反应详情

温度

90 °C

A mixture of (S)-1-(6-fluoro-7-methyl-1-phenyl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride (330 mg, 1.23 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (351 mg, 1.47 mmol) and DIPEA (320 μL, 2.45 mmol) in n-butanol (6 mL) was heated at 90° C. in a sealed vial for 18 h. After cooling to RT, the volatiles were removed under reduced pressure and the resulting residue purified by column chromatography (Si—PCC, gradient 0-10% MeOH in EtOAc). A solution of the compound thus obtained in MeOH (5 mL) and 4N HCl in dioxane (1 ml) was stirred at RT for 1 h then the volatiles were removed under reduced pressure. The resulting residue was partitioned between EtOAc and a saturated solution of NaHCO3. A white solid precipitated and was collected by filtration to afford 183 (333 mg, 70%). LCMS (Method K): RT 3.46 min [M+H]+ 388.1. 1H NMR (DMSO-d6, 400 MHz): δ 12.55 (1H, s), 8.06-8.00 (2H, m), 7.71-7.39 (7H, m), 7.05 (1H, dd, J=10.58, 8.77 Hz), 5.30 (1H, br s), 1.70 (3H, d, J=1.84 Hz), 1.53 (3H, d, J=6.84 Hz)

1. temperatureAfter cooling to RT
2. customthe volatiles were removed under reduced pressure
3. customthe resulting residue purified by column chromatography (Si—PCC, gradient 0-10% MeOH in EtOAc)
4. customA solution of the compound thus obtained in MeOH (5 mL)
5. customthe volatiles were removed under reduced pressure
6. customThe resulting residue was partitioned between EtOAc
7. customA white solid precipitated
8. filtrationwas collected by filtration