Reaction kinetics for the synthesis of an anti-cancer drug (adavosertib) precursor†

Abstract

The development of kinetic models which can accurately describe drug synthesis reactions is an important part of process design in the pharmaceutical industry. Correctly identifying these models can be difficult, since the reaction pathways used to manufacture new pharmaceutical compounds are often extremely complex. Consequently, many kinetic modelling and parameter estimation tools have been developed in recent years to allow drug manufacturers to test and compare a variety of reaction models before selecting the one which provides the best predictions. The present paper employs a multistart parameter estimation code (in MATLAB®) to parameterise a range of kinetic models describing the synthesis of a key intermediate required for the production of a new anti-cancer drug, Adavosertib (AZD1775). Furthermore, the Akaike and Bayesian Information Criteria are used to rank these models based upon their complexity and fidelity to reflect real-world experimentation.