New Practical Synthesis of the Key Intermediate of Candesartan

Abstract

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.