Purine nucleoside analogues. 10. A new synthetic route to 8-substituted-7(9)-alkoxyalkylguanines

The N-alkcoxyalkylation of 8-bromo-N-2-acetylguanine (1) under bar with alp ha-halogen and alpha-acetoxy ethers has been investigated. Treatment of (1) under bar with 2-haloethyl chloromethyl ethers in the presence of potassiu m carbonate afforded 8-bromo-7- and 8-bromo-9-alkoxyalkyl-N-2-acetylguanine s in high overall yields. Without added base the replacement of the bromine atom for chlorine at the 8 position of the heterocycle occurred providing 8-chloro-7- and 8-chloro-9-alkoxyalkyiated products. The acid catalyzed rea ction of (1) under bar with 2-acetoxyethyl acetoxymethyl ether afforded 8-b romo-7- and 8-bromo-9-(2-acetoxyethoxymethyl)-N-2-acetylguanines.