Practical synthesis of a HIV integrase inhibitor

Yong Li Zhong, Brenda Pipik, Jaemoon Lee, Yoshinori Kohmura, Shigemitsu Okada, Kazunobu Igawa, Chie Kadowaki, Akihiro Takezawa, Shinji Kato, David A. Conton, Hua Zhou, Anthony O. Ring, Robert A. Reamer, Donald R. Gauthier, David Askin

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


A practical and efficient synthesis of the potent HIV integrase inhibitor 1 is described. Starting from readily available 3,4-dihydro-2H-pyran, the six-step synthesis features a through process without purification of any of the intermediates until the isolation of crystalline intermediate 7. After deprotection and classical resolution, amine 8 was isolated with excellent enantiopurity. A final amide coupling completed the synthesis of 1 in 7.6% overall yield from DHP. This chromatography-free route is more cost effective and increases the overall yield by nearly 3 times when compared with the original Med Chem synthethic route. This improved chemistry was used successfully to prepare multikilogram quantities of integrase inhibitor 1.

Original languageEnglish
Pages (from-to)1245-1252
Number of pages8
JournalOrganic Process Research and Development
Issue number6
Publication statusPublished - Nov 21 2008

All Science Journal Classification (ASJC) codes

  • Physical and Theoretical Chemistry
  • Organic Chemistry


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