反应详情

To a solution of 4-azetidin-3-ylmorpholine (52 mg, 0.36 mmol) and NEt3 (84 μL, 0.61 mmol) in DCM (5 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 (100 mg, 0.12 mmol) in DCM (5 mL) and the resulting mixture warmed to RT after 10 min then stirred for 16 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 2-6% 2M NH3/MeOH in DCM then C18, gradient 20-50% MeOH in H2O). The resulting residue was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH affording 122 (40 mg, 65%). LCMS: RT 3.00 min [M+H]+ 500.3. 1H NMR (DMSO, 400 MHz): δ 8.87 (1H, d, J=2.40 Hz), 8.02 (1H, s), 7.94 (1H, d, J=0.62 Hz), 7.72 (1H, dd, J=8.62, 2.42 Hz), 7.32 (1H, d, J=8.62 Hz), 5.73-5.64 (1H, m), 4.64-4.63 (4H, m), 3.78 (2H, t, J=7.73 Hz), 3.58 (2H, dd, J=8.39, 5.80 Hz), 3.42 (4H, t, J=4.34 Hz), 3.03-3.01 (1H, m), 2.15-2.09 (4H, m), 1.49 (6H, d, J=6.62 Hz)

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 2-6% 2M NH3/MeOH in DCM
5. washwas washed with MeOH
6. washthe product eluted with 2M NH3/MeOH affording 122 (40 mg, 65%)