Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents

• Rodolfo H. V. Nishimura,
• Thiago dos Santos,
• Valter E. Murie,
• Luciana C. Furtado,
• Leticia V. Costa-Lotufo and
• Giuliano C. Clososki

Beilstein J. Org. Chem. 2021, 17, 2968–2975, doi:10.3762/bjoc.17.206

• , which allowed us to isolate the 4-anilinoquinazoline derivatives 10e and 10f in 87 and 84% yields, respectively (Table 1, entries 5 and 6). In contrast, no N-arylated products emerged when we used the ortho-methyl-substituted N-methylaniline 9d as nucleophile, even when we conducted the reactions at 120

• ). The EGFR inhibitor drugs bearing the 4-anilinoquinazoline moiety did not show potent cytotoxic activity against T98G cells (21.3 µM for erlotinib, and 37.8 µM for gefitinib). However, the tubulin polymerization inhibitor (verubulin), which contains 4-anilinoquinazoline in its chemical structure, was

• biologically active molecules are currently being investigated in our laboratories. Some antitumor agents containing the 4-anilinoquinazoline moiety. Examples of N-arylation reactions using 4-chloroquinazolines as substrates. Synthesis of verubulin analog. Synthesis of 4-chloro-6-halo-2-phenylquinazolines 8a