反应详情

温度

20 °C

H2O2 (70%, 0.39 mL, ca. 8.1 mmol) was added dropwise to a stirred solution of TFAA (1.12 mL, 8.1 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 20° C. for 10 min, then cooled to 0° C., added to a solution of 1-oxide 163 (265 mg, 0.81 mmol) and TFA (0.13 mL, 1.7 mmol) in CHCl3 (15 mL) at 0° C. The solution was stirred at 20° C. for 4.5 h, diluted with dilute aqueous NH3 solution until basic and extracted with CHCl3 (3×30 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (1-10%) of MeOH/DCM, to give (i) starting material 163 (62 mg, 23%) and (ii) 1,4-dioxide 164 (83 mg, 30%) as a yellow solid which was converted to the hydrochloride salt: mp 131-133° C.; 1H NMR δ 13.40 (br s, 1H, HCl), 8.30 (s, 1H, H-9), 8.25 (s, 1H, H-5), 4.32 (t, J=12.0 Hz, 2H, CH2), 4.00 (dd, J=12.0, 3.0 Hz, 2H, H-6, H-8), 3.48 (d, J=12.0 Hz, 2H, H-6, H-8), 3.32-3.39 (m, 2H, CH2), 3.20 (q, J=7.5 Hz, 2H, CH2), 3.06-3.09 (m, 2H, CH2), 2.88-2.94 (m, 4H, 2×CH2), 2.67-2.73 (m, 1H, H-7), 2.25-2.28 (m, 2H, CH2), 1.43 (t, J=7.5 Hz, 3H, CH3); 13C NMR δ 156.0, 152.6, 148.2, 139.3, 133.9, 116.3, 114.3, 63.6 (2), 56.5, 52.0 (2), 39.1, 38.6, 37.8, 28.5, 23.9, 9.3; HRMS (FAB+) calcd for C18H25N4O3 (MH+) m/z 344.1848, found 344.1846.

1. temperaturecooled to 0° C.
2. stirringThe solution was stirred at 20° C. for 4.5 h
3. extractionextracted with CHCl3 (3×30 mL)
4. customThe combined organic fraction was dried
5. customthe solvent evaporated
6. customThe residue was purified by chromatography
7. washeluting with a gradient (1-10%) of MeOH/DCM