Accession Number : AD0697814

Title :   THE SYNTHESIS OF 7-AZAINDOLE DERIVATIVES AS ANTIMALARIAL DRUGS.

Descriptive Note : Rept. no. 2 (Final) 1 Feb-31 Jul 69,

Corporate Author : INSTITUTE OF DRUG DESIGN INC SIERRA MADRE CALIF

Personal Author(s) : Verbiscar,Anthony J.

Report Date : 15 OCT 1969

Pagination or Media Count : 26

Abstract : 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-pyrrolo(2,3-b) pyridine-3-carboxaldehyde, 1-p-chlorobenzyl-7-azaindole, 7-p-chlorobenzyl-7H-pyrrolo(2,3-b)pyridine, 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)

Descriptors :   (*ANTIMALARIALS, SYNTHESIS(CHEMISTRY)), (*INDOLES, ANTIMALARIALS), PYRIDINES, INFRARED SPECTRA, HALOGENATED HYDROCARBONS, CHLORINE COMPOUNDS, ALCOHOLS, ALDEHYDES, CONDENSATION REACTIONS, ALKYLATION, PYRROLES

Subject Categories : Pharmacology
      Organic Chemistry

Distribution Statement : APPROVED FOR PUBLIC RELEASE