The ammonolysis of the cyano group of 4-amino-2-chlorobenzonitrile (I) with Me3Al and NH4Cl in refluxing p-xylene gives the benzamidine (II), which by reaction with NaNO2 and HCl, followed by reduction with SnCl2, yields 4-carboxamidino-3-clorophenylhydrazine (III). The condensation of (III) with acetophenone (IV) by means of TEA in refluxing ethanol affords the corresponding hydrazone (V), which is finally submitted to a Fisher indolization reaction with PPA at 155?C, providing a mixture of the 4-chloro and the target 6-chloro regioisomers that is resolved by preparative HPLC.

The reaction of 4-amino-2-chloro-5-iodobenzonitrile (VI) with Ms-Cl gives the corresponding mesylate (VII), which is cyclized with 3-ethynyl-2-methoxybiphenyl (VIII) by means of Pd(PPh3)2Cl2, CuI, TEA and TBAF or NaOH to yield the O-protected cyanoindole (IX). Finally, this compound is treated with hydroxylamine in refluxing ethanol and deprotected with HOAc, Ac2O and Zn to afford the target indole carboxamidine compound.