Phosphorus trichloride → HCID 67512461, compound

Participants

Reaction Steps

The arylaldehyde was nitrated using a mixture of fuming nitric acid and sulfuric acid to give a mixture of mono-, di- and tri-nitrated products. The mono-nitrohaloarylaldehyde was separated by conventional separation techniques (e.g. column chromatography) and again subjected to the nitrating conditions described above to give the corresponding dinitroarylhaloarylaldehyde. The dinitroarylhaoloaldehyde was reacted with a suitably substituted boronic acid or boronic acid derivative in the presence of a suitable catalyst (e.g. tetrakistriphenylphosphinepalladium(0)) and a suitable base (e.g. sodium carbonate) in a suitable solvent (e.g. toluene) as described by Miyaura and. Suzuki (see Miyaura, N.; Suzuki, A. J. Chem. Soc., Chem. Commun. 1979, 866-867) to give the corresponding dinitroaldehyde. The dinitroaldehyde was then reacted with a primary aryl- or alkyamine (e.g. 4-bromoaniline) in the presence of a cyanide source (e.g. sodium cyanide) and acetic acid and acetic anhydride to give the corresponding nitrocyanoindazole-N-oxide. The nitrocyanoindazole-N-oxide can be converted to the corresponding nitrocyanoindazole by treatment with a reagent such as phosphorus (III) trichloride. The cyano group of the nitrocyanoindazole can then be hydrolysed to the corresponding nitroindazole carboxylic acid (e.g. using sodium hydroxide in aqueous ethanol), which can then be coupled to an amine using standard peptide coupling conditions (e.g. HATU/DIPEA/acetonitrile) to give the a nitroindazoleamide. The nitroindazoleamide can then be reduced to the corresponding nitroindazoleamine using standard conditions normally associated with the reduction of an arylnitro-group to an aniline (e.g iron in the presence of an aqueous alcoholic solvent).

Provenance & Evidence