Dichloromethane → 1-(2-bromo-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)isoquinoline-6-sulfonamide

Participants

Reaction Conditions

Reaction Steps

A glass pressure tube was charged with 1-chloro-N-(4-methoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)isoquinoline-6-sulfonamide (690 mg, 1.54 mmol), potassium carbonate (107 mg, 7.72 mmol), 2-bromo-4-(trifluoromethyl)phenylboronic acid (498 mg, 1.85 mmol), tetrakis(triphenylphosphine)palladium(0) (178 mg, 0.154 mmol) in dioxane (10.300 mL) and water (5.15 mL). The reaction was purged with argon. The tube was sealed and heated in an oil bath at 100° C. After 35 min, the reaction was cooled down to room temperature. The mixture was extracted with EtOAc (3×30 mL). The organic layers were separated, combined, dried over MgSO4, filtered and concentrated to afford a yellow residue. The residue was absorbed onto a plug of silica gel and purified by chromatography through a silica gel column (40 g), eluting with a gradient of 0% to 20% DCM in heptane to remove PPh3 and then 20 to 90% DCM in heptane to provide 1-(2-bromo-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)isoquinoline-6-sulfonamide (0.86 g, 1.353 mmol) as a yellow solid. MS (ESI): 634.0 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 3.64 (s, 3H), 5.24 (s, 2H), 6.78 (d, J=8.90 Hz, 2H), 7.27 (d, J=8.80 Hz, 2H), 7.69 (d, J=10 Hz, 1H), 7.75 (d, J=8 Hz, 1H), 7.91-7.99 (m, 2H), 8.23-8.26 (m, 2H), 8.46 (s, 1H), 8.81-8.84 (m, 2H).

Provenance & Evidence