850649-61-5Relevant articles and documents
Development and Scale-Up of an Asymmetric Synthesis Process for Alogliptin
Yamada, Masatoshi,Hirano, Sayuri,Tsuruoka, Ryoji,Takasuga, Masahiro,Uno, Kenichi,Yamaguchi, Kotaro,Yamano, Mitsuhisa
, p. 327 - 336 (2021/03/01)
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.
Synthesis process of alogliptin benzoate
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, (2021/02/10)
The invention discloses a synthesis process of alogliptin benzoate. The synthesis process comprises the following steps: 1, preparing an initial raw material 6-chlorouracil; 2, preparing 2-((6-chlorine-2, 4-dioxo-3, 4-dihydro-2H-pyrimidine-1-radical)methyl)cyanophenyl; 3, preparing 2-[(6-chlorine-3, 4-dihydro-3-methyl-2, 4-dioxo-1(2H)-pyrimidinyl)methyl]benzonitrile; 4, preparing alogliptin; 5, preparing alogliptin benzoate. According to the invention, the alogliptin benzoate is synthesized by taking cheap and easily available 6-chlorouracil, alpha bromo-o-methylbenzonitrile and (R)-3-aminopiperidine as raw materials through reactions such as alkylation, methylation, affinity substitution, salification and the like; according to the synthetic route, raw materials are cheap and easy to obtain, the synthetic cost is reduced, all steps are classic reactions, and synthesis improvement is easy; the improved process is low in raw material cost, simple to operate, mild in reaction condition,simple in post-treatment and suitable for industrial production.
Simple preparation method of alogliptin benzoate
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, (2019/10/01)
The invention relates to an alogliptin benzoate preparation method, which comprises that 3,3-dihalogenated-N-methyl acrylamide sequentially reacts with (R)-3-Boc-aminopiperidine and 2-cyano benzylamine to prepare (R)-3-(3-Bocamino)piperidine-1-yl-3-(2-cyano)benzylamino-N-methacrylamide, the obtained material reacts with a carbonylation reagent to prepare alogliptin, and the alogliptin and benzoicacid are subjected to salt forming to prepare alogliptin benzoate. According to the present invention, the method has advantages of inexpensive and easily available raw materials, simple operation andless wastewater, and is suitable for the industrial production of alogliptin benzoate.