1-苯基吡唑并[3,4-d]嘧啶 | 53645-79-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 1-苯基吡唑并[3,4-d]嘧啶
• 英文名称: 1-phenyl-1H-pyrazolo[3,4-d]pyrimidine
• 英文别名: 1-phenylpyrazolo[3,4-d]pyrimidine；1-phenyl-1H-pyrazolo[3,4-d]pyrimidine
• CAS: 53645-79-7
• 化学式: C₁₁H₈N₄
• 分子量: 196.211
• InChiKey: BDIXKUKUFWHLIO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  43.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-苯基吡唑并[3,4-d]嘧啶 在 三氯化铝 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 13.58h， 生成 1-苯基吡唑并[3,4-d]嘧啶-4-腈
  参考文献：
  名称：

  Higashino, Takeo; Sato, Susumu; Miyashita, Akira, Chemical and pharmaceutical bulletin, 1986, vol. 34, # 11, p. 4569 - 4576

  摘要：

  DOI：
• 作为产物：
  描述：

  4-iodo-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine 在 indium 、 水 作用下， 反应 2.0h， 以30%的产率得到1-苯基吡唑并[3,4-d]嘧啶
  参考文献：
  名称：

  Dehalogenation and Barbier-Type Hydroxyalkylation of π-Deficient Haloheterocycles Using Indium

  摘要：

  The reaction of pi-deficient haloheterocycles with indium metal in water gave corresponding dehalogenated heterocycles. The use of diluted hydrochloric acid instead of water accelerated the reductive reactivity of indium metal. Furthermore, Barbier-type additions proceeded by reactions of alpha-iodoheterocycles with indium in the presence of pivalaldehyde.

  DOI：

  10.3987/com-08-s(f)95

文献信息

• Carbon-Carbon Bond Cleavage of .ALPHA.-Hydroxybenzylheteroarenes Catalyzed by Cyanide Ion: Retro-Benzoin Condensation Affords Ketones and Heteroarenes and Benzyl Migration Affords Benzylheteroarenes and Arenecarbaldehydes.
  作者：Yumiko SUZUKI、Yuki TAKEMURA、Ken-ichi IWAMOTO、Takeo HIGASHINO、AKira MIYASHITA

  DOI：10.1248/cpb.46.199

  日期：——

  4-(α-Benzyl-α-hydroxybenzyl)quinazoline (4a) underwent retro-benzoin condensation catalyzed by cyanide ion to give deoxybenzoin (2a) and quinazoline (5a). Similarly, several nitrogen-containing heteroarenes (4, 9, 12, 16-19) having an α-hydroxybenzyl group at the α-position of the nitrogen underwent retro-benzoin type condensation to afford ketones (2) and heteroarenes (5). However, similar reaction of pyrazolopyrimidines (13, 14, 15) having an α-benzyl-α-hydroxybenzyl group resulted in benzyl migration, giving benzylpyrazolopyrimidines (8) and arenecarbaldehydes (3). Tetrabutylammonium cyanide (11, Bu4NCN) was a more effective cyanide ion donor than KCN (10). The retro-benzoin condensation was applied to the synthesis of 2-substituted quinazolines (38) from 2-chloro-4-aroylquinazolines (34), using the aroyl group as a protecting and electron-withdrawing group.

  4-(α-苄基-α-羟基苄基)喹唑啉(4a)在氰离子催化下经历逆苯偶姻缩合反应，生成脱氧苯偶姻(2a)和喹唑啉(5a)。同样，多个含氮杂环芳烃(4, 9, 12, 16-19)在其氮原子的α位上具有α-羟基苄基的结构，也经历逆苯偶姻型缩合反应，生成了酮(2)和杂环芳烃(5)。然而，具有α-苄基-α-羟基苄基结构的吡唑嘧啶(13, 14, 15)在类似的反应中引发了苄基迁移，生成了苄基吡唑嘧啶(8)和芳烃羰醛(3)。四丁基铵氰(11, Bu4NCN)比KCN(10)更有效地作为氰离子的供体。逆苯偶姻缩合反应被应用于从2-氯-4-芳酰基喹唑啉(34)合成2-取代喹唑啉(38)，使用芳酰基作为保护和电子 withdrawing 基团。
• PYRAZOLOPYRIMIDINE ANALOGS AND THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS
  申请人：Zask Arie

  公开号：US20080234262A1

  公开（公告）日：2008-09-25

  The present invention relates to Pyrazolopyrimidine Analogs, methods of making Pyrazolopyrimidine Analogs, compositions comprising a Pyrazolopyrimidine Analog, and methods for treating mTOR-related disorders comprising administering to a subject in need thereof an effective amount of a Pyrazolopyrimidine Analog. The invention also relates to treating PI3K-related disorders comprising administering to a subject in need thereof an effective amount of a Pyrazolopyrimidine Analog.

  本发明涉及吡唑吡嘧啶类似物，制备吡唑吡嘧啶类似物的方法，包含吡唑吡嘧啶类似物的组合物，以及治疗mTOR相关疾病的方法，包括向需要的受试者施用有效量的吡唑吡嘧啶类似物。该发明还涉及治疗PI3K相关疾病的方法，包括向需要的受试者施用有效量的吡唑吡嘧啶类似物。
• NOVEL PYRAZOLO [3, 4 -D] PYRIMIDINE DERIVATIVES AS ANTI-CANCER AGENTS
  申请人：Konakanchi Durga Prasad

  公开号：US20100298351A1

  公开（公告）日：2010-11-25

  The invention relates to substituted pyrazolo[3,4-d]pyrimidine derivatives of the Formula-(I), or pharmaceutically-acceptable salts thereof, which possess anti-proliferative activity such as anti-cancer activity and are accordingly useful in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of substituted pyrazolo[3,4-d]pyrimidine derivatives, to pharmaceutical compositions containing the compound and to its use in the manufacture of medicaments for the production of an anti-proliferative effect in a warm-blooded animal such as man.

  该发明涉及式(I)的取代吡唑并[3,4-d]嘧啶衍生物或其药学上可接受的盐，其具有抗增殖活性，如抗癌活性，并因此在人体或动物体的治疗方法中有用。该发明还涉及制备取代吡唑并[3,4-d]嘧啶衍生物的方法，含有该化合物的药物组合物，以及其在制造药物时用于在诸如人类之类的温血动物体内产生抗增殖效果的用途。
• Studies on the reaction of .PI.-deficient heterocycles with aromatic aldehyde in the presence of cyanide ion.
  作者：TAKEO HIGASHINO、MASAMI GOI、EISAKU HAYASHI

  DOI：10.1248/cpb.24.238

  日期：——

  Dimerization of π-deficient heterocyles by the catalytic action of cyanide ion in DMSO was carried out. Thus, reaction of quinoxaline (V), 1-phenyl-1H-pyrazolo [3, 4-d] pyrimidine (VI), 1-methyl-1H-pyrazolo [3, 4-d] pyrimidine (VII), and pyrido [2, 3-b] pyrazine (VIII) with cyanide ion gave 2, 2'-biquinoxaline (IX), 4.4'-bis [1-phenyl-1H-pyrazolo [3, 4-d] pyrimidine] (X), 4, 4'-bis [1-methyl-1H-pyrazolo [3, 4-d] pyrimidine] (XI), and 2, 2'-bipyrido [2, 3-b] pyrazine (XII), respectively, although the yields of these dimers were very poor. The formation of dimer is assumed to be oxidation following a benzoin condensation-like reaction by the catalysis of cyanide ion. Also we carried out the reaction of π-deficient heterocycles with aromatic aldehyde (XVI) in the presence of cyanide ion in DMSO, and found that the expected cross benzoin condensation-like reaction has developed. Thus, 4-isoquinolinecarbonitrile (II) reacted with XVI to give α-aryl-4-cyano-1-isoquinolinemethanol (XIX) and aryl 4-cyano-1-isoquinolyl ketone (XX) together with 1, 1'-biisoquinoline-4, 4'-dicarbonitrile (IV). Similarly, V and XVI gave α-aryl-2-quinoxalinemethanol (XXI) and aryl 2-quinoxalinyl ketone (XXII), VI and XVI afforded α-aryl-1-phenyl-1H-pyrazolo [3, 4-d] pyrimidine-4-methanol (XXX) and aryl 1-phenyl-1H-pyrazolo [3, 4-d] pyrimidin-4-yl ketone (XXXI), VII and XVI produced α-aryl-1-methyl-1H-pyrazolo [3, 4-d] pyrimidine-4-methanol (XXXIV) and aryl 1-methyl-1H-pyrazolo [3, 4-d] pyrimidin-4-yl ketone (XXXV), and VIII and XVI formed aryl 2-pyrido [2, 3-b] pyrazinyl ketone (XXXIV). It seems that XIX, XXI, XXX, and XXXIV are a formal product of a cross benzoin condensation-like reaction, and XX, XXII, XXXI, XXXV, and XXXVI are oxidation product of a formal product of the reaction. And limitation of this reaction was also discussed.

  在DMSO中，通过氰离子的催化作用进行了π缺乏杂环的二聚反应。因此，喹喔啉（V）、1-苯基-1H-吡唑[3, 4-d]嘧啶（VI）、1-甲基-1H-吡唑[3, 4-d]嘧啶（VII）和吡啶[2, 3-b]嘧啶（VIII）与氰离子的反应分别生成了2, 2'-双喹喔啉（IX）、4, 4'-双[1-苯基-1H-吡唑[3, 4-d]嘧啶]（X）、4, 4'-双[1-甲基-1H-吡唑[3, 4-d]嘧啶]（XI）和2, 2'-双吡啶[2, 3-b]嘧啶（XII），尽管这些二聚体的产率非常低。假定二聚体的形成是氰离子催化下通过类似苯醇缩合反应的氧化反应。此外，我们还在氰离子的存在下，使用DMSO进行了π缺乏杂环与香豆醛（XVI）的反应，并发现预期的交叉苯醇缩合似反应得以进行。因此，4-异喹啉腈（II）与XVI反应生成α-芳基-4-氰-1-异喹啉甲醇（XIX）和芳基4-氰-1-异喹啉酮（XX），以及1, 1'-双异喹啉-4, 4'-二腈（IV）。类似地，V与XVI反应生成α-芳基-2-喹喔啉甲醇（XXI）和芳基2-喹喔啉酮（XXII），VI与XVI生成α-芳基-1-苯基-1H-吡唑[3, 4-d]嘧啶-4-甲醇（XXX）和芳基1-苯基-1H-吡唑[3, 4-d]嘧啶-4-酮（XXXI），VII与XVI生成α-芳基-1-甲基-1H-吡唑[3, 4-d]嘧啶-4-甲醇（XXXIV）和芳基1-甲基-1H-吡唑[3, 4-d]嘧啶-4-酮（XXXV），而VIII与XVI生成芳基2-吡啶[2, 3-b]嘧啶酮（XXXVI）。看起来XIX、XXI、XXX和XXXIV是交叉苯醇缩合类似反应的形式产物，而XX、XXII、XXXI、XXXV和XXXVI是该反应形式产物的氧化产物。同时还讨论了该反应的局限性。
• Higashino, Takeo; Sato, Susumu; Miyashita, Akira, Chemical and pharmaceutical bulletin, 1987, vol. 35, # 12, p. 4803 - 4812
  作者：Higashino, Takeo、Sato, Susumu、Miyashita, Akira、Katori, Tatsuhiko

  DOI：——

  日期：——

表征谱图