A Scalable Synthesis of Biaryl Unit of the HIV Protease Inhibitor Atazanavir

Title:A Scalable Synthesis of Biaryl Unit of the HIV Protease Inhibitor Atazanavir

Volume: 17 Issue: 1

Author(s): Chapala Vijayalakshmi, Malavattu G. Prasad, Naresh K. Katari*Pedavenkatagari N. Reddy*

Affiliation:

• Department of Chemistry, School of Technology, Gitam University, Hyderabad (T.S) 502329,India

• Department of Chemistry, School of Technology, Gitam University, Hyderabad (T.S) 502329,India

Keywords: Atazanavir, HIV protease inhibitor, Suzuki-Miyaura coupling, In situ reduction, grignard reagent, catalytic hydrogenation.

Abstract: Atazanavir is one of the most prescribed HIV-1 protease inhibitors approved by the FDA. It was the first protease inhibitor approved for once-a-day dosing to treat AIDS due to good oral bioavailability and favorable pharmacokinetic profile. This research aims to develop a new synthetic cost effective process for biaryl-hydrazine unit {tert-butyl 2-[4-(2-pyridinyl)benzyl]hydrazinecarboxylate} of atazanavir on a large scale. The synthesis involved palladium catalyzed Suzuki-Miyaura coupling of 2-chloropyridine and (4-cyanophenyl)boronic acid followed by DIBAL-H reduction of cyano group to aldehyde which is then treated with tert-butyl carbazate to furnish hydrazone subsequently in situ reduction with NaBH4. A large scale synthesis of biaryl-hydrazine unit of atazanavir was accomplished in three steps with 71% overall yield. We have developed a short and efficient synthesis of atazanavir key intermediate biaryl-hydrazine unit. The process does not require the usage of Grignard reagent, expensive catalyst, protection/deprotection of aldehyde moiety and catalytic hydrogenation.

Cite this article as:

Vijayalakshmi Chapala, Prasad G. Malavattu , Katari K. Naresh *, Reddy N. Pedavenkatagari *, A Scalable Synthesis of Biaryl Unit of the HIV Protease Inhibitor Atazanavir, Letters in Organic Chemistry 2020; 17 (1) . https://dx.doi.org/10.2174/1570178616666190514080155