1-(4-Methoxyphenyl)-6-(4-iodophenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester

473927-69-4

27143-07-3

473927-64-9

The reaction was carried out under inert atmosphere (argon). First, ethyl [(4-methoxyphenyl)hydrazinylidene]chloroacetate (14.1 g, 0.055 mol) was dissolved in 140 mL of ethyl acetate. The solution was cooled to 0-5 °C in an ice water bath. Under stirring conditions, 1-(4-iodophenyl)-3-morpholino-5,6-dihydropyridin-2(1H)-one (21.1 g, 0.055 mol) was added in batches. Subsequently, triethylamine (11.1 g, 0.110 mol) was added slowly and dropwise at 0-5 °C. The reaction mixture was then cooled to a temperature of 0.5 °C. Cooling was stopped and the reaction mixture was allowed to warm up to room temperature. Next, the reaction mixture was heated to reflux and maintained at reflux for about 1 hour. The progress of the reaction was monitored by HPLC to ensure that the reaction was completed within 120 minutes. The reaction mixture was again cooled to 0-5 °C and a 1:1 hydrochloric acid solution diluted from concentrated hydrochloric acid (27.5 mL, 0.275 mol) with an equal volume of distilled water was slowly added dropwise. After cooling, the reaction mixture was continued to be stirred for about 1 hour. Then, 55 mL of water was added and the suspension formed was continued to be stirred under cooling conditions for 2 hours. The product was isolated by filtration and dried under vacuum at 50 °C for 24 h to afford 6-(4-iodophenyl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid (Product III) in a yield of 21.3 g, 75% yield, and 95% purity by HPLC.