The reactivity of 5-chloro-2-(chloroacetamido)pyridine (2) towards nucleophilic substitution by various types of oxygen and sulfur nucleophiles was explored. The reaction of 2 with salicylaldehyde and/or ethyl 2-mercaptoacetate furnished the conforming substitution products 3 and 4. Treatment of 2 with 4,6-dimethyl-2-mercaptonicotinonitrile afforded the conforming N-(pyridin-2-yl)-2-(pyridin-2-yl-thio)acetamide derivative 5 which underwent heating in sodium ethoxide to furnish 3-amino-N-(5-chloropyridine-2-yl)-thieno[2,3-b]pyridine-2-carboxamide 6. Refluxing of 2 with ammonium thiocyanate gave 2-((5-chloropyridin-2-yl)imino)thiazolidine-4-one (7) which underwent condensation with different benzaldehyde derivative furnished the corresponding 5-arylidine-2-((5-chloropyridine-2-yl)imino)thiazolidine-4-ones 8a-e.