反应详情

A solution of 6-chloronicotinonitrile (1.0 g, 7.2 mmol), 4-aminobutyric acid tert-butyl ester hydrochloride (2.12 g, 10.8 mmol, Sennchem 09600) and DIEA (4.9 mL, 28.9 mmol) in anhydrous dioxane (20 mL) was heated at 80° C. After 48 hours, an additional amount of 4-aminobutyric acid tert-butyl ester hydrochloride (0.55 g, 2.80 mmol) was added. After 24 additional hours at 80° C., the reaction mixture was diluted with Et2O (100 mL) and washed with water (2×50 mL) and brine (50 mL). The organic layer was dried (MgSO4) and the solvents were removed under reduced pressure. After purification by flash chromatography (silica, EtOAc/cHex), the title compound was obtained as a beige powder. HPLC (Method A), Rt: 3.3 min (purity: 91%). UPLC/MS, M+(ESI): 262.1, M−(ESI): 260.2. 1H NMR (DMSO-d6, 300 MHz) δ 8.37 (d, J=2.2 Hz, 1H), 7.63 (m, 2H), 6.52 (d, J=8.9 Hz, 1H), 3.29 (m, 2H), 2.26 (t, J=7.4 Hz, 2H), 1.73 (tt, J=7.4, 7.0 Hz, 2H), 1.38 (s, 9H).

1. washwashed with water (2×50 mL) and brine (50 mL)
2. dry with materialThe organic layer was dried (MgSO4)
3. customthe solvents were removed under reduced pressure
4. customAfter purification by flash chromatography (silica, EtOAc/cHex)