An Efficient, Scalable Synthesis of the HIV Reverse Transcriptase Inhibitor Ziagen® (1592U89)

Abstract
Ziagen®, (1S,cis)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol, was synthesized from (1S,4R)-azabicyclo[2.2.1]hept-5-en-3-one by efficient processes which bypass problematic steps in earlier routes. 2-Amino-4,6-dichloro-5-formamidopyrimidine is a key intermediate which makes possible an efficient construction of the purine from a chiral cyclopentenyl precursor.