Synthesis method of 1-(-)-3-[5-(-)-1H-tetrazole-1-yl]-1H-pyrazole-5-carboxylic acid

Abstract

The invention relates to the technical field of research and development of chemical drugs, and discloses an efficient synthesis method of 1-(3-chloropyridine-2-yl)-3-[5-(trifluoromethyl)-1H-tetrazole-1-yl]-1H-pyrazole-5-carboxylic acid, which comprises the following steps: firstly, carrying out Vilsmeier-Haack reaction on 3-chloropyridine, DMF (Dimethyl Formamide) and POCl to prepare 3-chloropyridine-2-formaldehyde; then, trifluoroacetonitrile, sodium azide and ammonium chloride are subjected to a reaction in DMSO, and 5-(trifluoromethyl)-1H-tetrazole is generated; the preparation method comprises the following steps: carrying out condensation on 1-(3-chloropyridine-2-yl)-3-[5-(trifluoromethyl)-1H-tetrazole-1-yl]-1H-pyrazole-5-carboxylic acid ethyl ester and ethyl acetoacetate to obtain 1-(3-chloropyridine-2-yl)-3-[5-(trifluoromethyl)-1H-tetrazole-1-yl]-1H-pyrazole-5-carboxylic acid ethyl ester, carrying out alkali liquor hydrolysis and acidification on the product to obtain a crude product, carrying out primary impurity removal by using acetonitrile and active carbon, and carrying out gradient cooling recrystallization in a mixed solvent of acetonitrile and water to obtain the 1-(3-chloropyridine-2-yl)-3 therefore, a high-purity target product is obtained.