Scheme 1. Synthesis of Picolinamide Analogs 10–13 and 21–37.

Reagents and conditions: R¹ = H, Me, CHF₂; R² = H, Me, C₃H₅; A = N, CH, CF, CCl; R⁴ = 4-methylthiazol-2-yl or substituted pyridin-2-yl; (a) conc. HCl, reflux, 53–75%; (b) H₂O₂·urea, (F₃CCO)₂O, THF, 0 °C to rt, 44–99%; (c) Me₃SiCN, CH₂Cl₂, Me₂NCOCl, 75–86%; (d) 18, K₂CO₃, DMF, 80 °C, 45–77%; (e) 2 N aq. NaOH, dioxane, reflux, 82–99%; (f) H₂NR⁴, POCl₃, pyridine, −15 °C, 22–81%.