5-Bromo-1H-pyrazolo[3,4-b]pyridin-3-amine

5-bromo-lH~pyrazolo[3, 4-b]pyridin-3-amine (4); [00142] Compound 3 (307 mg, 1.4 mmol) was dissolved in EtOH (10 mL) in a microwave tube, to which 5 equivalent of NHInto a 100 mL sealed tube, was added 5-bromo-2-chloropyridine-3-carbonitrile (2.50 g, 11.5 mmol) and hydrazine hydrate (30 mL). The solution was stirred for 3 h at 130°C. The reaction mixture was concentrated under vacuum. The residue was dissolved in 30 mL of water. Precipitation occurred. The precipitates were collected by filtration. This resulted in 2.00 g (82percent) of 5-bromo-1 H-pyrazolo[3, 4-b]pyridin-3-amine as a yellow solid.To a stirred solution of compound 3 (700 mg, 3.2 mmol ) in 1-butanol ( 10.5 mL ) was added 'Step-3 [0070] To a stirred solution of compound 3 (700 mg, 3.2 mmol) in 1-butanol (10.5 mL) was added NHydrazine hydrate (4 ml) was added to a stirred solution of 5-bromo-2- chloronicotinonitrile (36A, 2 g) in i-PrOH (30 ml). The reaction mixture was stirred at 75 °C for 24 h. After cooling to RT, the solvent was removed under vacuum. The residue was washed with water (10 mL). The resulting solid was collected, washed with water, and dried to give 36B as yellow solid (1.8 g). ESI-MS m/z 2 12/214 (MH).5-Bromo-2-methoxy-nicotinonitrile (4 g, 18.8 mmol) obtained in the above step 2, Was dissolved in hydrazine (40 mL) and refluxed for 6 hours.The reaction mixture was cooled to room temperature, and the resulting solid was separated, washed with water, And dried to obtain 5-bromo-1H-pyrazolo [3, 4-b] pyridin-3-amine (3.2 g, 80percent).35 ml (23.47 mmol) of hydrazine is added at room temperature to 5 g (23.47 mmol) of 5-bromo-2-methoxynicotinonitrile. The reaction medium is carried at 100°C for 3 hours. After returning to room temperature, the precipitate obtained is filtered, rinsed with water and then dried at 50°C to yield 3.6 g (72percent) of 5-bromo-lH-pyrazolo[3, 4- b]pyridine-3 -amine in the form of a yellow solid.LCMS (EI, m/z): (M+l) 214.051H NMR: 6H ppm (400 MHz, DMSO): 12.18 (1H, s, H), 8.38 (1H, d, CH35 ml (23.47 mmol) of hydrazine is added at room temperature to 5 g (23.47 mmol) of 5-bromo-2-methoxynicotinonitrile. The reaction medium is carried at 100°C for 3 hours. After returning to room temperature, the precipitate obtained is filtered, rinsed with water and then dried at 50°C to yield 3.6 g (72percent) of 5-bromo-1H-pyrazolo[3, 4-b]pyridine-3-amine in the form of a yellow solid. LCMS (EI, m/z): (M+1) 214.05 5-bromo-lH-pyrazolo[3, 4-b]pyridine-3-amine 35 ml (23.47 mmol) of hydrazine is added at room temperature to 5 g (23.47 mmol) of 5-bromo-2-methoxynicotinonitrile. The reaction medium is carried at 100°C for 3 hours. After returning to room temperature, the precipitate obtained is filtered, rinsed with water and then dried at 50°C to yield 3.6 g (72percent>) of 5-bromo-lH-pyrazolo[3, 4- b]pyridine-3 -amine in the form of a yellow solid. LCMS (EI, m z): (M+l) 214.05 1H NMR: δΗ ρηι (400 MHz, DMSO): 12.18 (1H, s, NH), 8.38 (1H, d, CH5-bromo-lH-pyrazolo[3, 4-b]pyridine-3-amine 35 ml (23.47 mmol) of hydrazine is added at room temperature to 5 g (23.47 mmol) of 5-bromo-2-methoxynicotinonitrile. The reaction medium is carried at 100°C for 3 hours. After returning to room temperature, the precipitate obtained is filtered, rinsed with water and then dried at 50°C to yield 3.6 g (72percent>) of 5-bromo-lH-pyrazolo[3, 4- b]pyridine-3 -amine in the form of a yellow solid. LCMS (EI, m/z): (M+l) 214.05 1H NMR: 5H ppm (400 MHz, DMSO): 12.18 (1H, s, NH), 8.38 (1H, d, CH35 ml (23.47 mmol) of hydrazine is added at room temperature to 5 g (23.47 mmol) of 5-bromo-2-methoxynicotinonitrile. The reaction medium is carried at 100°C for 3 hours. After returning to room temperature, the precipitate obtained is filtered, rinsed with water and then dried at 50°C to yield 3.6 g (72percent) of 5-bromo-1H-pyrazolo[3, 4-b]pyridine-3-amine in the form of a yellow solid. LCMS (EI, m/z): (M+1) 214.05 5-bromo-lH~pyrazolo[3, 4-b]pyridin-3-amine (4); [00142] Compound 3 (307 mg, 1.4 mmol) was dissolved in EtOH (10 mL) in a microwave tube, to which 5 equivalent of NH2NH2 was added, and the reaction mixture was put on Microwave irradiation for 10 min at 1702C. Evaporated the solvent to obtain the title compound 4 in quantative yield.Into a 100 mL sealed tube, was added 5-bromo-2-chloropyridine-3-carbonitrile (2.50 g, 11.5 mmol) and hydrazine hydrate (30 mL). The solution was stirred for 3 h at 130C. The reaction mixture was concentrated under vacuum. The residue was dissolved in 30 mL of water. Precipitation occurred. The precipitates were collected by filtration. This resulted in 2.00 g (82%) of 5-bromo-1 H-pyrazolo[3, 4-b]pyridin-3-amine as a yellow solid.To a stirred solution of compound 3 (700 mg, 3.2 mmol ) in 1-butanol ( 10.5 mL ) was added '2'4'20 (962 mg, 17.8 mmol ). The reaction mixture was stirred at 80 C overnight and then cooled to room temperature. The concentrated mixture was poured into 30 mL of saturated NaHC03 solution and the resulting precipitate was collected by filtration, washed with water and dried under vacuum to give compound 4 (270 mg, 39.4%).Step-3 [0070] To a stirred solution of compound 3 (700 mg, 3.2 mmol) in 1-butanol (10.5 mL) was added N2H4.H2O (962 mg, 17.8 mmol). The reaction mixture was stirred at 80 C. overnight and then cooled to room temperature. The concentrated mixture was poured into 30 mL of saturated NaHCO3 solution and the resulting precipitate was collected by filtration, washed with water and dried under vacuum to give compound 4 (270 mg, 39.4%).(Step 7-i) To a solution of 5-bromo-2-chloropyridine-3-carbonitrile (2 g, 9.22 mmol) in 30 mL n-butanol was added 2 mL anhydrous hydrazine. The reaction mixture was heated under reflux for 14 hrs and allowed to cool to room temperature. The solvent was removed by evaporation and the residue was poured into a saturated NaHCO3 solution. The resulting precipitate was collected and washed with water. After drying in vacuo, the product, 5-bromo-lH-pyrazolo[3, 4-b]pyridin-3-amine, can be used directly without further purification5-Bromo-1H-pyrazolo[3, 4-b]pyridin-3-ylamine Hydrazine hydrate (19 ml, 391 mmol) was added to a stirred solution of 5-bromo-2-chloronicotinonitrile (34 g, 156 mmol) in ethanol (300 ml). The reaction mixture was stirred at reflux for 4 hours then the solvent was removed in vacuo. Water was added and the resulting solids were filtered, washed with water, and dried in vacuo to afford the title compound as a solid. 1H NMR delta (d6 DMSO) 12.2 (s, 1H), 8.4 (appd, 2H), 5.7 (s, 2H).Hydrazine hydrate (4 ml) was added to a stirred solution of 5-bromo-2- chloronicotinonitrile (36A, 2 g) in i-PrOH (30 ml). The reaction mixture was stirred at 75 C for 24 h. After cooling to RT, the solvent was removed under vacuum. The residue was washed with water (10 mL). The resulting solid was collected, washed with water, and dried to give 36B as yellow solid (1.8 g). ESI-MS m/z 2 12/214 (MH).N-(5-Bromo-1H-pyrazolo[3, 4-b]pyridin-3-yl-butyramide Butyryl chloride (2.1 ml, 20.7 mmol) was added to a stirred solution of General procedure: At room temperature, to2-Fluoro-5-bromobenzonitrile (5.0 g)Soluble in ethanol (30mL)80% hydrated hydrazine (7.82g) was added to the solution.After refluxing at 90 C. for 12 h, the reaction solution was cooled to room temperature.Concentrate under reduced pressure to remove the ethanol.The residue was slurried with dichloromethane for 1 h.Filter, wash with dichloromethane, dry, The title compound (5.3 g) was obtained.

Molecular Weight:213.03
XLogP3:1.2
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Exact Mass:211.96976
Monoisotopic Mass:211.96976
Topological Polar Surface Area:67.6
Heavy Atom Count:11
Complexity:154
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes