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

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.

1. stirringstirring
2. waitcontinued for 1.5 hours
3. stirringthe mixture was stirred at RT for 65 hours
4. concentrationconcentrated in vacuo
5. additionThe residue was diluted with EtOAc (100 ml) the emulsion
6. filtrationwas filtered through Celite® (filter material)
7. customThe phases were separated
8. extractionthe aqueous portion was extracted with EtOAc (50 ml)
9. washThe combined organic extracts were washed with brine
10. dry with materialdried (MgSO4)
11. concentrationconcentrated in vacuo
12. customThe residue was triturated with EtOAc (˜10 ml)

ORD record

ord-23b2ce746d6b464791e639e27a8d5bc0

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08754085B2