2-(4-chloro-6-((2-fluoro-4-methanesulfonylphenyl)amino)pyrimidin-5-yl)ethanol | 1416272-95-1

• 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: 2-(4-chloro-6-((2-fluoro-4-methanesulfonylphenyl)amino)pyrimidin-5-yl)ethanol
• 英文别名: 2-[4-Chloro-6-(2-fluoro-4-methylsulfonylanilino)pyrimidin-5-yl]ethanol；2-[4-chloro-6-(2-fluoro-4-methylsulfonylanilino)pyrimidin-5-yl]ethanol
• CAS: 1416272-95-1
• 化学式: C₁₃H₁₃ClFN₃O₃S
• 分子量: 345.782
• InChiKey: JXBXTNOEGSKWEK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-(4-chloro-6-((2-fluoro-4-methanesulfonylphenyl)amino)pyrimidin-5-yl)ethanol 在 sodium hydride 、 三乙胺 、 三氟乙酸 、 甲基磺酸酐 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 37.0h， 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 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 2-(4-chloro-6-((2-fluoro-4-methanesulfonylphenyl)amino)pyrimidin-5-yl)ethanol
  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

• 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.
• Discovery of 6,7-Dihydro-5<i>H</i>-pyrrolo[2,3-<i>a</i>]pyrimidines as Orally Available G Protein-Coupled Receptor 119 Agonists
  作者：Subba R. Katamreddy、Andrew J. Carpenter、Carina E. Ammala、Eric E. Boros、Ron L. Brashear、Celia P. Briscoe、Sarah R. Bullard、Richard D. Caldwell、Christopher R. Conlee、Dallas K. Croom、Shane M. Hart、Dennis O. Heyer、Paul R. Johnson、Jennifer A. Kashatus、Doug J. Minick、Gregory E. Peckham、Sean A. Ross、Shane G. Roller、Vicente A. Samano、Howard R. Sauls、Sarva M. Tadepalli、James B. Thompson、Yun Xu、James M. Way

  DOI：10.1021/jm301404a

  日期：2012.12.27

  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.