反应详情

温度

60 °C

(2R,3R,4R,5R)-2-(2-Chloro-6-{[trans-4-({[(1,1-dimethylethyl)oxy]carbonyl}amino)cyclohexyl]amino}-9H-purin-9-yl)-5-(2-ethyl-2H-tetrazol-5-yl)tetrahydrofuran-3,4-diyl diacetate (Intermediate 1) (5.4 mmol) was treated with 1:1 trifluoroacetic acid/dichloromethane (20 ml) at room temperature for ca. 1 h. This was concentrated in vacuo and the residue was partitioned between dichloromethane (50 ml) and aqueous sodium bicarbonate (50 ml). The organics were washed with aqueous sodium bicarbonate (50 ml), dried over sodium sulfate and concentrated in vacuo to give a white solid. This was dissolved in propan-2-ol (100 ml). To this was added N,N-diisopropylethylamine (4 m. eq.) and 2,4-dichloropyrimidine (1 m. eq.). The reaction mixture was heated at 60° C. overnight. The reaction mixture was concentrated in vacuo and the residue was partitioned between ethyl acetate (50 ml) and water (50 ml). The organics were washed with water (50 ml), dried over sodium sulfate and concentrated in vacuo. The crude product was purified by SPE (50 g, silica) eluting with x% ethyl acetate in dichloromethane where x=25, 50, 75. Fractions containing desired product were combined and concentrated in vacuo to yield the title compound as a colourless gum, 1.49 g.

1. concentrationThis was concentrated in vacuo
2. customthe residue was partitioned between dichloromethane (50 ml) and aqueous sodium bicarbonate (50 ml)
3. washThe organics were washed with aqueous sodium bicarbonate (50 ml)
4. dry with materialdried over sodium sulfate
5. concentrationconcentrated in vacuo
6. customto give a white solid
7. concentrationThe reaction mixture was concentrated in vacuo
8. customthe residue was partitioned between ethyl acetate (50 ml) and water (50 ml)
9. washThe organics were washed with water (50 ml)
10. dry with materialdried over sodium sulfate
11. concentrationconcentrated in vacuo
12. customThe crude product was purified by SPE (50 g, silica)
13. washeluting with x% ethyl acetate in dichloromethane where x=25, 50, 75
14. additionFractions containing desired product
15. concentrationconcentrated in vacuo