THE SYNTHESIS OF HIV REVERSE-TRANSCRIPTASE INHIBITORS [C-14] L.697,661, [C-14] L-697,639, [C-14] L-702,007

The synthesis of three carbon-14 labeled reverse transcriptase inhibit ors has been accomplished by elaboration of a common intermediate, thy l-6-methyl-3-amino-2-(1H)-[(4)-C-14]-pyridinone (7). Ethyl [1-C-14]for mate, prepared by esterification of sodium [C-14]formate, was combined with 2-pentanone under basic conditions to afford [3-C-14]carboxaldeh yde-2-pentanone sodium salt (2). The pyridinone ring was constructed b y condensation of 2 with nitro acetamide 4. Reduction of the nitro gro up afforded -ethyl-6-methyl-3-amino-2-(1H)-[4-C-14]-pyridinone (7)(spe cific activity 54 mCi/mmol). Subsequent alkylation of 7 provided the d esired reverse transcriptase inhibitors [C-14]L-697,661 [C-14]L-697,63 9, and [C-14]L-702,007.