反应详情

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)+.

1. customThe solution was evaporated to dryness
2. additionthen diluted with ethyl acetate (30 mL)
3. washwashed with water (2×10 mL) and brine (20 mL)
4. dry with materialdried (MgSO4)
5. filtrationfiltered
6. customthe solvent removed under reduced pressure
7. customThe residue was purified by flash chromatography on silica eluting with 50-100% ethyl acetate in isohexane