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

Abstract

Halogenated quinazolinones and quinazolines are versatile synthetic intermediates for the metal-catalyzed carbon-carbon bond formation reactions such as the Kumada, Stille, Negishi, Sonogashira, Suzuki-Miyaura and Heck cross-coupling reactions or carbon-heteroatom bond formation via the Buchwald-Hartwig cross-coupling to yield novel polysubstituted derivatives. This review presents an overview of the application of these methods on halogenated quinazolin-4-ones and their quinazolines to generate novel polysubstituted derivatives.

Recent Developments in Nanostructured Palladium and Other Metal Catalysts for Organic Transformation

“…Palladium-assisted nanocatalysts for carbon-carbon bond formation including Suzuki [32], Heck [33], Sonogashira [34], Negishi [35], Stille [36], Kumada [37], and Hiyama [38] cross-coupling reactions (Scheme 1) have made a huge impact on organic reactions because of mild reaction conditions and tolerance to various functional groups [39]. Such kinds of reactions showed extensive applications in the formation of pharmaceuticals, agrochemicals, and other important industrial products [40].…”

Synthesis and In Vitro Cytotoxic Properties of Polycarbo-Substituted 4-(Arylamino)quinazolines

“…Given the importance of carbon-substituted primary 4-anilino substituted quinazolines in pharmaceutical compounds or materials [18], we decided to develop efficient methods for the synthesis of novel unsymmetrical polycarbo-substituted 4-anilinoquinazolines based on the 2-aryl-6-bromo-4-chloro-8-iodoquinazolines. Herein we describe single-pot three-step sequential reactions involving initial amination of the 2-aryl-6-bromo-4-chloro-8-iodoquinazolines followed by two-step (bis-Suzuki-Miyaura, Sonogashira/Stille or Sonogashira/Suzuki-Miyaura) cross-coupling reaction to afford the requisite unsymmetrical 2,6,8-trisubstituted 4-(arylamino)quinazolines.…”

“…Moreover, the molecular ion region of their mass spectra revealed the absence of the M+ and M + 2 peaks in the ratio 3:1 due to the 35 Cl and 37 Cl isotope observed in the spectra of the corresponding substrates. We decided to take advantage of the trend in reactivity of the C-sp 2 -X bonds in transition metal catalyzed cross-coupling (trend: C-sp 2 -I > C(4)-Cl > C-sp 2 -Br > C(2)-Cl > C-sp 2 -Cl) [18] and subjected compounds 1a-d to one-pot successive two-and three-step reaction sequences involving initial amination and subsequent Pd catalyzed cross-coupling reactions to afford novel unsymmetrical polycarbosubstituted 4-anilinoquinazolines.…”

“…Hitherto, the 4-alkynyl-2-aryl-6,8-dibromoquinazolines [23] and the 6,8-dibromo-2,4-diaminoquinazoline [24,25] have been found to undergo Suzuki-Miyaura cross-coupling at the 6-and 8-positions without selectivity due to comparable We decided to take advantage of the trend in reactivity of the C-sp 2 -X bonds in transition metal catalyzed cross-coupling (trend: C-sp 2 -I > C(4)-Cl > C-sp 2 -Br > C(2)-Cl > C-sp 2 -Cl) [18] and subjected compounds 1a-d to one-pot successive two-and three-step reaction sequences involving initial amination and subsequent Pd catalyzed cross-coupling reactions to afford novel unsymmetrical polycarbo-substituted 4-anilinoquinazolines. Table 2).…”

Palladium‐Catalyzed Synthesis of Phenanthridine/Benzoxazine‐Fused Quinazolinones by Intramolecular CH Bond Activation

“…[12] Recently,h eteroaromatic ring-fused 4(3H)-quinazolinones and halogenated quinazolinones/quinazolines have been reporteda sv ersatile synthetic intermediates to generate novel biologically relevant poly-substituted derivatives. [13,14] In addition, quinazolinone derivatives are also used as inhibitors of various enzymes, including monoamine oxidase,a ldoser eductase,t umor necrosisf actor R, and thymidylate synthases. [15] Phenanthridine structural motifs representa nother class of biologically relevantc ompounds with extensive pharmacological activities and applications.…”