Diethyl Ether → HCID 54739184, compound

Participants

Reaction Steps

To a 5 mL microwave tube was added N-{[2-[(2-bromophenyl)methyl]-5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinyl]carbonyl}glycine (example 78(b), 75 mg, 0.177 mmol), 1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridinyl]piperazine (51.1 mg, 0.177 mmol), potassium carbonate (73.3 mg, 0.530 mmol), and tetrakis(triphenylphosphine)palladium (0) (6.13 mg, 5.30 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 (3 ml) and 1N HCl (1 mL). The mixture was then filtered to remove residual salts and purified by HPLC chromatography (ODS silica, gradient 10-75% acetonitrile/water (0.1% TFA)). The title compound, N-{[5-hydroxy-6-(1-methylethyl)-3-oxo-2-({2-[2-(1 -piperazinyl)-4-pyridinyl]phenyl}methyl)-2,3-dihydro-4-pyridazinyl]carbonyl}glycine (52 mg. 0.083 mmol, 47.0% yield), was obtained as a white solid (tfa salt) after trituration with ether. 1H NMR (400 MHz, DMSO-d6) d ppm 15.83 (s, 1 H), 13.02 (br. s., 1H), 10.07 (t, J=5.43 Hz, 1H), 8.79 (br. s., 2H), 8.19 (d, J=5.05 Hz, 1H), 7.39 (dd, J=5.68, 3.41 Hz, 2H), 7.24-7.31 (m, 1H), 7.21 (dd, J=5.43, 3.66 Hz, 1H), 6.93 (s, 1H), 6.78 (d, J=5.05 Hz, 1H), 5.30 (s, 2H), 4.08 (d, J=5.56 Hz, 2H), 3.69-3.85 (m, 4H), 3.20 (br. s., 4H), 3.12 (m, 1H), 1.12 (d, J=6.82 Hz, 6H). MS (ES+) m/e 507 [M+H]+.

Provenance & Evidence