Reaction Steps
A stirred suspension of 6-bromo-4-(3,3-dimethylpiperidin-4-ylamino)pyrrolo[1,2-b]pyridazine-3-carboxamide TFA salt (139.5 mg, 0.290 mmol, from Step 2), 6-chloropyridazine-3-carbonitrile (81 mg, 0.581 mmol) and N,N-diisopropylethylamine (0.152 mL, 0.871 mmol) in N,N-dimethylformamide (1 mL) was heated in a sealed tube at 90° C. for 2.5 h. The mixture was diluted with water (20 mL) and extracted with ethyl acetate. The organic extract was concentrated and purified by silica gel chromatography, eluting with 0-100% ethyl acetate in hexanes, to give the title compound as a brown glassy solid (0.0711 g, 52% yield). 1H NMR (400 MHz, chloroform-d) δ ppm 10.70 (1 H, d, J=9.02 Hz), 7.89 (1 H, s), 7.64 (1 H, d, J=1.76 Hz), 7.45 (1 H, d, J=9.68 Hz), 6.90 (1 H, d, J=9.46 Hz), 6.82 (1 H, d, J=1.54 Hz), 5.51 (2 H, br. s.), 4.39 (1 H, d, J=13.64 Hz), 4.18 (1 H, d, J=13.42 Hz), 4.09 (1 H, td, J=9.35, 3.96 Hz), 3.54 (1 H, ddd, J=13.75, 10.34, 3.41 Hz), 3.28 (1 H, d, J=13.86 Hz), 2.18-2.28 (1 H, m), 1.93 (1H, dddd, J=14.09, 10.01, 9.90, 4.29 Hz), 1.14 (3 H, s), 1.13 (3 H, s); MS (ES+) m/z: 469.2, 471.2 (M+H); LC retention time: 3.871 min (analytical HPLC Method H).
