fluoro-4-methylsulfonylphenyl)-5,6-dihydropyrrolo[2,3-d]pyrimidine
• CAS: 1001397-19-8
• 化学式: C₁₃H₁₁ClFN₃O₂S
• 分子量: 327.767
• InChiKey: FHFINPVOGJKNOK-UHFFFAOYSA-N

物化性质

• 熔点：
  165-167 °C
• 沸点：
  565.4±50.0 °C(Predicted)
• 密度：
  1.502±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  71.5
• 氢给体数：
  0
• 氢受体数：
  6

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  4-chloro-7-(2-fluoro-4-methanesulfonylphenyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine 在 sodium hydride 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 22.0h， 生成 n-butyl 4-({7-[2-fluoro-4-(methylsulfonyl)phenyl]-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl}oxy)-1-piperidinecarboxylate
  参考文献：
  名称：

  Discovery of 6,7-Dihydro-5H-pyrrolo[2,3-a]pyrimidines as Orally Available G Protein-Coupled Receptor 119 Agonists

  摘要：

  GPR119 is a 7-transmembrane receptor that is expressed in the enteroendocrine cells in the intestine and in the islets of Langerhans in the pancreas. Indolines and 6,7-dihydro-5H-pyrrolo[2,3-a]pyrimidines were discovered as G protein-coupled receptor 119 (GPR119) agonists, and lead optimization efforts led to the identification of 1-methylethyl 4-({7-[2-fluoro-4-(methylsulfonyl)phenyl]-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl}oxy)-1-piperidinecarboxylate (GSK1104252A) (3), a potent and selective GPR119 agonist. Compound 3 showed excellent pharmacokinetic properties and sufficient selectivity with in vivo studies supporting a role for GPR119 in glucose homeostasis in the rodent. Thus, 3 appeared to modulate the enteroinsular axis, improve glycemic control, and strengthen previous suggestions that GPR119 agonists may have utility in the treatment of type 2 diabetes.

  DOI：

  10.1021/jm301404a
• 作为产物：
  描述：

  5-烯丙基-4,6-二氯嘧啶 在 sodium hydride 、 臭氧 、 三乙胺 、 甲基磺酸酐 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 18.0h， 生成 4-chloro-7-(2-fluoro-4-methanesulfonylphenyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  Discovery of 6,7-Dihydro-5H-pyrrolo[2,3-a]pyrimidines as Orally Available G Protein-Coupled Receptor 119 Agonists

  摘要：

  GPR119 is a 7-transmembrane receptor that is expressed in the enteroendocrine cells in the intestine and in the islets of Langerhans in the pancreas. Indolines and 6,7-dihydro-5H-pyrrolo[2,3-a]pyrimidines were discovered as G protein-coupled receptor 119 (GPR119) agonists, and lead optimization efforts led to the identification of 1-methylethyl 4-({7-[2-fluoro-4-(methylsulfonyl)phenyl]-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl}oxy)-1-piperidinecarboxylate (GSK1104252A) (3), a potent and selective GPR119 agonist. Compound 3 showed excellent pharmacokinetic properties and sufficient selectivity with in vivo studies supporting a role for GPR119 in glucose homeostasis in the rodent. Thus, 3 appeared to modulate the enteroinsular axis, improve glycemic control, and strengthen previous suggestions that GPR119 agonists may have utility in the treatment of type 2 diabetes.

  DOI：

  10.1021/jm301404a

文献信息

• WO2008/8895
  申请人：——

  公开号：——

  公开（公告）日：——
• Facile Reductive Amination of Aldehydes with Electron-Deficient Anilines by Acyloxyborohydrides in TFA: Application to a Diazaindoline Scale-Up
  作者：Eric E. Boros、James B. Thompson、Subba R. Katamreddy、Andrew J. Carpenter

  DOI：10.1021/jo900157z

  日期：2009.5.1

  A scale-up of diazaindoline 1 was achieved in four stages and 32% overall yield. The key step involved rapid reductive amination of aldehyde 8 with aniline 5 by sodium triacetoxyborohydride (STAB-H) and TFA followed by ring closure of intermediate amine 9 to compound 1 in the same pot. These reaction conditions were also applied to facile reductive aminations with anilines known to have little reactivity under STAB-H/AcOH conditions. Spectral data supported the tris(trifluoroacetoxy)borohydride anion (16) as the active reducing agent.
• Lead generation and optimization of novel GPR119 agonists with a spirocyclic cyclohexane structure
  作者：Kazuhito Harada、Jun Mizukami、Takashi Watanabe、Genki Mori、Minoru Ubukata、Katsunori Suwa、Sumiaki Fukuda、Tamotsu Negoro、Motohide Sato、Takashi Inaba

  DOI：10.1016/j.bmcl.2018.12.041

  日期：2019.2

  We describe here the generation of a lead compound and its optimization studies that led to the identification of a novel GPR119 agonist. Based on a spirocyclic cyclohexane structure reported in our previous work, we identified compound 8 as a lead compound, being guided by ligand-lipophilicity efficiency (LLE), which linked potency and lipophilicity. Subsequent optimization studies of 8 for improvement of solubility afforded representative 21. Compound 21 had no inhibitory activity against six CYP isoforms and showed favorable pharmacokinetic properties and hypoglycemic activity in rats.
• [EN] 3-OXA-7-AZABICYCLO[3.3.1]NONANES<br/>[FR] 3-OXA-7-AZABICYCLO[3,3.1]NONANES
  申请人：PFIZER

  公开号：WO2010106457A3

  公开（公告）日：2010-11-18
• 3-OXA-7-AZABICYCLOÝ3.3.1¨NONANES
  申请人：Pfizer Inc.

  公开号：EP2408780A2

  公开（公告）日：2012-01-25