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Antineoplastics and Immunosuppressives/Hormones and Antihormones

A phenylacetonitrile is often formed by displacement of a benzyl chloride or bromide by cyanide.

Discussion. Each substituent on the central ring of anastrozole has a functional group (cyanide or 1,2,4‐triazole) which is likely introduced as a nucleophile. These features suggest disconnection strategies which have statistical product distribution problems. In a preferred strategy, the most significant problem is addressed in the preparation of the starting material.

Bromide is displaced by 1,2,4‐triazole in the final step. The bromomethyl group is formed by bromination of the methyl group.

Four methyl groups are added by α‐alkylation of the nitriles with iodomethane. The nitriles are formed by bromide displacement by sodium cyanide. The dibromide is formed by bromination of mesitylene.