反应详情

温度

5 °C

To a solution of 3-[2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]-3-hydroxy-azetidine-1-carboxylic acid tert-butyl ester (300 mg, 0.56 mmol) in THF (2 mL) at 5° C. was added a solution of bis-(2-methoxyethyl)aminosulfur trifluoride (275 μL, 0.62 mmol, 50% solution in THF) in THF (3 mL). The resulting mixture was allowed to stir at 5° C. for 15 min then warmed to r.t. and stirred for a further 15 min. The reaction mixture was partitioned between sat. aq. NaHCO3 and DCM, the organic phase dried (phase separator) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, EtOAc:cyclohexane, 35-85%) affording 828 as a pale yellow solid (238 mg, 79%). LCMS (method I): RT 4.65 min, [M+H]+ 537.4. 1H NMR (DMSO, 400 MHz): δ 8.05-8.04 (1 H, m), 7.64-7.64 (1 H, m), 7.26-7.25 (2 H, m), 4.77 (2 H, dd, J=20.08, 10.62 Hz), 4.60-4.10 (4 H, brd s), 4.48 (2 H, dd, J=21.54, 10.50 Hz), 3.79 (4 H, t, J=4.55 Hz), 3.76 (3 H, d, J=1.32 Hz), 3.28-3.27 (2 H, m), 1.42 (9 H, s), 1.34 (3 H, t, J=7.46 Hz)

1. temperaturethen warmed to r.t.
2. stirringstirred for a further 15 min
3. customThe reaction mixture was partitioned between sat. aq. NaHCO3 and DCM
4. customthe organic phase dried (phase separator)
5. concentrationconcentrated in vacuo
6. customThe resulting residue was purified by column chromatography (Si-PCC, EtOAc:cyclohexane, 35-85%)