反应详情

温度

70 °C

A mixture of [(S)-1-((R)-1-piperidin-3-yl-1H-benzoimidazol-2-yl)ethyl]-(9H-purin-6-yl)amine from Example 16 (150 mg, 0.414 mmol), 2-bromo-acetamide (57 mg, 0.414 mmol) and DIPEA (215 mL, 1.24 mmol) in IMS (2 mL) was stirred in a sealed vial at 70° C. for 20 h. After cooling to RT, volatiles were removed under reduced pressure and the resulting residue was purified by column chromatography (Si—PCC, gradient 0-15% 2M NH3/MeOH in DCM). The product containing fractions were concentrated in vacuo and the resulting residue was triturated with MeOH affording 133 (59 mg, 34%). LCMS: RT 1.80 min [M+H]+ 420.1. 1H NMR (DMSO, 400 MHz): δ 8.25 (1H, s), 8.14 (1H, s), 8.01-7.90 (1H, m), 7.74-7.66 (1H, m), 7.63-7.55 (1H, m), 7.28-7.03 (4H, m), 5.95 (1H, bs), 4.75 (1H, br), 3.04-2.86 (4H, m), 2.74 (1H, bd, J=11.16 Hz), 2.24 (1H, bt, J=11.70 Hz), 1.80-1.55 (5H, m), 1.35-1.19 (1H, m)

1. temperatureAfter cooling to RT
2. customvolatiles were removed under reduced pressure
3. customthe resulting residue was purified by column chromatography (Si—PCC, gradient 0-15% 2M NH3/MeOH in DCM)
4. additionThe product containing fractions
5. concentrationwere concentrated in vacuo
6. customthe resulting residue was triturated with MeOH affording 133 (59 mg, 34%)