A one-pot synthetic approach for the construction of a thiazolo[3,2-a]benzimidazole-linked quinazoline scaffoldviapalladium-catalyzed reactions

Abstract

4-(2-Substituted-[1,3]thiazolo[3,2-a]benzimidazol-3-yl)quinazolin-2-amines were prepared by the reaction of 2,4-dichloroquinazoline, terminal alkynes, secondary amines, and 1H-benzo[d]imidazole-2(3H)-thione in the presence of palladium catalyst.

Synthesis of Thiazolo[3,2‐b] [1,2,4]triazoles through Pd‐Catalyzed Copper‐Free Sonogashira Coupling Reaction

“…Recently, we reported the synthesis of pyrazolo[5,1‐b][1,3]oxazole derivatives using Sonogashira reaction of terminal alkynes with 2‐iodomethyl‐6‐methylpyrazolo[5,1‐b][1,3]oxazole . In continuation of our study on the synthesis of heterocyclic compounds through Sonogashira coupling reactions, herein, we report the synthesis of thiazolo[3,2‐b][1,2,4]triazoles via Sonogashira reaction of 6‐(iodomethyl)‐2‐methylthiazolo[3,2‐b][1,2,4]triazole with terminal alkynes.…”

Selective 5‐Exo‐Dig versus 6‐Endo‐Dig Cyclization of Benzoimidazole Thiols with Propargyl Alcohols

“…date, the most powerful and versatile processes for the synthesis of benzothiazolo imidazole are the cyclocondensation of N-(propynyl)-o-phenylenediamines with phenyl isothiocyanate, [36] NHC-catalyzed [3 + 3] annulation of mercaptobenzimidazoles with alkynyl acylazoliums, [37] palladium-catalyzed cyclocarbonylation of 2-(propynylthio)-1H-benzo[d]imidazoles, [38,39] copper-catalyzed cyclization of 2-alkynyl-3,3-difluoro-3H-indole and mercaptoimidazole, [40] organocatalytic cyclizations of 2-alkynyl-3,3-difluoro-3H-indoles with mercaptoimidazole, [41] palladium-catalyzed multicomponent reactions of 2,4-dichloroquinazoline, terminal alkynes, secondary amines, and mercaptoimidazole. [42] We can anticipate that the main features of our methodology are the high chemo-and regioselectivity, and the possibility of obtaining two important classes of heterocycles using the same substrates making a small change in the solvent. In addition, our methodology is based on transition metal-free conditions, demonstrating a clear economic impact and environmental benefits.…”

“…Benzothiazole derivatives show a large range of biological activities, such as antimicrobial, [28] antifungal, [29] antioxidant, [30] antiinflammatory [31] antidepressant, [32] anticonvulsant, [33] antitumor, [34] and anticancer [35] . To date, the most powerful and versatile processes for the synthesis of benzothiazolo imidazole are the cyclocondensation of N ‐(propynyl)‐o‐phenylenediamines with phenyl isothiocyanate, [36] NHC‐catalyzed [3+3] annulation of mercaptobenzimidazoles with alkynyl acylazoliums, [37] palladium‐catalyzed cyclocarbonylation of 2‐(propynylthio)‐1 H ‐benzo[ d ]imidazoles, [38,39] copper‐catalyzed cyclization of 2‐alkynyl‐3,3‐difluoro‐3 H ‐indole and mercaptoimidazole, [40] organocatalytic cyclizations of 2‐alkynyl‐3,3‐difluoro‐3 H ‐indoles with mercaptoimidazole, [41] palladium‐catalyzed multicomponent reactions of 2,4‐dichloroquinazoline, terminal alkynes, secondary amines, and mercaptoimidazole [42] . We can anticipate that the main features of our methodology are the high chemo‐ and regioselectivity, and the possibility of obtaining two important classes of heterocycles using the same substrates making a small change in the solvent.…”

Sonogashira coupling reactions: Synthesis of 4-substituted-6-methyl-2-(methylthio)pyrimidines catalyzed by Pd–Cu

“…12,13 This reaction is one of the most widely used C-C bond-forming reactions, 14,15 furnishing an impressive route to aryl alkynes, which are interesting intermediates for the preparation of a variety of natural products, [16][17][18][19] pharmaceuticals, 20 and organic materials. 21,22 Accordingly, and based on our progressive endeavors in developing Pd-catalyzed reactions of acetylenes leading to heterocyclic compounds of biological significance via environmentally benign synthetic methodologies, [23][24][25][26][27] herein we report the synthesis of new derivatives of 4-(3-arylprop-2-ynyloxy)-6-methyl-2-(methylthio) pyrimidine via the Pd-catalyzed Sonogashira coupling reactions of 4-methyl-2-(methylthio)-6-(prop-2-ynyloxy) pyrimidine with aryl iodides.…”