Premium
Antimalarials: Synthesis of 4‐aminoquinolines that circumvent drug resistance in malaria parasites
Author(s) -
De Dibyendu,
Byers Larry D.,
Krogstad Donald J.
Publication year - 1997
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570340149
Subject(s) - chemistry , sodium borohydride , regioselectivity , aminoquinolines , alkylation , amine gas treating , phenol , nucleophilic aromatic substitution , reductive amination , combinatorial chemistry , nucleophile , nucleophilic substitution , organic chemistry , catalysis
The strategies described here have permitted the synthesis of a series of 4‐aminoquinoline antimalarials. Substantive improvements over previous syntheses include nucleophilic substitution with neat amine rather than in phenol, regioselective reductive alkylation to convert the terminal primary amine (12a–20a) on the diaminoalkane side chain to a diethylamino group, and purification by column chromatography with basic alumina. The 1 H nmr spectra obtained after regioselective reductive alkylation with sodium borodeuteride (in comparison with sodium borohydride) demonstrated that this reductive alkylation proceeds via formation and subsequent reduction of the corresponding diamides in situ.