反应详情

温度

90 °C

A mixture of (S)-1-(6-fluoro-1-pyridin-3-yl-1H-benzoimidazol-2-yl)ethylamine (81 mg, 0.32 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (83 mg, 0.35 mmol) and DIPEA (162 μL, 0.95 mmol) in n-butanol (1 mL) was heated at 90° C. in a sealed vial for 65 h. After cooling to RT, the volatiles were removed under reduced pressure and the resulting residue was loaded onto an Isolute® SCX-2 cartridge which and with MeOH followed by 2M NH3/MeOH (purification by SCX cartridge repeated three times). The product containing fractions were combined and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% MeOH in DCM) and then triturated with MeOH to afford 176 as an off-white solid (47 mg, 40%). LCMS (Method K): RT 2.75 min [M+H]+ 375.0. 1H NMR (DMSO-d6, 400 MHz): δ 12.65 (1H, s), 8.79 (1H, d, J=2.46 Hz), 8.61 (1H, s), 8.15-7.91 (4H, m), 7.71 (1H, dd, J=8.80, 4.84 Hz), 7.55-7.46 (1H, m), 7.11 (1H, td, J=9.33, 2.43 Hz), 6.93 (1H, dd, J=8.91, 2.44 Hz), 5.49 (1H, s), 1.62 (3H, d, J=6.83 Hz)

1. temperatureAfter cooling to RT
2. customthe volatiles were removed under reduced pressure
3. additionThe product containing fractions
4. concentrationconcentrated in vacuo
5. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% MeOH in DCM)
6. customtriturated with MeOH