反应详情

温度

90 °C

A mixture of (S)-1-[6-fluoro-1-(5-fluoropyridin-3-yl)-1H-benzoimidazol-2-yl]ethylamine (46 mg, 0.17 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (44 mg, 0.18 mmol) and DIPEA (86 μL, 0.50 mmol) in n-butanol (1 mL) was heated at 90° C. in a sealed vial for 60 h. After cooling to RT, the resulting mixture was diluted with MeOH and loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH followed by 2M NH3/MeOH. The basic fractions were combined, concentrated in vacuo and the resulting residue purified by column chromatography (Si—PCC, gradient 0-10% MeOH in DCM) to afford 260 as a pale yellow solid (48 mg, 73%). LCMS (Method K): RT 3.04 min [M+H]+ 393.02. 1H NMR (DMSO-d6, 400 MHz): δ 8.63 (1H, s), 8.56 (1H, s), 8.14-8.05 (2H, m), 8.03-7.93 (2H, m), 7.72 (1H, dd, J=8.80, 4.85 Hz), 7.12 (1H, ddd, J=9.86, 8.79, 2.51 Hz), 7.05 (1H, dd, J=8.96, 2.48 Hz), 5.60 (1H, s), 1.65 (3H, d, J=6.80 Hz)

1. temperatureAfter cooling to RT
2. washThe cartridge was washed with MeOH
3. concentrationconcentrated in vacuo
4. customthe resulting residue purified by column chromatography (Si—PCC, gradient 0-10% MeOH in DCM)