Potassium Carbonate → HCID 118080609, compound

Temperature

80 °C

A 1.5 mL reaction vial was charged with 2,4-difluorophenyl (S)-4-acetyl-7-bromo-3-methyl-3,4-dihydroquinoxaline-1(2H)-carboxylate (0.02 mmol), tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidin-1-carboxylate (0.2 M solution in 1,4-dioxane, 225 μL, 0.03 mmol), and 1,4-dioxane (100 μL). Potassium carbonate (1 M solution in water, 60 μL, 0.06 mmol) was then added, and the reaction mixture was purged with nitrogen. [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.02 M solution in 1,2-dichloroethane, 150 μL, 0.003 mmol) was then added, the reaction was purged with nitrogen and heated to 80° C. on a heater shaker overnight. The reaction was diluted with ethyl acetate and washed with 1 N aqueous sodium hydroxide solution. The aqueous layer was separated and extracted with ethyl acetate (1 mL) and the combined organic layers were concentrated under a stream of nitrogen. The crude product was purified by mass triggered preparatory HPLC. The product-containing fractions were combined and concentrated. The residue was taken up in 1,2-dichloroethane (200 μL) and trifluoroacetic acid (100 μL was added. The reactions stirred at room temperature for 2 h. The reaction was concentrated, and diluted with ethyl acetate (0.5 mL) and saturated aqueous sodium bicarbonate solution (0.5 mL). The aqueous layer was separated and extracted with ethyl acetate (1 mL), and the combined organic layers were concentrated under a stream of nitrogen and vacuum. The crude product was purified by mass triggered preparatory HPLC. The product-containing fractions were combined and concentrated to afford 2,4-difluorophenyl (S)-4-acetyl-3-methyl-7-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-3,4-dihydroquinoxaline-1(2H)-carboxylate. MS (ESI, pos. ion) m/z 496 [M+H]+.

1. customA 1.5 mL reaction
2. customthe reaction mixture was purged with nitrogen
3. customthe reaction was purged with nitrogen
4. additionThe reaction was diluted with ethyl acetate
5. washwashed with 1 N aqueous sodium hydroxide solution
6. customThe aqueous layer was separated
7. extractionextracted with ethyl acetate (1 mL)
8. concentrationthe combined organic layers were concentrated under a stream of nitrogen
9. customThe crude product was purified by mass
10. concentrationconcentrated
11. additiontrifluoroacetic acid (100 μL was added
12. concentrationThe reaction was concentrated
13. additiondiluted with ethyl acetate (0.5 mL) and saturated aqueous sodium bicarbonate solution (0.5 mL)
14. customThe aqueous layer was separated
15. extractionextracted with ethyl acetate (1 mL)
16. concentrationthe combined organic layers were concentrated under a stream of nitrogen and vacuum
17. customThe crude product was purified by mass
18. concentrationconcentrated

ORD record

ord-7dd9c540b9b2431ca5e216386ba840ce

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09422281B2