1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 6-[5-(3-Fluoropyridin-2-yl)-[1,2,4]oxadiazol-3-yl]-N-methyl-N-phenyl-[1,3,5]triazine-2,4-diamine

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Reaction Steps

N-[3-(Dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (633 mg, 3.3 mmol) was added to a solution of 3-fluoropyridine-2-carboxylic acid (400 mg, 2.83 mmol) in anhydrous pyridine (6 mL) in a sealed tube at room temperature under nitrogen. The reaction mixture was stirred at room temperature for 1 h. 4-Amino-N-hydroxy-6-(methyl-3-methylphenyl-amino)-[1,3,5]triazine-2-carboxamidine (prepared in an analogous manner to Intermediate 1, 611 mg, 2.36 mmol) was added and the mixture was stirred at room temperature for approximately 18 h. A solution of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (315 mg, 1.15 mmol) in anhydrous pyridine (1 mL) was added and the mixture was stirred for 2 h. Further N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (100 mg, 0.52 mmol) and 3-fluoropyridine-2-carboxylic acid (70 mg, 0.5 mmol) were then added and the mixture was stirred at room temperature for 1 h and then at 60 C for approximately 18 h. The mixture was then diluted with EtOAc (75 mL) and washed with saturated aq. ammonium chloride (4×15 mL), then saturated aq. sodium bicarbonate (3×15 mL) and brine (15 mL). The organic layer was dried over sodium sulfate and evaporated under vacuum. The crude residue was purified by flash chromatography (0-2% MeOH in DCM) to afford the title compound (220 mg). 20 mg of this material was dissolved in hot DMSO (0.3 mL) and MeOH (0.5 mL) and then 1:1 MeCN:water (1 mL) was added. The resultant precipitate was filtered, the solids were washed with water (2×1 mL) and then dried under vacuum to afford the title compound as a white solid (14 mg, 2%).

Provenance & Evidence