Synthesis of [(14) C]omarigliptin

Abstract

An efficient synthesis for [C-14]Omarigliptin (MK-3102) is described. The initial synthesis of a key C-14-pyrazole moiety did not work due to the lack of stability of C-14-DMF-DMA reagent. Thus, a new radiolabeled synthon, C-14-biphenylmethylformate, was synthesized from C-14-sodium formate in one step in 92% yield and successfully used in construction of the key C-14-pyrazole moiety. Regioselective N-sulfonation of the pyrazole moiety was achieved through a dehydration-sulfonation-isomerization sequence. [C-14]MK 3102 was synthesized in five steps from C-14-biphenylmethylformate with 25% overall yield.