8-Hydroxyquinoline → N-Benzyl-4-methyl-2-(2-oxo-1-phenyl-1,2-dihydropyridine-4-carboxamido)thiazole-5-carboxamide

温度

130 °C

To a degassed solution of N-benzyl-4-methyl-2-(2-oxo-1,2-dihydropyridine-4-carboxamido)thiazole-5-carboxamide (0.060 g, 0.16 mmol), potassium carbonate (0.033 g, 0.24 mmol) and 8-hydroxyquinoline (0.0034 g, 0.024 mmol) in dimethyl sulfoxide (5 mL) were added iodobenzene (0.039 g, 0.19 mmol) and finally copper(I) iodide (0.0046 g, 0.025 mmol). The reaction mixture was heated at 130° C. for 16 hours, then cooled to ambient temperature and filtered. The solvent was removed in vacuo. The residue was dissolved in dichloromethane (40 mL) and washed with saturated aqueous sodium bicarbonate solution (2×20 mL), and brine (20 mL). The organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrate in vacuo. The residue was recrystallized from ethyl acetate and methanol to yield a colorless solid in 20% yield (0.012 g); m.p. 260-262° C.; 1H NMR (DMSO-d6, 300 MHz) δ 13.11 (s, br., 1H), 8.63 (t, J=5.8 Hz, 1H), 7.78 (d, J=7.1 Hz, 1H), 7.58-7.37 (m, 5H), 7.35-7.26 (m, 4H), 7.23-7.18 (m, 1H), 7.14 (d, J=1.5 Hz, 1H), 6.75 (dd, J=1.5, 7.1 Hz, 1H), 4.38 (d, J=5.8 Hz, 2H), 2.51 (s, 3H); 13C NMR (DMSO-d6, 75 MHz) δ 165.5, 162.0, 162.0, 161.3, 140.7, 140.2, 140.0, 139.9, 137.9, 129.6, 128.9, 128.7, 127.7, 127.2, 127.0, 120.9, 103.7, 43.1, 16.9; MS (ES+) m/z 445.0 (M+1).

1. temperaturecooled to ambient temperature
2. filtrationfiltered
3. customThe solvent was removed in vacuo
4. dissolutionThe residue was dissolved in dichloromethane (40 mL)
5. washwashed with saturated aqueous sodium bicarbonate solution (2×20 mL), and brine (20 mL)
6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
7. filtrationfiltered
8. concentrationthe filtrate was concentrate in vacuo
9. customThe residue was recrystallized from ethyl acetate and methanol
10. customto yield a colorless solid in 20% yield (0.012 g)

ORDレコード

ord-7326c1c8797b4bc1946991714a7757f9

出典データセット

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08541457B2