1-(3-Chlorophenyl)-1H-pyrazol-5-amine synthesis

Yield:-

Reaction Conditions:

Stage #1: m-chlorophenylhydrazine hydrochloride;2-Chloroacrylonitrilewith sodium hydrogencarbonate;potassium carbonate in water at 20;
Stage #2: with potassium hydroxide in methanol;water at 60;

Steps:

5.2. General procedure for the synthesis of compounds (4a-l)

General procedure: Add the mixture of raw material 2a-l (500 mg, 1eq), NaHCO3 (2eq)and K2CO3 (1eq) into the water and stir evenly, then add 2-chloroacrylonitrileand stir overnight at room temperature. Extract with ethyl acetate three times, dry the organic phase with anhydrous sodium sulfate,and dissolve it with methanol after decompression and concentration,then add KOH aqueous solution (0.1eq) to react at 60 °C for 3 h. Methanol was concentrated under reduced pressure and then extracted with ethyl acetate and water. The combined organic phase was dried with anhydrous sodium sulfate, and the crude product was evaporated to dryness to be directly used in the next step of the reaction, with a yield of 28%-55%.

References:

Cao, Yaquan;Yang, Pu;Yang, Yingxue;Lin, Zihui;Fan, Zhengmin;Wei, Xuliang;Yan, Lijie;Li, Yongchun;He, Zhangxu;Ma, Liying;Xu, Hongde;Wu, Chunli [European Journal of Medicinal Chemistry,2023,vol. 251,art. no. 115250] Location in patent:supporting information