Sodium Carbonate → 7-(2,2-Difluoro-benzo[1,3]dioxol-4-yl)-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazine

Participants

Reaction Conditions

Reaction Steps

7-Bromo-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazine (0.531 g, 2.18 mmol), 2,2-Difluorobenzo[1,3]dioxole-4-boronic acid (0.624 g, 3.09 mmol), Tetrakis(triphenylphosphine)palladium(0) (125 mg, 0.108 mmol), 2.00 M of Sodium carbonate in Water (2.70 mL), and 1,4-Dioxane (6.6 mL) were combined in a vial, degassed (freeze-pump-thaw) and was heated under an atmosphere of Nitrogen at 80° C. overnight. Conversion was ˜75%. Further heating for a second night lead to little additional product relative to bromide. The mixture was diluted with water (20 mL) then extracted with EtOAc (3×30 mL). The org. was washed with brine, dried, filtered through 7 mL silica gel, washing with EtOAc, then conc. in vacuo onto 7 g silica gel. Purification on an ISCO (80 g, 0-10% EtOAc:Hex) afforded first an impurity, then the product 7-(2,2-Difluoro-benzo[1,3]dioxol-4-yl)-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazine (0.440 g; Yield=63.0%). LCMS (HPLC): 1.46 min, 322 (M+H); 1H-NMR (DMSO-d6): 9.12 (s, 1H), 8.16 (d, 1H, J=8.1 Hz), 7.48 (d, 1H, J=7.9 Hz), 7.40 (m, 1H), 7.33 (d, 1H, J=4.8 Hz), 7.16 (d, 1H, J=4.8 Hz), 2.55 (s, 3H).

Provenance & Evidence