Development of practical syntheses of potent non-nucleoside reverse transcriptase inhibitors

The development of practical and efficient syntheses of the potent non-nucleoside reverse transcriptase inhibitors 1 and 2 is described. The preparation of 1 proceeded in four synthetic steps and in 48% overall yield from 3. The long-term synthesis of 2 proceeded in nine synthetic steps and in 47% overall yield from commercially available 2,6-diflurorpyridine. The route to 2 was highlighted by the three-step synthesis of intermediate 22 and the high yielding coupling between 18 and phenol 8. The overall sequence required no chromatography and has successfully been utilized for the manufacture of 2 on large scale.