benzyl-(2,6-dichloro-pyrimidin-4-yl)-carbamic acid tert-butyl ester | 270929-33-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: benzyl-(2,6-dichloro-pyrimidin-4-yl)-carbamic acid tert-butyl ester
• 英文别名: Tert-butyl benzyl(2,6-dichloropyrimidin-4-yl)carbamate；tert-butyl N-benzyl-N-(2,6-dichloropyrimidin-4-yl)carbamate
• CAS: 270929-33-4
• 化学式: C₁₆H₁₇Cl₂N₃O₂
• 分子量: 354.236
• InChiKey: GMPXTUCZSNXJCY-UHFFFAOYSA-N

物化性质

• 沸点：
  479.4±40.0 °C(Predicted)
• 密度：
  1.321±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  55.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  benzyl-(2,6-dichloro-pyrimidin-4-yl)-carbamic acid tert-butyl ester 在 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 N-benzyl-2-chloro-N'-phenethyl-pyrimidine-4,6-diamine
  参考文献：
  名称：

  2,4,6-氯二氨基和三氨基嘧啶的无痕固相合成

  摘要：

  已经开发了通过聚合物结合的4-烷氧基羰基氨基-2,6-二氯嘧啶的氨基脱氯反应有效地无痕固相合成氯二氨基嘧啶的方法。从聚合物中释放后，尽管具有适度的区域控制，但仍以良好至优异的纯度获得了目标分子。固体负载的N-烷氧基羰基-氯代-二氨基嘧啶与仲胺的进一步反应在温和条件下以良好的纯度提供了三氨基嘧啶，而到目前为止，在所探索的条件下亲核性较弱的伯胺表现不佳。

  DOI：

  10.1016/s0040-4020(03)01097-4
• 作为产物：
  描述：

  2,4,6-三氯嘧啶 、 苄基-氨基甲酸叔丁酯 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 1.5h， 以22%的产率得到benzyl-(2,6-dichloro-pyrimidin-4-yl)-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Blocking Estrogen Signaling After the Hormone: Pyrimidine-Core Inhibitors of Estrogen Receptor-Coactivator Binding

  摘要：

  As an alternative approach to blocking estrogen action, we have developed small molecules that directly disrupt the key estrogen receptor (ER)/coactivator interaction necessary for gene activation. The more direct, protein-protein nature of this disruption might be effective even in hormone-refractory breast cancer. We have synthesized a pyrimidine-core library of moderate size, members of which act as a-helix mimics to block the ER alpha/coactivator interaction. Structure-activity relationships have been explored with various C-, N-, O-, and S-substituents on the pyrimidine core. Time-resolved fluorescence resonance energy transfer and cell-based reporter gene assays show that the most active members inhibit the ER alpha/steroid receptor coactivator interaction with Ki's in the low micromolar range. Through these studies, we have obtained a refined pharmacophore model for activity in this pyrimidine series. Furthermore, the favorable activities of several of these compounds support the feasibility that this coactivator binding inhibition mechanism for blocking estrogen action might provide a potential alternative approach to endocrine therapy.

  DOI：

  10.1021/jm800698b

文献信息

• Efficient and regioselective 4-amino-de-chlorination of 2,4,6-trichloropyrimidine with N-sodium carbamates
  作者：Matteo Zanda、Patrice Talaga、Alain Wagner、Charles Mioskowski

  DOI：10.1016/s0040-4039(00)00048-4

  日期：2000.3

  4-N-Alkoxycarbonyl-2,6-dichloropyrimidines have been synthesized with good to excellent regioselectivity and yields from 2,4,6-trichloropyrimidine and N-sodium carbamates in DMF, at room temperature, in 15-30 minutes. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Regioselective 4-amino-de-chlorination of trichloro- and dichloro-pyrimidines with N-sodium carbamates
  作者：Dario Montebugnoli、Pierfrancesco Bravo、Eleonora Corradi、Giovanna Dettori、Charles Mioskowski、Alessandro Volonterio、Alain Wagner、Matteo Zanda

  DOI：10.1016/s0040-4020(02)00084-4

  日期：2002.3

  4-N-Alkoxycarbonylamino-2,6-dichloro- and -2-chloro-pyrimidines have been synthesized in good to excellent regioselectivity and yields from N-sodium carbamates and, respectively, 2,4,6-trichloropyrimidine and 2,4-dichloropyrimidine, in DNIF, rt, 15-30 min. The reaction is effective also with 4,6-dichloropyrimidine, producing 4-N-alkoxycarbonylamino-6-chloropyrimidines in good yields. Some conformational features of 4-N-alkoxycarbonylamino-2,6-dichloro-pyrimidines have been investigated by X-ray diffraction and H-1 NMR spectroscopy. (C) 2002 Published by Elsevier Science Ltd.