反应详情

To a 5 mL microwave tube was added N-{[2-[(4-bromophenyl)methyl]-5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinyl]carbonyl}glycine (example 61, 31 mg, 0.073 mmol), 2,6-difluoropyridine-4-boronic acid (11.61 mg, 0.073 mmol), potassium carbonate (30.3 mg, 0.219 mmol), and tetrakis(triphenylphosphine)palladium (0) (2.53 mg, 2.192 μmol) in 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 (4 ml), acidified with 1N HCl (1 ml), and diluted with methanol (2 ml) then filtered to remove any residue followed by purification by HPLC chromatography (ODS silica, gradient 10-75% acetonitrile/water (0.1% TFA)) to afford the title compound N-{[2-{[4-(2,6-difluoro-4-pyridinyl)phenyl]methyl}-5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinyl]carbonyl}glycine (15 mg, 0.033 mmol, 44.8% yield) as a white powder. 1H NMR (400 MHz, DMSO-d6) d ppm 15.91 (s, 1H), 12.98 (s, 1H), 10.17 (t, J=5.56 Hz, 1H), 7.89 (d, J=8.34 Hz, 2H), 7.57 (s, 2H), 7.45 (d, J=8.34 Hz, 2H), 5.33 (s, 2H), 4.10 (d, J=5.56 Hz, 2H), 3.20 (sept, J=6.82 Hz, 1H), 1.21 (d, J=6.82 Hz, 6H). MS (ES+) m/e 459 [M+H]+.

1. customThe mixture was irradiated at 100° C. for 20 minutes
2. filtrationthen filtered
3. customto remove any residue
4. customfollowed by purification by HPLC chromatography (ODS silica, gradient 10-75% acetonitrile/water (0.1% TFA))