Acetic Acid → 2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-10-(4-(pentan-3-yl)piperazin-1-ylsulfonyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

Participants

Reaction Steps

A mixture of 2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-9-(piperazine-1-sulfonyl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene (35 mg, 0.08 mmol), pentanone (25 μL, 0.24 mmol), AcOH (9 μL, 0.16 mmol) and 4 Å molecular sieves in DCE (2 mL) was stirred at RT for 1 h before the addition of sodium triacetoxyborohydride (33 mg, 0.16 mmol). The resulting mixture was stirred for 16 h before further pentanone (100 μL, 0.92 mmol) and sodium triacetoxyborohydride (198 mg, 0.96 mmol) were added. The mixture was stirred for 20 h then loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH. The resulting residue was purified by column chromatography (Si-PCC, gradient 0-10% MeOH in DCM) to afford 134 (10 mg, 25%) as a white solid. LCMS: RT 3.13 min [M+H]+ 514.4. 1H NMR (CDCl3, 400 MHz): δ 8.95 (1H, d, J=2.36 Hz), 7.88 (1H, s), 7.70 (1H, s), 7.65 (1H, dd, J=8.59, 2.37 Hz), 7.17 (1H, d, J=8.60 Hz), 5.94-5.85 (1H, m), 4.59-4.58 (2H, m), 4.52-4.51 (2H, m), 3.05 (4H, s), 2.61 (4H, s), 2.13-2.10 (1H, m), 1.60 (6H, d, J=6.64 Hz), 1.46-1.35 (2H, m), 1.29-1.27 (2H, m), 0.83 (6H, t, J=7.36 Hz)

Provenance & Evidence