4-Nitro-1H-indole → 4-NITROGRAMINE

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Reaction Steps

Scheme M illustrates a general method of preparing compounds of the invention (for a synthesis of intermediate amine 8, see also J. Hester J. Org. Chem. 1967, 32, 4095). 4-Nitroindole and formaldehyde/dimethylamine were condensed to form 4-nitrogramine (2). Compound 2 underwent nucleophilic substitution with diethyl malonate to afford diester 3, which was then reduced to the amine 4 via hydrogenolysis over palladium-on-carbon. Indole 4 was cyclized thermally to lactam 5, and then underwent decarboxylation by treatment with potassium hydroxide followed by heating neat to give unsubstituted lactam 7. The lactam 7 was reduced with LAH to afford amine 8, which was acylated with acid chloride 9 (prepared by acylation of methyl 4-aminobenzoate with 2-biphenylcarbonyl chloride followed by sodium hydroxide-mediated saponification of the ester to the acid, and then thionyl chloride-mediated conversion to the acid chloride 9) to give the final product compound 10.

Provenance & Evidence