反应详情

温度

0 °C

To an ice-cooled solution of 9-(1-isopropylpiperidin-4-ylsulfanyl)-2-(3-methylpyridin-2-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene from Example 7 (70 mg, 0.161 mmol) in DCM (10 mL) was added TFA (62 μL, 0.805 mmol) followed by a solution of m-CPBA (31 mg, 0.177 mmol) in DCM (2 mL). The resulting mixture was stirred for 15 min at 0° C. then volatiles were removed under reduced pressure. The crude material 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 was eluted with 0.5M NH3 in MeOH affording 204 as a pale orange foam (65 mg, 90%). LCMS: RT1.92 min [M+H]+ 451.1. 1H NMR (DMSO, 400 MHz): δ 8.66 (1H, d, J=2.27 Hz), 8.40 (1H, dd, J=4.69, 1.63 Hz), 7.89 (1H, s), 7.64 (1H, ddd, J=7.65, 1.72, 0.84 Hz), 7.49 (1H, dd, J=8.50, 2.30 Hz), 7.23 (1H, d, J=8.72 Hz), 7.18 (1H, dd, J=7.96, 4.16 Hz), 4.60-4.53 (4H, m), 2.85-2.77 (2H, m), 2.73-2.59 (5H, m), 2.13-2.02 (2H, m), 1.76 (1H, bd, J=12.29 Hz), 1.58 (1H, bd, J=12.37 Hz), 1.52-1.38 (2H, m), 0.90 (6H, d, J=6.54 Hz)

1. customwere removed under reduced pressure
2. customThe crude material 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 was eluted with 0.5M NH3 in MeOH affording 204 as a pale orange foam (65 mg, 90%)