反应详情

温度

100 °C

To a 20 mL microwave reaction tube was added 2-fluoro-5-(morpholinomethyl)pyridin-3-ylboronic acid (Example 129, Step 3) (2.00 g, 8.33 mmol), 4-chloro-6-methyl-1,3,5-triazin-2-amine (Example 9, 0.501 g, 3.47 mmol), Am-Phos (Aldrich, 0.124 g, 0.175 mmol) and potassium acetate (Aldrich, 1.14 g, 11.6 mmol) in EtOH (10 mL) and water (1 mL). The mixture was degassed by bubbling argon through for 10 min. The tube was heated in a microwave reactor (Biotage) at 100° C. for 20 min. After the reaction mixture was cooled to room temperature, insoluble material was removed via filtration. The filtrate was partitioned between saturated aqueous sodium chloride (60 mL) and 10% isopropanol in chloroform (60 mL). The aqueous phase was extracted with 10% isopropanol in chloroform (2×60 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by silica gel column chromatography (100 g, eluent: iPrOH in CHCl3 0% to 25%) to afford 4-(2-fluoro-5-(morpholinomethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (0.27 g, 26% yield) as a white foam. 1H NMR (400 MHz, CDCl3) δ ppm 8.46 (dd, J=9.00, 2.35 Hz, 1H) 8.27 (s, 1H) 5.83 (br. s., 2H) 3.70-3.75 (m, 4H) 3.56 (s, 2H) 2.54 (s, 3H) 2.44-2.50 (m, 4H). m/z (ESI, positive ion): 305.0 (M+H)+.

1. customThe mixture was degassed
2. customby bubbling argon through for 10 min
3. temperatureAfter the reaction mixture was cooled to room temperature
4. custominsoluble material was removed via filtration
5. customThe filtrate was partitioned between saturated aqueous sodium chloride (60 mL) and 10% isopropanol in chloroform (60 mL)
6. extractionThe aqueous phase was extracted with 10% isopropanol in chloroform (2×60 mL)
7. dry with materialThe combined organic phases were dried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe crude product was purified by silica gel column chromatography (100 g, eluent: iPrOH in CHCl3 0% to 25%)