Cesium carbonate → HCID 86732170, compound

Participants

Reaction Conditions

Reaction Steps

To a resealable vial was added (4S,6S)-4-(6-bromo-3-fluoropyridin-2-yl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (0.200 g, 0.535 mmol), 5-cyanopicolinamide (0.118 g, 0.802 mmol), 1,4-dioxane (4 mL), and cesium carbonate (Strem Chemicals; 0.435 g, 1.337 mmol). The reaction vessel was carefully evacuated and backfilled with N2. This was repeated twice. To the solution was added tris(dibenzylideneacetone)dipalladium (0) (Aldrich; 0.049 g, 0.053 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Aldrich; 0.062 g, 0.107 mmol). The reaction vessel was carefully evacuated and backfilled with N2. This was repeated twice. The solution was stirred and heated at 100° C. for 3 h. The reaction mixture was allowed to cool to rt and poured into sat NaHCO3 (50 mL) and extracted with EtOAc (2×100 mL). The combined extracts were washed with water (100 mL) and brine (50 mL) and then dried (Na2SO4) and concentrated onto silica. Purification by silica gel chromatography (Gradient; 0.0 to 10% MeOH/CH2Cl2, Silicycle HP column, 40 g) followed by further purification by reverse phase preparative-HPLC afforded N-(6-((4S,6S)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-5-fluoropyridin-2-yl)-5-cyanopicolinamide (0.0675 g, 0.153 mmol, 28.7% yield) as a white solid. MS m/z=440.9 [M+H]+. Calculated for C18H13F5N6O2: 440.1.

Provenance & Evidence