反应详情

A mixture 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 (50 mg, 0.08 mmol), and pyridine (11 mg, 0.14 mmol) in dichloromethane (1 mL) was stirred at room temperature under N2 protection. Then acetyl chloride (11 mg, 0.14 mmol) was added and the solution was stirred at room temperature for 1.5 hours. Then the mixture was diluted with water (50 mL) and extracted with EtOAc (10 mL*3). The combined organic layer was washed with brine (30 mL), dried over Na2SO4 and concentrated in vacuo. The resulting residue was purified using prep-TLC (dichloromethane:MeOH=10:1) to provide 546-(acetamidomethyl)-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 (30 mg, yield: 56.3%). And after SFC separation, two enantiomers were obtained. Column: Chiralpak AD-3 50*4.6 mm I.D., 3 um. Mobile phase: 60% ethanol (0.05% DEA) in CO2. Flow rate: 3 mL/min. Wavelength: 220 nm. Compound 129: RT=0.449 min, Compound 130: RT=1.264 minutes.

1. stirringthe solution was stirred at room temperature for 1.5 hours
2. extractionextracted with EtOAc (10 mL*3)
3. washThe combined organic layer was washed with brine (30 mL)
4. dry with materialdried over Na2SO4
5. concentrationconcentrated in vacuo
6. customThe resulting residue was purified