The First Kilogram Synthesis of Beclabuvir, an HCV NS5B Polymerase Inhibitor,Organic Process Research & Development

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The First Kilogram Synthesis of Beclabuvir, an HCV NS5B Polymerase Inhibitor
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2018-08-16 00:00:00 , DOI: 10.1021/acs.oprd.8b00214
Jeffrey Bien ₁ , Akin Davulcu ₁ , Albert J. DelMonte ₁ , Kenneth J. Fraunhoffer ₁ , Zhinong Gao ₁ , Chao Hang ₁ , Yi Hsiao ₁ , Wenhao Hu ₁ , Kishta Katipally ₁ , Adam Littke ₁ , Aghogho Pedro ₁ , Yuping Qiu ₁ , Maria Sandoval ₁ , Richard Schild ₁ , Michelle Soltani ₁ , Anthony Tedesco ₁ , Dale Vanyo ₁ , Purushotham Vemishetti ₁ , Robert E. Waltermire ₁

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The process development and kilogram-scale synthesis of beclabuvir (BMS-791325, 1) is described. The convergent synthesis features the use of asymmetric catalysis to generate a chiral cyclopropane fragment and coupling with an indole fragment via an alkylation. Subsequent palladium-catalyzed intramolecular direct arylation efficiently builds the central seven-membered ring. The target was prepared in 12 linear steps with five isolations in an overall yield of 8%.

中文翻译：

HCV NS5B聚合酶抑制剂Beclabuvir的第一个千克合成

的beclabuvir工艺开发和公斤规模合成（BMS-791325，1）进行说明。收敛合成的特征在于使用不对称催化产生手性环丙烷片段并通过烷基化与吲哚片段偶联。随后的钯催化的分子内直接芳基化有效地建立了中央的七元环。以12个线性步骤制备目标，并进行5次分离，总收率为8％。

更新日期：2018-08-16

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