反应详情

A suspension of 6-[(2,2-diphenylethyl)amino]-N-[2-(1-piperidinyl)ethyl]-9H-purine-2-carboxamide (Preparation 11) (0.2 g, 0.42 mmol) in 1,1,1-trichloroethane (10 ml) was treated with N,O-bis(trimethylsilylacetamide) (0.65 ml, 2.65 mmol) and the mixture was heated under reflux for 2 hours. The solvent was removed under reduced pressure and the residue was twice azeotroped with toluene. The residue was dissolved in toluene (5 ml) and treated sequentially with a solution of (2R,3R,4R)-4,5-bis(acetyloxy)-2-(2-ethyl-2H-tetrazol-5-yl)tetrahydro-3-furanyl acetate (WO-A-9967265) (0.175 g, 0.51 mmol) in toluene (5 ml) and then trimethylsilyltriflate (0.1 ml, 0.55 mmol). The mixture was heated under reflux for 3 hours and then allowed to stand at room temperature overnight. The solution was diluted with ethyl acetate (40 ml), washed sequentially with saturated aqueous sodium hydrogen carbonate solution (20 ml) and brine (20 ml) and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a gradient system of dichloromethane:methanol (93:7 by volume) gradually changing to dichloromethane:methanol (90:10 by volume) to afford the title compound (0.235 g).

1. temperaturethe mixture was heated
2. temperatureunder reflux for 2 hours
3. customThe solvent was removed under reduced pressure
4. customthe residue was twice azeotroped with toluene
5. dissolutionThe residue was dissolved in toluene (5 ml)
6. temperatureThe mixture was heated
7. temperatureunder reflux for 3 hours
8. washwashed sequentially with saturated aqueous sodium hydrogen carbonate solution (20 ml) and brine (20 ml)
9. customevaporated under reduced pressure
10. customThe residue was purified by column chromatography on silica gel eluting with a gradient system of dichloromethane:methanol (93:7 by volume)