4-pyridin-2-yl-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine(SALTDATA: H2O) synthesis

Yield:887405-39-2 20%

Reaction Conditions:

with potassium hydroxide in ethanol; for 48 h;Reflux;

Steps:

21

A mixture of histamine (0.1 1 mmol), potassium hydroxide (0.33 mmol) and 2-formylpyridine (0.13 mmol) were refluxed in ethanol for 48 h, after which the solvent was evaporated and the products chromatographed on silica (1% methanol/DCM to 12% methanol saturated with ammonia) to yield 4-(pyrid-2-yl)-4,5,6,7-tetrahydro-lH-imidazo[4,5-c]pyridine (18.8 mg; 20%) as a white solid. ¹H NMR (400 MHz, CD₃OD) δ 8.49 (d, J= 5.4 Hz, IH), 7.87 (t, J = 5.4 Hz, IH), 7.62 (s, IH), 7.54-7.40 (m, 2H),3.3-2.7 (m, 4H); ¹³C NMR (100 MHz, CD₃OD) δ 160.0, 149.4, 138.8, 135.7, 131.4 (b), 128.3 Qo), 123.0, 58.2, 49.5, 41.0, 22.6;0 m/z 201 (100; M+H⁺).4-(Pyrid-2-yl)-4,5,6,7-tetrahydro-lH-imidazo[4,5-c]pyridine (0.05 mmol) and IBX (0.075 mmol) were dissolved in DMSO (300 μL) and heated to 45 °C for 7 hours. Flash chromatography on silica gel (1% methanol/DCM to 12% methanol saturated with ammonia) yielded 4-(pyrid-2-yl)- lH-imidazo[4,5-c]pyridine (9 mg; 90%) as a paleS yellow solid ¹H NMR (400 MHz, CD₃OD) δ 8.74 (m, 2H), 8.55 (d, J = 5.4 Hz, IH), 8.32 (s, IH), 7.92 (t, IH), 7.85 (d, IH), 7.38 (dd, IH); m/z 197 (100; M+H⁺)

References:

WO2009/152584,2009,A1 Location in patent:Page/Page column 31