- Development and Scale-Up of an Asymmetric Synthesis Process for Alogliptin
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Alogliptin (1) benzoate is a potent, highly selective inhibitor of serine protease dipeptidyl-peptidase IV, approved by US FDA for the treatment of type 2 diabetes. Herein, we report a more cost-effective process that includes ruthenium-catalyzed asymmetric hydrogenation followed by Hofmann rearrangement of 2-((6-chloro-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)benzonitrile (10) to introduce a chiral amino moiety at a late stage. Use of an inexpensive and readily available nicotinamide (6) for a chiral aminopiperidine core and iodobenzene diacetate (PIDA) under mild and specific conditions allowed us to access 1 with excellent total yield and comparable quality to that manufactured by the original process.
- Yamada, Masatoshi,Hirano, Sayuri,Tsuruoka, Ryoji,Takasuga, Masahiro,Uno, Kenichi,Yamaguchi, Kotaro,Yamano, Mitsuhisa
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p. 327 - 336
(2021/03/01)
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- PROCESS FOR PRODUCING HETEROCYCLIC COMPOUND
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The present invention provides a method of efficiently producing an optically active 6-(3-aminopiperidin-1-yl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine derivative. The optically active piperidine-3-carboxamide or a derivative thereof, which is obtained by subjecting 1,4,5,6-tetrahydropyridine-3-carboxamide or a derivative thereof to an asymmetric reduction in the presence of a catalyst, is used as an intermediate.
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Paragraph 0274-0280
(2017/04/11)
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