反应详情

温度

100 °C

To a stirred solution of 1-(4-amino-5-bromopyrrolo[2,1-f][1,2,4]triazin-7-yl)-2-morpholin-4-ylethanone (90 mg, 0.27 mmol) and tetrakis(triphenylphosphine)palladium(0) (61 mg, 0.05 mmol), in degassed 1,4-dioxane (1.0 mL) and DMF (2.0 mL) was added 2-benzyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-indazole (97 mg, 0.29 mmol), K2CO3 (80 mg, 0.58 mmol), and H2O (0.3 mL). The mixture was degassed and heated (100° C.) for 17 h and then cooled to rt. The mixture was partitioned between ethyl acetate (25 mL) and saturated aqueous K2CO3 solution (25 mL). The layers were separated and the organic phase was washed, dried (Na2SO4), and concentrated to dryness. The residue was purified by preparative HPLC using a gradient elution from 10% to 70% acetonitrile to obtain 20 mg (16%) of the desired product. 1H-NMR (DMSO-d6) 8.57 (s, 1H), 8.13 (s, 1H), 7.82 (d, 1H), 7.65 (s, 1H), 7.39 (s, 1H), 7.36-7.28 (m, 5H), 7.14 (d, 1H), 5.65 (s, 2H), 3.93 (s, 2H), 3.58-3.56 (m, 4H), 2.56-2.53 (m, 4H); LC-MS [M+H]+=468, RT=2.27 min.

1. customThe mixture was degassed
2. temperaturecooled to rt
3. customThe mixture was partitioned between ethyl acetate (25 mL) and saturated aqueous K2CO3 solution (25 mL)
4. customThe layers were separated
5. washthe organic phase was washed
6. dry with materialdried (Na2SO4)
7. concentrationconcentrated to dryness
8. customThe residue was purified by preparative HPLC
9. washa gradient elution from 10% to 70% acetonitrile