865758-96-9Relevant articles and documents
Synthesis process of alogliptin benzoate
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Paragraph 0007; 0092; 0121-0144, (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.
3, 4-dihydropyrimidine benzonitrile derivative as well as preparation method and application thereof
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Paragraph 0026-0027; 0065, (2021/03/13)
The invention provides a 3, 4-dihydropyrimidine benzonitrile derivative as well as a preparation method and application thereof. The invention discloses a structure of a specific impurity (RRT is an impurity of 1.22) generated in the process of preparing alogliptin benzoate by adopting the route of the original research patent for the first time. The series of impurities have a warning structure,and the content of the impurities in the alogliptin benzoate finished product needs to be detected according to related limits of the genetically toxic impurities. The invention further provides a preparation and purification method of the high-purity compound shown in the formula (A) and a detection method of the content of the impurity compound in the alogliptin benzoate medicine, and thereforequality control over the alogliptin benzoate medicine is achieved.
Novel preparation process of alogliptin benzoate
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Paragraph 0027; 0038-0040; 0047-0048; 0049-0050; 0051-0052, (2021/05/08)
The invention discloses a novel preparation process of alogliptin benzoate. The method comprises the steps: reacting 3-methyl-6-chlorouracil serving as an initial raw material with 2-cyanobenzyl bromide under an alkaline condition by taking toluene as a solvent to obtain 2-[(6-chloro-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl)methyl]benzonitrile, then reacting the solvent system with (R)-3-Boc-aminopiperidine under an alkaline condition, dissociating a protecting group by using acid to obtain alogliptin, and carrying out salifying reaction on the alogliptin and benzoic acid to finally prepare the alogliptin benzoate which is an anti-type 2 diabetes medicine. The preparation method adopts a one-pot method, has the advantages of low raw material cost, high yield, reduction of post-treatment operation of each chemical reaction in multi-step reaction, great shortening of the production period, few impurities generated in the reaction, high product quality, relative reduction of the use amount of chemical reagents, relatively environmental protection and the like, and is beneficial to industrial production.