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With sodium hydroxide In tetrahydrofuran; methanol at 20℃; for 0.5 h;
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).
With sodium hydroxide; In tetrahydrofuran; methanol; at 20℃; for 0.5h;
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).
20 g of 1-pyrazolo[4,3-b]pyridin-1-yl-ethanone obtained by Production example 408 was dissolved in a mixed solution of 20 mL methanol/80 mL tetrahydrofuran, added with 10 mL of 2N sodium hydroxide aqueous solution at room temperature and stirred for 0.5 hours. The reaction solution was neutralized by adding 2 mL of 5N hydrochloric acid, then added with about 50 mL of silica gel powder, and the solvent was evaporated. The residue was purified by silica gel column chromatography (ethyl acetate :methanol =100:2), to afford 14.6 g of the title compound as pale yellow cubic crystals.1H-NMR (400 MHz, CDCl3) delta7.35 (1H, dd, J = 4.3, 8.6 Hz), 7.89 (1H, d, J = 8.6 Hz), 8.36 (1H, bs), 8.64 (1H, dd, J= 1.5, 4.3 Hz).
Stage #1: 2-methyl-3-pyridinamine; acetic anhydride In chloroform at 0 - 20℃;
Stage #2: With potassium acetate; isopentyl nitrite In chloroform Reflux;
98.1 Step 11 -Pyrazo lo [4 ,3 -b ]pyridin- 1 -yl-ethanone
Example 98.2-(l -Methyl- 1 H-pyrazolo [4,3 -b]pyridin-3 -yl)-5H-pyrrolo [2,3 -b]pyrazine-7-carboxylic acid [(R)- 2-(3 -cyano-azetidin- 1 -yl)- 1 -methyl-2-oxo-ethyl]-amideStep 11 -Pyrazo lo [4 ,3 -b ]pyridin- 1 -yl-ethanoneTo a solution of 3-amino-2-methylpyridine (1.0 g, 9.25 mmol) in CHCI3 (24 ml) at 0°C was slowly added acetic anhydride (2.0 ml, 21.3 mmol). The reaction mixture was warmed to room temperature and stirred for 1 h. Potassium acetate (272 mg, 2.77 mmol) was added followed by slow addition of isoamyl nitrite (2.7 ml, 19.9 mmol). The reaction mixture was heated at reflux overnight. The reaction mixture was cooled to room temperature and concentrated. The residue was dissolved in EtOAc and washed with water, sat'd NaHC03 and brine then dried over MgSC^ and concentrated. The residue was purified by silica gel chromatography with 20% to 100% EtO Ac/heptane to give 973 mg (65%) of l-pyrazolo[4,3-b]pyridin-l -yl-ethanone as a light yellow solid.