Novel preparation process of alogliptin benzoate

Abstract

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.

Description

technical field [0001] The invention belongs to the technical field of medicine synthesis, and in particular relates to a new preparation process of alogliptin benzoate, a medicine for treating type 2 diabetes. Background technique [0002] Alogliptin benzoate, also known as alogliptin, is a serine protease dipeptidyl peptidase IV (DPP-IV) inhibitor developed by Takeda Corporation of Japan. This product can maintain the levels of glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) in the body, promote the secretion of insulin, and thus play a hypoglycemic effect. Alogliptin and its pharmaceutical composition are orally effective specific DPP-Ⅳ inhibitors after sitagliptin and vildagliptin came into the market, and provide a new and important treatment option for patients with type 2 diabetes. application prospects. Alogliptin benzoate was officially launched in my country in early 2014. It is the first batch of type 2 diabetes treatment d...

AI Technical Summary

Problems solved by technology

[0011] 1) The cost of starting materials and reagents; 2) The cost of equipment, safety, and environmental protection; 3) The cost of three wastes treatment; 4) Labor cost

[0012] After a comprehensive analysis, 2-4 are the key points of cost, and one of the keys is the problem of the three wastes: the generation of the three wastes directly leads to the treatment cost of the three wastes, the cost of safety and environmental protection, and the cost of labor

In the traditional synthesis method of alogliptin benzoate, organic bases need to be added as acid-binding agents during the reaction process, and acid-base neutralization produces a large amount of salt, and the waste water has obvious defects;

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