反应详情

To a solution of 2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-8-piperidin-4-yl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene 375 TFA salt (250 mg, 0.49 mmol) in THF (5 mL) was added potassium carbonate (136 mg, 0.98 mmol) followed by N-tert-butyl-2-chloroacetamide (81 mg, 0.54 mmol). The reaction mixture was stirred for 65 hours before being diluted with DCM and water. The organic layer was dried over anhydrous magnesium sulfate and concentrated in vacuo. The resulting residue was purified by silica gel flash chromatography (SiO2, gradient 0-3% methanol in DCM) then freeze-dried from methanol and water to give 510 as a beige solid (158 mg, 63%). LCMS: RT=3.67 min, [M+H]+=509. 1H NMR δ (ppm) (CDCl3): 8.34 (1 H, d, J=8.18 Hz), 7.93 (1 H, s), 7.10-7.06 (2 H, m), 6.96 (1 H, d, J=1.81 Hz), 5.92-5.91 (1 H, m), 4.42 (2 H, t, J=5.03 Hz), 3.42 (2 H, t, J=5.05 Hz), 3.00-2.91 (4 H, m), 2.61-2.48 (1 H, m), 2.35-2.24 (2 H, m), 1.96-1.87 (3 H, m), 1.83-1.71 (1 H, m), 1.64 (6 H, d, J=6.63 Hz), 1.39 (9 H, s)

1. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
2. concentrationconcentrated in vacuo
3. customThe resulting residue was purified by silica gel flash chromatography (SiO2, gradient 0-3% methanol in DCM)
4. dry with materialthen freeze-dried from methanol and water