Ethyl Acetate → HCID 10146066, compound

N,O-Bistrimethylsilylacetamide (0.5 ml, 2.02 mmol) was added to a suspension of N′-({6-[(2,2-diphenylethyl)amino]-9H-purin-2-yl}methyl)-N-methyl-N-[2-(2-pyridinyl) ethyl]urea (0.16 g, 0.31 mol) (Preparation 26) in 1,1,1-trichloroethane (15 ml). The suspension was heated to reflux. When all suspended solid had dissolved the reaction mixture was allowed to cool to room temperature and the solvent was removed under reduced pressure. The residue was twice dissolved in toluene (50 ml) and the solvent was removed under reduced pressure. The residue was then dissolved in toluene (15 ml) and (2R,3R,4R,5S)-4,5-bis(acetyloxy)-2-[(acetyloxy)methyl]tetrahydro-3-furanyl acetate (0.112 g, 0.36 mol) was added. The solution was stirred at room temperature and trimethylsilyltrifluoromethanesulphonate (0.17 ml, 0.94 mmol) was added. The resulting solution was heated under reflux for 2 hours and then allowed to cool to room temperature. The reaction mixture was diluted by the addition of ethyl acetate (75 ml) and then washed with saturated aqueous sodium hydrogen carbonate solution (two portions of 30 ml) and saturated aqueous sodium chloride solution (30 ml). The organic layer was dried over anhydrous magnesium sulphate. The solvent was removed under reduced pressure to give a solid that was purified by column chromatography on silica gel eluting with dichloromethane:methanol:0.88 concentrated aqueous ammonia (97:3:0.5 by volume). This material was dissolved in methanol (50 ml) and a stream of ammonia gas was passed through the solution until it was saturated. The solution was allowed to stand at room temperature for 4 hours. The solvent was removed under reduced pressure to give a residue that was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:0.88 concentrated aqueous ammonia (90:10:1 by volume) to give the title compound (0.05 g) as a white solid.

1. temperatureThe suspension was heated to reflux
2. dissolutionWhen all suspended solid had dissolved the reaction mixture
3. customthe solvent was removed under reduced pressure
4. dissolutionThe residue was twice dissolved in toluene (50 ml)
5. customthe solvent was removed under reduced pressure
6. dissolutionThe residue was then dissolved in toluene (15 ml)
7. temperatureThe resulting solution was heated
8. temperatureunder reflux for 2 hours
9. temperatureto cool to room temperature
10. washwashed with saturated aqueous sodium hydrogen carbonate solution (two portions of 30 ml) and saturated aqueous sodium chloride solution (30 ml)
11. dry with materialThe organic layer was dried over anhydrous magnesium sulphate
12. customThe solvent was removed under reduced pressure
13. customto give a solid
14. customthat was purified by column chromatography on silica gel eluting with dichloromethane
15. dissolutionThis material was dissolved in methanol (50 ml)
16. customThe solvent was removed under reduced pressure
17. customto give a residue that
18. customwas purified by flash chromatography on silica gel eluting with dichloromethane

ORD record

ord-ab37268e53e84ae89bb0883e05812904

Source dataset

uspto-grants-2007_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07238676B2