Trimethylsilyl triflate → Methyl 9-[(2R,3R,4R,5R)-3,4-bis(acetyloxy)-5-(2-ethyl-2H-tetraazol-5-yl)tetrahydro-2-furanyl]-6-[(2,2-diphenylethyl)amino]-9H-purine-2-carboxylate

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Reaction Steps

A suspension of methyl 6-[(2,2-diphenylethyl)amino]-9H-purine-2-carboxylate (Preparation 29) (0.4 g, 1.07 mmol) in 1,1,1-trichloroethane (25 ml) was treated with N,O-bis(trimethylsilylacetamide) (1.6 ml, 6.54 mmol) and the mixture was heated under reflux for one hour. 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) (0.45 g, 1.31 mmol) in toluene (20 ml) and then trimethylsilyltriflate (0.25 ml, 1.37 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), dried (anhydrous magnesium sulphate) and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a gradient system of dichloromethane:ethyl acetate (80:20 by volume) gradually changing to dichloromethane:ethyl acetate (60:40 by volume) to afford the title compound (0.44 g).

Provenance & Evidence