Potassium Carbonate → N,N-Dimethyl-5-[3-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-5-[(5-methylpyrazin-2-yl)carbamoyl]phenoxy]pyrazine-2-carboxamide

Participants

Reaction Steps

A mixture of 3-hydroxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamide (Intermediate 18) (188 mg, 0.55 mmol), 5-(azetidin-1-ylcarbonyl)-2-chloropyrazine (CAS no. 915949-00-7) (712 mg, 3.6 mmol) and potassium carbonate (152 mg, 0.55 mmol) in acetonitrile (5 mL) was stirred at 120° C. for 2 hours. The solution was evaporated to dryness then diluted with ethyl acetate (30 mL), washed with water (2×10 mL) and brine (20 mL), dried (MgSO4), filtered and the solvent removed under reduced pressure. The residue was purified by flash chromatography on silica eluting with 50-100% ethyl acetate in isohexane to afford the product (210 mg, 78%). 1H NMR δ (300 MHz, CDCL3) 2.15-2.31 (m, 1H), 2.52-2.68 (m, 1H), 2.56 (s, 3H), 2.95 (s, 3H), 3.17 (d, 6H), 3.35-3.59 (m, 2H), 4.95 (t, 1H), 7.15 (s, 1H), 7.37 (s, 1H), 7.56 (s, 1H), 8.14 (s, 1H), 8.39 (s, 1H), 8.52 (s, 2H), 9.54 (s, 1H); m/z 492 (M+H)+.

Provenance & Evidence