Ethanol → HCID 44481643, compound

Participants

Reaction Steps

To a solution of 3-[4-(1-{[1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carbonyl]-amino}-butyl)-pyridine-2-sulfonyl]-propionic acid methyl ester (200 mg, 0.39 mmol) in anhydrous THF (10 mL) is added sodium methoxide in methanol (2.6 M solution freshly prepared by dissolving 140 mg of sodium in 2.4 mL of methanol, 0.15 mL, 0.39 mmol). After stirring at room temperature for 10 min, the reaction mixture is concentrated in vacuo. Anhydrous THF (10 mL) is added and the concentration process is repeated. The resultant residue is dried under high vacuum for 5 min, dissolved in THF (10 mL) and treated with chloramine T (180 mg, 0.77 mmol). The reaction mixture is stirred at room temperature for 15 min and then treated with methyl amine in ethanol (33% solution in ethanol, 0.48 mL, 3.9 mmol) in one portion. After 20 min the reaction mixture is diluted with saturated aqueous sodium bicarbonate (20 mL) and water (8 mL), and extracted with EtOAc (2×35 mL). The combined organic layers are washed with brine (10 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The residue is purified by preparative reverse phase HPLC (eluted with 10 to 90% CH3CN/H2O and 0.1% TFA as additive) to afford 1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic acid [1-(2-methylsulfamoyl-pyridin-4-yl)-butyl]-amide (160 mg, 90%).

Provenance & Evidence