tert-butyl N-(1-iodo-2-(trifluoroacetamido)naphthalen-4-yl)carbamate | 1456523-30-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: tert-butyl N-(1-iodo-2-(trifluoroacetamido)naphthalen-4-yl)carbamate
• 英文别名: tert-butyl N-[4-iodo-3-[(2,2,2-trifluoroacetyl)amino]naphthalen-1-yl]carbamate
• CAS: 1456523-30-0
• 化学式: C₁₇H₁₆F₃IN₂O₃
• 分子量: 480.225
• InChiKey: PDLKYQUCSHZWPF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl N-(1-iodo-2-(trifluoroacetamido)naphthalen-4-yl)carbamate 在 吡啶 、 potassium tert-butylate 、 三正丁基氢锡 、 1-羟基苯并三唑 、 溶剂黄146 、 甲基磺酰氯 、 sodium hydroxide 、 N,N'-二异丙基碳二亚胺 、 锌 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 208.5h， 生成 1,1-dimethylethyl N-(1-chloromethyl-3-(5-(2-dimethylaminoethoxy)indole-2-carbonyl)-2,3-dihydrobenzo[e]indol-5-yl)carbamate
  参考文献：
  名称：

  Initial development of a cytotoxic amino-seco-CBI warhead for delivery by prodrug systems

  摘要：

  Cyclopropabenzaindoles (CBIs) are exquisitely potent cytotoxins which bind and alkylate in the minor groove of DNA. They are not selective for cancer cells, so prodrugs are required. CBIs can be formed at physiological pH by Winstein cyclisation of 1-chloromethyl-3-substituted-5-hydroxy-2,3-dihydro-benzo[e] indoles (5-OH-seco-CBIs). Corresponding 5-NH2-seco-CBIs should also undergo Winstein cyclisation similarly. A key triply orthogonally protected intermediate on the route to 5-NH2-seco-CBIs has been synthesised, via selective monotrifluoroacetylation of naphthalene-1,3-diamine, Boc protection, electrophilic iodination, selective allylation at the trifluoroacetamide and 5-exo radical ring-closure with TEMPO. This intermediate has potential for introduction of peptide prodrug masking units (deactivating the Winstein cyclisation and cytotoxicity), addition of diverse indole-amide side-chains (enhancing non-covalent binding prior to alkylation) and use of different leaving groups (replacing the usual chlorine, allowing tuning of the rate of Winstein cyclisation). This key intermediate was elaborated into a simple model 5-NH2-seco-CBI with a dimethylaminoethoxyindole side-chain. Conversion to a bio-reactive entity and the bioactivity of this system were confirmed through DNA-melting studies (Delta T-m = 13 degrees C) and cytotoxicity against LNCaP human prostate cancer cells (IC50 = 18 nM). (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.04.034
• 作为产物：
  描述：

  1,3-萘二胺 在 N-碘代丁二酰亚胺 、 对甲苯磺酸 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 54.0h， 生成 tert-butyl N-(1-iodo-2-(trifluoroacetamido)naphthalen-4-yl)carbamate
  参考文献：
  名称：

  Observation by NMR of cationic Wheland-like intermediates in the deiodination of protected 1-iodonaphthalene-2,4-diamines in acidic media

  摘要：

  在三氟乙酸/氯仿中，1-碘萘-2,4-二胺通过最初的分子内质子化作用，产生了可通过核磁共振观测到的稳定的惠兰四面体阳离子物种。动态平衡允许芳香质子进行质子-氘交换，为 1-碘萘-2,4-二胺的脱碘反应提供了一种机制。

  DOI：

  10.1039/c3ob41386a