sodium 6-tert-butyl-4-ethoxynicotinate | 1415334-30-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: sodium 6-tert-butyl-4-ethoxynicotinate
• 英文别名: Sodium 6-tert-butyl-4-ethoxynicotinate；sodium;6-tert-butyl-4-ethoxypyridine-3-carboxylate
• CAS: 1415334-30-3
• 化学式: C₁₂H₁₆NO₃*Na
• 分子量: 245.254
• InChiKey: FHOJKQARBCEHHV-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -1.85
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  62.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  sodium 6-tert-butyl-4-ethoxynicotinate 在 2,6-二甲基吡啶 、 四磷十氧化物 、 sodium carbonate 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 2-甲基四氢呋喃 、 二氯甲烷 、 水 、 乙酸乙酯 、 甲苯 为溶剂， 反应 3.17h， 生成 2-{1-[(4S,5R)-2-(6-tert-butyl-4-ethoxy-pyridin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperidin-4-yl}-acetamide
  参考文献：
  名称：

  Efficient Large-Scale Synthesis of a 2,4,5-Triarylimidazoline MDM2 Antagonist

  摘要：

  An improved, kilogram-scale synthesis of a triarylimidazoline MDM2 antagonist is reported. The nicotinic acid component was prepared in three steps from ethyl 2-dimethylaminomethylene-3-oxo-butyrate. The coupling of the nicotinic acid with the meso-diamine selectively produced the monoamide which was cyclized in the presence of p-TSA/pyridine to give the imidazoline core. Phosgenation using bis(trichloromethyl) carbonate provided the key carbamoyl chloride intermediate, which was coupled with the side-chain amine, followed by chiral resolution with (R)-camphorsulfonic acid to give the final API.

  DOI：

  10.1021/op300294g
• 作为产物：
  描述：

  ethyl 2-[(dimethylamino)methylene]-3-oxobutanoate 在 potassium carbonate 、 sodium hydroxide 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.33h， 生成 sodium 6-tert-butyl-4-ethoxynicotinate
  参考文献：
  名称：

  Efficient Large-Scale Synthesis of a 2,4,5-Triarylimidazoline MDM2 Antagonist

  摘要：

  An improved, kilogram-scale synthesis of a triarylimidazoline MDM2 antagonist is reported. The nicotinic acid component was prepared in three steps from ethyl 2-dimethylaminomethylene-3-oxo-butyrate. The coupling of the nicotinic acid with the meso-diamine selectively produced the monoamide which was cyclized in the presence of p-TSA/pyridine to give the imidazoline core. Phosgenation using bis(trichloromethyl) carbonate provided the key carbamoyl chloride intermediate, which was coupled with the side-chain amine, followed by chiral resolution with (R)-camphorsulfonic acid to give the final API.

  DOI：

  10.1021/op300294g

文献信息

• Efficient Large-Scale Synthesis of a 2,4,5-Triarylimidazoline MDM2 Antagonist
  作者：Lianhe Shu、Chen Gu、Yan Dong、Robert Brinkman

  DOI：10.1021/op300294g

  日期：2012.12.21

  An improved, kilogram-scale synthesis of a triarylimidazoline MDM2 antagonist is reported. The nicotinic acid component was prepared in three steps from ethyl 2-dimethylaminomethylene-3-oxo-butyrate. The coupling of the nicotinic acid with the meso-diamine selectively produced the monoamide which was cyclized in the presence of p-TSA/pyridine to give the imidazoline core. Phosgenation using bis(trichloromethyl) carbonate provided the key carbamoyl chloride intermediate, which was coupled with the side-chain amine, followed by chiral resolution with (R)-camphorsulfonic acid to give the final API.