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%.

中文翻译：

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GPR6 受体的反向激动剂 CVN424 的可扩展合成

CVN424 是一种候选药物，正在临床试验中对其进行研究，以治疗与帕金森病相关的运动波动。我们在此描述了一种有效合成路线的工艺开发，该路线可提供数公斤的原料药。合成包括将市售的 3,4-二氨基吡啶1用草酸二乙酯进行二酰基化，得到2，然后用 POCl ₃氯化，得到吡啶并 [3,4- b ] 吡嗪3，然后进行两个连续的亲核芳族取代。中间体7的最终氢化和乙酰化提供了 CVN424。总的来说，开发了一种安全可靠的合成方法，它分五个线性步骤进行，总产率为 15%。