反应详情

温度

90 °C

A mixture of (S)-1-(1-phenyl-1H-imidazo[4,5-b]pyridin-2-yl)ethylamine (330 mg, 1.38 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (460 mg, 1.94 mmol) and DIPEA (440 μL, 2.49 mmol) in n-butanol (2 mL) was heated at 90° C. in a sealed vial for 16 h. After cooling to RT, the volatiles were removed under reduced pressure and the resulting residue loaded onto an Isolute® SCX-2 cartridge and washed with MeOH followed by 2M NH3/MeOH. The product containing fractions were combined and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-15% 2M NH3/MeOH in DCM) and then crystallised from EtOAc and MeOH to afford 199 as a white solid (178 mg, 36%). LCMS (Method K): RT 2.72 min [M+H]+ 357.0. 1H NMR (DMSO-d6, 400 MHz): δ 8.42 (1H, dd, J=4.73, 1.53 Hz), 8.20-7.94 (3H, m), 7.68 (2H, d, J=7.55 Hz), 7.63-7.48 (4H, m), 7.23 (1H, dd, J=8.06, 4.74 Hz), 5.51 (1H, br s), 1.60 (3H, d, J=6.85 Hz)

1. temperatureAfter cooling to RT
2. customthe volatiles were removed under reduced pressure
3. washwashed with MeOH
4. additionThe product containing fractions
5. concentrationconcentrated in vacuo
6. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-15% 2M NH3/MeOH in DCM)
7. customcrystallised from EtOAc and MeOH