Hydrochloric Acid → 4'-{[5-{[(Carboxymethyl)amino]carbonyl}-4-hydroxy-3-(1-methylethyl)-6-oxo-1(6H)-pyridazinyl]methyl}-3'-fluoro-4-biphenylcarboxylic acid

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Reaction Steps

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-carboxybenzeneboronic 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 HPLC chromatography (ODS silica, gradient 15-95% acetonitrile/water (0.1% TFA)) to afford the title compound (20 mg, 0.041 mmol, 24% yield) as a white powder. 1H NMR (400 MHz, DMSO-d6) d ppm 15.93 (s, 1H), 13.03 (br. s., 2H), 10.15 (t, J=5.43 Hz, 1H), 8.01 (d, J=8.34 Hz, 2H), 7.83 (d, J=8.59 Hz, 2H), 7.64 (dd, J=11.37, 1.77 Hz, 1H), 7.57 (dd, J=7.96, 1.64 Hz, 1H), 7.38 (t, J=7.96 Hz, 1H), 5.35 (s, 2H), 4.10 (d, J=5.81 Hz, 2H), 3.19 (sept, J=6.86 Hz, 1H), 1.19 (d, J=6.82 Hz, 6 H). MS (ES+) m/e 484 [M+H]+.

Provenance & Evidence