Anastrozole is a non-steroidal aromatase-inhibiting drug approved for treatment of breast cancer after surgery, as well as for metastasis in both pre and post-menopausal women. The severity of breast cancer is increased by estrogen, as sex hormones cause hyperplasia, and differentiation at estrogen receptor sites. The synthesis begins with nucleophilic substitution of two benzylic bromides in α,α'-dibromomesitylene with cyanide by treatment with potassium cyanide under phase transfer conditions, affording the dinitrile. Exhaustive methylation with methyl iodide and sodium hydride leads to the replacement of the more acidic side chain hydrogen atoms by methyl groups. The treatment with bromine in the presence of benzoyl peroxide leads to the formation of the corresponding benzyl bromide. Reaction of that product with 1,2,4-triazole in the presence of a base completes the synthesis of the aromatase inhibitor.
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