A safe and efficient synthesis of 6-chloro-5-methylpyridin-2-amine, a key intermediate for lumacaftor, is described, which avoids the utilization of peroxide. In this four-step sequence, starting from 2-amino-6-chloropyridine, the crucial 5-position methylation was achieved via a Suzuki-Miyaura cross-coupling reaction. By adopting this synthetic route, 6-chloro-5-methylpyridin-2-amine was produced on a hectogram scale with 62.4% overall yield and 99.49% purity.

中文翻译：

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改进的6-氯-5-甲基吡啶-2-胺的合成：制备鲁马卡托的关键中间体

描述了一种安全有效的合成方法6-氯-5-甲基吡啶-2-胺，它是鲁马卡托的关键中间体，它避免了过氧化物的利用。在这四个步骤中，从2-氨基-6-氯吡啶开始，关键的5位甲基化是通过Suzuki-Miyaura交叉偶联反应实现的。通过采用这种合成途径，以百克规模生产了6-氯-5-甲基吡啶-2-胺，总产率为62.4％，纯度为99.49％。