反应详情

To a solution of dimethyl-piperidin-4-yl-amine (45 mg, 0.35 mmol) and NEt3 (83 μL, 0.59 mmol) in DCM (15 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 (93 mg, 0.12 mmol) in DCM (5 mL) and the resulting mixture warmed to RT after 10 min then stirred for 1 h. 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 0-16% MeOH in EtOAc) then freeze-dried from MeCN/H2O affording 131 (29 mg, 52%) as a white solid. LCMS: RT 2.83 min [M+H]+ 486.3. 1H NMR (DMSO, 400 MHz): δ 8.79 (1H, d, J=2.42 Hz), 8.00 (1H, s), 7.93 (1H, d, J=0.62 Hz), 7.63 (1H, dd, J=10.74, 2.40 Hz), 7.26 (1H, d, J=8.62 Hz), 5.72-5.71 (1H, m), 4.61-4.60 (4H, m), 3.60-3.57 (2H, m), 2.40-2.39 (2H, m), 2.15-2.05 (1H, m), 2.10 (6H, s), 1.77-1.73 (2H, m), 1.49 (6H, d, J=6.62 Hz), 1.46-1.37 (2H, m)

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 0-16% MeOH in EtOAc)
5. dry with materialthen freeze-dried from MeCN/H2O affording 131 (29 mg, 52%) as a white solid