3-{5-(6-amino-1H-pyrazolo[3,4-b]pyridin-3-ylmethoxy)-2-chlorophenoxy}-5-chlorobenzonitrile p-toluenesulfonate salt | 1134115-04-0

• 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: 3-{5-(6-amino-1H-pyrazolo[3,4-b]pyridin-3-ylmethoxy)-2-chlorophenoxy}-5-chlorobenzonitrile p-toluenesulfonate salt
• 英文别名: 3-{5-(6-amino-1H-pyrazolo[3,4-b]pyridin-3-ylmethoxy)-2-chlorophenoxy}-5-chlorobenzonitrile tosylate salt
• CAS: 1134115-04-0
• 化学式: C₇H₈O₃S*C₂₀H₁₃Cl₂N₅O₂
• 分子量: 598.466
• InChiKey: FUCFAXUUOSNZCX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.33
• 重原子数：
  40.0
• 可旋转键数：
  6.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  164.21
• 氢给体数：
  3.0
• 氢受体数：
  8.0

反应信息

• 作为产物：
  描述：

  在 三氟乙酸 作用下， 以 乙腈 为溶剂， 反应 2.5h， 以65%的产率得到3-{5-(6-amino-1H-pyrazolo[3,4-b]pyridin-3-ylmethoxy)-2-chlorophenoxy}-5-chlorobenzonitrile p-toluenesulfonate salt
  参考文献：
  名称：

  Development of practical syntheses of potent non-nucleoside reverse transcriptase inhibitors

  摘要：

  The development of practical and efficient syntheses of the potent non-nucleoside reverse transcriptase inhibitors I and 2 is described. The preparation of I proceeded in four synthetic steps and in 48% overall yield from 3. The long-term synthesis of 2 proceeded in nine synthetic steps and in 47% overall yield from commercially available 2,6-diflurorpyridine. The route to 2 was highlighted by the three-step synthesis of intermediate 22 and the high yielding coupling between 18 and phenol 8. The overall sequence required no chromatography and has successfully been utilized for the manufacture of 2 on large scale. (C) 2009 Published by Elsevier Ltd.

  DOI：

  10.1016/j.tet.2009.03.084

文献信息

• Development of a Sequential Tetrahydropyran and Tertiary Butyl Deprotection: High-Throughput Experimentation, Mechanistic Analysis, and DOE Optimization
  作者：Jeffrey T. Kuethe、David M. Tellers、Steven A. Weissman、Nobuyoshi Yasuda

  DOI：10.1021/op8002739

  日期：2009.5.15

  The synthesis of compound 1 by deprotection of the THP, tert-butyl protected amino-pyrazolopyridine (2), is described. The original conditions for this transformation were conducted in a one-pot procedure and necessitated the use of large quantities of either TsOH or benzenesulfonic acid (5 equiv) and trifluoroacetic acid (10-25 equiv) and produced I in moderate yield (50-65%). A series of high-throughput screens of Bronstead acids, Lewis acids, and solvents was rapidly performed with the goal of identifying improved efficiency and reaction yield. Through these screens, sulfuric acid was discovered to be a suitable replacement; however, yields of I were still unacceptable. A decoupling of the two deprotection steps revealed that the THP byproduct resulting from removal of the THP protecting group was problematic in the subsequent removal of the tert-butyl group. Consequently, a two-step deprotection protocol was developed which, in combination with design of experiment (DOE) optimization, improved the overall yield to similar to 86%.