Potassium Carbonate → N-(5-((4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-6-methoxypyridin-3-yl)-5-chloropicolinamide

Participants

Reaction Conditions

Reaction Steps

A microwave vial was charged with (4S,6S)-4-(5-bromo-2-methoxypyridin-3-yl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (0.100 g, 0.272 mmol), 5-chloropicolinamide (0.064 g, 0.407 mmol), copper(I) iodide (10.35 mg, 0.054 mmol) and potassium carbonate powder (0.113 g, 0.815 mmol). The vial was purged with nitrogen followed by the addition of 1,4-dioxane 1 mL and (1R,2R)-(−)-N,N″-dimethylcyclohexane-1,2-diamine (0.043 ml, 0.272 mmol). The vial was sealed and heated at 120° C. overnight. The reaction mixture was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc three times. The organic layers were combined, washed with brine and dried over sodium sulfate, filtered and concentrated. The crude material was purified by column chromatography using a gradient of 15-85% EtOAc/hexane to give N-(5-((4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-6-methoxypyridin-3-yl)-5-chloropicolinamide (0.029 g, 0.065 mmol, 24.06% yield). MS m/z=443.9 [M+H]+. Calculated for C18H17ClF3N5O3: 443.8

Provenance & Evidence