Robert L. Ellsworth

The synthesis of HIV reverse transcriptase inhibitors [14C]L-697,661, [14C]L-697,639, [14C]L-702,007

The synthesis of three carbon-14 labeled reverse transcriptase inhibitors has been accomplished by elaboration of a common intermediate, 5-ethyl-6-methyl-3-amino-2-(1H)-[4- 14 C] -pyridinone (7). Ethyl [l- 14 C]formate, prepared by esterification of sodium [ 14 C]formate, was combined with 2-pentanone under basic conditions to afford 3-[ 14 C]carboxaldehyde-2-pentanone sodium salt (2). The pyridinone ring was constructed by condensation of 2 with nitro acetamide 4. Reduction of the nitro group afforded 5-ethyl-6-methyl-3-amino-2-(1H)-[4- 14 C]-pyridinone (7)(specific activity 54 mCi/mmol). Subsequent alkylation of 7 provided the desired reverse transcriptase inhibitors [ 14 C]L-697,661, [ 14 C]L-697,639. and [ 14 C]L-702.007.