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 | 1005407-72-6

• 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 (4S)-2,2,4-trimethyl-4-{5-[4-(n-octyloxy)-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}-1,3-oxazolidine-3-carboxylate
• 英文别名: (S)-tert-butyl 2,2,4-trimethyl-4-(5-(4-(octyloxy)-3-(trifluoromethyl)phenyl)-1,3,4-thiadiazol-2-yl)oxazolidine-3-carboxylate；1,1-dimethylethyl (4S)-2,2,4-trimethyl-4-{5-[4-(octyloxy)-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}-1,3-oxazolidine-3-carboxylate；tert-butyl (4S)-2,2,4-trimethyl-4-[5-[4-octoxy-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl]-1,3-oxazolidine-3-carboxylate
• CAS: 1005407-72-6
• 化学式: C₂₈H₄₀F₃N₃O₄S
• 分子量: 571.705
• InChiKey: JIZPPOGARFLXAH-MHZLTWQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.6
• 重原子数：
  39
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  102
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  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 作用下， 以 醋酸异丙酯 、 水 、 甲苯 为溶剂， 反应 34.0h， 生成 1,1-dimethylethyl ((1S)-2-hydroxy-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
• 作为产物：
  描述：

  4-氟-3-(三氟甲基)苯甲酸 在 劳森试剂 、 sodium hexamethyldisilazane 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 2-甲基四氢呋喃 、 异丙醇 为溶剂， 反应 32.5h， 生成 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
  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

文献信息

• [EN] THE HEMI-FUMARATE SALT OF A 1,3,4-THIADIAZOLYL DERIVATIVE AS MODULATOR OF THE SPHINGOSINE 1-PHOSPHATE RECEPTOR<br/>[FR] SEL HÉMI-FUMARATE D'UN DÉRIVÉ DE 1,3,4-THIADIAZOLYLE COMME MODULATEUR DU RÉCEPTEUR DE LA SPHINGOSINE 1-PHOSPHATE
  申请人：GLAXO GROUP LTD

  公开号：WO2009098193A1

  公开（公告）日：2009-08-13

  The invention relates to the compound (2S)-2-amino-2-5-[4-(octyloxy)-3- (trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}-1-propanol hemi-fumarate, processes for its preparation, pharmaceutical compositions containing them and its use in the treatment of conditions or disorders which are mediated via the S1 P1 receptor.

  该发明涉及化合物（2S）-2-氨基-2-5-[4-(辛氧基)-3-（三氟甲基）苯基]-1,3,4-噻二唑-2-基}-1-丙醇半富马酸盐，其制备方法，含有该化合物的药物组合物以及其在通过S1 P1受体介导的病症或紊乱的治疗中的用途。
• HEMI-FUMARATE SALT OF A 1,3,4-THIADIAZOLYL DERIVATIVE AS MODULATOR OF THE SPHINGOSINE 1-PHOSPHATE RECEPTOR
  申请人：Anson Michael Simon

  公开号：US20110034524A1

  公开（公告）日：2011-02-10

  The invention relates to the compound (2S)-2-amino-2-5-[4-(octyloxy)-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}-1-propanol hemi-fumarate, processes for its preparation, pharmaceutical compositions containing them and its use in the treatment of conditions or disorders which are mediated via the S1P1 receptor.

  本发明涉及化合物(2S)-2-氨基-2-5-[4-(辛氧基)-3-(三氟甲基)苯基]-1,3,4-噻二唑-2-基}-1-丙醇半富马酸盐、其制备方法、含有该化合物的药物组合物以及其在治疗通过S1P1受体介导的疾病或疾病中的应用。
• WO2008/16692
  申请人：——

  公开号：——

  公开（公告）日：——
• THE HEMI-FUMARATE SALT OF A 1,3,4-THIADIAZOLYL DERIVATIVE AS MODULATOR OF THE SPHINGOSINE 1-PHOSPHATE RECEPTOR
  申请人：Glaxo Group Limited

  公开号：EP2252603A1

  公开（公告）日：2010-11-24
• Development of a Fully Telescoped Synthesis of the S1P1 Agonist GSK1842799
  作者：Michael S. Anson、Jonathan P. Graham、Alastair J. Roberts

  DOI：10.1021/op2000095

  日期：2011.5.20

  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.