Reaction Steps
A stirred, degassed mixture of 7-(4-benzylmorpholin-2-yl)-5-bromopyrrolo[2,1-f][1,2,4]triazin-4-amine (701 mg, 1.81 mmol) and tetrakis(triphenylphosphine)palladium(0) (350 mg, 0.30 mmol) in DMF (2 mL) was stirred under N2 for 30 min at 80 C, then treated with 2-benzyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-2H-indazole (754 mg, 2.26 mmol), K3PO4 (765 mg, 3.61 mmol) and H2O (165 mg, 9 mmol). The reaction was heated (100° C.) for 1 h and then cooled to rt. The mixture was partitioned between ethyl acetate (25 mL) and MeOH (2.5 mL) and the mixture filtered through a long silica plug. After removal of the volatiles in vacuo, the residue was purified by ISCO® chromatography using a gradient of 1% to 10% MeOH in CH2Cl2 to afford 401 mg (43%) of the desired product. 1H NMR (300 MHz, DMSO-d6) δ 8.54 (s, 1 H), 7.90 (s, 1 H), 7.79 (d, 1 H, J=9 Hz), 7.57 (s, 1 H), 7.21-7.38 (m, 5 H), 7:12 (d, 1 H, J=9 Hz), 6.73 (s, 1 H), 5.65 (s, 2 H), 5.10 (dd, 1H, J=10, 2Hz), 3.88 (d, 1H, J=12 Hz), 3.69 (dd, 1H, J=10, 9 Hz), 3.57 (d, 1H, J=13 Hz), 3.51 (d, 1H, J=13 Hz), 2.97 (d, 1H, J=12 Hz), 2.17-2.28 (m, 1H), 2.67 (d, 1H, J=11 Hz), 2.36 (t, 1H, J=11 Hz); ES-MS m/z 516.3 [M+H]+, HPLC RT (min) 2.80.
