RESUMO
Halide anions can increase or decrease the transmetallation rate of the Stille reaction through in situ halide metathesis. Although the influence of the halogen present in oxidative addition complexes on the transmetallation rate with organostannanes was already known, the application of in situ halide metathesis to accelerate cross-coupling reactions with organometallic reagents is not described in the literature yet. In addition a second unprecedented role of halides was discovered. Halide anions stabilize the [Pd(0)(L)(2)] catalyst in Stille reactions, by means of [Pd(0)X(L)(2)](-) formation (X=Cl, I), hereby preventing its leaching from the catalytic cycle. Both arene (iodobenzene) and azaheteroarene (2-halopyridine, halopyrazine, 2-halopyrimidine) substrates were used.
RESUMO
A set of regioisomeric 2-substituted pyridazin-3(2H)-ones containing a 3-oxo-3-phenylprop-1-en-1-yl fragment at either position 4, 5 or 6 and 2-substituted pyridazin-3(2H)-ones containing the same fragment both at positions 4 and 5 have been synthesized and evaluated as antiplatelet agents. The study allows the identification of a new highly potent platelet aggregation inhibitor (4c).
Assuntos
Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/farmacologia , Piridazinas/química , Piridazinas/farmacologia , Desenho de Fármacos , Inibidores da Agregação Plaquetária/síntese química , Piridazinas/síntese química , Relação Estrutura-AtividadeRESUMO
[reaction: see text] The synthesis of dipyrido[1,2-a:2',3'-d]imidazole and hitherto unknown benzo and aza analogues is described. These relatively complex polycyclic heterocycles could be smoothly prepared in one step from commercially available building blocks. Mechanistically, the developed procedure involves orthogonal (Pd and Cu catalyst) or auto-tandem (Pd catalyst) catalysis via regioselective inter- and intramolecular C-N bond formation.
RESUMO
As part of the optimization process of the lead compound I a focussed library of diversely substituted pyridazin-3(2H)-ones containing a 3-oxo-3-phenylprop-1-en-1-yl or 3-phenylprop-2-enoyl fragment at position 5 has been obtained and evaluated as antiplatelet agents. The structural modification at positions 2, 6 and 4 of the heterocyclic moiety allowed us to obtain preliminary information on the structure-activity relationship in this family.
Assuntos
Inibidores da Agregação Plaquetária/síntese química , Agregação Plaquetária/efeitos dos fármacos , Piridazinas/síntese química , Piridazinas/farmacologia , Estrutura Molecular , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/farmacologia , Piridazinas/química , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
Evidence for an interphase deprotonation of Pd(II)-amine complexes with weak carbonate base has been gained for the first time. When a rate-limiting deprotonation step is involved in the catalytic cycle, controlling the structure (shape and size of the particles) and/or molar excess of the carbonate base used can significantly increase the reaction rate of Buchwald-Hartwig aminations. By taking such a "base effect" into account a general protocol for the intermolecular amination of aryl iodides with all types of amines has been developed based on a standard Pd-BINAP catalyst, using cesium carbonate as the base.