<unk>  is a derivative of adenine and this was the chemical starting point for its first published synthesis which was included in patents to the compound. During drug development, attention switched to the phosphonate ester derivative,<unk> , which was the subject of extensive process chemistry to provide a viable manufacturing route. :650px Adenine is first reacted with a chiral version of propylene carbonate with R absolute configuration, using sodium hydroxide as base. Under these conditions, the reaction is regioselective, with alkylation occurring exclusively in the imidazole ring and at the less-hindered carbon of the dioxolane. In the second step, the hydroxyl group is reacted with a phosphonic acid derivative, using tert-butyllithium as base to ensure selective O-alkylation, with the formation of an ether bond.<unk>  is formed when the diethyl phosphonate group is converted to its acid using trimethylsilyl chloride in the presence of sodium bromide, a further refinement of the original manufacturing route. The synthesis of the alternative ester in<unk>  is completed by alkylation with the appropriate chloromethyl ether derivative and this may be purified as its fumarate salt.
Tenofovir disoproxil
Tenofovir alafenamide
Rilpivirine
Brincidofovir
Daclatasvir
Cidofovir
Telbivudine
Sorivudine