Dimethylacetamide → HCID 90373121, compound

Participants

Reaction Conditions

Reaction Steps

A microwave vial was charged with N-(3-((4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4,5-difluorophenyl)-5-chloro-3-fluoropicolinamide (0.182 g, 0.390 mmol), zinc cyanide (0.056 g, 0.468 mmol, Sigma Aldrich), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1′1′-biphenyl (0.032 g, 0.078 mmol, Strem), and tris(dibenzylideneacetone)dipalladium (0) (0.036 g, 0.039 mmol, Strem). The vial was sealed and evacuated/backfilled with nitrogen three times. 1 ml of a premixed 99:1 DMA:water solution was added and the reaction was heated to 120° C. in the microwave for 20 minutes. Upon cooling, the reaction was diluted with water and EtOAc. The organic layer was separated, washed with brine and dried over magnesium sulfate. The crude residue was purified via silica gel flash chromatography using a gradient of 20-100% EtOAc in hexanes) to afford the title compound (0.0904 g, 0.198 mmol, 50.7% yield) as a yellow solid. MS m/z=458.0 [M+H]+. Calculated for C19H13F6N5O2: 457.329.

Provenance & Evidence