1H-PYRAZOLO[4,3-B]PYRIDINE

Step 21 H-Pyrazo lo [4 , 3 -b ]pyridinePyrazolo[4, 3-b]pyridin-l-yl-ethanone (973 mg, 6.04 mmol) was dissolved in THF/MeOH (1 :1 , 16 mL) and 10percent NaOH (1.8 mL) was added. The reaction mixture was stirred at room temperature for 30 min then neutralized with 1.0 M HC1, diluted with water and extracted with EtOAc (2x). The combined organics were washed with brine then dried over MgSC^ and concentrated to afford 687 mg (96percent>) of lH-pyrazolo[4, 3-b]pyridine as a light yellow solid. 1H NMR (DMSO-dg, 300 MHz): ' (ppm) 13.29 (br. s., 1H), 8.50 (d, J=4.5 Hz, 1H), 8.27 (s, 1H), 8.00 (d, J=8.7 Hz, 1H), 7.34 (dd, J=8.7, 4.5 Hz, 1H).A mixture of 3-fluoro-2-pyridinecarboxaldehyde (4 g, 32 mmol) and hydrazine (20.5 g) was kept at 115 A mixture of 3-fluoro-2-pyridinecarboxaldehyde (4 g, 32 mmol) and hydrazine (20.5 g) was kept at 115 0C for 7 hr, then cooled to rt. The reaction mixture was diluted with water and extracted with EtOAc. The organic phases were combined, washed with brine, and dried. Concentration followed by flash chromatography afforded 1 H-3-bromo-lH-Intermediate A-11H-Pyrazolo [4, 3-b] pyridine A solution of 3-fluoropicolinaldehyde (12.5 g, 100 mmol) in N2H4. H2O (80, 200 mL) was stirred at 120 for 16 h. After TLC (petroleum etherEtOAc 51) showed the reaction was completed, the mixture solution was poured into water (400 mL) and extracted by EtOAc (400 mL). The organic layer was then washed with brine, dried over anhy. Na2SO4, filtered, and concentrated in vacuo to give a crude title compound (11 g, 96yield) as yellow solid. MS 120.3 [M+H] +. 1H NMR (400 MHz, CHCl3-d1) delta 11.15 (br, 1H) , 8.65-8.63 (m, 1H) , 8.37 (s, 1H) , 7.90 (d, J 11.6 Hz, 1H) , 7.36-7.32 (m, 1H).