反应详情

To a Parr shaker flask was added N-({5-hydroxy-6-(1-methylethyl)-2-[(4′-nitro-2-biphenylyl)methyl]-3-oxo-2,3-dihydro-4-pyridazinyl}carbonyl)glycine (example 89, 65 mg, 0.139 mmol) and palladium on carbon (7.41 mg, 0.070 mmol) in Methanol (10 ml) and Ethyl acetate (2.500 ml) under a nitrogen atmosphere. The mixture was placed on a Parr shaker under 50 psi Hydrogen for 1 hour. The reaction mixture was filtered to remove the palladium on carbon followed by removal of the solvent by rotary evaporation and purification by HPLC chromatography (ODS silica, gradient 10-85% acetonitrile/water (0.1% TFA)) to afford the title compound N-{[2-[(4′-amino-2-biphenylyl)methyl]-5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinyl]carbonyl}glycine (29 mg, 0.063 mmol, 45.3% yield) as a white powder. 1H NMR (400 MHz, DMSO-d6) d ppm 15.86 (s, 1H), 10.11 (t, J=5.56 Hz, 1H), 7.19-7.36 (m, 5 H), 7.05 (d, J=7.07 Hz, 1H), 6.93 (d, J=7.33 Hz, 2H), 5.25 (s, 2H), 4.08 (d, J=5.56 Hz, 2H), 3.16 (sept, J=6.82 Hz, 1H), 1.15 (d, J=6.82 Hz, 6H). MS (ES+) m/e 437 [M+H]+.

1. filtrationThe reaction mixture was filtered
2. customto remove the palladium on carbon
3. customfollowed by removal of the solvent by rotary evaporation and purification by HPLC chromatography (ODS silica, gradient 10-85% acetonitrile/water (0.1% TFA))