tert-butyl 6-[2-methoxyethenyl]-4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxylate | 1233706-56-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: tert-butyl 6-[2-methoxyethenyl]-4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxylate
• CAS: 1233706-56-3
• 化学式: C₁₈H₂₀N₂O₄
• 分子量: 328.368
• InChiKey: DNTHDIVWCDTCDB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.34
• 重原子数：
  24.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  62.58
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  ethyl (2-formyl-6-nitrophenoxy)acetate 在 盐酸 、 tin(II) chloride dihdyrate 、 potassium tert-butylate 、 氯磷酸二乙酯 作用下， 以 四氢呋喃 、 2-甲基四氢呋喃 、 水 为溶剂， 反应 1.0h， 生成 、 tert-butyl 6-[2-methoxyethenyl]-4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxylate
  参考文献：
  名称：

  Development of an Efficient Large-Scale Synthesis for a 4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxamide Derivative for Depression and Anxiety

  摘要：

  The development and scale-up of an optimized synthesis for a novel drug candidate for depression and anxiety is presented. The updated synthesis represents a convergent and efficient four-stage approach to the API, overcoming high cost of goods (COG), general lack of convergence, and low yield of previous routes. A lower cost of goods resulted from using 3-nitrosalicylaldehyde as a starting material and introducing the expensive side chain (2-methyl-5-(piperazin-1-yl)quinoline) at a later stage. Green chemistry principles were applied when a direct amidation enabled a straightforward conversion of the 4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxylate to the corresponding amide in the last step. In addition, the total number of stages was reduced from seven to four, and solvent usage was greatly minimized. The modified synthesis NUS demonstrated on a kilogram pilot scale, allowing the isolation of the API in 17% overall yield with the required purity.

  DOI：

  10.1021/op100103v