A kind of preparation method of cetirizat

Abstract

The invention provides a method for preparing cetilistat. According to the method, 2-amidogen-5-methyl benzoic acid is adopted as an initial raw material, under existence of pyridine, the 2-amidogen-5-methyl benzoic acid reacts with chlorine acid cetyl alcohol ester in the first place, a midbody 2-(((hexadecane oxygroup) carbonyl) amidogen)-5-methyl benzoic acid is obtained, then dehydrogenation cyclization reagent is utilized to obtain the cetilistat, and the feeding sequence in step 1 is the 2-amidogen-5-methyl benzoic acid, alkali and the chlorine acid cetyl alcohol ester in sequence. The method has the remarkable advantages that the route is simple, operation is less, atom economy is better than that of other routes, and the cetilistat is suitable for large-scale production; the purity of the cetilistat at the reaction endpoint is larger than 98%, and through simple postprocessing, a final product which meets medical standards can be obtained, wherein the purity is larger than 99.5%, and the single impurity is smaller than 0.1%; the utilized solvent including dichloromethane and pyridine can be recycled for mechanical application, and the method is environmentally friendly.

Description

technical field

[0001] The invention relates to the technical field of medicine preparation methods. Background technique

[0002] Cetilistat (2-hexadecyloxy-6-methyl-4H-3,1-benzoxazin-4-one, Cetilistat) is a long-acting and potent specific Anti-gastrointestinal lipase inhibitors, non-systemic weight management drugs. Cetiristat mainly forms a covalent bond with the active serine site of gastric lipase and pancreatic lipase in the lumen of the stomach and small intestine to inactivate the enzyme and exert its therapeutic effect. Inactivated enzymes are unable to hydrolyze dietary fats (mainly triglycerides) into absorbable non-esterified fatty acids and monoacylglycerols. Unbroken triglycerides cannot be absorbed by the intestine, thereby reducing calorie intake and keeping weight under control. This medicine does not need to be absorbed throughout the body to be effective. The structural formula of cetilistat is as follows:

[0003]

[0004] Cetilistat is a kind of ...

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