合成路线1

Regioselective ring opening of 3-nitrophthalic anhydride (I) with ammonia yielded amide (II), which was subjected to a Hofmann degradation with Br2 and KOH to afford 3-nitroanthranilic acid (III). Esterification of (III) to ster (IV) using MeOH/HCl, followed by reduction of the nitro group by catalytic hydrogenation, gave methyl 2,3-diaminobenzoate (V). Alternatively, diamino ester (V) was prepared by reduction of nitro acid (III), followed by catalytic esterification. Methyl 2,3-diaminobenzoate (V) was then selectively acylated at the 3-amino group with 4-methoxybenzoyl chloride (VI) producing amide (VII), which was cyclized to the benzimidazole (VIII) upon refluxing in HOAc. The corresponding amide (IX) was obtained by reaction of ester (VIII) with liquid ammonia at 100 C in a pressure vessel. Finally, the methyl ether group of (IX) was cleaved to the title phenol by treatment with boron tribromide.