[Synthesis]
General procedure for the synthesis of pyrazolo[1,5-a]pyridin-5-amine from ethyl 5-((Boc)amino)pyrazolo[1,5-a]pyridine-3-carboxylate: ethyl 5-((Boc)amino)pyrazolo[1,5-a]pyridine-3-carboxylate (10.0 g, 32.751 mmol) was mixed with 40% H2SO4 (80 mL) and reacted at the reflux temperature for 4 hours. After completion of the reaction, the mixture was dissolved in water (100 mL) and the pH was adjusted to 8.0 with 20% NaOH aqueous solution. the aqueous phase was extracted with ethyl acetate (3 x 100 mL), the organic phases were combined, washed with brine (2 x 50 mL) and dried over anhydrous sodium sulfate. After concentration under reduced pressure, 2.5 g (57% yield) of pyrazolo[1,5-a]pyridin-5-amine was obtained as a light brown solid. The product was confirmed by NMR (400 MHz, DMSO-d6): δ 8.25 (d, J = 5.4 Hz, 1H), 7.65 (d, J = 1.5 Hz, 1H), 6.40 (d, J = 1.8 Hz, 1H), 6.31 (dd, J = 1.8, 5.4 Hz, 1H), 5.98 (d, J = 1.2 Hz, 1H), 5.56 (s, 2H). ESI-LC/MS analysis showed m/z 133.9 ([M+H]+); retention time 1.53 min [using an Agilent ion trap detector; XBridge-C18, 3.5 μm, 4.6 × 75 mm column; gradient elution conditions: 80:20 H2O (0.005 M ammonium bicarbonate):CH3CN to 10 :90 H2O (0.01 M ammonium bicarbonate):CH3CN, 4.0 min, hold 3.0 min, flow rate 1.0 mL/min]. |