Development of a Practical Synthesis of a Farnesyltransferase Inhibitor

The development of a new and practical synthesis for a farnesyltransferase inhibitor 1 is described. The new route started from 2-nitro-5-cyanotoluene (9) and afforded desired 1 in eight chemical transformations. The key step involved formation of sulfonamide 13 from a hindered β-hydroxyamine 12 through an in situ protection of the hydroxyl group by forming TMS ether. Ultimately, this new route was successfully demonstrated to generate >10 kg of API in 29% overall yield.

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