反应详情

To a solution of piperazine-1-carboxylic acid tert-butyl ester (216 mg, 1.16 mmol) and NEt3 (272 μL, 1.93 mmol) in DCM (30 mL) at 0° C. was added a suspension of 2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene-9-sulfonyl chloride from Example 121 (270 mg, 0.39 mmol) in DCM (20 mL) and the resulting mixture warmed to RT after 10 min then stirred for 30 min. The reaction mixture was diluted with DCM, washed with a saturated aqueous NaHCO3 solution then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, gradient 0-5% MeOH in DCM) affording 4-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene-9-sulfonyl]piperazine-1-carboxylic acid tert-butyl ester (196 mg, 93%) as a white solid. LCMS: RT 4.72 min [M+H]+ 544.3. 1H NMR (DMSO, 400 MHz): δ 8.77 (1H, d, J=2.43 Hz), 8.01 (1H, s), 7.94 (1H, d, J=0.61 Hz), 7.63 (1H, dd, J=8.64, 2.44 Hz), 7.28 (1H, d, J=8.64 Hz), 5.75-5.71 (1H, m), 4.67-4.57 (4H, m), 3.44-3.38 (4H, m), 2.91 (4H, t, J=4.83 Hz), 1.50 (6H, d, J=6.62 Hz), 1.32 (9H, s)

1. washwashed with a saturated aqueous NaHCO3 solution
2. dry with materialthen dried (Na2SO4)
3. concentrationconcentrated in vacuo
4. customThe resulting residue was purified by column chromatography (Si-PCC, gradient 0-5% MeOH in DCM)