THE SYNTHESIS OF 7-AZAINDOLE DERIVATIVES AS ANTIMALARIAL DRUGS.
Rept. no. 2 (Final) 1 Feb-31 Jul 69,
INSTITUTE OF DRUG DESIGN INC SIERRA MADRE CALIF
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The purpose of the work discussed was to explore the 7-azaindoles as potential antimalarial drugs. To this end, a single diasterioisomer of 1-p-chlorobenzyl-7-azaindole-3-alpha-piperidyl methanol was prepared, and also a mixture of the two diasterioisomers as the dibenzoyl-d-tartrate salt. Ten intermediates were also prepared including 7-azaindole, 3-nitro-7-azaindole, 3-bromo-7-azaindole, 7-azaindole-3-carboxaldehyde, 1-p-chlorobenzyl-7-azaindole-3-carboxaldehyde, 7-p-chlorobenzyl-7H-pyrrolo2,3-b pyridine-3-carboxaldehyde, 1-p-chlorobenzyl-7-azaindole, 7-p-chlorobenzyl-7H-pyrrolo2,3-bpyridine, 1-p-chlorobenzyl-3-carboxy-7-azaindole and 1-p-chlorobenzyl-7-azagramine. Several chemical reactions were developed including a one step Duff reaction to 3-formylate 7-azaindole, methods to 1-alkylate 7-azaindole and 7-azaindole-3-carboxaldehyde with a minimum of quaternization, a mild oxidation of the 3-carboxaldehyde to the 3-carboxy acid and a Vilsmeier 3-formylation of 1-p-chlorobenzyl-7-azaindole. The side chain pyridyl ring of 1-p-chlorobenzyl-7-azaindole-3-alpha-pyridy methanol, was selectively hydrogenated to give the target alpha-piperdyl methanol, which was stable. Diazomethane 1-methylates 7-azaindole-3-carboxaldehyde but not 7-azaindole. There are indications that the 7-azaindole nucleus is susceptible to attack by 2-pyridyllithium and dimethylsuflonium methylide, probably at the 2-position. Author
- Organic Chemistry