反应详情

温度

0 °C

To an ice-cooled solution of 2-{4-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl]piperidin-1-yl}isobutyramide from Example 192 (233 mg, 0.470 mmol) in DCM (20 mL) was added TFA (109 μL, 1.41 mmol) followed by a solution of m-CPBA (89 mg, 0.512 mmol) in DCM (2 mL). The resulting mixture was stirred for 30 min at 0° C. then volatiles were removed under reduced pressure. The crude material was purified by column chromatography (C18, gradient 10-40% 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 193 as a colorless foam (116 mg, 48%). LCMS: RT 2.42 min [M+H]+ 512.1. 1H NMR (DMSO, 400 MHz): δ 8.61 (1H, d, J=2.26 Hz), 7.98 (1H, s), 7.93 (1H, s), 7.55 (1H, dd, J=8.53, 2.28 Hz), 7.26 (1H, d, J=8.53 Hz), 7.09 (1H, d, J=3.29 Hz), 6.87 (1H, d, J=3.29 Hz), 5.78-5.67 (1H, m), 4.61-4.54 (4H, m), 2.80 (2H, bd, J=10.79 Hz), 2.74-2.64 (1H, m), 2.13-2.00 (2H, m), 1.78 (1H, bd, J=12.05 Hz), 1.69-1.55 (3H, m), 1.49 (3H, d, J=6.6 Hz), 1.47 (3H, d, J=6.6 Hz), 1.02 (6H, s)

1. customwere removed under reduced pressure
2. customThe crude material was purified by column chromatography (C18, gradient 10-40% 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 193 as a colorless foam (116 mg, 48%)