Sodium Sulfate → 6-{[(2-{4-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]-1-piperazinyl}ethyl)amino]methyl}-2H-pyrido[3,2-b][1,4]thiazin-3(4H)-one

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Reaction Steps

To a solution of (2-{4-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]-1-piperazinyl}ethyl)amine (155 mg, 0.508 mmol) in DCM-EtOH (5 mL, 1:1) were added Na2SO4 (144 mg, 1.02 mmol) and 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehyde (99 mg, 0.508 mmol). After 12 h at 25° C., the imine was quenched by addition of NaBH4 (29 mg, 0.762 mmol) in one portion. After an additional 1 h, the solution was partitioned between H2O-DCM. The aqueous phase was washed several times with DCM and the combined organic fractions were dried (Na2SO4), concentrated and purified by column chromatography (silica, 1% MeOH in DCM (1% NH4OH)) affording the title compound (73 mg, 30%) as a light yellow solid: LCMS (ES) m/e 484 (M+H)+; 1H NMR (CD3OD, 400 MHz) δ 8.46 (d, J=4.8 Hz, 1H), 8.11 (d, J=9.1 Hz, 1H), 7.74 (d, J=7.9 Hz, 1H), 7.13 (d, J=9.1 Hz, 1H), 7.07 (d, J=7.9 Hz, 1H), 4.06 (s, 3H), 3.92 (s, 2H), 3.83 (bs, 4H), 3.54 (bs, 2H), 2.88 (s, 2H), 2.66-2.72 (m, 6H).

Provenance & Evidence