Development of a Continuous Plug Flow Process for Preparation of a Key Intermediate for Brivanib Alaninate
Category
Published on CMKC
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
DOI
Type of publication
Affiliations
- Bristol-Myers Squibb
Article Classification
Classification Areas
- Intermediate