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-chloro-N,N-dimethylacetamide (43 μL, 0.414 mmol) and DIPEA (215 μL, 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) followed by HPLC purification (Phenomenex Gemini 5 μm C18 on a 20 min gradient 5-50% 0.1% NH4OH in acetonitrile/water). The product containing fractions were concentrated in vacuo affording 151 as a white solid (8 mg, 4%). LCMS: RT 1.87 min [M+H]+ 448.1. 1H NMR (DMSO, 400 MHz): δ 8.24 (1H, s), 8.10 (1H, s), 7.95 (1H, bs), 7.73-7.68 (1H, m), 7.65-7.58 (1H, m), 7.21-7.12 (2H, m), 4.66-4.55 (1H, m), 3.22 (2H, s), 3.06-2.88 (6H, m), 2.80 (3H, s), 2.75-2.68 (1H, m), 2.21 (1H, t, J=11.73 Hz), 2.10-1.96 (1H, m), 1.77-1.64 9 4 H, m), 1.55 (1H, bd, J=13.18 Hz), 1.13-0.98 (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. customfollowed by HPLC purification (Phenomenex Gemini 5 μm C18 on a 20 min gradient 5-50% 0.1% NH4OH in acetonitrile/water)
5. additionThe product containing fractions
6. concentrationwere concentrated in vacuo