Cesium carbonate → N-(6-((4R,6S)-2-benzamido-4-(difluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-5-fluoropyridin-2-yl)-5-chloropicolinamide

Participants

Reaction Conditions

Reaction Steps

A round-bottomed flask was charged with Pd2(dba)3 (2.91 mg, 3.17 μmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (7.35 mg, 0.013 mmol), N-((4R,6S)-4-(6-bromo-3-fluoropyridin-2-yl)-4-(difluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide (21 mg, 0.042 mmol), 5-chloropicolinamide (9.61 mg, 0.061 mmol), and cesium carbonate (34.5 mg, 0.106 mmol). The flask was evacuated under vacuum and then flushed with nitrogen. Dioxane (0.5 mL) was then added and the reaction was stirred in a 90° C. oil bath for 10 h. The reaction mixture was cooled to RT, filtered through celite and washed with EtOAc. The filtrate was concentrated and the residue was purified by chromatography through a Redi-Sep pre-packed silica gel column (12 g), eluting with a gradient of 0% to 30% EtOAc in hexane, to provide N-(6-((4R,6S)-2-benzamido-4-(difluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-5-fluoropyridin-2-yl)-5-chloropicolinamide (17 mg, 0.030 mmol, 70.2% yield) as white solid. MS m/z=572, 574 M+, Calculated for C24H16ClF6N5O3: 571.86.

Provenance & Evidence