反应详情

A mixture of 2-(2-ethylbenzoimidazol-1-yl)-8-(3-methoxyazetidin-3-yl)-9-methyl-6-morpholin-4-yl-9H-purine (150 mg, 0.33 mmol), 2-hydroxy-2-methylpropionic acid (52 mg, 0.50 mmol), HOBt (50 mg, 0.37 mmol), NMM (81 μL, 0.74 mmol) and EDCI (96 mg, 0.50 mmol) in THF (3 mL) was allowed to stir at r.t. for 4 h. The resulting mixture was diluted with DCM and washed with sat. aq. NaHCO3, dried (phase separator) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, THF:EtOAc, 0-50%) then triturated with Et2O/cyclohexane. The resulting solid was collected by filtration and dried in vacuo affording 811 (108 mg, 60%). LCMS (method I): RT 3.21 min, [M+H]+ 535.3. 1H NMR (DMSO, 400 MHz): δ 8.06-8.05 (1 H, m), 7.64-7.63 (1 H, m), 7.26-7.25 (2 H, m), 5.23 (1 H, s), 5.05 (1 H, d, J=10.74 Hz), 4.67 (1 H, d, J=10.76 Hz), 4.55 (1 H, d, J=10.69 Hz), 4.29 (4 H, brd s), 4.16 (1 H, d, J=10.75 Hz), 3.79 (4 H, t, J=4.62 Hz), 3.73 (3 H, s), 3.29-3.27 (2 H, m), 3.09 (3 H, s), 1.35 (3 H, t, J=7.43 Hz), 1.30 (3 H, s), 1.25 (3 H, s)

1. washwashed with sat. aq. NaHCO3
2. customdried (phase separator)
3. concentrationconcentrated in vacuo
4. customThe resulting residue was purified by column chromatography (Si—PCC, THF:EtOAc, 0-50%)
5. customthen triturated with Et2O/cyclohexane
6. filtrationThe resulting solid was collected by filtration
7. customdried in vacuo