Hydrochloric Acid → N-{[5-hydroxy-6-(1-methylethyl)-2-({4-[6-(4-methyl-1-piperazinyl)-3-pyridinyl]phenyl}methyl)-3-oxo-2,3-dihydro-4-pyridazinyl]carbonyl}glycine

Participants

Reaction Steps

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), 1-methyl-4-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridinyl]piperazine (22.16 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) and acidified with 1N HCl (1 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-{[5-hydroxy-6-(1-methylethyl)-2-({4-[6-(4-methyl-1-piperazinyl)-3-pyridinyl]phenyl}methyl)-3-oxo-2,3-dihydro-4-pyridazinyl]carbonyl}glycine (23 mg, 0.036 mmol, 49.7% yield) as a white powder tfa salt. 1H NMR (400 MHz, DMSO-d6) d ppm 15.87 (s, 1H), 10.19 (t, J=5.68 Hz, 1H), 9.94 (s, 1 H), 8.48 (d, J=2.53 Hz, 1H), 7.94 (dd, J=9.09, 2.53 Hz, 1H), 7.62 (d, J=8.34 Hz, 2H), 7.38 (d, J=8.34 Hz, 2 H), 7.06 (d, J=9.09 Hz, 1H), 5.28 (s, 2H), 4.47 (d, J=13.39 Hz, 2H), 4.10 (d, J=5.56 Hz, 2H), 3.53 (dd, J=10.23, 6.44 Hz, 2H), 2.99-3.26 (m, 5H), 2.85 (s, 3H), 1.22 (d, J=6.82 Hz, 6H). MS (ES+) m/e 521 [M+H]+.

Provenance & Evidence