1-[[2-(Trifluoromethyl)phenyl]methyl]indazole-5-carbaldehyde | 1548128-59-1

• 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-[[2-(Trifluoromethyl)phenyl]methyl]indazole-5-carbaldehyde
• CAS: 1548128-59-1
• 化学式: C₁₆H₁₁F₃N₂O
• 分子量: 304.271
• InChiKey: KRGWVIZHGSMENO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  34.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-bromo-1-(4-chloro-2-(trifluoromethyl)benzyl)-1H-indazole-5-carbaldehyde 在 5%-palladium/activated carbon 、 水 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 20.0 ℃ 、34.47 kPa 条件下， 反应 3.0h， 以97%的产率得到1-(4-hloro-2-(trifluoromethyl)benzyl)-1H-indazole-5-carbaldehyde
  参考文献：
  名称：

  Process Development for Scale-Up of a Novel 3,5-Substituted Thiazolidine-2,4-dione Compound as a Potent Inhibitor for Estrogen-Related Receptor 1

  摘要：

  The development of a reproducible process for multihundred gram production of (Z)-5-((1-(4-chloro-2-(trifluoromethyl)benzyl)-1H-indazol-5-yl)methylene)-3-((3R,4R)-3-fluoro-1-methylpiperidin-4-yl)thiazolidine-2,4-dione (26), a potent and selective inhibitor of estrogen-related receptor 1 (ERR!), is described. This multihundred gram synthesis was achieved via magnesium perchlorate-catalyzed regioselective epoxide ring-opening of tert-butyl 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate (9) with thiazolidine-2,4-dione (6, TZD) to form a diastereomeric mixture tert-butyl 4-(2,4-dioxothiazolidin-3-yl)-3-hydroxypiperidine-1-carboxylate (17), of which the 3-hydroxyl group was functionally transformed to 3-fluoro derivative 19 after treatment with Deoxo-Fluor. Chiral separation of 19 provided the desired diastereomer (3R,4R)-21 that was converted to the secondary amine 23 TFA salt. Reductive amination of 23 produced the key intermediate N-methyl 24. Knoevenagel condensation of 24 with 1-(4-chloro-2-(trifluoromethyl)benzyl)-1H-indazole-5-carbaldehyde (5) produced the final product 26 in 10% overall yield (99.7% HPLC area% with >= 99.5% de) after a convergent eight synthetic steps with the only column purification being the chiral HPLC separation of 3R,4R-21 from 3S,4S-22.

  DOI：

  10.1021/op400325r