反应详情
EQUATION
反应方程式
REACTANTS
反应物
PRODUCTS
生成物
AUXILIARIES
试剂、催化剂与溶剂
CONDITIONS
反应条件
- 温度
- 100 °C
PROCEDURE
实验过程
To a suspension of 5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)-2-(6-oxo-1,6-dihydropyridin-3-yl)benzofuran-3-carboxamide (40 mg, 0.06 mmol) in MeCN (5 mL) was added F2ClCCOONa (20 mg, 0.13 mol) under N2, and then the mixture was stirred at 100° C. for 12 hours. After concentrated in vacuo, the resulting residue was suspended in H2O and extracted with DCM. The combined organic layer was washed with H2O, brine, dried over Na2SO4, filtrated and concentrated in vacuo. The residue was purified by prep-HPLC to give the product of 2-(6-(difluoromethoxy)pyridin-3-yl)-5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide and 2-(1-(difluoromethyl)-6-oxo-1,6-dihydropyridin-3-yl)-5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide. 2-(6-(difluoromethoxy)pyridin-3-yl)-5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (20 mg, yield: 47%). 1H-NMR (CDCl3, 400 MHz) δ 8.84 (d, J=2.0 Hz, 1H), 8.43˜8.47 (m, 1H), 7.96 (s, 1H), 7.73 (s, 0.25H), 7.69 (s, 1H), 7.55 (s, 0.5H), 7.50˜7.52 (m, 2H), 7.37 (s, 0.25H), 7.20˜7.24 (m, 2H), 7.13 (d, J=4.4 Hz, 1H), 7.04 (d, J=4.2 Hz, 1H), 6.84˜6.87 (m, 1H), 6.07 (s, 1H), 5.99 (s, 2H), 3.35 (s, 3H), 3.05 (d, J=4.8 Hz, 3H), 2.78 (s, 3H). MS (M+H)+: 664. 2-(1-(difluoromethyl)-6-oxo-1,6-dihydropyridin-3-yl)-5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (10 mg, yield: 23%). 1H-NMR (CDCl3, 400 MHz) δ 8.67 (d, J=2.0 Hz, 1H), 8.12˜8.15 (m, 1H), 7.92 (s, 1H), 7.76 (s, 0.25H), 7.69 (s, 0.5H), 7.61 (s, 0.25H), 7.51˜7.53 (m, 2H), 7.50 (s, 1H), 7.21˜7.24 (m, 2H), 7.14 (d, J=8.0 Hz, 1H), 6.84˜6.89 (m, 1H), 6.67 (d, J=8.0 Hz, 1H), 6.14 (s, 1H), 6.02 (s, 2H), 3.35 (s, 3H), 3.08 (d, J=4.8 Hz, 3H), 2.81 (s, 3H). MS (M+H)+: 664.
WORKUP
后处理
- concentrationAfter concentrated in vacuo
- extractionextracted with DCM
- washThe combined organic layer was washed with H2O, brine
- dry with materialdried over Na2SO4
- filtrationfiltrated
- concentrationconcentrated in vacuo
- customThe residue was purified by prep-HPLC