Toluene → HCID 86732230, compound

Participants

Reaction Steps

To a microwave vial were charged with N-(3-((4S,6S)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4,5-difluorophenyl)-5-bromopicolinamide (0.144 g, 0.282 mmol, Example 157), cyclopropylacetylene, 70 wt. % solution in toluene (0.061 mL, 0.507 mmol), copper(I) iodide (8.05 mg, 0.042 mmol), tetrakis(triphenylphosphine)palladium (0.016 g, 0.014 mmol), diethylamine (0.175 mL, 1.690 mmol) and DMF (2.0 mL). The vial was purged with N2 for 5 min, and then microwaved at 90° C. for 50 min. LCMS indicated full conversion to the desired product with MS+=497 (M+1). The reaction mixture was partitioned between EtOAc and water. The separated organic layer was concentrated and the resulted residue was purified by Shimadzu HPLC to afford N-(3-((4S,6S)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4,5-difluorophenyl)-5-(cyclopropylethynyl)picolinamide (0.093 g, 0.187 mmol, 66.5% yield) as light yellow solid. MS m/z=497.1 [M+H]+. Calculated for C23H18F6N4O2: 496.4

Provenance & Evidence