Development of a Manufacturing Process for 1-(1-Pyridin-2-yl methyl-piperidin-4-yl)-1H-indole: A Key Intermediate for Protein Kinase C Inhibitor LY317615

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• 作者：Sathish Boini ; Kenneth P. Moder ; Radhe K. Vaid ; Micheal Kopach ; M. Kobierski
• 刊名：Organic Process Research & Development
• 出版年：2006
• 出版时间：November 2006
• 年：2006
• 卷：10
• 期：6
• 页码：1205 - 1211
• 全文大小：85K
• 年卷期：v.10,no.6(November 2006)
• ISSN：1520-586X

文摘

This contribution describes process development leading to theproduction of 1-(1-pyridin-2-yl methyl-piperidin-4-yl)-1H-indole(11). The title compound 11 was produced via a Leimgruber-Batcho indole synthesis using key intermediates 2-(2,2-dimethoxyethyl)benzenamine (6) and, 1-(2-pyridinylmethyl)-4-piperidinone camphor sulfonate (9). Direct crystallization of 11 fromIPA or ethanol-water was developed to provide (11) with <1%impurities and high yield (78%). The combined process leadsto a five-step synthesis of 11 that was efficient and reflectedEli Lilly and Company's commitment to implementation ofenvironmental friendly processes whenever feasible.