反应详情

To a solution of 2-methyl-2-piperazin-1-ylpropan-1-ol (71 mg, 0.45 mmol) and NEt3 (105 μL, 0.75 mmol) in DCM (10 mL) at 0° C. was added 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 (97 mg, 0.15 mmol) and the resulting mixture warmed to RT after 10 min then stirred for 16 h. The reaction mixture was 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 0-10% MeOH in DCM then C18, gradient 10-40% 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 then freeze-dried from MeCN/H2O to afford 138 (20 mg, 26%) as a white solid. LCMS: RT 2.86 min [M+H]+ 516.4. 1H NMR (CDCl3, 400 MHz): δ 8.95 (1H, d, J=2.37 Hz), 7.88 (1H, s), 7.69 (1H, s), 7.64 (1H, dd, J=8.60, 2.40 Hz), 7.19 (1H, d, J=8.61 Hz), 5.86-5.84 (1H, m), 4.62-4.57 (2H, m), 4.54-4.50 (2H, m), 3.28-3.11 (6H, m), 2.69 (4H, brd s), 1.60 (6H, d, J=6.63 Hz), 1.03 (6H, brd s)

1. washThe reaction mixture was washed 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 0-10% MeOH in DCM
5. washwas washed with MeOH
6. washthe product eluted with 2M NH3/MeOH
7. dry with materialthen freeze-dried from MeCN/H2O