反应详情

To a stirred solution of 3-[5-(2-amino-pyrimidin-5-yl)-1-tert-butyl-1H-benzimidazol-2-yl]-4-1,2,4-triazol-1-yl-phenol (50 mg, 0.12 mmol) in DMF (3 mL) is added potassium carbonate (24 mg, 0.18 mmol) followed by iodoethane (9.4 ul, 0.12 mmol). The resulting mixture is stirred at room temperature for 3 hours and then is warmed to 65° C. for 4 hours. The reaction is cooled to room temperature, poured into water and the product extracted into EtOAc (2×). The combined organics are dried (MgSO4), filtered, and concentrated. The remaining residue is purified by silica gel flash column chromatography (12 g silica gel, 2-8% MeOH/DCM). Product-containing fractions are combined and concentrated to give a solid which is diluted with acetonitrile. The white solid is collected via filtration and washed with acetonitrile to afford the title compound (20 mg, 38%). LCMS (ESMS): m/z 455.74 (M++1)

1. temperatureis warmed to 65° C. for 4 hours
2. temperatureThe reaction is cooled to room temperature
3. extractionthe product extracted into EtOAc (2×)
4. dry with materialThe combined organics are dried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated
7. customThe remaining residue is purified by silica gel flash column chromatography (12 g silica gel, 2-8% MeOH/DCM)
8. concentrationconcentrated
9. customto give a solid which
10. filtrationThe white solid is collected via filtration
11. washwashed with acetonitrile