Potassium Carbonate → 5-(4,4-diethyl-2-oxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)-1-methyl-1H-pyrrole-2-carbonitrile

Participants

Reaction Steps

To a solution of 1-methyl-1H-pyrrole-2-carbonitrile (4.1 g, 35 mmol) and triisopropylborate (8.9 mL, 38.5 mmol) in THF (80 mL) at 0° C. was added lithium diisopropylamide (22.8 mL, 45.5 mmol). The reaction mixture was allowed to warm to room temperature. Upon completion by TLC, the reaction was added dropwise to a 65° C. solution of 6-bromo-4,4-diethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one (2.0 g, 7.0 mmol), potassium carbonate (2.9 g, 21 mmol) dissolved in (25 mL water), and tetrakistriphenylphosphine palladium (0) (0.4 g, 0.35 mmol) in tetrahydrofuran (20 mL). Upon completion by TLC of the reaction, it was poured into a saturated solution of ammonium chloride (200 mL), extracted with ethyl acetate (100 mL), dried with magnesium sulfate, and concentrated. Trituration of the residue with ethyl acetate/dichloromethane gave 5-(4,4-diethyl-2-oxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)-1-methyl-1H-pyrrole-2-carbonitrile (1.2 g, 55%) as an off-white solid. 1H NMR (DMSO-d6): δ 10.26 (s, 1H), 7.37 (d, 1H, J=8.2, 1.6 Hz), 7.31 (d, 1H, J=1.8 Hz), 7.03 (d, 1H, J=4.0 Hz), 6.96 (d, 1H, J=8.2 Hz), 6.32 (d, 1H, J=4.0 Hz), 3.69 (s, 3H), 2.02 (m, 2H, J=7.3 Hz), 1.88 (m, 2H, J=7.3 Hz), 0.78 (t, 6H, J=7.3 Hz). MS (ESI) m/z 310 ([M+H]+); MS (ESI) m/z 308 ([M−H]−). HRMS: calcd for C18H19N3O2, 309.1477; found (ESI_FT), 310.15488;

Provenance & Evidence