反应详情

温度

25 °C

A solution of 8-(4-amino-benzyl)-3-cyclopropylmethyl-1-(2-fluoro-benzyl)-3,7-dihydro-purine-2,6-dione (45 mg, 0.11 mmol) in N,N-dimethylformamide (1.0 mL) at 25° C. was treated with dimethylamino-acetic acid (11 mg, 0.11 mmol), O-benzotriazol-1-yl-N,N.N′N′-tetramethyluronium hexafluorophosphate (45 mg, 0.12 mmol), and N,N-diisopropylethylamine (56 μL, 0.32 mmol). The resulting solution was stirred at 25° C. for 48 h. At this time, the reaction was concentrated in vacuo. The residue was dissolved in chloroform and then was washed with a saturated aqueous sodium chloride solution (1×10 mL). The organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting residue was purified by HPLC (15–60% acetonitrile/water/0.075% trifluoroacetic acid over 30 min). Fractions with the desired product were combined and concentrated in vacuo. The resulting residue was diluted with dichloromethane (100 mL) and was washed with a saturated aqueous sodium bicarbonate solution (25 mL). The aqueous layer was re-extracted with dichloromethane (1×50 mL). The combined organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting solid was dried in vacuo for 24 h to afford N-{4-[3-cyclopropylmethyl-1-(2-fluoro-benzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenyl}-2-dimethylamino-acetamide (24 mg, 44.3%) as an off-white solid: LR-MS for C27H29FN6O3 (M+H)+ at m/z=505.

1. concentrationAt this time, the reaction was concentrated in vacuo
2. dissolutionThe residue was dissolved in chloroform
3. washwas washed with a saturated aqueous sodium chloride solution (1×10 mL)
4. dry with materialThe organics were dried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe resulting residue was purified by HPLC (15–60% acetonitrile/water/0.075% trifluoroacetic acid over 30 min)
8. concentrationconcentrated in vacuo
9. additionThe resulting residue was diluted with dichloromethane (100 mL)
10. washwas washed with a saturated aqueous sodium bicarbonate solution (25 mL)
11. extractionThe aqueous layer was re-extracted with dichloromethane (1×50 mL)
12. dry with materialThe combined organics were dried over magnesium sulfate
13. filtrationfiltered
14. concentrationconcentrated in vacuo
15. customThe resulting solid was dried in vacuo for 24 h