1,1'-Carbonyldiimidazole → 6-{5-[3-(Cyclopropylamino)pyridin-2-yl]-1,2,4-oxadiazol-3-yl}-2-N-methyl-2-N-phenyl-1,3,5-triazine-2,4-diamine

関与物質

反応手順

1,1′-Carbonyldiimidazole (62 mg, 0.380 mmol) was added to a solution of 3-fluoropyridine-2-carboxylic acid (50 mg, 0.354 mmol) in anhydrous pyridine (1 mL) in a sealed tube at room temperature and the mixture was stirred 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, 66 mg, 0.253 mmol) was added and the mixture was stirred at room temperature for 60 min and then at 90 C for approximately 18 h. The mixture was then treated with cyclopropanamine (300 μL, 4.32 mmol) and stirred at 80 C for 7 h. The mixture was then diluted with EtOAc (35 mL) and washed with water (10 mL), saturated aq. ammonium chloride (2×6 mL) and 2M hydrochloric acid (3×5 mL). The combined hydrochloric acid extractions were washed with DCM (2×6 mL) and then made alkaline by the addition of 2M aq. sodium hydroxide. The resulting solution was extracted with DCM (4×7 mL), the combined organic extractions were washed with brine (10 mL), dried over sodium sulfate and evaporated under vacuum. The crude residue was purified by flash chromatography (0-3% MeOH in DCM) to afford the title compound (17 mg, 17%).

情報源と証拠