New amino protective reagents and phosphate types of coupling agents

Abstract

New amino-protective reagents, t-butyl 2-pyridon-1-yl carbonate (TPC) was prepared by the reaction of 2-pyridon-1-yl chloroformate, t-butyl alcohol and pyridine at -10$^\circ$C, and benzyl 2-pyridon-1-yl carbonate(BPC) was prepared by the reaction of benzyl chloroformate, 1-hydroxy-2(1H)-pyridone, and triethylamine at room temperature. The reaction of these reagents with amino compounds proceeds rapidly under mild condition to give the corresponding N-Boc and N-Cbz compounds in good yields. New coupling reagents, pyrimidin-2-yl diphenyl phosphate (PPP) and bis (pyrimidin-2-yl) phenyl phosphate (BPP) were easily prepared in essentially quantitative yields. Using PPP or BPP in the presence of 1,1,3,3-tetramethylguanidine or triethylamine, carboxylic acids and amines were cleanly converted to the corresponding amides in acetonitrile at 80$^\circ$C within 3h. Especially, BPP is found to be effective for the synthesis of esters and racemization-free peptides.