Potassium Carbonate → 3-Cyano-N-(2,4-dimethoxybenzyl)-4-[2-pyridazin-4-yl-4-(trifluoromethyl)benzyl]-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-cyano-N-(2,4-dimethoxybenzyl)-4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide (Preparation 29, 100 mg, 0.19 mmol) in tetrahydrofuran (2 mL) was added a 2 M aqueous solution of potassium carbonate (270 μL, 0.54 mmol) and 4-[2-(bromomethyl)-5-(trifluoromethyl)phenyl]pyridazine (Preparation 33, 57 mg, 0.18 mmol). The solution was sparged with nitrogen before the addition of tetrakis(triphenylphosphine)palladium (0) (20.8 mg, 0.018 mmol). The reaction mixture was heated at 65° C. for 6 hours. The reaction mixture was cooled to ambient temperature and partitioned between a saturated aqueous solution of ammonium chloride (5 mL) and ethyl acetate (2×10 mL). A saturated aqueous solution of sodium chloride was added to aid the separation. The combined organic layer was dried over anhydrous magnesium sulphate, filtered and concentrated in vacuo to give a brown oil. The material was purified by silica gel column chromatography (ISCO™ companion, 12 g column, 0-30% ethyl acetate in heptane gradient elution). Fractions containing product were combined and concentrated in vacuo to obtain the title compound as a foam.

Provenance & Evidence