6-benzylsulfanyl-2-iodo-9-(tetrahydropyran-2-yl)-9H-purine | 403620-90-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 6-benzylsulfanyl-2-iodo-9-(tetrahydropyran-2-yl)-9H-purine
• 英文别名: 6-Benzylsulfanyl-2-iodo-9-(oxan-2-yl)purine
• CAS: 403620-90-6
• 化学式: C₁₇H₁₇IN₄OS
• 分子量: 452.319
• InChiKey: ACWLOSPJBJPSIV-UHFFFAOYSA-N

物化性质

• 熔点：
  186-187 °C(Solv: ethanol (64-17-5))
• 沸点：
  632.2±65.0 °C(Predicted)
• 密度：
  1.76±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  78.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-benzylsulfanyl-2-iodo-9-(tetrahydropyran-2-yl)-9H-purine 在 tris(dibenzylideneacetone)dipalladium (0) 偶氮二甲酸二异丙酯 、 三苯基膦 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.17h， 生成 N-(6-benzylsulfanyl-9-isopropyl-9H-purin-2-yl)-3-methylbutyramide
  参考文献：
  名称：

  A Pd(0) based cross-coupling approach to the synthesis of 2-amidopurines and their evaluation as CDK inhibitors

  摘要：

  Two new series of 2-amido- and 2-aminocarbonylpurines have been synthesized using a Pd catalyst cross-coupling reaction either with amides or amines in the presence of CO. Moderate in vitro inhibitory activity against CDK1 and CDK5 was observed with IC50 of 0-9 mu M for the most active compound (18c). (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.10.003
• 作为产物：
  描述：

  6-氯嘌呤 在 三丁基氯化锡 、 2,2,6,6-tetramethylpiperidinyl-lithium 、 对甲苯磺酸 、 三乙胺 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 2.5h， 生成 6-benzylsulfanyl-2-iodo-9-(tetrahydropyran-2-yl)-9H-purine
  参考文献：
  名称：

  Cyclin-dependent kinase (CDK) inhibitors: development of a general strategy for the construction of 2,6,9-trisubstituted purine libraries. Part 1

  摘要：

  To validate a proposed solid support synthesis strategy for the construction of 2,6,9-trisubstituted purine based CDK inhibitors, the N-9 THP protected 6-benzylthio-2-iodopurine 11 was reacted with piperidine-2-methanol to give 12. Alternatively, intermediate It was converted to the C-2 acetylenyl substituted purine 16 in five steps, involving N-9 alkylation (Mitsunobu reaction), a Pd(0)-CuI-catalyzed acetylene coupling, selective activation of the 6-sulfur substituent and its displacement by ArCH2NH2. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(01)01751-8

文献信息

• Traceless solid-phase synthesis of 2,6,9-trisubstituted purines from resin bound 6-thiopurines
  作者：Virginie Brun、Michel Legraverend、David S Grierson

  DOI：10.1016/s0040-4020(02)00905-5

  日期：2002.9

  adapted to solid support, wherein 23 is connected to Merrifield resin via a 6-thiovaleric ester linker. The presence of the linker, in combination with the use of palladacycle type catalysts improved the yield of palladium(0)-catalyzed Suzuki and Sonogashira cross-coupling reactions. This strategy opens a new route to combinatorial chemistry library synthesis of trisubstituted purines on the solid support

  由6-氯嘌呤在三个高产率步骤中获得了6-氯-2-碘-9-四氢吡喃基嘌呤（2）的制备。然后，该衍生物通过与苄硫醇反应在C-6处选择性取代，得到3，这是一种通用的中间体，用于合成2,6,9-三取代的嘌呤。钯催化的交叉偶联反应中3的反应（包括室温下的Sonogashira偶联）以及在C-2处选择性地发生胺类亲核取代。通过氧化成相应的砜将6-硫代苄基取代基活化，并用各种苄基或苯胺代替。此策略随后适应了坚实的支持，其中23通过6-硫代戊酸酯连接基连接到Merrifield树脂。连接子的存在，结合使用palladacycle型催化剂，提高了钯（0）催化的Suzuki和Sonogashira交叉偶联反应的收率。该策略为固体载体上三取代嘌呤的组合化学文库合成开辟了一条新途径。
• Cyclin-dependent kinase (CDK) inhibitors: development of a general strategy for the construction of 2,6,9-trisubstituted purine libraries. Part 2
  作者：Virginie Brun、Michel Legraverend、David S Grierson

  DOI：10.1016/s0040-4039(01)01752-x

  日期：2001.11

  Purine bound resins 1a-c were obtained by the reaction of 6-thiopurines 2 or 6-chloropurines 3-5 with Merrifield-Cl or -SH resins (DMF, 70 degreesC, base). S-Oxidation of resins 1c and reaction of the desired sulfone with p-methoxybenzyl a mine to give 6, proved effective for release of the purine from the resin and simultaneous C-6 substitution. Reaction of resin le with pyrrolidine and pyrrolidine-2-methanol prior to S-oxidation led to the C-2 amine substituted resin bound purines 8 and 9. Activation of sulfur in these intermediates, followed by reaction with Ar CH-NH, gave the 2,6,9-trisubstituted purines 10-14 in 42-60% yields. (C) 2001 Elsevier Science Ltd. All rights reserved.