Reaction Steps
2-(3-Oxo-5-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-3,5-dihydro-2H-pyrazolo[4,3-c]quinolin-2-yl)benzoic acid (Example 611, 41 mg, 0.089 mmol) was suspended in dichloromethane (3 mL), treated with (1H-1,2,3-benzotriazol-1-yloxy) (tripyrrolidin-1-yl)phosphonium hexafluorophosphate (PyBOP, 69 mg, 0.13 mmol, 1.5 equiv) and methylamine (1.0 mL, 2 M tetrahydrofuran solution, 2.0 mmol, 22 equiv). After stirring for 1 hour, the mixture was poured into sodium bicarbonate (20 mL, aqueous saturated) and extracted with chloroform (3×25 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate), providing the titled compound: 1H-NMR (400 MHz, d6-DMSO) δ 9.11 (1H, s), 8.45 (1H, d, J=2.5 Hz), 8.16 (1H, dd, J=7.9, 1.5 Hz), 8.11 (1H, q, J=5.0 Hz), 7.83 (2H, d, J=8.6 Hz), 7.76 (1H, d, J=8.5 Hz), 7.72 (1H, d, J=1.5 Hz), 7.70 (1H, d, J=7.9 Hz), 7.61 (1H, ddd, J=8.3, 7.3, 1.8 Hz), 7.56-7.52 (2H, m), 7.49 (1H, dd, J=7.7, 1.5 Hz), 7.46 (2H, d, J=8.9 Hz), 7.36 (1H, td, J=7.5, 1.1 Hz), 6.53 (1H, dd, J=2.4, 1.8 Hz), 5.76 (2H, s), 2.66 (3H, d, J=4.6 Hz) ppm; high resolution mass spectrometry (ES+) m/z 475.1896 [(M+H)+; calculated for C28H23N6O2: 475.1877].
