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-bromoethanol (30 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 sonication in cyclohexane and 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 150 as a white solid (8 mg, 5%). LCMS: RT 1.72 min [M+H]+ 407.1. 1H NMR (DMSO, 400 MHz): 8.30-8.07 (2H, m), 7.95 (1H, bs), 7.73-7.68 (1H, m), 7.63-7.58 (1H, m), 7.20-7.11 (2H, m), 5.93 (1H, bs), 4.68-4.57 (1H, m), 4.36 (1H, bs), 3.48 (2H, bs), 3.03-2.97 (1H, m), 2.89-2.77 (2H, m), 2.52-2.39 (3H, m), 2.14-2.98 (2H, m), 1.74-1.66 (4H, m), 1.61-1.53 (1H, m), 1.24-1.10 (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 sonication in cyclohexane
5. customHPLC purification (Phenomenex Gemini 5 μm C18 on a 20 min gradient 5-50% 0.1% NH4OH in acetonitrile/water)
6. additionThe product containing fractions
7. concentrationwere concentrated in vacuo