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Development of a Continuous Plug Flow Process for Preparation of a Key Intermediate for Brivanib Alaninate

By LaPorte, Thomas L.; Spangler, LoriHamedi, Mourad; Lobben, Paul; Chan, Steven H.; Muslehiddinoglu, Jale; Wang, Steve S. Y.

Published on

Abstract

A thermal runaway potential was identified for the conversion of a tertiary alcohol to a hydroxypyrrolotriazine intermediate in the synthesis of brivanib alaninate. A continuous process was developed to mitigate the potential thermal runaway and allow for safer scale-up. This paper describes the hazard analysis, process development, reactor development, reaction engineering model development, and scale-up of the continuous process. The process includes three separate and stable feed streams that are mixed in distinct order using in-line static mixers. Heat exchangers are arranged and connected to facilitate a “plug flow” reactor scheme allowing sufficient residence time for reaction completion. The process has been scaled-up to the pilot plant and to manufacturing.

Journal

Organic Process Research & Development. Volume 18, 2014, 1492–1502

DOI

10.1021/op500176z

Type of publication

Peer-reviewed journal

Affiliations

  • Bristol-Myers Squibb

Article Classification

Research Article

Classification Areas

  • Intermediate

Tags