| dc.description.abstract | The extensive testing and approval needed before a new active pharmaceutical can be used in treatments of patients has lead to an increased interest in drug repurposing of older approved drugs as treatments for other diseases. A former anti-malaria drug, Quinacrine, is one such drug and have been found to have anti-leukaemia and among other properties. Thus, this study aims to investigate the synthesis process and look for ways to improve it in terms of yields, safety and environmental aspects. This was attempted by investigating the modern method of C-N coupling, namely Buchwald-Hartwig amination, and compare it to traditional and established methods. Also, traditional reaction steps was attempted optimised and improved via experimental design and multiple linear regression models. Further more, a principal component analysis was performed on a data set of 334 solvents with 56 descriptors, in order to use the scores as a representative solvent space in one of the experimental designs and regressions. In addition, a cheap and adaptable semi-continuous filtration robot was designed and built, as a tool for improving flow processes management. The experimental based on solvent PCA data, was unsuccessful on accurately predicting and optimising the reaction using and we were unable to replicate results found in literature for this Ullmann type reaction. The second design, was performed on a modernised nucleophilic aromatic substitution, and was able to improve the reaction yields by 15% compared to literature. All other experiments were replicated as reported in literature, and was not investigated because of already high yields. The filtration robot, was only partly completed, but testing showed a proof of concept. In conclusion, we were partly successful in the improvement of the overall synthesis process for the compound quinacrine. The approaches done towards improving the C-N coupling failed, but simultaneously highlighted flaws in the methodology used. Thus, there might yet be possibilities to improve the reaction, by means of updated methods. | |
