Substituted benzoquinazolinones. Part 2: Synthesis of amino-, and sulfanyl-derivatives of benzo[f]- and benzo[h]quinazolinones

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• 作者：Monika Nowak^a ; ^{Monika.Nowak@uni.lodz.pl" class="auth_mail" title="E-mail the corresponding author} ; Zbigniew Malinowski^a ; ^{zbigmal@uni.lodz.pl" class="auth_mail" title="E-mail the corresponding author} ; Emilia Fornal^b ; Andrzej Jó ; źwiak^a ; Ewa Parfieniuk^b ; Gabriela Gajek^c ; Renata Kontek^c
• 关键词：Beznoquinazolinones ; Bromine&ndash ; lithium exchange ; aza-Fries rearrangement ; Buchwald&ndash ; Hartwig reaction ; Palladium coupling ; Anticancer activity
• 刊名：Tetrahedron
• 出版年：2015
• 出版时间：16 December 2015
• 年：2015
• 卷：71
• 期：50
• 页码：9463-9473
• 全文大小：587 K

文摘

Amino- and sulfanyl-derivatives of benzoquinazolinones 16a–c, 20a–c and 21a–c were prepared under palladium-catalyzed Buchwald–Hartwig coupling reaction using bromobenzoquinazolinones 15, 19a, 19b and 1-substituted piperazines or mercaptans. The combination of Pd(OAc)₂ with XantPhos proved to be the best for these conversions in the presence of KOt-Bu, in 1,4-dioxane as a solvent, at 90–100 °C.

The 8-bromobenzo[f]quinazolin-1(2H)-one 15 was synthesized via condensation of the ethyl or tert-butyl 2-amino-8-bromonaphthalene-1-carboxylate 6, 10 with formamide, followed by reaction with 3,4-dimethoxybenzyl bromide. However, the 6-bromobenzo[h]quinazolin-4(3H)-ones 19a, 19b were prepared from ethyl 4-bromo-1-[(tert-butoxycarbonyl)amino]naphthalene-2-carboxylate (17).

Biological screening of the potential cytotoxicity of compounds 16a, 20a, 20c on HT29 and HCT116 cell lines, has shown that compound 20a has a significant anticancer activity.