Sodium Carbonate → HCID 46941213, compound

Participants

Reaction Steps

Dioxane (2 mL) and 2M aq Na2CO3 (0.5 mL) were added to 2,4-difluoro-N-[2-methoxy-5-(5-iodoimidazo[2,1-b][1,3,4]thiadiazol-2-yl)-pyridin-3-yl]-benzenesulfon-amide (100 mg) and pyridazin-4-boronic acid pinacol ester (80 mg), and the suspension was degassed under vacuum and filled with argon (2×). The catalyst (30 mg) was quickly added, and the reaction mixture was stirred at reflux for 2 h. Further boronate (50 mg) was added, and the mixture was degassed again, then more catalyst was added (25 mg) and stirring was continued at reflux for 4 h. The solvents were evaporated, and the residue was stirred in water for 36 h. The precipitate that had formed was removed by filtration, and the filtrate was concentrated and taken up in aq. NH4Cl. A precipitate formed overnight and was filtered off, washed with water followed by ether and dried. The solid was purified by flash chromatography (DCM/MeOH 98:2 to 9:1, affording 24 mg of crude product) and subsequently by preparative HPLC to give the desired product (5 mg). HPLC-MS (5-100% B in 8 min at 0.8 mL): tR=4.57 min, [M+H]+ m/z 502.1; 1H NMR (300 MHz, DMSO) δ=10.56 (s, 1H), 9.82 (s, 1H), 9.25 (d, J=5.5 Hz, 1H), 8.57 (s, 1H), 8.35-8.16 (m, 2H), 8.06 (s, 1H), 7.79 (dd, J=15.0, 8.6 Hz, 1H), 7.50 (s, 1H), 7.20 (t, J=8.3 Hz, 1H), 3.70 (s, 3H) ppm.

Provenance & Evidence