Nitrogen → HCID 86686744, compound

Participants

Reaction Steps

N-{1-[7-(bis{[2-(trimethylsilyl)ethoxy]methyl}amino)-6-bromo-3-(6-fluoroquinolin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl]ethyl}-2,2,5-trimethyl-1,3-dioxane-5-carboxamide (63.7 mg, 0.078 mmol) and tetrakis(triphenylphosphine)palladium(0) (9.0 mg, 0.0078 mmol) were combined in a microwave tube, and the cap was crimped on. The headspace was purged with dry N2 (×2), and tributyl[1-(ethyloxy)ethenyl]stannane (53 μL, 0.16 mmol) and 1,4-dioxane (0.69 mL) were added. The suspension was sparged with dry N2 for ca. 3 min. The tube was lowered into a pre-heated 100° C. oil bath and stirred over night. The dark reaction mixture was then cooled, partitioned between aq. KF (2 mL, 0.5 M) and ether (ca. 3 mL). The layers were separated, and the aqueous was extracted with ether (1×3 mL), the organics were combined, washed with brine (2 mL), dried with magnesium sulfate, filtered, and concentrated in vacuo. The crude matrial (105 mg) was adsorbed into silica gel, and purified by flash chromatography (15 g silica, hexanes to 25% EtOAc in hexanes, the 5% MeOH in DCM). Like fractions were combined, and concentrated to give N-{1-[7-(bis{[2-(trimethylsilyl)ethoxy]methyl}amino)-6-(1-ethoxyvinyl)-3-(6-fluoroquinolin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl]ethyl}-2,2,5-trimethyl-1,3-dioxane-5-carboxamide (52.5 mg, 83%) as a yellow film. The material contained a small amount of triphenylphosphine oxide, and carried on as is.

Provenance & Evidence