6-[(2-chloropyridin-4-yl)methoxy]-7H-purin-2-amine | 192441-48-8

• 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-[(2-chloropyridin-4-yl)methoxy]-7H-purin-2-amine
• CAS: 192441-48-8
• 化学式: C₁₁H₉ClN₆O
• 分子量: 276.685
• InChiKey: NQPVJXJZVAREAC-UHFFFAOYSA-N

物化性质

• 沸点：
  694.6±65.0 °C(Predicted)
• 密度：
  1.592±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-[(2-chloropyridin-4-yl)methoxy]-7H-purin-2-amine 、 8-bromooctyl 2,3,4,6-tetra-O-benzoyl-β-D-glucopyranoside 在 lithium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以40%的产率得到[(2R,3R,4S,5R,6R)-6-[8-[2-amino-6-[(2-chloropyridin-4-yl)methoxy]purin-9-yl]octoxy]-3,4,5-tribenzoyloxyoxan-2-yl]methyl benzoate
  参考文献：
  名称：

  Synthesis of 2-amino-6-(2-[18F]fluoro-pyridine-4-ylmethoxy)-9-(octyl-β-d-glucosyl)-purine: a novel radioligand for positron emission tomography studies of the O6-methylguanine-DNA methyltransferase (MGMT) status of tumour tissue

  摘要：

  The synthesis of the novel glucose conjugated O-6-methylguanine-DNA methyltransferase (MGMT) inhibitor 2-amino-6-(2-[F-18]fluoro-pyridine-4-ylmethoxy)-9-(octyl-alpha-D-glucosyl)-purine is reported. This compound might serve as a radiotracer for the determination of the MGMT status of tumour tissue. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(02)01394-1
• 作为产物：
  描述：

  2-氯吡啶-4-甲酰氯 在 sodium tetrahydroborate 、 sodium hydride 作用下， 反应 2.0h， 生成 6-[(2-chloropyridin-4-yl)methoxy]-7H-purin-2-amine
  参考文献：
  名称：

  Inactivation of O⁶-Alkylguanine-DNA Alkyltransferase. 1. Novel O⁶-(Hetarylmethyl)guanines Having Basic Rings in the Side Chain

  摘要：

  A number of novel guanine derivatives containing heterocyclic moieties at the O-6-position have been synthesized using a purine quaternary salt which reacts with alkoxides under mild conditions. Initially O-6-substituents were investigated in which the benzene ring of the known agent, O-6-benzylguanine, was replaced by unsubstituted heterocyclic rings. The ability of these agents to inactivate the DNA repair protein O-6-alkylguanine-DNA alkyltransferase (ATase), both as pure recombinant protein and in the human lymphoblastoid cell line Raji, has been compared with that of O-6-benzylguanine. The present paper focuses on O-6-substituents with basic rings, and under standard conditions several of them proved more effective than benzyl for inactivation of both recombinant and Raji ATase. Among the pyridine derivatives, the 2-picolyl compound 7 is not very active in contrast to the 3- and 4-picolyl compounds, and this influenced our choice of isomers of other basic ring systems for study. Since halogen substitution in the thiophene ring considerably increased the activity (17 versus 6), similar modifications in the pyridine series were examined. The more polar O-6-substituents in this study are on the whole compatible with the stereochemical requirements of the ATase protein, and their pharmacological properties may be valuable in subsequent in vivo investigations, particularly the thenyl (6), 5-thiazolylmethyl (12), 5-bromothenyl (17), and 2-chloro-4-picolyl (21) derivatives.

  DOI：

  10.1021/jm9708644

文献信息

• Dimethylpyridin-4-ylamine-Catalysed Alcoholysis of 2-Amino-N,N,N-Trimethyl-9H-purine-6-ylammonium Chloride: An Effective Route to O6-Substituted Guanine Derivatives from Alcohols with Poor Nucleophilicity
  作者：Ralf Schirrmacher、Björn Wängler、Esther Schirrmacher、Thorsten August、F. Rösch

  DOI：10.1055/s-2002-20970

  日期：——

  (DMAP)-catalysed reactions of 2-amino-N,N,N-trimethyl-9H-purine-6-ylammonium chloride with fluoropyridine methoxides and various other alkoxides in DMSO at 60 °C gave the corresponding coupling products in moderate to good yields between 20-87%. Under these reaction conditions, fluorinated O 6 -substituted Guanine derivatives have been synthesized which could not be obtained via known analogous literature

  二甲基吡啶-4-基胺 (DMAP) 催化 2-氨基-N,N,N-三甲基-9H-嘌呤-6-基氯化铵与氟吡啶甲醇盐和各种其他醇盐在 DMSO 中在 60 °C 反应得到相应的偶联产物中等至良好的产量在 20-87% 之间。在这些反应条件下，合成了氟化的O 6 -取代的鸟嘌呤衍生物，其不能通过已知的类似文献程序获得。使用该方法可以显着提高已知O 6 取代鸟嘌呤衍生物的各自产率。因此已经证明了在 O 6 取代的鸟嘌呤衍生物的合成中，DMAP 作为一种优异的亲核催化剂的有效使用。