A three-step synthesis of 4-(4-iodo-1H-pyrazol-1-yl)piperidine, a key intermediate in the synthesis of Crizotinib

作者：Fussell Steven J; Luan Amy^*; Peach Philip; Scotney Gemma

来源：Tetrahedron Letters, 2012, 53(8): 948-951.

DOI：10.1016/j.tetlet.2011.12.044

• Iodination
• Hydrogenation
• Nucleophilic aromatic substitution
• Palladium
• Piperidine

4-(4-Iodo-1H-pyrazol-1-yl)piperidine is a key intermediate in the synthesis of Crizotinib. We report a robust three-step synthesis that has successfully delivered multi-kilogram quantities of the key intermediate. The process includes nucleophilic aromatic substitution of 4-chloropyridine with pyrazole, followed by hydrogenation of the pyridine moiety and subsequent iodination of the pyrazole which all required optimization to ensure successful scale-up.

• 出版日期2012-2-22