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Condensation reactions of activated picolines with anthranilate esters and o ‐nitrobenzaldehyde: Improved syntheses of the antiarrhythmic drug encainide
Author(s) -
Dillon John L.,
Spector Richard H.,
Madding Gary D.,
Wire Mary E.
Publication year - 1993
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.5570300321
Subject(s) - chemistry , acylation , yield (engineering) , amide , catalysis , alcohol , olefin fiber , condensation reaction , condensation , medicinal chemistry , combinatorial chemistry , organic chemistry , materials science , physics , metallurgy , thermodynamics
Two new and improved syntheses of the antiarrhythmic drug Encainide, 1 , are presented. The first approach is based on the condensation of 2‐picolyllithium with the p ‐anisoyl amide of methyl anthranilate, 3 , followed by a series of catalytic hydrogenations and methylation. The second route relies on a particularly facile condensation reaction between N ‐methylpicolinium methyl sulfate and o ‐nitrobenzaldehyde to produce the alcohol 17c in high yield which is converted to the olefin 18c by a novel dehydration procedure and then to the final molecule, by catalytic hydrogenation over platinum followed by acylation.