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Synthesis and anticonvulsant activity of 3‐[3‐[(dimethylamino)‐methyl]‐5‐methyl‐4 H ‐1,2,4‐triazol‐4‐yl]‐4‐( o ‐chlorobenzoyl)pyridine
Author(s) -
Arora Vinod K.,
Knaus Edward E.
Publication year - 1999
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.5570360130
Subject(s) - chemistry , pyridine , medicinal chemistry , hydrazone , triethyl orthoformate , hydrochloride , hydrazide , ring (chemistry) , stereochemistry , organic chemistry , catalysis
Wolff‐Kishner reduction of 3‐amino‐4‐( o ‐chlorobenzoyl)pyridine ( 3 ) afforded 3‐amino‐4‐( o ‐chlorobenzyl)pyridine ( 5 ), which on subsequent reaction with triethyl orthoformate and then acetyl hydrazide yielded 1‐acetyl‐2‐[ N ‐[4‐( o ‐chlorobenzyl)pyridin‐3‐yl]formimidoyl]hydrazone ( 7 ). Cyclization of hydrazone 7 gave 3‐(3‐methyl‐4 H ‐1,2,4‐triazol‐4‐yl)‐4‐( o ‐chlorobenzyl)pyridine ( 8 ), which on Jones oxidation yielded 3‐(3‐methyl‐4 H ‐1,2,4‐triazol‐4‐yl)‐4‐( o ‐chlorobenzyl)pyridine ( 9 ). The Mannick reaction of 3‐(3‐methyl‐4 H ‐l,2,4‐triazol‐4‐yl)‐4‐( o ‐chlorobenzyl)pyridine ( 9 ) with aqueous formalin and dimethylamine hydrochloride afforded 3‐[3‐[(dimethylamino)methyl]‐5‐methyl‐4 H ‐1,2,4‐triazol‐4‐yl]‐4‐( o ‐chlorobenzoyl)‐pyridine ( 10 ). 3‐[3‐[(Dimethylamino)methyl]‐5‐methyl‐4 H ‐1,2,4‐triazol‐4‐yl]‐4‐( o ‐chlorobenzoyl)pyridine ( 10 ) exhibited good anticonvulsant activity in the subcutaneous pentylenetetrazole anticonvulsant screen indi cating that an appropriately substituted‐pyridine ring moiety can serve as a bioisostere of a chlorobenzene ring with respect to anticonvulsant activity.