1,4-Dioxane → HCID 86687546, compound

Participants

Reaction Steps

To a microwave vial charged with (2-methoxyphenyl)boronic acid (25.6 mg, 0.168 mmol), 4-bromo-N-(4-methoxybenzyl)-N-(thiazol-2-yl)isoquinoline-7-sulfonamide (Intermediate PPPP) (75 mg, 0.153 mmol), and potassium phosphate tribasic (38.0 μl, 0.459 mmol) was added dioxane (613 μl) and water (204 μl). The mixture was purged with argon prior to the addition of 1,1-bis[(di-t-butyl-p-methylaminophenyl]palladium(II) chloride (10.83 mg, 0.015 mmol). The mixture was irradiated at 100° C. in a microwave for 30 min. The organics were decanted, the aqueous rinsed with EtOAc and the organics combined and dried under reduced pressure. The crude material was dissolved in DCM (1.5 ml) and TFA (0.5 ml) was added and the mixture shaken at room temperature for 2 hrs. The resulting mixture was dried under reduced pressure and purified with a 25 g Interchim HP spherical silica column (Interchim, Mouintlucon, France) (15 μm) ramping EtOAc in heptane (0 to 100%, 10% DCM throughout) with product eluting at 100% polar eluent to afford 4-(2-methoxyphenyl)-N-(thiazol-2-yl)isoquinoline-7-sulfonamide (40 mg, 0.101 mmol, 65.8% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 6.87 (d, J=4.60 Hz, 1H) 7.08-7.16 (m, 1H) 7.22 (d, J=8.22 Hz, 1H) 7.25-7.35 (m, 2H) 7.48-7.55 (m, 1H) 7.61 (d, J=8.90 Hz, 1H) 8.00 (dd, J=8.85, 1.91 Hz, 1H) 8.48 (s, 1H) 8.71 (d, J=1.76 Hz, 1H) 9.55 (s, 1H) 12.87 (br. s., 1H). m/z (ESI) 398.2 (M+H)+.

Provenance & Evidence