反应详情

To an ice-cooled solution of 9-(1-isopropylpiperidine-4-sulfinyl)-2-(3-methylpyridin-2-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene 204 (40 mg, 0.088 mmol) in DCM (10 mL) was added TFA (34 μL, 0.44 mmol) followed by a slow addition of a solution of m-CPBA (23 mg, 0.132 mmol) in DCM (2 mL) and the resulting mixture was stirred for 1 h at RT. Volatiles were removed under reduced pressure and the resulting residue was purified by column chromatography (C18, gradient 5-40% MeOH in 0.5% TFA/H2O) and then loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the product eluted with 0.5M NH3 in MeOH. Further purification by column chromatography (Si-PCC, gradient 2-8% 2M NH3/MeOH in DCM) afforded 205 as a white solid (28 mg, 68%). LCMS: RT 2.04 min [M+H]+ 467.1. 1H NMR (DMSO, 400 MHz): δ 8.94 (1H, d, J=2.41 Hz), 8.42 (1H, dd, J=4.69, 1.62 Hz), 7.93 (1H, s), 7.70-7.63 (2H, m), 7.29 (1H, d, J=8.61 Hz), 7.20 (1H, dd, J=7.64, 4.66 Hz), 4.67-4.56 (4H, m), 3.21-3.11 (1H, m), 2.86-2.78 (2H, m), 2.72 (3H, s), 2.69-2.60 (1H, m), 2.09 (2H, bt, J=11.50 Hz), 1.89 (2H, bd, J=12.09 Hz), 1.50-1.38 (2H, m), 0.90 (6H, d, J=6.55 Hz)

1. customVolatiles were removed under reduced pressure
2. customthe resulting residue was purified by column chromatography (C18, gradient 5-40% MeOH in 0.5% TFA/H2O)
3. washThe cartridge was washed with MeOH
4. washthe product eluted with 0.5M NH3 in MeOH
5. customFurther purification by column chromatography (Si-PCC, gradient 2-8% 2M NH3/MeOH in DCM)