Study On The Synthesis And Technology Of Acipimox

At present it is generally accepted that hyperlipidemia, including hypercholesterolemia, hypertriglyceridemia and compound hyperlipidemia is associated with an increased risk of atherosclerosis and coronary atherosclerotic heart disease. Medical scientists had high regard for the research of the the therapy of the hyperlipidemia and have paid more and more attention to the development of the lipid regulating drugs.Acipimox is a new synthesized regulating drug related to nicotinic acid. It produces obvious effect on lowering triglyceride. And the effects produced by acipimox on plasma triglyceride are better than that produced by nicotinic acid and the adverse effects are less than nicotinic acid too. Acipimox is used in the treatment of type IIa, IIb, IV hyperlipoproteinemias. Acipimox has been shown to be effective in the treatment of hyperlipidemia with diabetic, gout and coronary heart disease patients.This article is a research on the synthesis technology of acipimox. Under the comparison of the synthesis methods, 5-methylpyrazine-2-carboxylic acid 4-oxide is synthesized from pyruvic aldehyde and diaminomaleonitrile by condensing, hydrolysis, decarboxylation, oxidation with H2O2 in 40% overall yield. This synthesis method fit for the situation of our country with mild condition, easy obtained raw material, short production cycle and stable technology.Orthogonal design method is used to statistical analysis the reaction conditions, that is temperature, pH, the amount of catalyzer Na2WO4.2H2O and oxidant H2O2 , in the N-oxidation from 5-methylpyrazine-2-carboxylic acid to 5-methylpyrazine-2-carboxylic acid 4-oxide(acipimox).Markedness test is carried out to test each condition. Then the best technologic conditions as well as the main factors and the secondary factors affecting the N-oxidation are determined. Meanwhile, all the factors related to the reaction are general analyzed. Based on the analytical result, the reaction yield brings up to 91%(European patent literature: 73%, Japanese patent literature: 86%).