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 → 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

Participants

Reaction Steps

To a solution of 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 (2.8 g, 4.1 mmol) in MeOH (25 mL) at room temperature, 5% wet Pd/C (300 mg) was added and stirred under hydrogen atmosphere (30 psi) overnight. The reaction mixture was filtered. The filtrate was concentrated and the resulting residue was purified using silica gel column chromatography (dichloromethane:MeOH=20:1) to provide racemic 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 (1.5 g, yield: 62.5%). And after SFC separation, Compound 114 and 115 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 114: RT=0.605 min, Compound 115: RT=1.393 minutes.

Provenance & Evidence