Synthesis of [(14) C]omarigliptin

J Labelled Comp Radiopharm. 2016 Aug;59(10):386-90. doi: 10.1002/jlcr.3421. Epub 2016 Jun 23.

Abstract

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

Keywords: 14C-pyrazole; DPP-4; MK-3102; human AME; omarigliptin; sulfonation/isomerization.

MeSH terms

  • Carbon Radioisotopes*
  • Chemistry Techniques, Synthetic
  • Heterocyclic Compounds, 2-Ring / chemical synthesis*
  • Heterocyclic Compounds, 2-Ring / chemistry
  • Isomerism
  • Isotope Labeling
  • Pyrans / chemical synthesis*
  • Pyrans / chemistry

Substances

  • 2-(2,5-difluorophenyl)-5-(2-(methylsulfonyl)-2,6-dihydropyrrolo(3,4-c)pyrazol-5(4H)-yl)tetrahydro-2H-pyran-3-amine
  • Carbon Radioisotopes
  • Heterocyclic Compounds, 2-Ring
  • Pyrans