Chung, John Y. L. published the artcileEvolution of a Manufacturing Route to Omarigliptin, A Long-Acting DPP-4 Inhibitor for the Treatment of Type 2 Diabetes, Name: 2-(Methylsulfonyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole benzenesulfonate, the main research area is omarigliptin diastereoselective enantioselective preparation manufacturing route; stereoselective reductive amination arylaminopyranone mesylpyrrolopyrazole deprotection; ruthenium catalyzed enantioselective hydrogenation cycloisomerization oxidation preparation omarigliptin.
Development of a convergent synthesis of omarigliptin [MK-3102, I (R = H; Ms = MeSO2)] suitable for com. manufacture is described. I (R = H) was prepared by the diastereoselective reductive amination of a nonracemic Boc-protected amino(aryl)pyranone II with mesylated pyrrolopyrazole III•PhSO3H (R1 = H) [generated in situ from its Boc-protected precursor III (R1 = Boc) due to its instability and potential genotoxicity] followed by Boc deprotection. The synthesis of II relies on three Ru-catalyzed reactions: the dynamic kinetic resolution/hydrogenation of a rac-α-aminoketone in the presence of an areneruthenium diamine complex, cycloisomerization of the bis-homopropargylic alc. product to a dihydropyran, and ruthenium-catalyzed oxidation of a pyranol (generated by hydroboration of the dihydropyran). III (R1 = Boc) was prepared regioselectively in 30:1 regioselectivity by mesylation followed by base-promoted isomerization. The Boc deprotection of III (R1 = Boc) and its reductive amination reaction with II were telescoped by using the crystallization of I (R = Boc) to remove byproducts, allowing handling of III•PhSO3H (R1 = H) to be avoided and improving the overall diastereoselectivity and efficiency of the route.
Organic Process Research & Development published new progress about Cycloisomerization. 1280210-80-1 belongs to class pyrazoles-derivatives, name is 2-(Methylsulfonyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole benzenesulfonate, and the molecular formula is C12H15N3O5S2, Name: 2-(Methylsulfonyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole benzenesulfonate.
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Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics