1,1-dimethylethyl ((1S)-2-{[bis(ethyloxy)phosphoryl]oxy}-1-methyl-1-{5-[4-(n-octyloxy)-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}ethyl)carbamate | 1277165-17-9

• 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: 1,1-dimethylethyl ((1S)-2-{[bis(ethyloxy)phosphoryl]oxy}-1-methyl-1-{5-[4-(n-octyloxy)-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}ethyl)carbamate
• CAS: 1277165-17-9
• 化学式: C₂₉H₄₅F₃N₃O₇PS
• 分子量: 667.727
• InChiKey: FJOQTJJIIWPZRR-NDEPHWFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.9
• 重原子数：
  44.0
• 可旋转键数：
  18.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  118.1
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  1,1-dimethylethyl ((1S)-2-{[bis(ethyloxy)phosphoryl]oxy}-1-methyl-1-{5-[4-(n-octyloxy)-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}ethyl)carbamate 在 三甲基溴硅烷 作用下， 以 二氯甲烷 为溶剂， 反应 23.0h， 以90%的产率得到(S)-2-amino-2-(5-(4-(octyloxy)-3-(trifluoromethyl)phenyl)-1,3,4-thiadiazol-2-yl)propyldihydrogen phosphate
  参考文献：
  名称：

  Development of a Fully Telescoped Synthesis of the S1P1 Agonist GSK1842799

  摘要：

  The development of a fully telescoped synthesis of the potent and selective S1P1 agonist GSK1842799 is described. Key features in the synthesis, which has been implemented on a multikilogram scale, include a nucleophilic aromatic substitution to install a lipophilic 1-octyloxy chain, introduction of a chiral quaternary centre, and the use of Lawesson's reagent to form a thiadiazole ring. Due to the lack of crystalline intermediates, workup protocols that took advantage of the lipophilic nature of the compounds were developed. This allowed full combination of the five chemistry stages and a salt formation, with the only isolation being that of the final hemifumarate salt of the drug substance. The synthesis of the O-phosphorylated active metabolite is also described.

  DOI：

  10.1021/op2000095
• 作为产物：
  描述：

  1,1-dimethylethyl (4S)-2,2,4-trimethyl-4-{5-[4-(n-octyloxy)-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}-1,3-oxazolidine-3-carboxylate 在 硫酸 、 水 、 碳酸氢钠 、 三乙胺 作用下， 以 醋酸异丙酯 、 水 、 甲苯 为溶剂， 反应 40.0h， 生成 1,1-dimethylethyl ((1S)-2-{[bis(ethyloxy)phosphoryl]oxy}-1-methyl-1-{5-[4-(n-octyloxy)-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}ethyl)carbamate
  参考文献：
  名称：

  Development of a Fully Telescoped Synthesis of the S1P1 Agonist GSK1842799

  摘要：

  The development of a fully telescoped synthesis of the potent and selective S1P1 agonist GSK1842799 is described. Key features in the synthesis, which has been implemented on a multikilogram scale, include a nucleophilic aromatic substitution to install a lipophilic 1-octyloxy chain, introduction of a chiral quaternary centre, and the use of Lawesson's reagent to form a thiadiazole ring. Due to the lack of crystalline intermediates, workup protocols that took advantage of the lipophilic nature of the compounds were developed. This allowed full combination of the five chemistry stages and a salt formation, with the only isolation being that of the final hemifumarate salt of the drug substance. The synthesis of the O-phosphorylated active metabolite is also described.

  DOI：

  10.1021/op2000095