反应详情

To a solution of (3S,4S)-4-(aminomethyl)-1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-pyrrolidinol (230 mg, 0.719 mmol) in DCM-DMF (6:1, 7 mL) at 25° C. were added 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carboxylic acid (140 mg, 0.719 mmol), EDC (134 mg, 0.836 mmol) and HOBT (117 mg, 0.863 mmol). After 12 h, the solution was concentrated and purified by column chromatography (silica, 2-3% MeOH in DCM (1% NH OH)) yielding the title compound (130 mg, 36%) as a yellow foam: LC/MS (ES) m/e 497 (M+H); H NMR (CD OD, 400 Hz) δ 8.4 (s, 1H), 7.95 (d, J=9.1 Hz, 1H), 7.53 (d, J=8.2 Hz, 1H), 7.19 (d, J=8.2 Hz, 1H), 6.93 (d, J=9.1 Hz, 1H), 4.63 (AB quart., 2H), 4.20-4.24 (m, 1H), 3.9 (s, 3H), 3.55-3.59 (m, 1H), 3.40-3.43 (m, 1H), 3.23-3.28 (m, 2H), 3.16-3.19 (m, 1H), 2.91-2.94 (m, 1H), 2.7-2.82 (m, 2H), 2.49-2.52 (m, 2H), 2.37-2.42 (m, 1H).

1. concentrationthe solution was concentrated
2. custompurified by column chromatography (silica, 2-3% MeOH in DCM (1% NH OH))