A practical fit-for-purpose synthesis of dual leucine zipper kinase (DLK) inhibitor GNE-834 (1) was developed. The key CC bond was constructed via a Suzuki–Miyaura cross-coupling of iodopyrazole 2 and pyridine boronic ester 3 to afford ketone 12. Subsequent selective reductive amination of ketone 12 with morpholine followed by a resolution via tosylate salt formation provided GNE-834 (1) in 39% overall yield from iodide 2 with 98.9 A% HPLC purity.

中文翻译：

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适合合成的双亮氨酸拉链激酶（DLK）抑制剂GNE-834

开发了一种实用的双亮氨酸拉链激酶（DLK）抑制剂GNE-834（1）的合成方法。关键的C C键是通过Suzuki-Miyaura的碘吡唑2和吡啶硼酸酯3的交叉偶联而得到的，从而得到酮12。随后用吗啉对酮12进行选择性还原胺化，然后通过甲苯磺酸盐的形成进行拆分，从而提供了GNE-834（1），其碘化物2的总收率为39％，HPLC纯度为98.9 A％。