反应详情

A sealed pressure flask, flushed with N2, containing a mixture of crude [(4-Amino-phenyl)-hydroxy-phosphinoylmethyl]-phosphonic acid (8.29 mmol), 9-{2-[3-(tert-Butyl-dimethyl-silanyloxy)-phenyl]-ethyl}-6-chloro-2-fluoro-9H-purine (3.37 g, 8.29 mmol), and N,N-diisopropylethylamine (7.2 mL, 41.5 mmol) in 45.0 mL DMSO was heated at 110–120° C. for 13 h. Upon removing excess N,N-diisopropylethylamine (N2 flow, slight heat) the slightly brown solution was cooled to ambient temperature and added ˜500 mL of H2O to produce a milky, off-white solution. Further precipitation occurred upon addition of TFA (final pH=1–2), at which time the mixture was heated (100° C. hot plate) and stirred vigorously for ˜20 min, filtered while hot, then washed with acidified H2O (TFA, pH=1–2; 4×20 mL), EtOH (2×20 mL), and Et2O (4×20 mL). Isolation of a second crop from the concentrated filtrate in the same manner as described above, followed by removal of excess solvent (in vacuo) provided 2.47 g of an off-white solid: m/z 506 (M−H).

1. customA sealed pressure flask, flushed with N2
2. additioncontaining
3. temperaturewas heated at 110–120° C. for 13 h
4. customUpon removing excess N,N-diisopropylethylamine (N2 flow, slight heat) the slightly brown solution
5. additionadded ˜500 mL of H2O
6. customto produce a milky, off-white solution
7. customFurther precipitation
8. additionoccurred upon addition of TFA (final pH=1–2), at which time the mixture
9. temperaturewas heated (100° C. hot plate)
10. filtrationfiltered while hot,
11. washthen washed with acidified H2O (TFA, pH=1–2; 4×20 mL), EtOH (2×20 mL), and Et2O (4×20 mL)
12. customfollowed by removal of excess solvent (in vacuo)