Reaction Steps
A mixture of Pd(OAc)2 (0.570 mg, 2.54 μmol), 1-(2-hydroxy-2-methylpropyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one (22.3 mg, 0.076 mmol), 4-(((1R,3S)-3-amino-2,2,3-trimethylcyclopentyl)amino)-6-bromopyrrolo[1,2-b]pyridazine-3-carboxamide (19.3 mg, 0.051 mmol, Intermediate 48), dicyclohexyl(2′,4′,6′-triisopropyl-[1,1′-biphenyl]-2-yl)phosphine (2.42 mg, 5.1 μmol), and 2 M K3PO4 (0.08 mL, 0.15 mmol) in dioxane (0.5 mL) was degassed then heated at 95° C. for 18 h. The reaction mixture was cooled to rt, diluted with MeOH and purified directly via preparative HPLC. 1H NMR (CD3OD, 400 MHz) δ 8.24 (s, 1H), 8.16 (d, J=1.5 Hz, 1H), 7.71 (d, J=7.3 Hz, 1H), 7.33 (d, J=1.8 Hz, 1H), 6.93 (d, J=1.8 Hz, 1H), 6.83 (dd, J=7.0, 2.0 Hz, 1H), 4.71 (t, J=9.0 Hz, 1H), 4.10 (s, 2H), 2.52 (dtd, J=13.7, 9.0, 4.6 Hz, 1H), 2.23-2.00 (m, 2H), 1.92-1.73 (m, 1H), 1.61-1.47 (m, 3H), 1.28-1.16 (m, 9H), 1.16-0.98 (m, 3H). MS (ES+) m/z: 467.19 (M+H); LC retention time: 2.63 min (Analytical HPLC conditions: Chromalith Speedrod, C18, 4.6×50 mm, 10% MeOH/water to 90% MeOH/water with 0.2% H3PO4, 4 min gradient, 4 mL/min)
