反应详情

A mixture of {1-[6-fluoro-1-(3-fluoropyridin-2-yl)-1H-benzoimidazol-2-yl]ethyl}-carbamic acid tert-butyl ester (84 mg, 0.22 mmol) in DCM (1 mL) and TFA (1 mL) was stirred at RT for 2 h. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge and washed with MeOH followed by 2M NH3/MeOH. The basic fractions were combined and concentrated in vacuo to afford a dark orange oil. A mixture of this residue, 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (53 mg, 0.22 mmol) and DIPEA (110 μL, 0.63 mmol) in n-butanol (0.5 mL) was heated at 100° C. in a sealed vial for 16 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% 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 238 as a white solid (14 mg, 16%). LCMS (Method K): RT 3.09 min [M+H]+ 393.01. 1H NMR (DMSO-d6, 400 MHz): δ 8.40 (1H, s), 8.07-7.81 (4H, m), 7.73 (1H, dd, J=8.86, 4.85 Hz), 7.56 (1H, s), 7.18-7.04 (2H, m), 5.68 (1H, s), 1.70 (3H, d, J=6.75 Hz)

1. washwashed with MeOH
2. concentrationconcentrated in vacuo
3. customto afford a dark orange oil
4. temperaturewas heated at 100° C. in a sealed vial for 16 h
5. temperatureAfter cooling to RT
6. washThe cartridge was washed with MeOH
7. concentrationconcentrated in vacuo
8. customthe resulting residue purified by column chromatography (Si—PCC, gradient 0-10% MeOH in DCM)