3,5-Dibromo-6-chloropyrazin-2-amine → 2-bromo-3-chloro-7,8-dihydropyrido[2,3-b]pyrazin-6(5H)-one

Participants

Reaction Steps

A mixture comprising 3,5-dibromo-6-chloropyrazin-2-amine (step 1) (1.0 g, 3.48 mmol) and bistriphenylphosphinepalladium(II)chloride (0.122 g, 0.174 mmol) in THF (15 ml) under nitrogen was treated with (3-ethoxy-3-oxopropyl)zinc(II) bromide 0.5 M in THF (15.31 ml, 7.66 mmol) and the mixture was stirred at room temperature for 3 hours. A further portion of (3-ethoxy-3-oxopropyl)zinc(II) bromide 0.5 M in THF (7.5 mL, 3.8 mmol) was added and stirring continued for 1.5 hours. More (3-ethoxy-3-oxopropyl)zinc(II) bromide 0.5 M in THF (3.8 mL, 1.9 mmol) was added and the mixture was stirred at RT for 65 hours. The mixture was diluted with water (10 ml) and concentrated in vacuo. The residue was diluted with EtOAc (100 ml) the emulsion was filtered through Celite® (filter material). The phases were separated and the aqueous portion was extracted with EtOAc (50 ml). The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. The residue was triturated with EtOAc (˜10 ml) to afford the title compound as yellow solid.

Provenance & Evidence