Sodium Carbonate → 2-(3-Fluoro-phenyl)-pyrimidine-5-carboxylic acid 3-methylsulfamoyl-benzylamide

Participants

Reaction Steps

To a mixture of 2-(3-fluoro-phenyl)-pyrimidine-5-carboxylic acid (545 mg, 2.5 mmol) and DCM (35 mL) is added oxalyl chloride (635 mg, 5 mmol) followed by the addition of DMF (20 μL). The reaction is stirred at room temperature for 3 hours. Anhydrous toluene (10 mL) is added and the reaction mixture is concentrated in vacuo. The residue is dissolved in EtOAc (30 mL). The resulting solution is added to a mixture of 3-aminomethyl-N-methyl-benzenesulfonamide hydrochloride (590 mg, 2.5 mmol), sodium carbonate (530 mg, 5 mmol) and water (10 mL) at 0° C. The resulting reaction mixture is warmed to room temperature and stirred overnight. Approximately 80% of EtOAc is removed in vacuo, and heptane is added to precipitate the product. The precipitate is collected by filteration, and recrystallized twice in EtOAc to afford 2-(3-fluoro-phenyl)-pyrimidine-5-carboxylic acid 3-methylsulfamoyl-benzylamide (400 mg). The mother liquors are concentrated and the residue is purified by flash chromatography to afford additional 2-(3-fluoro-phenyl)-pyrimidine-5-carboxylic acid 3-methylsulfamoyl-benzylamide (130 mg) as a powder. MS: 401 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 2.41 (d, 3H), 4.64 (d, 2H), 7.42-7.50 (m, 2H), 7.57-7.70 (m, 4H), 7.78 (s, 1H), 8.16 (d, 1H), 8.31 (d, 1H), 9.33 (s, 2H), 9.53 (t, 1H). IC50=9.5 nM.

Provenance & Evidence