4,6-二氯-5-硝基-2-嘧啶胺 | 134716-82-8

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 中文名称: 4,6-二氯-5-硝基-2-嘧啶胺
• 英文名称: 2-amino-4,6-dichloro-5-nitropyrimidine
• 英文别名: 4,6-Dichloro-5-nitropyrimidin-2-amine
• CAS: 134716-82-8
• 化学式: C₄H₂Cl₂N₄O₂
• mdl: MFCD17169373
• 分子量: 208.991
• InChiKey: KIOZJDBYVRMAGM-UHFFFAOYSA-N

物化性质

• 熔点：
  248-250℃
• 密度：
  1.834±0.06 g/cm3 (20℃ 760 Torr)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  97.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4,6-二氯-5-硝基-2-嘧啶胺 、 4,4'-二氨基二苯甲烷 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成
  参考文献：
  名称：

  Towards more specific O6-methylguanine-DNA methyltransferase (MGMT) inactivators

  摘要：

  Searching for a novel family of inactivators of the human DNA repair protein O-6-methylguanine-DNA methyltransferase (MGMT) which is known to bind to the DNA minor groove, we have computationally modelled and synthesised two series of 2-amino-6-aryloxy-5-nitropyrimidines with morpholino or aminodiaryl substituents (potential minor groove binders) at the 4-position. Synthesis of these compounds was achieved by successive substitution of each of the two Cl atoms of 2-amino-4,6-dichloro-nitropyrimidine by the corresponding amino and aryloxy derivatives. Biochemical evaluation of these compounds as MGMT inactivators showed poor activities, but in general the 4-bromothenyloxy derivatives showed better inactivation than the benzyloxy versions. DNA binding assessment was not possible due to insolubility problems. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.01.038
• 作为产物：
  描述：

  2-氨基-4,6-二氯嘧啶 在 硫酸 、 硝酸 作用下， 以 三氟乙酸酐 为溶剂， 反应 48.0h， 以73%的产率得到4,6-二氯-5-硝基-2-嘧啶胺
  参考文献：
  名称：

  一种2-氨基-4,6-二氯-5-硝基嘧啶的制备方法

  摘要：

  本发明公开了一种2‑氨基‑4,6‑二氯‑5‑硝基嘧啶的制备方法，其包括如下步骤：(1)使2‑氨基‑6‑羟基‑4[1H]‑嘧啶酮经氯化反应生成2‑氨基‑4,6‑二氯嘧啶；(2)使2‑氨基‑4,6‑二氯嘧啶与硝化试剂在酸或酸酐中反应，生成2‑氨基‑4,6‑二氯‑5‑硝基嘧啶；其中，硝化试剂为浓硝酸，浓硝酸为质量分数为55％‑85％的硝酸水溶液，酸为浓硫酸，浓硫酸为质量分数为70％‑98.5％的硫酸水溶液，酸酐为三氟乙酸酐和/或醋酸酐，该方法不仅步骤少，而且收率高、纯度好，使得成本低、操作工艺简单，适于工业化应用。

  公开号：

  CN113292506B

文献信息

• Syntheses of 2-amino-4,6-dichloro-5-nitropyrimidine and 2-amino-4,5,6-trichloropyrimidine: an unusual aromatic substitution
  作者：Sergio Lopez、Thomas McCabe、R. Stanley McElhinney、T. Brian H. McMurry、Isabel Rozas

  DOI：10.1016/j.tetlet.2009.08.029

  日期：2009.11

  2-Amino-4,6-dichloro-5-nitropyrimidine is an intermediate required for the preparation of nitropyrimidines as inactivators of the DNA repairing protein MGMT. When attempting its synthesis, 2-amino-4,5,6-trichloropyrimidine is obtained instead, via unusual aromatic substitution of the nitro group in 2-amino-4-hydroxy-5-nitropyrimidin-6-one by chloride. The synthesis, the reactivity of 4,5,6-trichloropyrimidine and the efficient preparation of 2-amino-4,6-dichloro-5-nitropyrimidine are presented. (C) 2009 Elsevier Ltd. All rights reserved.
• US4988703A
  申请人：——

  公开号：US4988703A

  公开（公告）日：1991-01-29
• 一种2-氨基-4,6-二氯-5-硝基嘧啶的制备方法
  申请人：江苏美迪克化学品有限公司

  公开号：CN113292506B

  公开（公告）日：2022-04-29

  本发明公开了一种2‑氨基‑4,6‑二氯‑5‑硝基嘧啶的制备方法，其包括如下步骤：(1)使2‑氨基‑6‑羟基‑4[1H]‑嘧啶酮经氯化反应生成2‑氨基‑4,6‑二氯嘧啶；(2)使2‑氨基‑4,6‑二氯嘧啶与硝化试剂在酸或酸酐中反应，生成2‑氨基‑4,6‑二氯‑5‑硝基嘧啶；其中，硝化试剂为浓硝酸，浓硝酸为质量分数为55％‑85％的硝酸水溶液，酸为浓硫酸，浓硫酸为质量分数为70％‑98.5％的硫酸水溶液，酸酐为三氟乙酸酐和/或醋酸酐，该方法不仅步骤少，而且收率高、纯度好，使得成本低、操作工艺简单，适于工业化应用。
• Towards more specific O6-methylguanine-DNA methyltransferase (MGMT) inactivators
  作者：Sergio Lopez、Geoffrey P. Margison、R. Stanley McElhinney、Alessandra Cordeiro、T. Brian H. McMurry、Isabel Rozas

  DOI：10.1016/j.bmc.2011.01.038

  日期：2011.3

  Searching for a novel family of inactivators of the human DNA repair protein O-6-methylguanine-DNA methyltransferase (MGMT) which is known to bind to the DNA minor groove, we have computationally modelled and synthesised two series of 2-amino-6-aryloxy-5-nitropyrimidines with morpholino or aminodiaryl substituents (potential minor groove binders) at the 4-position. Synthesis of these compounds was achieved by successive substitution of each of the two Cl atoms of 2-amino-4,6-dichloro-nitropyrimidine by the corresponding amino and aryloxy derivatives. Biochemical evaluation of these compounds as MGMT inactivators showed poor activities, but in general the 4-bromothenyloxy derivatives showed better inactivation than the benzyloxy versions. DNA binding assessment was not possible due to insolubility problems. (C) 2011 Elsevier Ltd. All rights reserved.