Potassium Carbonate → HCID 86687545, compound

Participants

Reaction Steps

A microwave vial charged with 4-bromo-N-(4-methoxybenzyl)-N-(thiazol-2-yl)isoquinoline-7-sulfonamide (Intermediate PPPP) (0.066 g, 0.135 mmol), 2-methoxy-4-(trifluoromethyl)phenylboronic acid (Combi-Blocks, San Diego, Calif.) (0.044 g, 0.202 mmol), potassium carbonate (0.093 g, 0.673 mmol), dioxane (0.673 ml) and water (0.224 ml) was purged with argon prior to the addition of Pd(PPh3)4 (0.016 g, 0.013 mmol). The vessel was sealed and irradiated at 100° C. for 30 min. The resulting mixture was diluted with EtOAc and extracted with water, the aqueous phase was extracted with EtOAc and the combined organics were dried under reduced pressure. To the crude brown oil was added DCM (3 ml) and TFA (1 ml) and the resulting solution stirred overnight at RT affording conversion to desired product. The mixture was dried under reduced pressure and purified with a 25 g HP spherical silica gel (Interchim, Mouintlucon, France, 15 μm) ramping EtOAc in heptane (0 to 50%, 10% DCM isocratic throughout) providing product as a film which was lyophilized from MeOH/H2O to provide 4-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)isoquinoline-7-sulfonamide (38 mg, 0.082 mmol, 60.7% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 6.87 (d, J=4.60 Hz, 1H) 7.28 (d, J=4.60 Hz, 1H) 7.46-7.53 (m, 2H) 7.54-7.59 (m, 1H) 7.61 (d, J=8.90 Hz, 1H) 8.02 (dd, J=8.85, 1.91 Hz, 1H) 8.53 (s, 1H) 8.75 (d, J=1.56 Hz, 1H) 9.55-9.66 (m, 1H) 12.88 (br. s., 1H). m/z (ESI) 466.2 (M+H)+.

Provenance & Evidence