反应详情

温度

115 °C

200 mg of 2-cyano-3,5-difluoropyridine, 236 mg of 4-aminotetrahydropyran hydrochloride, 395 mg of potassium carbonate and 173.4 mg of triethylamine in 3 ml of dimethyl sulphoxide are introduced into a 5 ml microwave tube reactor. The mixture is then heated in a microwave for 1 hour at 115° C. The reaction medium is run into 50 ml of water and 50 ml of ethyl acetate. The aqueous phase is re-extracted twice with 25 ml of ethyl acetate. The combined organic phases are washed with water and then with a saturated aqueous solution of sodium chloride, dried over sodium sulphate and concentrated under reduced pressure. After purification by flash chromatography on 25 g of silica gel, elution being carried out with mixtures of ethyl acetate and heptane (40/60 then 60/40 by volume), and the first eluted product being recovered, 80 mg of 2-cyano-5-fluoro-3-(tetrahydropyran-4-yl)aminopyridine are thus obtained in the form of an ecru powder, the characteristics of which are the following:

1. extractionThe aqueous phase is re-extracted twice with 25 ml of ethyl acetate
2. washThe combined organic phases are washed with water
3. dry with materialwith a saturated aqueous solution of sodium chloride, dried over sodium sulphate
4. concentrationconcentrated under reduced pressure
5. customAfter purification by flash chromatography
6. washon 25 g of silica gel, elution
7. custom60/40 by volume), and the first eluted product being recovered