ABSTRACT
A new transition metal-catalyzed orthogonal solid-phase protocol for the synthesis of highly substituted 2(1H)-pyrazinones was developed, on the basis of Chan-Lam arylation and Liebeskind-Srogl cross-coupling reactions. This strategy opens the way for the generation of small libraries of 2(1H)-pyrazinone analogues for biological screening.
Subject(s)
Combinatorial Chemistry Techniques/methods , Pyrazines/chemical synthesis , Sulfhydryl Compounds/chemistry , Transition Elements/chemistry , Catalysis , Molecular Structure , Pyrazines/chemistry , StereoisomerismABSTRACT
The "click chemistry" approach has been explored on the 2-(1H)-pyrazinone scaffold for the generation of pharmacologically interesting heterocyclic moieties. Huisgen 1,3-dipolar cycloaddition has been evaluated as the key step for the construction of the 1,2,3-triazole ring at the C-3 position of 2-(1H)-pyrazinones. Two different pathways have been successfully evaluated: (1) via C-C or C-O linkage of the acetylenic part to the C-3 position of the 2-(1H)-pyrazinone scaffold or (2) via azide introduction in the C-3 position. The subsequent application of "click chemistry" resulted in the formation of hitherto unknown skeletons. Microwave irradiation has successfully been applied in different steps of the sequence.
Subject(s)
Chemistry, Pharmaceutical , Combinatorial Chemistry Techniques , Microwaves , Pyrazines/chemical synthesis , Acetylene/chemistry , Azides/chemistry , Heterocyclic Compounds/chemistry , Heterocyclic Compounds/pharmacology , Models, Chemical , Molecular Structure , Pyrazines/pharmacologyABSTRACT
The first solid-phase synthesis of the 2(1H)-pyrazinone scaffold is described. The diversity at position C6 of the pyrazinone ring is determined by the choice of the starting aldehyde. Microwave-enhanced transition metal-catalyzed reactions allow easy introduction of a variety of substituents at the C3 position. This opens a way for the generation of libraries of diversely substituted 2(1H)-pyrazinones that will be screened for biological activities.
Subject(s)
Combinatorial Chemistry Techniques , Pyrazines/chemical synthesis , Catalysis , Microwaves , Molecular Structure , Pyrazines/chemistryABSTRACT
It is demonstrated that microwave-assisted Diels-Alder reactions of substituted 2(1H)-pyrazinones with ethylene are significantly more effective utilizing pre-pressurized (up to 10 bar) reaction vessels.
ABSTRACT
The 2(1H)-pyrazinones have been demonstrated to be versatile building blocks for the synthesis of biologically active compounds. Here, an efficient method is described for the decoration of these interesting scaffolds. Microwave-assisted palladium catalyzed reactions allow the easy introduction of different substituents at the C3- and even at the rather unreactive C5-position of the pyrazinones. Stille, Suzuki, Heck, Sonogashira reactions, in addition to reductive dechlorinations, and cyanation reactions are investigated.
