(R)-tert-butyl 4-(5-(4-bromo-2-cyanobenzyloxy)pyrimidin-2-yl)-3-methylpiperazine-1-carboxylate | 1379522-59-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (R)-tert-butyl 4-(5-(4-bromo-2-cyanobenzyloxy)pyrimidin-2-yl)-3-methylpiperazine-1-carboxylate
• CAS: 1379522-59-4
• 化学式: C₂₂H₂₆BrN₅O₃
• 分子量: 488.384
• InChiKey: TYYUBAUKRZESBQ-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.14
• 重原子数：
  31.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  91.58
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (R)-tert-butyl 4-(5-(4-bromo-2-cyanobenzyloxy)pyrimidin-2-yl)-3-methylpiperazine-1-carboxylate 、 sodium methansulfinate 在 copper(l) iodide 、 L-脯氨酸 、 sodium hydroxide 作用下， 以 二甲基亚砜 为溶剂， 反应 48.0h， 以50%的产率得到tert-butyl (3R)-4-(5-{[2-cyano-4-(methylsulfonyl)benzyl]oxy}pyrimidin-2-yl)-3-methylpiperazine-1-carboxylate
  参考文献：
  名称：

  Use of Small-Molecule Crystal Structures To Address Solubility in a Novel Series of G Protein Coupled Receptor 119 Agonists: Optimization of a Lead and in Vivo Evaluation

  摘要：

  G protein coupled receptor 119 (GPR119) is viewed as an attractive target for the treatment of type 2 diabetes and other elements of the metabolic syndrome. During a program toward discovering agonists of GPR119, we herein describe optimization of an initial lead compound, 2, into a development candidate, 42. A key challenge in this program of work was the insolubility of the lead compound. Small-molecule crystallography was utilized to understand the intermolecular interactions in the solid state and resulted in a switch from an aryl sulphone to a 3-cyanopyridyl motif. The compound was shown to be effective in wild-type but not knockout animals, confirming that the biological effects were due to GPR119 agonism.

  DOI：

  10.1021/jm300310c
• 作为产物：
  描述：

  tert-butyl (R)-4-(5-bromopyrimidin-2-yl)-3-methylpiperazine-1-carboxylate 在 sodium peroxoborate tetrahydrate 、 potassium acetate 、 palladium diacetate 、 potassium carbonate 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 34.0h， 生成 (R)-tert-butyl 4-(5-(4-bromo-2-cyanobenzyloxy)pyrimidin-2-yl)-3-methylpiperazine-1-carboxylate
  参考文献：
  名称：

  Use of Small-Molecule Crystal Structures To Address Solubility in a Novel Series of G Protein Coupled Receptor 119 Agonists: Optimization of a Lead and in Vivo Evaluation

  摘要：

  G protein coupled receptor 119 (GPR119) is viewed as an attractive target for the treatment of type 2 diabetes and other elements of the metabolic syndrome. During a program toward discovering agonists of GPR119, we herein describe optimization of an initial lead compound, 2, into a development candidate, 42. A key challenge in this program of work was the insolubility of the lead compound. Small-molecule crystallography was utilized to understand the intermolecular interactions in the solid state and resulted in a switch from an aryl sulphone to a 3-cyanopyridyl motif. The compound was shown to be effective in wild-type but not knockout animals, confirming that the biological effects were due to GPR119 agonism.

  DOI：

  10.1021/jm300310c