Implementation of a High-Temperature Claisen Approach for Early Phase Delivery of a Benzopyran Derivative

Control of trace inorganics and an understanding of reaction kinetics and impurity generation proved critical in allowing safe and reliable scale-up of a high-temperature Claisen reaction in support of multikilogram manufacture of a key chromene intermediate 4. Implementation of a Medicinal Chemistry route allowed for rapid early phase delivery of 1 to support early clinical studies.