2,4,6-Trimethylpyridine → 1-methyl-piperidine-4-carboxylic Acid {[3-(9-chloro-3-methyl-4-oxo-5H-isoxazolo[4,3-c]quinolin-5-yl)-cyclohexylcarbamoyl]-phenyl-methyl}-amide

Participants

Reaction Steps

A product from Example 638 (50 mg; 0.108 mmol) was dissolved in anhydrous dimethylformamide (10 mL) under a nitrogen atmosphere, mixed with 1-methyl-piperidine-4-carboxylic acid hydrochloride (58.0 mg; 0.323 mmol; 3 equiv), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (61.8 mg; 0.323 mmol; 3 equiv), 2,4,6-trimethylpyridine (86 μL; 0.645 mmol; 6 equiv), and 1-hydroxy-7-azabenzotriazole (43.9 mg; 0.323 mmol; 3 equiv), and stirred overnight at room temperature. The reaction solution was diluted with 2 volumes ethyl acetate, 10 volumes water, and 1 volume saturated NaHCO3(aq). The organic layer was separated and then washed with saturated NaCl(aq), dried over Na2SO4(S), filtered, and concentrated in vacuo. The resulting material was purified by radial chromatography on a 2 mm thick silica gel rotor with a 2% then 4% methanol/dichloromethane (v/v) mobile phase and finally a 2% methanol/0.5% triethylamine/dichloromethane (v/v/v) mobile phase. The desired product was isolated as a white solid in 74% yield (47 mg).

Provenance & Evidence