Synthesis and anticonvulsant activity of 3-[3-[(dimethylamino)methyl]- 5-methyl-4H-1,2,4-triazol-4-yl]-4-(o-chlorobenzoyl)pyridine

Article abstract of DOI:10.1002/jhet.5570360130

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-4H-1,2,4-triazol-4-yl)-4-(o- chlorobenzyl)pyridine (8), which on Jones oxidation yielded 3-(3-methyl-4H- 1,2,4-triazol-4-yl)-4-(o-chlorobenzyl)pyridine (9). The Mannick reaction of 3-(3-methyl-4H-1,2,4-triazol-4-yl)-4-(o-chlorobenzyl)pyridine (9) with aqueous formalin and dimethylamine hydrochloride afforded 3-[3- [(dimethylamino)methyl]-5-methyl-4H-1,2,4-triazol-4-yl]-4-(o- chlorobenzoyl)pyridine (10). 3-[3-[(Dimethylamino)methyl]-5-methyl-4H-1,2,4- triazol-4-yl]-4-(o-chlorobenzoyl)pyridine (10) exhibited good anticonvulsant activity in the subcutaneous pentylenetetrazole anticonvulsant screen indicating that an appropriately substituted-pyridine ring moiety can serve as a bioisostere of a chlorobenzene ring with respect to anticonvulsant activity.