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

• -anilinoquinazoline; anticancer agents; N-arylation; 4-chloroquinazoline; microwave irradiation; Introduction N-Heterocyclic compounds are commonly present in pharmaceuticals, bioactive natural products, agrochemicals, and synthetic drugs [1][2]. Quinazoline, a benzo-fused N-heterocyclic framework (benzo-1,3-diazine

• of the anticancer agent verubulin. Thus, after regioselective 4-chloroquinazoline metalation by an in situ trapping metalation strategy, reaction quenching with iodine allowed us to isolate 4-chloro-8-iodoquinazoline in 83% yield. Surprisingly, further reaction of 4-chloro-8-iodoquinazoline with 4

• -bromo-4-chloro-2-phenylquinazoline (8a), which provided the respective products 15e–g in yields ranging from 92 to 96% (Scheme 4). Finally, to illustrate the importance and scope of the methodology, we used the commercially available 4-chloroquinazoline (16) and 4-chloro-2-methylquinazoline (17), which

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• quinazolinones 89. Subsequent chlorination of the quinazolinone resulted in the formation of 4-chloroquinazoline intermediates 90. The subsequent Pd-catalyzed coupling of 90 and arylboronic acid 91 gave the methoxy intermediates 92 in reasonable yields. The demethylation of the 2-(2-pyridyl)methoxy intermediate