Module 3 Presentations

14/05/2024

Final Route Selection - 1  Synthetic route almost always changes during development, for example to o Improve step or overall yield o Increase purity of DS o Remove toxic reactants or reagents and limit genotoxic impurity formation o Control commercial cost: • EtOAc 99.5% = £79.65 for 2.5 L • EtOAc 99% = £68.60 for 2.5 L (more extensively tested) • EtOAC 99% = £46.40 for 2.5 L (lab reagent grade)

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Final Route Selection - 2  Usually multiple routes to the API

o Not all are industrially feasible (cost, difficulty, safety) o Prefer convergent synthesis for yield (cost) reasons o Patent infringement issues  Choice is dictated by inter alia o Starting materials (availability, cost, purity, GMP status) o Reagents (availability, cost, purity, safety) o Plant capabilities and availability – general or specialist (eg high pressure hydrogenation may be contracted out)  Cost of API affects cost of goods and hence profit margin and possibly reimbursement price

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