Preparation of 6-aminoquinazolin-4(3H)-ones via direct SNAr on the quinazoline ring

2-Aryl-6,8-dibromo-2,3-dihydroquinazolin-4(1<i>H</i>)-ones as substrates for the synthesis of 2,6,8-triarylquinazolin-4-ones

“…A series of the analogous 2,3-disubstituted 6,8-dibromoquinazolin-4(3H)-one derivatives has nevertheless been synthesized before from the reaction of 6,8-dibromo-2-methyl-1-benzoxazin-3(4H)-one with nitrogen nucleophiles such as hydrazine hydrate, sulpha drugs and 4'-aminoacetophenone [21]. The 6-fluoro-8-(iodo/bromo)-2-methylquinazolin-4(3H)-ones, on the other hand, have been prepared via the reaction of 6-fluoro-8-iodo/bromo-2-methyl-1-benzoxazin-3(4H)-ones with aqueous ammonia under reflux [22]. The need to access a diverse range of the 2,3-dihydroquinazolin-4(1H)-ones bearing carboncontaining substituents on the fused benzo ring, in conjunction with limited contemporary synthetic approach to such systems prompted us to elaborate compounds 3a-d via palladiumcatalyzed Suzuki-Miyaura cross-coupling with arylboronic acids as coupling partners.…”

Synthesis and Photophysical Property Studies of the 2,6,8-Triaryl-4-(phenylethynyl)quinazolines

“…In this investigation, we exploited the combined electrophilic (cyclocondensation) and oxidative (dehydrogenation) properties of iodine on 3,5-dibromobenzamide 1 and benzaldehyde derivatives 2a-d in ethanol under reflux for 7 h to afford products 3a-d in a single-pot operation (Scheme 1). A series of the analogous 2,3-disubstituted 6,8-dibromoquinazolin-4(3H)-ones have been prepared before via the reaction of 6,8-dibromo-2-methyl-1-benzoxazin-4(3H)-one with nitrogen nucleophiles such as hydrazine hydrate, sulpha drugs and 4-aminoacetophenone [19]. Likewise, the 6-fluoro-8-iodo/bromo-2-methyl-1-benzoxazin-4(3H)-ones reacted with aqueous ammonia under reflux to yield the 6-fluoro-8-(iodo/bromo)-2-methylquinazolin-4(3H)-ones [20].…”

Advances in Metal-Catalyzed Cross-Coupling Reactions of Halogenated Quinazolinones and Their Quinazoline Derivatives

“…Baarlaam et al performed the amination of 3-( p -methoxybenzyl) protected 8-bromo-6-fluoro-2-methylquinazolino-4(3 H )-one 101 with primary and secondary amines without the use of transition metal catalyst and isolated 6-amino substituted products 102 as major or sole products (Scheme 35) [55]. A halogen atom (X = Br, I) meta to the fluorine leaving group is envisioned to exert a sufficient inductive effect to permit the substitution under standard laboratory conditions.…”

“…A halogen atom (X = Br, I) meta to the fluorine leaving group is envisioned to exert a sufficient inductive effect to permit the substitution under standard laboratory conditions. However, this reaction could not be extended to the alkoxides due to deprotonation and deactivation of the quinazoline ring towards substitution [55].…”

“…An excess of the strong σ-donor cyanide ion which has high affinity for palladium tend to poison the catalyst and, in turn, retard the progress of reaction [56]. A microwave assisted cyanation of 8-bromo-6-fluoro-2-methylquinazolino-4(3 H )-one 104 using zinc cyanide in the presence of tris(dibenzylideneacetone)dipalladium(0) (Pd 2 (dba) 3 )–xanthphos catalyst complex afforded the C8–CN substituted product 105 , exclusively (Scheme 36) [55]. Zn(CN) 2 in this case serves as a source of low concentration of cyanide ion during the reaction to avoid poisoning the catalyst.…”