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

Participants

Reaction Conditions

Reaction Steps

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]+.

Provenance & Evidence