反应详情

A mixture of N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(6-(trifluoromethyl)pyridin-3-yl)benzofuran-3-carboxamide (121 mg, 0.22 mmol), 2-chloro-11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridine (50 mg, 0.18 mmol) and K3CO3 (51 mg, 0.37 mmol) in dioxane/water (2 mL/0.4 mL) was stirred at room temperature for 10 min under N2 protection. Then Pd2(dba)3 (18 mg, 0.02 mmol) and X-Phos (17 mg, 0.04 mmol) were added to the reaction solution. The mixture was stirred at 90° C. for 2 hours under N2 protection. The mixture was then cooled to room temperature, added EA (10 mL) and then filtered through a Celite pad. The combined organic phase was washed with water and brine, dried over Na2SO4 and concentrated. The residue was purified by prep-HPLC to afford the desired product (crude: 70 mg, yield: 58%). 1H-NMR (CDCl3, 400 MHz) δ 9.29 (s, 1H), 8.63 (d, J=7.2 Hz, 1H), 7.95 (s, 1H), 7.67˜7.79 (m, 3H), 7.45 (d, J=7.6 Hz, 3H), 7.14˜7.24 (m, 3H), 6.78˜6.80 (m, 1H), 6.14˜6.15 (m, 1H), 4.33 (t, J=6.8 Hz, 1H), 3.29˜3.33 (m, 5H), 3.02 (d, J=4.8 Hz, 3H), 2.74 (s, 3H). MS (M+H)+: 663.

1. stirringThe mixture was stirred at 90° C. for 2 hours under N2 protection
2. temperatureThe mixture was then cooled to room temperature
3. filtrationfiltered through a Celite pad
4. washThe combined organic phase was washed with water and brine
5. dry with materialdried over Na2SO4
6. concentrationconcentrated
7. customThe residue was purified by prep-HPLC