New practical synthesis of the key intermediate of candesartan

The development of a new, practical synthesis of methyl 3-amino-N-[(2'-cyanobiphenyl-4-yl)methyl]anthranilate, key intermediate of candesartan, is described, starting from methyl anthranilate. The features of our approach are as follows: (i) introduction of the 3-nitro group by acid catalysed rearrangement of the corresponding methyl N-nitroanthranilate; (ii) introduction of a (2'-cyanobiphenyl-4-yl)methyl side chain by N-alkylation of the appropriate N-nitroanthranilic acid derivative. In the most efficient procedure methyl N,3-dinitroanthranilate was N-alkylated with 4'-bromomethyl-biphenyl-2-nitrile. Catalytic reduction of the aromatic nitro group was accompanied with the removal of the N-nitro function to afford the required key intermediate in good yield.