Trifluoroacetic acid → 2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-9-(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 2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-8-(1-isopropylpiperidine-4-sulfinyl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene 242 (38 mg, 0.078 mmol) in DCM (4 mL) was added TFA (30 μL, 0.39 mmol) followed by a solution of m-CPBA (18 mg, 0.101 mmol) in DCM (1 mL). The resulting mixture was stirred for 3 h at 0° C. then volatiles were removed under reduced pressure. The crude material 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. The basic fractions were combined and concentrated in vacuo and the resulting residue was purified by column chromatography (Si-PCC, gradient 3-15% MeOH in DCM) affording 244 as a white solid (31 mg, 81%). LCMS: RT 2.77 min [M+H]+ 499.1. 1H NMR (CD3OD, 400 MHz): δ 8.73 (1H, d, J=8.46 Hz), 7.84 (1H, s), 7.60 (1H, dd, J=8.47, 1.85 Hz), 7.55 (1H, d, J=1.82 Hz), 5.95-5.82 (1H, m), 4.65-4.57 (4H, m), 3.22-3.11 (1H, m), 2.99 (2H, bd, J=11.61 Hz), 2.77-2.64 (1H, m), 2.37 (3H, s), 2.20 (2H, t, J=11.89 Hz), 2.01 (2H, d, J=12.72 Hz), 1.73 (2H, td, J=12.41, 3.93 Hz), 1.55 (6H, d, J=6.65 Hz), 1.03 (6H, d, J=6.56 Hz)

Provenance & Evidence