6-bromo-3-(4-methoxybenzyl)benzo[h]quinazolin-4(3H)-one | 1619257-98-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 6-bromo-3-(4-methoxybenzyl)benzo[h]quinazolin-4(3H)-one
• 英文别名: 6-Bromo-3-[(4-methoxyphenyl)methyl]benzo[h]quinazolin-4-one；6-bromo-3-[(4-methoxyphenyl)methyl]benzo[h]quinazolin-4-one
• CAS: 1619257-98-5
• 化学式: C₂₀H₁₅BrN₂O₂
• 分子量: 395.255
• InChiKey: CLAWVWAECUGPNO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  41.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  吗啉 、 6-bromo-3-(4-methoxybenzyl)benzo[h]quinazolin-4(3H)-one 在 potassium tert-butylate 、 palladium diacetate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 1,4-二氧六环 为溶剂， 反应 10.0h， 以45%的产率得到3-(4-methoxybenzyl)-6-(morpholin-4-yl)benzo[h]quinazolin-4(3H)-one
  参考文献：
  名称：

  Substituted benzoquinazolinones. Part 1: Synthesis of 6-aminobenzo[h]quinazolinones via Buchwald–Hartwig amination from 6-bromobenzo[h]quinazolinones

  摘要：

  6-(Morpholin-4-yl)benzothlquinazolin-4(3H)-one derivatives 18a,b were prepared under Buchwald-Hartwig conditions by reacting 6-bromobenzo[h]quinazolin-4(3H)-ones 13a,b with morpholine in the presence of a Pd(OAc)(2)/XantPhos system in 1,4-dioxane as solvent. The starting 6-bromobenzo[h] quinazolin-4(3H)-ones 13 were synthesized via condensation of the ethyl 1-amino-4-bromonaphthalene-2-carboxylate (11) with formamide (Niementowski reaction), and then reaction of the obtained benzoquinazolinone 9 with appropriates benzyl bromides. Compound 11 was prepared using a three-step procedure involving (a) metalation of the N-Boc- or N-Piv-protected 1-aminonaphthalenes with t-BuLi, followed by reaction with ethyl chloroformate, (b) bromination of the naphthalene ring of ester 3 using NBS, and next (c) deprotecion of the amine group with TFA or HCI. Biological screening of the potential cytotoxicity of compounds 8, 9, 18b on A549 and HT29 cell lines, as well as on the lymphocytes showed that compound 18b has interesting anticancer activities. The detailed synthesis, spectroscopic data, and biological assays were reported. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2014.05.117
• 作为产物：
  描述：

  ethyl 1-[(tert-butoxycarbonyl)amino]naphthalene-2-carboxylate 在 N-溴代丁二酰亚胺(NBS) 、 碳酸氢铵 、 potassium carbonate 、 三氟乙酸 作用下， 以 二氯甲烷 、 丙酮 、 乙腈 为溶剂， 反应 24.33h， 生成 6-bromo-3-(4-methoxybenzyl)benzo[h]quinazolin-4(3H)-one
  参考文献：
  名称：

  Substituted benzoquinazolinones. Part 1: Synthesis of 6-aminobenzo[h]quinazolinones via Buchwald–Hartwig amination from 6-bromobenzo[h]quinazolinones

  摘要：

  6-(Morpholin-4-yl)benzothlquinazolin-4(3H)-one derivatives 18a,b were prepared under Buchwald-Hartwig conditions by reacting 6-bromobenzo[h]quinazolin-4(3H)-ones 13a,b with morpholine in the presence of a Pd(OAc)(2)/XantPhos system in 1,4-dioxane as solvent. The starting 6-bromobenzo[h] quinazolin-4(3H)-ones 13 were synthesized via condensation of the ethyl 1-amino-4-bromonaphthalene-2-carboxylate (11) with formamide (Niementowski reaction), and then reaction of the obtained benzoquinazolinone 9 with appropriates benzyl bromides. Compound 11 was prepared using a three-step procedure involving (a) metalation of the N-Boc- or N-Piv-protected 1-aminonaphthalenes with t-BuLi, followed by reaction with ethyl chloroformate, (b) bromination of the naphthalene ring of ester 3 using NBS, and next (c) deprotecion of the amine group with TFA or HCI. Biological screening of the potential cytotoxicity of compounds 8, 9, 18b on A549 and HT29 cell lines, as well as on the lymphocytes showed that compound 18b has interesting anticancer activities. The detailed synthesis, spectroscopic data, and biological assays were reported. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2014.05.117

文献信息

• Substituted benzoquinazolinones. Part 1: Synthesis of 6-aminobenzo[h]quinazolinones via Buchwald–Hartwig amination from 6-bromobenzo[h]quinazolinones
  作者：Monika Nowak、Zbigniew Malinowski、Andrzej Jóźwiak、Emilia Fornal、Alina Błaszczyk、Renata Kontek

  DOI：10.1016/j.tet.2014.05.117

  日期：2014.8

  6-(Morpholin-4-yl)benzothlquinazolin-4(3H)-one derivatives 18a,b were prepared under Buchwald-Hartwig conditions by reacting 6-bromobenzo[h]quinazolin-4(3H)-ones 13a,b with morpholine in the presence of a Pd(OAc)(2)/XantPhos system in 1,4-dioxane as solvent. The starting 6-bromobenzo[h] quinazolin-4(3H)-ones 13 were synthesized via condensation of the ethyl 1-amino-4-bromonaphthalene-2-carboxylate (11) with formamide (Niementowski reaction), and then reaction of the obtained benzoquinazolinone 9 with appropriates benzyl bromides. Compound 11 was prepared using a three-step procedure involving (a) metalation of the N-Boc- or N-Piv-protected 1-aminonaphthalenes with t-BuLi, followed by reaction with ethyl chloroformate, (b) bromination of the naphthalene ring of ester 3 using NBS, and next (c) deprotecion of the amine group with TFA or HCI. Biological screening of the potential cytotoxicity of compounds 8, 9, 18b on A549 and HT29 cell lines, as well as on the lymphocytes showed that compound 18b has interesting anticancer activities. The detailed synthesis, spectroscopic data, and biological assays were reported. (C) 2014 Elsevier Ltd. All rights reserved.