New preparation method of lanoconazole

Abstract

Methanol and concentrated sulphuric acid are taken as solvent and 2-chloric mandelic acid is taken as raw material for esterification reaction, sodium hydroxide is added to be neutral after full reaction, reducing reaction is carried out with sodium borohydride, diluted hydrochloric acid is used for neutralization and water is added for dilution, distillation and extraction by 1, 2-dichloroethane are carried out to obtain 1-2-(2-chlorphenyl)-1, 2-ethylene glycol, then triethylamine and mesyl chloride are added into the 1-2-(2-chlorphenyl)-1, 2-ethylene glycol for esterification reaction, and then diluted hydrochloric acid, sodium bicarbonate and drinking water are respectively used for washing, reduced pressure distillation is carried out to remove solvent, so as to obtain sticky grease, ethyl acetate is added at the temperature below 77 DEG C for dissolution, heating is carried out until refluxing, temperature reduction, crystallization, centrifugation and drying are carried out, thus obtaining yellow solid 1-(2-chlorphenyl)-1, 2-glycol dimethyl sulphonate. Then dimethyl sulphoxide and potassium hydroxide are taken as raw materials, mixed liquid of 1-imidazoly acetonitrile, carbon disulphide and dimethyl sulphoxide is dropwise added for condensation reaction, mixed liquid of dimethyl sulphoxide and 1-(2-chlorphenyl)-1, 2-glycol dimethyl sulphonate is dropwise added for ring formation reaction, and ice analysis, extraction by ethyl acetate and reduce pressure distillation are carried out, thus obtaining E / Z-alpha-[4-(2-chlorphenyl)-1, 3-dithiolane-2-subunit]-1H-imidazolyl acetonitrile. The E / Z-alpha-[4-(2-chlorphenyl)-1, 3-dithiolane-2-subunit]-1H-imidazolyl acetonitrile is separated by silicagel column and then added with active carbon, distillation is carried out to remove most solvent, hot pressing filtering, temperature reduction, crystallization, centrifugation and drying are carried out, thus obtaining almost white or white lanoconazole powder solid.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a new method for preparing lanoconazole. Background technique [0002] Background technology of the present invention is as follows: [0003] In the past 20 years, the research on antifungal drugs has progressed rapidly, and new antifungal drugs have emerged in an endless stream. The country is also actively developing and applying clinical new drugs. [0004] Mycoses can be divided into two categories: superficial and deep. Antifungal drugs can be used externally or internally for superficial mycosis, while deep ones must be applied systemically. After a long period of slow development, antifungal drugs developed rapidly in the 1960s, and the marketed drugs increased significantly. So far, more than 80 antifungal drugs have been used clinically. The antibacterial range and mechanism of action of these drugs have their own characteristics. According to their chem...

AI Technical Summary

Problems solved by technology

In addition, animal experiments also suggest that lanoconazole can promote wound healing, but its clinical significance remains to be further observed