Vipadenant

442908-07-8

442908-10-3

Example 4: Preparation of 3-(4-amino-3-methylbenzyl)-7-(furan-2-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine (1) To a 250 mL two-necked round-bottomed flask under nitrogen protection was added 7-(furan-2-yl)-3-(3-methyl-4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine (3.0 g, 8.5 mmol) and 5% Pd/C catalyst (0.46 g, 0.073 mmol). Subsequently, THF (72 mL) and triethylamine (9.0 mL, 65 mmol) were added via syringe and the mixture was stirred to form a slurry. Formic acid (2.3 mL, 46.03 mmol) was then added all at once and the reaction mixture was heated in a 70 °C oil bath. After 5 hours of reaction, it was cooled to 25°C. Water (60 mL) was added and concentrated hydrochloric acid was added dropwise until the product was completely dissolved. The reaction solution was filtered through Celite 545 to remove the catalyst and the filter cake was washed with additional water (2 x 5 mL). A 50% aqueous sodium hydroxide solution was added to the pale yellow filtrate to precipitate the product. After continued stirring for 1 hour, the product was separated by filtration. The filter cake was washed sequentially with water (10 mL) and methanol (10 mL). The product was dried under vacuum to constant weight to give 2.79 g (92% yield) of the target compound 3-(4-amino-3-methylbenzyl)-7-(furan-2-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine.