Development of a Synthesis of a 2,3-Disubstituted 4,7-Diazaindole Including Large-Scale Application of CH3Li/TiCl4-Mediated Methylation of an Enolizable Ketone

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• 作者：Franz J. Weiberth ; Harpal S. Gill ; George E. Lee ; Duc P. Ngo ; Frederick L. Shrimp ; II ; Xuemin Chen ; Geoffrey D鈥橬etto ; Bryan R. Jackson ; Ying Jiang ; Narendra Kumar ; Frederick Roberts ; Evgeny Zlotnikov
• 刊名：Organic Process Research & Development
• 出版年：2015
• 出版时间：July 17, 2015
• 年：2015
• 卷：19
• 期：7
• 页码：806-811
• 全文大小：257K
• ISSN：1520-586X

文摘

The chemical development of a 2,3-disubstituted 4,7-diazaindole is described. The requisite tertiary carbinol substrate was prepared employing in situ-generated CH₃TiCl₃ as a chemoselective and preferred reagent compared to CH₃MgX for methyl addition to an enolizable ketone. The 4,7-diazaindole ring system was efficiently assembled via an intramolecular Chichibabin transformation. The optimized processes were performed on pilot-plant scale to provide kilogram quantities of the target molecule.