Sodium Carbonate → (S)-4-isopropyl-3-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)oxazolidin-2-one

Temperatur

90 °C

To a sealed tube was added (S)-3-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-one (2.5 g, 7.69 mmol), 2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole (4.62 g, 11.5 mmol), dioxane (76.9 mL, 7.69 mmol) and 2.0M Na2CO3 (11.5 mL, 23.1 mmol). The mixture was degassed by bubbling N2 through the solution. Pd2 dba3 (0.704 g, 0.769 mmol) and dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.367 g, 0.769 mmol) were added and the vessel was sealed under a N2 atmosphere. The mixture was heated at 90° C. for 72 hours. The reaction mixture was diluted with H2O (150 mL) and EtOAc (150 mL), separated, and the aqueous layer was further extracted with EtOAc. The combined organic extracts were washed with brine, dried (Na2SO4), filtered and concentrated. Purification of the crude material by normal phase chromatography, eluting with 0-4% (9:1 MeOH:NH4OH)/dichloromethane, provided (S)-4-isopropyl-3-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)oxazolidin-2-one as a bright yellow-orange foamy solid, 2.09 g (52%). LCMS (APCI+) m/z 519 [M+H]+.

1. customThe mixture was degassed
2. customby bubbling N2 through the solution
3. customthe vessel was sealed under a N2 atmosphere
4. customseparated
5. extractionthe aqueous layer was further extracted with EtOAc
6. washThe combined organic extracts were washed with brine
7. dry with materialdried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated
10. customPurification of the crude material by normal phase chromatography
11. washeluting with 0-4% (9:1 MeOH:NH4OH)/dichloromethane

ORD-Eintrag

ord-c510a635badb4da48a83d64d2f5f2c8f

Quelldatensatz

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08865726B2