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), 1 g, 2.261 mmol), 4-nitrobenzenboronic acid (0.377 g, 2.261 mmol), potassium carbonate (0.938 g, 6.78 mmol), tetrakis(triphenylphosphine)palladium (0) (0.078 g, 0.068 mmol), 1,4-Dioxane (5 ml) and Water (1.667 ml). The mixture was irradiated at 100° C. for 20 minutes. The reaction mixture was diluted with water (10 ml) and acidified with 1N HCl to give a off-white precipitate that was collected by filtration. The mixture of products was purified by HPLC chromatography (ODS silica, gradient 10-100% acetonitrile/water (0.1% TFA)) to afford the title compound (450 mg, 0.920 mmol, 40.7% yield). 1H NMR (400 MHz, DMSO-d6) d ppm 15.93 (s, 1H), 12.97 (br. s., 1H), 10.14 (t, J=5.68 Hz, 1H), 8.30 (td, J=9.16, 2.65, 2.34 Hz, 2H), 8.01 (td, J=9.16, 2.65, 2.34 Hz, 2H), 7.73 (dd, J=11.37, 1.77 Hz, 1H), 7.63 (dd, J=7.96, 1.89 Hz, 1H), 7.41 (t, J=7.96 Hz, 1H), 5.37 (s, 2H), 4.10 (d, J=5.56 Hz, 2H), 3.19 (sept, J=6.86 Hz, 1H), 1.19 (d, J=6.82 Hz, 6H). MS (ES+) m/e 485 [M+H]+.

1. customThe mixture was irradiated at 100° C. for 20 minutes
2. customto give a off-white precipitate that
3. filtrationwas collected by filtration
4. additionThe mixture of products
5. customwas purified by HPLC chromatography (ODS silica, gradient 10-100% acetonitrile/water (0.1% TFA))