To a stirred solution of tert-butyl 3-(4-amino-5-bromopyrrolo[2,1-f][1,2,4]triazin-7-yl)hexahydropyrazino[2,1-c][1,4]oxazine-8(1H)-carboxylate (1.50 g, 3.31 mmol) and tetrakis(triphenylphosphine)palladium(0) (764 mg, 0.66 mmol), in degassed 1,4-dioxane (15 mL) and DMF (15 mL) was added 2-benzyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-indazole (1.33 g, 3.97 mmol), K2CO3 (1.10 g, 7.94 mmol), and H2O (3.9 mL). The mixture was degassed and heated (100° C.) for 17 h and then cooled to rt. The mixture was partitioned between ethyl acetate (250 mL) and saturated aqueous K2CO3 solution (200 mL). The layers were separated and the organic phase was washed, dried (Na2SO4), and concentrated to dryness. The residue was purified by recrystallization from acetonitrile to obtain 750 mg (39%) of the desired product. 1H-NMR (DMSO-d6) 8.53 (s, 1H), 7.91 (s, 1H), 7.79 (d, 1H), 7.57 (s, 1H), 7.35-7.28 (m, 5H), 7.11 (d, 1H), 6.71 (s, 1H), 5.64 (s, 2H), 5.14-5.10 (m, 1H), 3.88-3.71 (m, 3H), 3.33-3.26 (m, 2H), 3.03-2.99 (m, 1H), 2.89-2.69 (m, 2H), 2.42-2.38 (m, 1H), 2.12-2.08 (m, 2H), 1.38 (s, 9H); LC-MS [M+H]+=581, RT=2.57 min.
