Synthesis And Process Optimization Of Pharmaceutical Intermediates Based On Suzuki And Buchwald-Hartwig Coupling Reactions

In this paper,the synthesis and process optimization of 5-(4-oxo-3,4-dihydroquin azoline-6-yl)furan-2-formaldehyde and 5-(N-BOC-piperazinyl)salicylaldehyde were studied in the case of Suzuki coupling reaction and Buchwald-Hartwig coupling reaction.The advantages of this catalyst combination over other catalyst combinations and the effects of temperature,oxygen and alkali were studied.The results showed that the combination of palladium acetate and tri-tert-butylphosphine tetrafluoroborate could be used in these two kinds of coupling reactions,and for the reaction yield was higher than 80%and the purity of the product was higher than 90%,which was better than the combination of other catalysts.The experiment should not be less than 50 degrees and the oxygen in the solvent should not exceed 7 mg/L.In the synthesis of 5-(4-oxo-3,4-dihydroquinazoline-6-yl)furan-2-formaldehyde,potassium acetate as a base can make the reaction more stable and the conversion of raw materials can reach to 95%.The present study can promote the progress of palladium-catalyzed coupling reactions in drug synthesis.The results can provide a basis and reference for the large-scale production of palladium-catalyzed C-C and C-N bond coupling reactions.It has imporant theoretical reference value and practical application value.