A flexible approach to pyrido[4,3-b]carbazoles. The syntheses of 8,10-dimethoxy-5-methyl-, 5,11-dimethoxy-7,10-dimethyl- and 9-fluoro-5,11-dimethylpyrido[4,3-b]carbazoles by variations of the 'type D' route

Abstract

Syntheses of three different pyridocarbazoles are described. Palladium acetate oxidation of 4-cyano-N-(3,5-dimethoxyphenyl)-2-methylaniline 19 and reduction of the resultant 3-cyano-4,6-dimethoxy-1-methylcarbazole 23 with diisobutylaluminium hydride gave the corresponding formylcarbazole 22. Modified Pomeranz–Fritsch cyclisation then gave, as the major product, 8,10-dimethoxy-5-methylpyrido[4,3-b]carbazole 32. Acid-catalysed condensation of 4,7-dimethoxyindole with hexane-2,5-dione gave 5,8-dimethoxy-1,4-dimethylcarbazole 37 which underwent an atypical regiospecific formylation to give 3-formyl-1,4-dimethoxy-5,8-dimethylcarbazole 39. This was converted by standard methods into 5,11-dimethoxy-7,10-dimethylpyrido[4,3-b]carbazole 7. The cyclisation reactions of the formylcarbazoles 26 and 43 were studied by 1H NMR spectroscopy which enabled the isolation of intermediate N-tosyl-1,2-dihydropyridocarbazoles. An unambiguous synthesis of 9-fluoroellipticine 8 is described from 5-fluoroindole for the first time.