Trifluoroacetic acid → 9-fluoro-2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-10-(1-isopropylpiperidin-4-ylsulfonyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

Participants

Reaction Conditions

Reaction Steps

To an ice-cooled solution of 8-fluoro-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-9-(1-isopropylpiperidine-4-sulfinyl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene 210 (51 mg, 0.102 mmol) in DCM (8 mL) was added TFA (24 μL, 0.306 mmol) followed by a slow addition of a solution of m-CPBA (21 mg, 0.122 mmol) in DCM (1 mL) and the resulting mixture was stirred for 2.5 h at 0° C. Additional m-CPBA (9 mg) in DCM (0.5 mL) was added and the mixture was stirred for 1 h at RT. Volatiles were then removed under reduced pressure and the resulting residue was purified by column chromatography (C18, gradient 20-50% 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 5-10% MeOH in DCM) afforded 211 as a white solid (22 mg, 41%). LCMS: RT 2.76 min [M+H]+ 517.1. 1H NMR (DMSO, 400 MHz): δ 8.88 (1H, d, J=8.22 Hz), 7.94 (1H, s), 7.25 (1H, d, J=11.17 Hz), 5.67-5.55 (1H, m), 4.73-4.54 (4H, m), 3.28-3.15 (1H, m), 2.89-2.79 (2H, m), 2.72-2.60 (1H, m), 2.26 (3H, s), 2.13 (2H, bt, J=11.43 Hz), 1.89 (2H, bd, J=12.04 Hz), 1.58-1.41 (8H, m), 0.91 (6H, d, J=6.55 Hz)

Provenance & Evidence