* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With lithium aluminium tetrahydride In tetrahydrofuran at -70℃; for 2.25 h;
To a solution of 5-bromo-3-fluoro-N-methoxy-N-methylpicolinamide (8.0 g, 30.41 mmol eql) in THE (70 mL), the LAH solution (1M in THF) (15.2 mL, 15.2 mmol, 0.5 eq) was added at -70°C for 15 mm. Reaction was continued at the same temperature for another 2 h. After completion of reaction (monitored by TLC), RM was quenched with sat. Na2SO4 solution and extracted with EtOAc (3x250 mL). The organic layer was washed with water (300 mL), brine (200 mL), dried over Na2SO4, filtered and evaporated under reduced pressure to get the crude. The crude was purified by CC to afford 5-bromo-3-fluoropicolin-aldehyde (5.5 g, 88.70percent) as a brown gum.
Stage #1: With diisobutylaluminium hydride In dichloromethane; toluene at -78 - 0℃; Stage #2: With hydrogenchloride In dichloromethane; water; toluene at -78℃;
(1) Synthesis of 5-bromo-3-fluoropyridine-2-carbaldehyde [172-1] (hereinafter referred to as a compound [172-1]) 5-Bromo-3-fluoropyridin-2-carbonitrile obtained by the method described in the document () (4. 5 g) was dissolved in dichloromethane (140 mL) and cooled to -78°C. 1.0M toluene solution (33 mL) of diisobutylaluminum hydride was added at -78°C, and then the reaction mixture was warmed to 0°C and stirred for 5 minutes. The reaction mixture was cooled again to -78°C, and added 3N-hydrochloric acid, and extracted with chloroform. The obtained organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the titled compound (848 mg) as a yellow solid. 1H-NMR (400 MHz, CDCl3) δ: 10.17 (1H, s), 8.69 (1H, s), 7.80 (1H, dd, J = 9.1, 1.3 Hz).
848 mg
With diisobutylaluminium hydride In dichloromethane; toluene at -78 - 0℃; for 0.0833333 h;
(1) Synthesis of 5-bromo-3-fluoropyridine-2-carboaldehyde [47-1] (hereinafter referred to as a compound [47-1]) 5-Bromo-3-fluoropyridine-2-carbonitrile (4.5 g), which was obtained by the method described in the document (Journal of Organic Chemistry, 2009, Vol. 74, 4547), was dissolved in dichloromethane (140 mL), and the solution was cooled to -78°C. 1.0M toluene solution of diisobutylaluminum hydride (33 mL) was added to the mixture at -78°C, and the solution was warmed to 0°C and the solution was stirred for 5 minutes. The reaction mixture was cooled again to -78°C, 3N-hydrochloric acid was added to the reaction mixture, and the mixture was extracted with chloroform. The obtained organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the titled compound (848 mg) as a yellow solid. 1H-NMR (400 MHz, CDCl3) δ: 10.17 (1H, s), 8.69 (1H, s), 7.80 (1H, dd, J = 9.1, 1.3 Hz).
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 13, p. 3608 - 3612
4
[ 669066-91-5 ]
[ 669066-93-7 ]
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 13, p. 3608 - 3612
5
[ 669066-89-1 ]
[ 669066-93-7 ]
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 13, p. 3608 - 3612
6
[ 15862-37-0 ]
[ 669066-93-7 ]
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 13, p. 3608 - 3612
7
[ 573675-25-9 ]
[ 669066-93-7 ]
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 13, p. 3608 - 3612
8
[ 15862-34-7 ]
[ 669066-93-7 ]
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 13, p. 3608 - 3612
9
[ 669066-93-7 ]
[ 1150617-54-1 ]
Yield
Reaction Conditions
Operation in experiment
275 mg
With hydrazine hydrate In ethylene glycol at 140℃; for 23 h;
To a solution of the compound [172-1] obtained in the process (1) (426 mg) in ethylene glycol (2.1 mL) was added hydrazine monohydrate (197 µL) at room temperature, and then the reaction mixture was stirred at 140°C for 23 hours. After cooling to room temperature, to the reaction mixture was added water, and extracted with a mixed solution of chloroform/isopropanol (volume ratio 10/1). The obtained organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the titled compound (275 mg) as a yellow solid. 1H-NMR (400 MHz, CDCl3) δ: 10.17 (1H, br), 8.65 (1H, d, J = 1.7 Hz), 8.31 (1H, s), 8.04 (1H, s). ESI-MS found: 198 [M+H]+
275 mg
With hydrazine hydrate In ethylene glycol at 140℃; for 23 h;
(2) Synthesis of 6-bromo-1H-pyrazolo[4,3-b]pyridine [47-2] (hereinafter referred to as a compound [47-2]) To a solution of the compound [47-1] (426 mg) in ethylene glycol (2.1 mL) was added hydrazine monohydrate (197 µL) at room temperature, and the mixture was stirred at 140°C for 23 hours. After cooling to room temperature, water was added to the reaction mixture, and the mixture was extracted with a mixed solution of chloroform/isopropanol (volume ratio 10/1). The obtained organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the titled compound (275 mg) as a yellow solid. 1H-NMR (400 MHz, CDCl3) δ: 10.17 (1H, br), 8.65 (1H, d, J = 1.7 Hz), 8.31 (1H, s), 8.04 (1H, s). ESI-MS found: 198 [M + H]+
With hydrazine hydrate; In ethylene glycol; at 140℃; for 23h;
To a solution of the compound [172-1] obtained in the process (1) (426 mg) in ethylene glycol (2.1 mL) was added hydrazine monohydrate (197 muL) at room temperature, and then the reaction mixture was stirred at 140C for 23 hours. After cooling to room temperature, to the reaction mixture was added water, and extracted with a mixed solution of chloroform/isopropanol (volume ratio 10/1). The obtained organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the titled compound (275 mg) as a yellow solid. 1H-NMR (400 MHz, CDCl3) delta: 10.17 (1H, br), 8.65 (1H, d, J = 1.7 Hz), 8.31 (1H, s), 8.04 (1H, s). ESI-MS found: 198 [M+H]+
275 mg
With hydrazine hydrate; In ethylene glycol; at 140℃; for 23h;
(2) Synthesis of 6-bromo-1H-pyrazolo[4,3-b]pyridine [47-2] (hereinafter referred to as a compound [47-2]) To a solution of the compound [47-1] (426 mg) in ethylene glycol (2.1 mL) was added hydrazine monohydrate (197 muL) at room temperature, and the mixture was stirred at 140C for 23 hours. After cooling to room temperature, water was added to the reaction mixture, and the mixture was extracted with a mixed solution of chloroform/isopropanol (volume ratio 10/1). The obtained organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the titled compound (275 mg) as a yellow solid. 1H-NMR (400 MHz, CDCl3) delta: 10.17 (1H, br), 8.65 (1H, d, J = 1.7 Hz), 8.31 (1H, s), 8.04 (1H, s). ESI-MS found: 198 [M + H]+
(1) Synthesis of 5-bromo-3-fluoropyridine-2-carbaldehyde [172-1] (hereinafter referred to as a compound [172-1]) 5-Bromo-3-fluoropyridin-2-carbonitrile obtained by the method described in the document () (4. 5 g) was dissolved in dichloromethane (140 mL) and cooled to -78C. 1.0M toluene solution (33 mL) of diisobutylaluminum hydride was added at -78C, and then the reaction mixture was warmed to 0C and stirred for 5 minutes. The reaction mixture was cooled again to -78C, and added 3N-hydrochloric acid, and extracted with chloroform. The obtained organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the titled compound (848 mg) as a yellow solid. 1H-NMR (400 MHz, CDCl3) delta: 10.17 (1H, s), 8.69 (1H, s), 7.80 (1H, dd, J = 9.1, 1.3 Hz).
848 mg
With diisobutylaluminium hydride; In dichloromethane; toluene; at -78 - 0℃; for 0.0833333h;
(1) Synthesis of 5-bromo-3-fluoropyridine-2-carboaldehyde [47-1] (hereinafter referred to as a compound [47-1]) 5-Bromo-3-fluoropyridine-2-carbonitrile (4.5 g), which was obtained by the method described in the document (Journal of Organic Chemistry, 2009, Vol. 74, 4547), was dissolved in dichloromethane (140 mL), and the solution was cooled to -78C. 1.0M toluene solution of diisobutylaluminum hydride (33 mL) was added to the mixture at -78C, and the solution was warmed to 0C and the solution was stirred for 5 minutes. The reaction mixture was cooled again to -78C, 3N-hydrochloric acid was added to the reaction mixture, and the mixture was extracted with chloroform. The obtained organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the titled compound (848 mg) as a yellow solid. 1H-NMR (400 MHz, CDCl3) delta: 10.17 (1H, s), 8.69 (1H, s), 7.80 (1H, dd, J = 9.1, 1.3 Hz).
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
