反应详情

To a stirred solution of 3-(aminomethyl)-1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-pyrrolidinol hydrochloride salt (0.21 mmole) in dry CH2Cl2 (25 mL) and dry EtOH (20 mL) at RT was added 3-oxo-3,4-dihydro-2H-pyrido[1,4]thiazine-6-carboxaldehyde (0.04 g, 0.21 mmole) and Et3N (0.06 mL, 0.42 mmole). After 24 h at RT was added NaBH4 (0.01 g, 0.23 mmole). After 2 h, silica gel (5 g) was added to the reaction solution and the suspension was concentrated under vacuum to a dry solid. Purification on silica (CHCl3/MeOH, 9:1 containing 5% NH4OH) afforded the title compound (0.075 g, 72%) as light yellow solid: 1H NMR (400 MHz, CDCl3) δ 8.51 (s, 1H), 8.08 (d, J=9.0 Hz, 1H), 7.54 (d, J=7.8 Hz, 1H), 7.00 (d, J=9.0 Hz, 1H), 6.88 (d, J=7.8 Hz, 1H), 4.38 (s, 2H), 4.03 (s, 3H), 3.81 (m, 2H), 3.37 (m, 4H), 3.12 (m, 4H), 2.72 (m, 2H), 2.54 (m, 2H), 1.92 (m, 2H). LC-MS (ES) m/e 499 (M+H)+.

1. additionsilica gel (5 g) was added to the reaction solution
2. concentrationthe suspension was concentrated under vacuum to a dry solid
3. customPurification on silica (CHCl3/MeOH, 9:1 containing 5% NH4OH)