Acetic Acid → O-(6)-Methylguanine

Participants

Reaction Conditions

Reaction Steps

To a solution of 6-chloro-9-[2-(diethoxyphosphorylmethoxy)ethoxy]-2-formamidopurine (0.25 g, 0.61 mmol) in methanol (5 ml), was added sodium methoxide solution (30 wt % in methanol; 0.5 ml, 2.62 mmol). The mixture was stirred and heated at 50° C. for 4 hours. After cooling to ambient temperature, 80% aqueous acetic acid (0.5 ml) was added to give a solution of pH6. The solution was evaporated to dryness and the residue partitioned between dichloromethane (10 ml) and aqueous sodium bicarbonate solution (10 ml). The aqueous phase was washed with dichloromethane (2×10 ml), the combined organic extracts dried (magnesium sulphate), and evaporated to dryness under reduced pressure. The residue obtained was chromatographed on silica gel (eluant dichloromethane: methanol 90:10) to give a 2-amino-6-methoxypurine derivative (0.20 g) which was used without any further purification. The chromatographed material (0.20 g) was dissolved in dichloromethane (2 ml), trimethylsilyl bromide (0.7 ml, 5.3 mmol) added, and the solution left at ambient temperature for 2 days. The solvent was evaporated under reduced pressure and the residue obtained co-evaporated with methanol (×2) to leave a white solid which crystallised from hot water giving the title compound as a white solid (0.105 g, 56%) m.p. 275°-278° C., identical in all respects with the compound obtained in Method A.

Provenance & Evidence