1-(difluoromethyl)-8-phenyl[1,2,4]triazolo[4,3-a][1,5]-naphthyridin-7-yl trifluoromethanesulfonate | 1370618-02-2

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 1-(difluoromethyl)-8-phenyl[1,2,4]triazolo[4,3-a][1,5]-naphthyridin-7-yl trifluoromethanesulfonate
• 英文别名: [1-(Difluoromethyl)-8-phenyl-[1,2,4]triazolo[4,3-a][1,5]naphthyridin-7-yl] trifluoromethanesulfonate
• CAS: 1370618-02-2
• 化学式: C₁₇H₉F₅N₄O₃S
• 分子量: 444.341
• InChiKey: CKUAQSGDDWSIGX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  94.8
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  1-(difluoromethyl)-8-phenyl[1,2,4]triazolo[4,3-a][1,5]-naphthyridin-7-yl trifluoromethanesulfonate 、 tert-butyl {trans-3-Hydroxy-3-methyl-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclobutyl}carbamate 在 2-甲基四氢呋喃 、 potassium phosphate 作用下， 以 乙醇 、 水 为溶剂， 反应 26.66h， 生成 trans-3-mmino-3-{4-[1-(difluoromethyl)-8-phenyl-[1,2,4]triazolo[4,3-a][1,5]naphthyridin-7-yl]phenyl}-1-methylcyclobutanol
  参考文献：
  名称：

  Convergent, Kilogram Scale Synthesis of an Akt Kinase Inhibitor

  摘要：

  The development of a convergent, chromatography-free synthesis of an allosteric Akt kinase inhibitor is described. The route comprised 17 total steps and was used to produce kilogram quantities of the target molecule. A key early transformation, for which both batch and flow protocols were developed, was formylation of a dianion derived by deprotonation and subsequent lithium-halogen exchange from a 2-bromo-3-aminopyridine precursor. Improved reaction yield and practicality were achieved in the continuous processing mode. Further significant process developments included the safe execution of a high temperature and pressure hydrazine displacement, separation of substituted cyclobutane diastereomers by means of chemoselective ester hydrolysis, and a late-stage Suzuki fragment coupling under mild conditions.

  DOI：

  10.1021/op300031r
• 作为产物：
  描述：

  2-溴-6-氯吡啶-3-氨基甲酸叔丁酯 在 吡啶 、 1,3-二甲基-2-咪唑啉酮 、 甲基锂 、 caesium carbonate 、 N,N-二异丙基乙胺 、 肼 作用下， 以 四氢呋喃 、 二乙氧基甲烷 、 水 、 乙腈 为溶剂， -55.0~155.0 ℃ 、344.75 kPa 条件下， 反应 20.5h， 生成 1-(difluoromethyl)-8-phenyl[1,2,4]triazolo[4,3-a][1,5]-naphthyridin-7-yl trifluoromethanesulfonate
  参考文献：
  名称：

  Convergent, Kilogram Scale Synthesis of an Akt Kinase Inhibitor

  摘要：

  The development of a convergent, chromatography-free synthesis of an allosteric Akt kinase inhibitor is described. The route comprised 17 total steps and was used to produce kilogram quantities of the target molecule. A key early transformation, for which both batch and flow protocols were developed, was formylation of a dianion derived by deprotonation and subsequent lithium-halogen exchange from a 2-bromo-3-aminopyridine precursor. Improved reaction yield and practicality were achieved in the continuous processing mode. Further significant process developments included the safe execution of a high temperature and pressure hydrazine displacement, separation of substituted cyclobutane diastereomers by means of chemoselective ester hydrolysis, and a late-stage Suzuki fragment coupling under mild conditions.

  DOI：

  10.1021/op300031r