反应详情

温度

0 °C

A glass microwave reaction vessel was charged with 4′-aminoacetanilide (69.0 mg, 0.460 mmol, Aldrich, St. Louis, Mo.) and 6-(2-fluoropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (120 mg, 0.383 mmol) in THF (5 mL), Ar was bubbled in for 2 minutes and the reaction was sealed. The reaction mixture was cooled to 0° C., lithium bis(trimethylsilyl)amine (1 N in THF, 1.2 mL, 1.2 mmol) was added dropwise and the solution was stirred at 0° C. for 1 h. After warming to room temperature, the reaction mixture was diluted with saturated NH4Cl (10 mL) and extracted with EtOAc (3×). The organic extracts were washed with brine and dried over Na2SO4. The solution was filtered and concentrated in vacuum. The crude material was purified by chromatography through a RediSep®, Teledyne ISCO, Lincoln, Nebr., pre-packed silica gel column (25 g), eluting with a gradient of 2% to 10% 2 M NH3/MeOH in CH2Cl2, to provide N-(4-(3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-ylamino)phenyl)acetamide (115 mg, 0.259 mmol, 67.7% yield) as a yellow solid. MS (ESI positive ion) m/z 444 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 12.68 (s, 1H); 9.86 (s, 1H); 9.72 (d, J=8.02 Hz, 1H); 8.86 (s, 1H); 8.34 (d, J=2.15 Hz, 1H); 7.75 (d, J=7.82 Hz, 2H); 7.56 (d, J=7.63 Hz, 2H); 6.98 (s, 1H); 5.84 (d, J=10.95 Hz, 1H); 3.92-4.22 (m, 1H); 3.64-3.87 (m, 1H); 2.90 (s, 3H); 2.30-2.33 (m, 1H); 2.03 (s, 3H); 1.99-2.01 (m, 2H); 1.79-1.82 (m, 1H); 1.48-1.71 (m, 2H).

1. customA glass microwave reaction vessel
2. customwas bubbled in for 2 minutes
3. customthe reaction was sealed
4. temperatureAfter warming to room temperature
5. extractionextracted with EtOAc (3×)
6. washThe organic extracts were washed with brine
7. dry with materialdried over Na2SO4
8. filtrationThe solution was filtered
9. concentrationconcentrated in vacuum
10. customThe crude material was purified by chromatography through a RediSep®, Teledyne ISCO, Lincoln, Nebr
11. wash, pre-packed silica gel column (25 g), eluting with a gradient of 2% to 10% 2 M NH3/MeOH in CH2Cl2