Novel preparation process of trelagliptin succinate

Abstract

The invention discloses a novel preparation process of trelagliptin succinate. According to the method, 3-methyl-6-chlorouracil is taken as a starting raw material, toluene, DMF or NMP is taken as a solvent to react with 2-cyano-5-fluorobenzyl bromide under the alkaline condition to obtain 2-[(6-chloro-3, 4-dihydro-3-methyl-2, 4-dioxo-1 (2H)-pyrimidinyl) methyl]-4-fluorobenzonitrile, then the solvent system reacts with (R)-3-Boc-aminopiperidine under the alkaline condition, and the protective group is dissociated by using acid to obtain trelagliptin, and salt forming reaction is carried out on trelagliptin and succinic acid (SM4) to finally obtain the trelagliptin succinate serving as a type 2 diabetes resistant medicine. By adopting a one-pot method, the method has the advantages that the raw material cost is low, the yield is high, the post-treatment operation of each step of chemical reaction in multi-step reaction is reduced, the production period is greatly shortened, few impurities are generated in the reaction, the product quality is high, the use amount of chemical reagents is relatively reduced, and the method is relatively green and environment-friendly, 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 troxagliptin succinate, a medicine for treating type 2 diabetes. Background technique [0002] Trexagliptin succinate controls blood sugar levels by selectively and persistently inhibiting DPP-4. It is an ultra-long-acting dipeptidyl peptidase IV (DPP-4) inhibitor. Trexagliptin is the first once-weekly oral hypoglycemic drug marketed in the world, while similar DPP-4 inhibitors on the market need to be taken orally once a day. Zafatek's drug advantages will undoubtedly provide a more convenient treatment option for diabetic patients , significantly improving patient convenience and compliance. [0003] Trexagliptin succinate tablets are developed and manufactured by Takeda Pharmaceuticals (Takeda), trade name Standard 100mg / tablet for the treatment of type 2 diabetes. This product was approved for marketing by the Japanese M...

AI Technical Summary

Problems solved by technology

[0012] 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

[0013] 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 troxagliptin succinate, during the reaction process, it is necessary to add an organic base as an acid-binding agent, and a large amount of salt is produced by acid-base neutralization, and the waste water has obvious defects;

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