Familiarization, process optimization and non- GMP manufacturing & supply of 3.0 kg of HPAPI product

Challenges: Establishing appropriate reaction conditions for all the stages by optimizing mole equivalents of reagents and isolation procedure to improve yield and quality. Identifying a suitable crystallization procedure for all the stages to achieve the desired quality. Major challenge associated with API stage as acid intermediate is highly unstable. Identification of impurities and its control is very challenging. Aurigene solution: Replaced the base pyridine with NaOAc and to reduce the time for process operations and better scalability of the process in plant, avoided the distillation and simplified the product isolation in stage-1. Screening of ketone for Oppenaur oxidation, identified 2-butanone for reaction which is preferred over other ketone due to homogeneous nature of the reaction mass. Sequence of reagents were optimized for API stage to get stable reaction conditions and product isolation process was simplified for robust scalable process. Adapting a fit-for-purpose process development strategy helped to deliver the API quickly for pre-clinical study.Crystallization procedure were established and optimized to attain constant yield and quality.Process controls were well defined to monitor the reactions in all stages. Outcome:

Suitable process controls were established in the process for pilot plant suitability enable the smooth execution. Consistent yield and quality were obtained with the optimized process. Achieved all the pre-defined product specifications with the optimized process.Manufactured 3.0 kg of final product in HPAPI facility and delivered to customer.