title: Synthesis of [(14) C]omarigliptin.
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.
authors.affiliation: Merck Research Laboratories, Labeled Compound Synthesis Group, Department of Process and Analytical Chemistry, Rahway, NJ, USA.
authors.forename: Sumei
authors.initials: S
authors.lastname: Ren
authors.affiliation: Merck Research Laboratories, Labeled Compound Synthesis Group, Department of Process and Analytical Chemistry, Rahway, NJ, USA.
authors.forename: Donald
authors.initials: D
authors.lastname: Gauthier
authors.affiliation: Merck Research Laboratories, Labeled Compound Synthesis Group, Department of Process and Analytical Chemistry, Rahway, NJ, USA.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Marques
authors.affiliation: Merck Research Laboratories, Labeled Compound Synthesis Group, Department of Process and Analytical Chemistry, Rahway, NJ, USA.
authors.forename: Roy
authors.initials: R
authors.lastname: Helmy
authors.forename: David
authors.initials: D
authors.lastname: Hesk
mesh_terms: D002250:Carbon Radioisotopes; D060326:Chemistry Techniques, Synthetic; D006574:Heterocyclic Compounds, 2-Ring / Q000138:chemical synthesis* / Q000737:chemistry; D007536:Isomerism; D007553:Isotope Labeling; D011714:Pyrans / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: C587539:2-(2,5-difluorophenyl)-5-(2-(methylsulfonyl)-2,6-dihydropyrrolo(3,4-c)pyrazol-5(4H)-yl)tetrahydro-2H-pyran-3-amine; D002250:Carbon Radioisotopes; D006574:Heterocyclic Compounds, 2-Ring; D011714:Pyrans
keywords: 14C-pyrazole; DPP-4; MK-3102; human AME; omarigliptin; sulfonation/isomerization