Preparation method of alogliptin benzoate

Abstract

The invention relates to the field of preparation of medicaments and specifically relates to a preparation method of alogliptin benzoate. The preparation method comprises the following steps of: taking 6-chlorouracil as a starting raw material, reacting with o-cyanobenzyl bromide to obtain 2-((6-chloro-2, 4-dioxo-3, 4-dihydro-2H-pyrimidin-1-yl) methyl) benzonitrile, further performing methylation with iodomethane to obtain 2-((6-chloro-3-methyl-2, 4-dioxo-3, 4-dihydro-2H-pyrimidin-1-yl) methyl) benzonitrile, then reacting with (3R)-3-tert-butoxycarbonylamino-piperidine to obtain N-(3-(2-cyano-benzyl)-1-methyl-2, 6-dioxo-1, 2, 3, 6-tetrahydro-pyrimidin-4-yl) piperidine-(3R)-3-tert-butyl carbamate, performing deprotection by hydrogen chloride gas, and further forming a salt with benzoic acid to obtain the alogliptin benzoate. According to the preparation method of the alogliptin benzoate, disclosed by the invention, the raw materials which are low in cost and easy to purchase are selected, an alogliptin benzoate product is finally generated by reaction, and the overall manufacturing cost is low; and the temperature is strictly controlled in the steps, byproducts are few, the yield is high, and no toxicity is generated.

Description

technical field [0001] The invention relates to the field of medicine preparation, in particular to a preparation method of alogliptin benzoate. Background technique [0002] Diabetes is a series of clinical syndromes caused by absolute or relative insufficiency of insulin in the body. At present, the treatment of diabetes is mainly a combination of diet control and hypoglycemic drugs (for type Ⅱ diabetes) or insulin supplementation. According to the "Prevalence of Diabetes in China" report released by the New England Journal of Medicine, the prevalence of diabetes in China is as high as 10%, that is, one out of every 10 adults is diabetic. The underlying diabetes prevalence rate is as high as 15.5%. Statistics show that the direct medical costs of type Ⅱ diabetes patients and their complications in mainland cities account for 4% of the total national medical and health expenditure, about 19 billion yuan, and this figure is still rising. Most of the diabetic patients are Ⅱ...

AI Technical Summary

Problems solved by technology

[0003] Dipeptidyl peptidase IV (DPP-IV) is one of the key enzymes that mainly promote the degradation and inactivation of glucagon-like peptide-1 (GLP-1) in vivo and in vitro. It has been confirmed in medicine that DPP-IV inhibitors are A new type of diabetes treatment drug, clinical results show that this type of drug has a good hypoglycemic effect, and no adverse reactions such as weight gain and hypoglycemia, which are common in other diabetes drugs, have been found

[0005] Alogliptin Benzoate Tablets are manufactured by Takeda Pharmaceutical Co., Ltd., Japan. The trade name is NESINA. The specifications are 6.25mg / tablet, 12.5mg / tablet, and 25mg / tablet. They are used for the treatment of type 2 diabetes. On April 16, 2010 Listed on the market, approved by the FDA in 2011 and listed in the United States, the cost of raw materials for preparation is high and expensive

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