Process Design and Optimization in the Pharmaceutical Industry: A Suzuki-Miyaura Procedure for the Synthesis of Savolitinib

J Org Chem. 2019 Apr 19;84(8):4735-4747. doi: 10.1021/acs.joc.8b02351. Epub 2018 Oct 30.

Abstract

A multidisciplinary approach covering synthetic, physical, and analytical chemistry, high-throughput experimentation and experimental design, process engineering, and solid-state chemistry is used to develop a large-scale (kilomole) Suzuki-Miyaura process. Working against clear criteria and targets, a full process investigation and optimization package is described highlighting how and why key decisions are made in the development of large-scale pharmaceutical processes.

MeSH terms

  • Drug Design*
  • Drug Industry*
  • High-Throughput Screening Assays
  • Molecular Structure
  • Pyrazines / chemical synthesis*
  • Pyrazines / chemistry
  • Triazines / chemical synthesis*
  • Triazines / chemistry

Substances

  • Pyrazines
  • Triazines
  • 1-(1-(imidazo(1,2-a)pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-(1,2,3)triazolo(4,5-b)pyrazine