Once a robust synthetic route suitable for the manufacturing process was developed and optimized, the next step was to prove scalability and reproducibility. This was done by following the developed route on a 100-400 g and 5 kg scale at least three times (100-400g) as shown in Table , analysing the intermediates and products by GC-MS, IR, NMR, MP and HPLC. There were no significant changes required to the route on a 300 g scale, however, as the scale was increased to 5 kg, temperature and time became the major optimization points. The larger the reactor, the longer it took to heat up the reaction as required, therefore heating the reaction and subsequently cooling to adjust the pH after hydrolysis of the Mannich base ( ), followed by condensation with 4,7-DCQ (5) at 90 °C was not feasible. It then became necessary to adjust the pH under hot conditions at 50 °C, which did not cause any problems or impurity formation despite our concerns.