Scalable Synthesis of CVN424, an Inverse Agonist of the GPR6 Receptor

CVN424 is a drug candidate, which is being investigated in clinical trials for the treatment of motor fluctuations associated with Parkinson's disease. We herein describe the process development of an efficient synthetic route that delivered several kilograms of the drug substance. The synthesis included diacylation of commercially available 3,4-diaminopyridine 1 with diethyl oxalate to give 2 and chlorination with POCl3 to give pyrido[3,4-b]pyrazine 3, followed by two sequential nucleophilic aromatic substitutions. A final hydrogenation and acetylation of intermediate 7 provided CVN424. Overall, a safe and robust synthesis was developed, which occurred in five linear steps with an overall yield of 15%.

Automated summary

CVN424 is a drug candidate being investigated in clinical trials for treating motor fluctuations in Parkinson's disease. Efficient synthesis of several kilograms of the drug substance was achieved through a synthetic route involving diacylation, chlorination, nucleophilic aromatic substitution, hydrogenation, and acetylation. The developed synthesis process was safe and robust, with a five-step linear sequence and an overall yield of 15%.