To a solution of 5-(6-(aminomethyl)-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 (200 mg, 0.31 mmol) and ethyl 2-oxoacetate (64 mg, 0.62 mmol) in CH2Cl2 (4 mL) was added acetic acid (4 mg, 0.06 mmol). The mixture was stirred at room temperature for 1 hour, and then NaBH(AcO)3 (144 mg, 0.68 mmol) added to the mixture. After stirring overnight, the mixture diluted with CH2Cl2, washed with brine, dried over Na2SO4 and concentrated in vacuo. The resulting residue was purified using prep-HPLC give the product of ethyl 2-(((11-fluoro-2-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-6-yl)methyl)amino)acetate (45 mg, yield: 20%). 1H-NMR (CDCl3, 400 MHz) δ 8.01 (s, 1H), 7.96 (dd, J=8.4, 5.2 Hz, 2H), 7.67 (s, 1H), 7.50 (s, 2H), 7.13˜7.25 (m, 5H), 6.84 (dd, J=9.2, 8.0 Hz, 1H), 6.50 (dd, J=7.6, 3.6 Hz, 1H), 5.99 (br s, 1H), 4.12 (q, J=7.2 Hz, 2H), 3.29˜3.44 (m, 5H), 3.20 (dd, J=12.8, 8.4 Hz, 1H), 3.00 (d, J=4.8 Hz, 3H), 2.86˜2.96 (m, 1H), 2.67 (s, 3H), 1.22 (t, J=7.2 Hz, 3H). MS (M+H)+: 730.
