反应详情

To a 5 ml microwave tube was added N-{[2-[(4-bromo-2-fluorophenyl)methyl]-5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinyl]carbonyl}glycine (example 46(b), 75 mg, 0.17 mmol), [4-(methylthio)phenyl]boronic acid (34 mg, 0.20 mmol), potassium carbonate (70 mg, 0.51 mmol), and tetrakis(triphenylphosphine)palladium (0) (6 mg, 5 μmol), 1,4-Dioxane (1.5 ml) and Water (0.500 ml). The mixture was irradiated at 100° C. for 20 minutes. The reaction mixture was diluted with water (5 ml), acidified with 1N HCl (2 ml), and extracted with ethyl acetate (20 ml). The organic phase was washed with brine, dried over MgSO4, filtered, and solvents removed under reduced pressure. The crude residue was purified by low pressure reverse phase c18 (ODS silica, gradient 15-95% acetonitrile/water) to afford the title compound (5 mg, 0.010 mmol, 6% yield) as an off white powder. 1H NMR (400 MHz, DMSO-d6) d ppm 15.92 (s, 1H), 12.95 (s, 1H), 10.16 (t, J=5.43 Hz, 1H), 7.65 (d, J=8.34 Hz, 2H), 7.54 (dd, J=11.62, 1.52 Hz, 1H), 7.48 (dd, J=7.96, 1.64 Hz, 1H), 7.30-7.38 (m, 3H), 5.33 (s, 2H), 4.10 (d, J=5.81 Hz, 2 H), 3.31-3.34 (m, 3H), 3.18 (m, 1H), 1.19 (d, J=6.82 Hz, 6H). MS (ES+) m/e 486 [M+H]+.

1. customThe mixture was irradiated at 100° C. for 20 minutes
2. extractionextracted with ethyl acetate (20 ml)
3. washThe organic phase was washed with brine
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. customsolvents removed under reduced pressure
7. customThe crude residue was purified by low pressure reverse phase c18 (ODS silica, gradient 15-95% acetonitrile/water)