139756-04-0

2100-31-4

139756-02-8

139756-04-0

Step 8 Synthesis of 2-methyl-4-(2-propoxybenzoylamino)-5-propyl-2H-pyrazole-3-carboxamide: 2-Propoxybenzoic acid (13.7 g, 76.1 mmol) was mixed with thionyl chloride (36.2 g, 304.4 mmol) in anhydrous dichloromethane (80 mL) and heated at reflux for 3 hours. Upon completion of the reaction, the solvent and excess thionyl chloride were removed by distillation under reduced pressure. The resulting chloride intermediate was dissolved in anhydrous dichloromethane (60 mL) and slowly added to an anhydrous solution containing 4-amino-2-methyl-5-propyl-2H-pyrazole-3-carboxamide (12.6 g, 69.2 mmol), dry triethylamine (7 g, 69.2 mmol), and 4-(N,N-dimethylamino)pyridine (84.5 mg, 0.7 mmol). dichloromethane (200 mL) solution, maintaining the reaction temperature at 0°C. After stirring the reaction mixture for 1 h, it was washed sequentially with water (150 mL), saturated aqueous sodium carbonate solution (200 mL) and saturated brine (200 mL). The organic layer was dried over anhydrous magnesium sulfate and filtered, the filtrate was concentrated to about 60 mL and a white solid product (22 g, 92% yield) was precipitated by addition of hexane (150 mL). The product was confirmed by 1H NMR (300 MHz, CDCl3) and LC-MS (m/z = 345 [M + H]+) characterization.