Chlorosuccinimide → HCID 44481371, compound

Participants

Reaction Steps

To a solution of 3-[5-(1-{[1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carbonyl]-amino}-butyl)-pyridine-2-sulfonyl]-propionic acid methyl ester (150 mg, 0.29 mmol) in anhydrous THF (15 mL) is added sodium methoxide in methanol (2.6 M solution freshly prepared by dissolving 120 mg of sodium in 2.0 mL of methanol, 0.12 mL, 0.32 mmol). After stiffing at room temperature for 15 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 (15 mL) and treated with N-chlorosuccinimide (77 mg, 0.58 mmol). The reaction mixture is stirred at room temperature for 15 min and then tetrahydro-pyran-4-ylamine (130 mg, 1.3 mmol) is added in one portion. After 20 min the reaction mixture is concentrated in vacuo and purified directly by preparative reverse phase HPLC (eluted with 10 to 90% CH3CN/H2O and 0.1% TFA as additive) followed preparative TLC (eluted with 70% EtOAc/hexanes) to afford 1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic acid {1-[6-(tetrahydro-pyran-4-ylsulfamoyl)-pyridin-3-yl]-butyl}-amide (14 mg, 9%) and 5-(1-{[1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carbonyl]-amino}-butyl)-pyridine-2-sulfonic acid (15 mg, 12%).

Provenance & Evidence