反应详情

A mixture of (S)-1-(6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine.2HCl (195 mg, 0.59 mmol), 6-chloro-9H-purin-2-ylamine (106 mg, 0.62 mmol) and DIPEA (415 μL, 2.38 mmol) in n-butanol (1 mL) was heated at 100° C. in a sealed vial for 24 h. After cooling to RT, the reaction 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% 2M NH3/MeOH in DCM) followed by reverse phase HPLC (Phenomenex Gemini 5 μm C18 on a gradient 5-60%, 0.1% NH4OH in acetonitrile/water) to afford 310 as a white solid (52 mg, 23%). LCMS (Method K): RT 2.89 min [M+H]+ 389.02. 1H NMR (CDCl3, 400 MHz): δ 7.67 (1H, dd, J=8.67, 4.59 Hz), 7.62-7.38 (5H, m), 7.20 (1H, s), 7.00 (1H, td, J=9.19, 2.45 Hz), 6.79 (1H, dd, J=8.61, 2.46 Hz), 5.65 (1H, s), 4.92 (1H, s), 1.64 (3H, d, J=6.94 Hz)

1. washThe cartridge was washed with MeOH
2. concentrationconcentrated in vacuo
3. customthe resulting residue purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM)