Synthesis and antinociceptive activity of some 3-chlorophenyl- and 6-chloropyridin-2-yl derivatives

Derivatives of 2-chloro-6-(4-hydroxy-1-methylpiperidin-4-yl)pyridine (2b) w ere prepared and tested as analgesics. 2-Chloro-6-lithiopyridine treated wi th quinuclidin-3-one, 1-methylpyrrolidin-3-one, 2-(dimethylaminomethyl) cyc lohexanone, and ethyl 1-methylpiperidin-4-ylcarboxylate provided the corres ponding alcohols 5, 6, 13a, and 6-chloro-2-pyridyl 1l-methylpiperidin-4-yl ketone (9). The ketone was reduced with sodium borohydride or treated with methylmagnesium chloride or phenyllithium to provide the corresponding alco hols 11, 12a and 12b, respectively. 1-[4-(6-Chloro-2-pyridyl)1-methyrpiperi din-4-yl]1-methylethanol (4b) was prepared from 2-chloro-6-(1-methyl-1,2,5, 6-tetrahydropyridin-4-yl)pyridine (14b) by treatment with butyllithium and acetone followed by reduction of intermediate 15b with sodium cyanoborohydr ide.