Cesium carbonate → 1-(2-methoxy-4-methylphenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide

Participants

Reaction Steps

A microwave vial containing Cs2CO3 (0.175 g, 0.538 mmol), (2-methoxy 4-methyl phenyl)boronic acid (27 mg, 0.175 mmol) and 1-chloro-N-(4-methoxybenzyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (Intermediate JJJ; 0.06 g, 0.135 mmol) in DME (1.500 ml) and water (0.225 ml) was purged with nitrogen and Pd(PPh3)4(0.016 g, 0.013 mmol) was added and the reaction was irradiated under microwave irradiation at 125° C. for 1.5 h. The aqueous layer was discarded and the organic layer was concentrated. To this was then added DCM (1 mL) and TFA (0.5 mL) and the reaction was shaken for 2 h. The reaction mixture was purified by reverse-phase chromatography with 0.1% NH4OH in ACN and water as mobile phase to obtain 1-(2-methoxy-4-methylphenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (28 mg, 51%) as a light yellow solid. 1H NMR (500 MHz, DMSO-d6) δ ppm 12.87 (br. s., 1H) 8.65 (d, J=5.61 Hz, 1H) 8.51 (s, 1H) 8.05 (d, J=5.73 Hz, 1H) 7.85 (dd, J=8.88, 1.66 Hz, 1H) 7.71 (d, J=8.94 Hz, 1H) 7.27 (d, J=4.58 Hz, 1H) 7.20 (d, J=7.56 Hz, 1H) 7.04 (s, 1H) 6.93 (d, J=7.45 Hz, 1H) 6.87 (d, J=4.58 Hz, 1H) 3.63 (s, 3H) 2.43 (s, 3H); m/z (ESI) 416.0 (M+H)+.

Provenance & Evidence