Potassium Carbonate → HCID 86687489, compound

Participants

Reaction Conditions

Reaction Steps

A microwave vial was charged with 1-chloro-N-(2,4-dimethoxybenzyl)-4-fluoro-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (Intermediate PPP; 0.041 g, 0.083 mmol), (2-methoxy-4-(trifluoromethyl)phenyl)boronic acid (0.027 g, 0.125 mmol), Pd(PPh3)4 (9.59 mg, 8.30 μmol), and potassium carbonate (0.057 g, 0.415 mmol). Dioxane (0.415 mL) and water (0.138 mL) were added, the vial was flushed with argon and sealed, and heated in a microwave reactor at 100° C. for 30 minutes. The reaction was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The material was purified via silica gel chromatography (12 g, gradient elution 0 to 100% EtOAc:Heptane) to afford N-(2,4-dimethoxybenzyl)-4-fluoro-1-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide. The material was dissolved in DCM and TFA (0.1 mL, 1.298 mmol) was added. The reaction was stirred for 30 minutes at room temperature after which time the reaction was concentrated and triturated with diethyl ether. The solids were filtered, washed with diethyl ether, and vacuum dried to afford 4-fluoro-1-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (0.008 g, 0.017 mmol, 19.94% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm=13.00 (s, 1H), 8.74 (d, J=1.6 Hz, 1H), 8.51 (d, J=1.4 Hz, 1H), 7.99 (dd, J=1.7, 8.9 Hz, 1H), 7.79 (dd, J=1.8, 9.0 Hz, 1H), 7.61-7.55 (m, 1H), 7.55-7.46 (m, 2H), 7.31 (d, J=4.6 Hz, 1H), 6.90 (d, J=4.6 Hz, 1H), 3.75 (s, 3H). m/z (ESI) 484.2 (M+H)+.

Provenance & Evidence