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.
Preparation method of alogliptin benzoate
-
Paragraph 0028; 0031; 0033; 0036, (2021/01/29)
The invention discloses a preparation method of alogliptin benzoate. Main starting materials of the preparation method are 6-chloro-3-methyluracil, o-cyanobenzyl bromide, (R)-3-Boc-aminopiperidine andbenzoic acid. According to the method, all indexes meet the specification, meanwhile, dangerous reagents such as sodium hydride and highly toxic methyl iodide are prevented from being used in the reaction process, the requirement for the operation process is not strict, and water-free and oxygen-free conditions are not needed; a high-boiling-point mixed solvent is not used in the reaction, and the solvent is easy to recycle; the selected starting materials are available in the market and easy to obtain, and large-scale production is facilitated; in addition, starting materials or intermediates in the synthetic route are good in stability and convenient to store and control, and genotoxic impurities are avoided in the reaction process; and the synthesis process is environment-friendly.
Preparation method of alogliptin
-
Paragraph 0019; 0020; 0023-0028, (2019/06/08)
The invention provides a preparation method of alogliptin. 2-(6-chlorine-3-methyl-2,4-prohexadione-3,4-dihydro-2H-pyrimidine-1-yl-methyl)benzonitrile, (R)-3-aminopiperidine dihydrochloride and sodiumbicarbonate or potassium bicarbonate react in an organic solvent to prepare a compound, the yield of the alogliptin and alogliptin benzoate is increased, the purity of the alogliptin and the alogliptin benzoate is improved, operation is easy, environmental protection is achieved, and the preparation method is suitable for industrial production of the alogliptin and the alogliptin benzoate.