Sodium Sulfate → (+/-)-6-{[((1S,5R,6S)-3-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-azabicyclo[3.2.0]hept-6-yl)amino]methyl}-2H-pyrido[3,2-b][1,4]thiazin-3(4H)-one

Participants

Reaction Steps

To a solution of (±)-(1S,5R,6S)-3-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-azabicyclo[3.2.0]heptan-6-amine (31 mg, 0.098 mmol) in EtOH:DCM (1 mL, 1:1) were added Na2SO4 (21 mg, 0.15 mmol) followed by 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehyde (19 mg, 0.097 mmol). After 12 h at 25° C., NaBH4 (6 mg, 0.15 mmol) was added. After an additional 1 hr, the reaction was concentrated and the residue was partitioned between DCM/H2O. The combined organic fractions were dried over MgSO4, concentrated and purified via column chromatography (silica, 0-3% MeOH in DCM (1% NH4OH)) yielding the title compound (17 mg, 35%) as a yellow oil: LC/MS (ES) m/e 495 (M+H)+; 1H NMR (CD3OD, 400 Hz) δ 8.62 (s, 1H), 8.20 (d, J=9.1 Hz, 1H), 7.69 (d, J=7.8 Hz, 1H), 7.18 (d, J=9.1 Hz, 1H), 6.98 (d, J=7.9 Hz, 1H), 4.92 (s, 3H), 3.66-3.7 (m, 2H), 3.50-3.58 (m, 4H), 2.88-3.09 (m, 5H), 2.79-2.88 (m, 1H), 2.6-2.63 (m, 1H), 2.19-2.24 (m, 2H), 1.88-1.94 (m, 2H).

Provenance & Evidence