RESUMEN
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.
Asunto(s)
Diseño de Fármacos , Industria Farmacéutica , Pirazinas/síntesis química , Triazinas/síntesis química , Ensayos Analíticos de Alto Rendimiento , Estructura Molecular , Pirazinas/química , Triazinas/químicaRESUMEN
A scalable, transferable, cooling crystallisation route to the elusive, metastable, form II of the API acetaminophen (paracetamol) has been developed using a multicomponent "templating" approach, delivering 100% polymorphic phase pure form II at scales up to 120 g. Favourable solubility and stability properties are found for the form II samples.