A facile and scaleable synthesis of a potent and selective histamine H₃ receptor antagonist, ABT-239 (1), was developed starting from commercially available 4‘-hydroxy-biphenyl-4-carbonitrile (2). The synthesis comprised four chemical steps and a salt formation step with an overall yield of 40%. A highly selective monoiodination of a phenol was developed and used to prepare iodophenol (3b) in near quantitative yield using NIS in AcOH in the presence of a small amount of H₂SO₄. A Pd-catalyzed cross coupling reaction of the iodophenols (3b) with butyn-3-ol (4a) provided benzofuran (5) in one step in >80% yield, en route to 1. The new process required no chromatographic purification throughout the synthesis and was successfully demonstrated on scale-up to prepare 1.7 kg of the target ABT-239 (1).

中文翻译：

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苯呋喃类化合物H ₃拮抗剂ABT-239的简便，可缩放合成

从市场上可买到的4'-羟基-联苯-4-腈（2）开始开发了一种有效且选择性的有效的选择性组胺H ₃受体拮抗剂ABT-239（1）的合成方法。该合成包括四个化学步骤和一个成盐步骤，总产率为40％。苯酚的高选择性单碘化反应得到了发展，并用于在少量H ₂ SO ₄存在的情况下在OH中使用NIS在OH中以接近定量的产率制备碘代苯酚（3b）。碘酚（3b）与丁炔醇（4a）的钯催化交叉偶联反应提供了苯并呋喃（5），一步一步即可获得> 80％的收率，然后转到1。该新方法无需在整个合成过程中进行色谱纯化，并已成功放大证明可制备出1.7千克的目标ABT-239（1）。