Tricyclic Pyridine Process Optimization

Lonafarnib (SCH66336) is a new anti-cancer drug targeted the cell signaling molecule, this thesis is focused on the organic syhthesis and process optimization for tricyclic pyridine-the core part of SCH66336.1.Developed the raw material 2-amino-3-methyl pyridine.2. Mergered process to improve the qualification and yield of intermediate.3.The intermediate was purified with methanol-water to eliminate the effect of inorganic salt on the reaction.4. Optimized LDA's dropping temperature, dropping mode and the amount of LDA to improve process stability.5.Optimized the dropping temperature and dropping mode of sodium nitrite to improve the qualification and yield of the final product,We optimized the novel production process of tricyclic pyridine, reduced the whole production cost dramatically and delivered a competitive product of tricyclic pyridine to commercial market.