反应详情

To a stirred solution of (1S)-2-[(3S)-3-(aminomethyl)-1-pyrrolidinyl]-1-[6-(methyloxy)-1,5-naphthyridin-4-yl]ethanol (72 mg, 0.24 mmole) in dry CH2Cl2 (25 mL) and dry EtOH (20 mL) at RT was added 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehyde (47 mg, 0.24 mmole). After 24 h at RT, was added NaBH4 (10 mg, 0.26 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 (61 mg, 54%) as light yellow solid: 1H NMR (400 MHz, CDCl3) δ 8.81 (d, J=4.5 Hz, 1H), 8.23 (d, J=9.1 Hz, 1H), 7.84 (d, J=4.5 Hz, 1H), 7.56 (d, J=8.0 Hz, 1H), 7.12 (d, J=9.1 Hz, 1H), 6.92 (d, J=8.0 Hz, 1H), 5.74 (m, 1H), 4.04 (s, 3H), 3.82 (s, 2H), 3.46 (s, 2H), 3.00-3.11 (m, 1H), 2.58-2.83 (m, 6H), 2.33-2.58 (m, 1H), 2.01 (m, 2H), 1.65 (m, 1H). LC-MS (ES) m/e 481 (M+H)+.

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