3-[5-[[6-(Tert-butylamino)-1-(oxan-2-yl)pyrazolo[3,4-b]pyridin-3-yl]methoxy]-2-chlorophenoxy]-5-chlorobenzonitrile | 1134115-00-6

• 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: 3-[5-[[6-(Tert-butylamino)-1-(oxan-2-yl)pyrazolo[3,4-b]pyridin-3-yl]methoxy]-2-chlorophenoxy]-5-chlorobenzonitrile
• CAS: 1134115-00-6
• 化学式: C₂₉H₂₉Cl₂N₅O₃
• 分子量: 566.487
• InChiKey: XVCQQHQEVVBXPN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  39
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  94.2
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-[5-[[6-(Tert-butylamino)-1-(oxan-2-yl)pyrazolo[3,4-b]pyridin-3-yl]methoxy]-2-chlorophenoxy]-5-chlorobenzonitrile 在 1-辛硫醇 、 硫酸 作用下， 以 乙腈 为溶剂， 反应 1.5h， 以95%的产率得到3-{5-(6-tert-butylamino-1H-pyrazolo[3,4-b]pyridin-3-ylmethoxy)-2-chlorophenoxy}-5-chlorobenzonitrile bis-sulfate salt
  参考文献：
  名称：

  Development of a Sequential Tetrahydropyran and Tertiary Butyl Deprotection: High-Throughput Experimentation, Mechanistic Analysis, and DOE Optimization

  摘要：

  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%.

  DOI：

  10.1021/op8002739
• 作为产物：
  描述：

  3-氯-5-(2-氯-5-羟基苯氧基)苯甲腈 、 [6-tert-butylamino-1-(tetrahydropyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl]methanol 在 甲基磺酰氯 、 N,N-二异丙基乙胺 、 cesium fluoride 、 potassium iodide 作用下， 以 2-甲基四氢呋喃 、 N,N-二甲基乙酰胺 为溶剂， 反应 12.0h， 以93%的产率得到3-[5-[[6-(Tert-butylamino)-1-(oxan-2-yl)pyrazolo[3,4-b]pyridin-3-yl]methoxy]-2-chlorophenoxy]-5-chlorobenzonitrile
  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