反应详情

温度

50 °C

To a suspension of 2-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (500 mg) and 2,2-dimethylpentanol (3.8 mL) at 50° C. was added sodium hydride (396 mg, 60% dispersion) in portions. To the resultant viscous foam was added a further portion of 2,2-dimethylpentanol (1.5 mL). The reaction was stirred at 50° C. for 72 h. The reaction mixture was cooled then carefully quenched with water (10 mL) and extracted with EtOAc (3×25 mL). The organics were combined, washed with brine (30 mL), dried over MgSO4, filtered and concentrated in vacuo to give a yellow oil. This was azeotroped with toluene (×3) and the resulting viscous yellow oil was purified by C18 reverse phase chromatography (ISCO) using water (0.1% formic acid)-acetonitrile (0.05% formic acid) as eluent (30-80%) to afford the title compound as a brown solid (372 mg).

1. temperatureThe reaction mixture was cooled
2. customthen carefully quenched with water (10 mL)
3. extractionextracted with EtOAc (3×25 mL)
4. washwashed with brine (30 mL)
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customto give a yellow oil
9. customThis was azeotroped with toluene (×3)
10. customthe resulting viscous yellow oil was purified by C18 reverse phase chromatography (ISCO)