Cesium fluoride → HCID 178461600, compound

Participants

Reaction Conditions

Reaction Steps

4-Chloro-6-fluoro-1H-indole (72 mg, 0.42 mmol) was dissolved in 4 mL of dioxane under argon. Bis(pinacolato)diboron (198 mg, 778 μmol), tricyclohexylphospine (19.8 mg, 71 μmol), bis(dibenzylidenacetone)palladium (20.3 mg, 35 μmol), and potassium acetate (104 mg, 1.06 mmol) were added under argon. The reaction was stirred for 24 hours at 80° C. The reaction mixture was cooled to room temperature and diluted with 30 mL of EtOAc. The organic layer was washed with 20 mL of brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was filtered through a column (40 g SiO2; EtOAc/heptane in a gradient from 0/100 to 12/88) to yield a mixture, which was concentrated under reduced pressure, and then dissolved in 2 mL of acetonitrile and 0.2 mL of water under argon. 8-Bromo-2-((S)-3-methylmorpholin-4-yl-)-6-((R)-3-methyl-morpholin-4-yl)-9H-purine (100 mg, 153 μmol) was added, followed by cesium fluoride (25.8 mg, 170 μmol) and tetrakis(triphenylphospine)palladium (26 mg, 23 μmol). The reaction mixture was stirred at 135° C. for 2 hours in a sealed vial. The reaction mixture was cooled to room temperature and diluted with 40 mL of EtOAc. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography (10 g SiO2; tertbutylmethylether) to give the title compound as a foam (36 mg, 19% over 2 steps).

Provenance & Evidence