合成路线1

The synthesis of BBE was accomplished using a modified version of a published procedure, as outlined in Scheme 17960101a: Following acetylation (II) of the amine group, 4-aminobenzonitrile (I) was nitrated with potassium nitrate and the acetyl group removed with boiling sulfuric acid to give the mono-nitro product (III). The nitrile was converted to the corresponding amidine in two steps via the Pinner amidine synthesis (1, 2) to give 4-amino-3-nitrobenzamidine (IV). Reduction of the nitro group with 10% Pd-C in a Parr hydrogenator afforded a 60% yield (from compound I) of 3,4-diaminobenzamidine (V). The di-imidate (VII) of fumaronitrile (VI) was prepared by reacting the dinitrile in freshly distilled ethanol with dry HCl gas at 10 C. The di-imidate (VII) was reacted immediately with a 1/2 molar equivalent of 3,4-diaminobenzamidine in refluxing glacial acetic acid. The final product was isolated by trituration with ethyl acetate and filtration. BBE was purified by two recrystallizations from 4% HCl. The yield of the purified product was 15%.