Hydrochloric Acid → 2-(tert-butylamino)-N-(2,3-dichlorophenyl)pyridine-3-carboxamide

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Crude 2-(tert-butylamino)-N-(2,3-difluorophenyl)pyridine-3-carboxamide (1.5 g) was dissolved in dry toluene (24 mL), combined with Lawesson's reagent (1.4 g, 0.7 eq), heated at 90° C. for 10 hours, then evaporated to near dryness. The residue was diluted DCM (20 mL) and EtOH (20 mL) and treated with NH2NH2. The mixture was stirred at RT for 2 hours then concentrated in vacuo. The residue was diluted with Et2O and washed with sat NaHCO3 three times. The Et2O layer washed with 6N HCl solution (2×20 mL), and the combined HCl extracts treated with NaNO2 (3 eq) in water at RT for 30 min. The resulting mixture was neutralized with 6N NaOH (to pH 7-8) and extracted with EtOAc. The combined extracts were dried over MgSO4, filtered, and concentrated in vacuo to afford crude N-tert-butyl-3-(1-(2,3-difluorophenyl)-1H-tetrazol-5-yl)pyridin-2-amine. Using the same procedure, N-tert-butyl-3-(1-(2,3-dichlorophenyl)-1H-tetrazol-5-yl)pyridin-2-amine and N-tert-butyl-3-(1-(3-chloro-2-fluorophenyl)-1H-tetrazol-5-yl)pyridin-2-amine can be produced from 2-(tert-butylamino)-N-(2,3-dichlorophenyl)pyridine-3-carboxamide and 2-(tert-butylamino)-N-(3-chloro-2-fluorophenyl)pyridine-3-carboxamide, respectively.

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