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抗肿瘤药物dacomitinib的合成工艺

Synthetic process of antitumor drug dacomitinib

  • 摘要: 对抗肿瘤药物dacomitinib合成工艺进行改进。以4-氟-2-氨基苯甲酸为原料,经环合、硝化、卤代、偶联以及还原等反应,得到dacomitinib。目标化合物经质谱、核磁共振氢谱确证化学结构。以11步反应总收率36.1%,单步收率75%~90%合成目标化合物,无需特殊试剂和复杂分离纯化过程,降低了成本,优化了反应条件,操作更加简单实用。

     

    Abstract: This paper describes a practical process for the preparation of antitumor drug dacomitinib. It was synthesized by eleven steps from 2-amino-4-fluorobenzoic acid by cyclization, nitration, halogenation, coupling and reduction reactions with the total yield of 36. 1% and one-step yield of 75%-90 %. The intermediates and target compound were characterized by NMR and MS. This practical synthetic process of dacomitinib highlights comparable yield, low-cost, optimized condition and easier purification.

     

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