反应详情

温度

100 °C

To 5′-chloro-2′-fluoro-N-(3-fluorobenzyl)-2,4′-bipyridin-6-amine (100 mg, 0.301 mmol), was added (1S,3R)-3-aminocyclopentanecarboxylic acid (117 mg, 0.904 mmol), powdered potassium hydroxide (85 mg, 1.507 mmol) and dioxane (1 ml). The reaction mixture was stirred at 100° C. for 18 hr in a sealed vessel and followed by LCMS. The crude reaction mixture was partitioned between 30 mL saturated ammonium chloride and 30 mL ethyl acetate. The organic layer was removed, dried over sodium sulfate, and reduced. This was redissolved in 1.5 mL DMSO, filtered, and purified through prep LC. The product fractions were combined and extracted with 50 mL ethyl acetate, which was dried over sodium sulfate, and concentrated to constant mass. 10 mg of the desired compound was obtained. LCMS (m/z): 441.2 (MH+), retention time=0.68 min. 1H NMR (400 MHz, CHLOROFORM-d, 25° C.) δ ppm 1.59 (m, 2H) 1.83 (m, 2H) 1.99 (m, 1H) 2.72 (m, 1H) 3.40 (br. s., 1H) 3.78 (br. s., 1H) 4.42 (br. s., 1H) 5.48 (br. s., 1H) 6.29 (d, J=8.22 Hz, 1H) 6.50 (s, 1H) 6.80-6.92 (m, 2H) 6.95-7.10 (m, 2H) 7.16-7.25 (m, 1H) 7.38 (t, J=8.02 Hz, 1H) 7.89 (s, 1H).

1. customThe crude reaction mixture
2. customwas partitioned between 30 mL saturated ammonium chloride and 30 mL ethyl acetate
3. customThe organic layer was removed
4. dry with materialdried over sodium sulfate
5. dissolutionThis was redissolved in 1.5 mL DMSO
6. filtrationfiltered
7. custompurified through prep LC
8. extractionextracted with 50 mL ethyl acetate, which
9. dry with materialwas dried over sodium sulfate
10. concentrationconcentrated to constant mass