反应详情

温度

90 °C

To a mixture of 6-(azidomethyl)-2-chloro-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole (1.4 g, 4.25 mmol), 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (1.8 g, 3.73 mmol) and K3PO4.3H2O (3.4 g, 12.75 mmol) in Dioxane/water (10 mL/1 mL), Pd2(dba)3 (195 mg, 0.21 mmol) and X-Phos (200 mg, 0.42 mmol) were added. The reaction mixture was stirred at 90° C. for 2 hours under N2 protection. Then cooled to room temperature and added EtOAc, then filtered through a Celite pad. The combined organic phase was washed with water and brine, dried over Na2SO4. The solvent was concentrated in vacuo giving 5-(6-(azidomethyl)-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide. The crude product was used in the next step without purification. 1H-NMR (CDCl3, 400 MHz) δ 2.73 (s, 3H), 2.97˜3.03 (d, J=4.8 Hz, 3H), 3.04˜3.15 (d, J=10.8 Hz, 1H), 3.20˜3.32 (m, 1H), 3.40 (s, 3H), 5.93˜6.02 (m, 1H), 6.33˜6.40 (m, 1H), 6.81˜6.89 (m, 1H), 7.14˜7.26 (m, 5H), 7.45˜7.53 (m, 2H), 7.67 (s, 1H), 7.93˜8.01 (m, 2H), 8.03 (s, 1H). MS (M+H)+: 670.

1. additionwere added
2. temperatureThen 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. concentrationThe solvent was concentrated in vacuo