* 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.
Reference:
[1] Recueil des Travaux Chimiques des Pays-Bas, 1953, vol. 72, p. 125,131
2
[ 39856-50-3 ]
[ 1072-97-5 ]
[ 14916-65-5 ]
Reference:
[1] Recueil des Travaux Chimiques des Pays-Bas, 1953, vol. 72, p. 125,131
3
[ 39856-50-3 ]
[ 64-17-5 ]
[ 7664-41-7 ]
[ 1072-97-5 ]
[ 14916-65-5 ]
Reference:
[1] Recueil des Travaux Chimiques des Pays-Bas, 1953, vol. 72, p. 125,131
4
[ 52092-47-4 ]
[ 14916-65-5 ]
Yield
Reaction Conditions
Operation in experiment
26%
With ammonia In ethanol; water at 150℃;
To a solution of 5-chloro-2-nitropyridine (3 g, 19 mmol) in EtOH (30 mL) was added saturated NH3.H2O (20 mL) ' the mixture was stirred under 50 psi at 150 °C overnight. TLC showed that the reaction was complete. After the reaction mixture was cooled to r.t, the resulting solid was collected by filtration. The solid was washed with PE (100 mL) to give 0.7 g (yield: 26percent) of 6-nitro-pyridin-3-ylamine as a yellow solid. MS: m/z 140.1 (M+H+).
With hydrogenchloride; In dimethyl sulfoxide; at 120℃; for 2h;
General procedure: A round bottom flask equipped with reflux condenser and magnetic stirring bar was charged with substituted heteroaryl chloride (5 mmol), sodium azide (10 mmol), triphenylphosphine (10 mmol) and DMSO (40 ml). The reaction mixture was stirred at 120 C. Reaction progress was monitored by TLC. In 3-5 hours starting material was disappeared and new product was confirmed by TLC. 1N HCl (8 mL) was added to the reaction mixture and continued to stir at 120 C for additional 1-2 hour. Reaction mixture was cooled to room temperature and diluted with 1N HCl (8 mL). The resulting mixture was poured into distilled water (100 mL) and aqueous layer was washed with EtOAc (2 X 50 mL) to remove triphenylphosphine oxide. Aqueous layer was slowly neutralized with saturated aqueous NaHCO3 solution and extracted with EtOAc (2 X 50 mL). The combined organic layers were washed with water (40 mL), brine(40 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure to afford substituted heteroaryl amine with high purity without column purification (purity was achieved in some products by washing solid compound with n-Pantane).
To a solution of <strong>[14916-65-5]6-nitro-pyridin-3-ylamine</strong> (50 mg, 0.33 mmol) in DMF (3 mL) was added NaH (60% in mineral oil, 25 mg, 0.66 mmol), and the mixture was stirred at r.t for 30 min. Then 5-bromo-2-methoxy-benzenesulfonyl chloride (86 mg, 0.3 mmol) was added and the mixture was stirred at 50 C overnight. TLC showed that the reaction was complete. The resultant was concentrated in vacuum to remove DMF. The residue was diluted with DCM (30 mL) and the mixture was washed with IN HC1 (30 mL x3) .The organic layer dried over Na2S04 and concentrated to dryness in vacuum. The residue was purified by silica gel column (PE/EtOAc, 1/1) to give 30 mg (yield: 26%) of 5-bromo-2-methoxy-N-(6-nitro-pyridin-3-yl)- benzenesulfonamide as a brown solid.
With ammonia; In ethanol; water; at 150℃; under 2585.81 Torr;
To a solution of 5-chloro-2-nitropyridine (3 g, 19 mmol) in EtOH (30 mL) was added saturated NH3.H2O (20 mL) ' the mixture was stirred under 50 psi at 150 °C overnight. TLC showed that the reaction was complete. After the reaction mixture was cooled to r.t, the resulting solid was collected by filtration. The solid was washed with PE (100 mL) to give 0.7 g (yield: 26percent) of 6-nitro-pyridin-3-ylamine as a yellow solid. MS: m/z 140.1 (M+H+).
With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 20℃; for 1h;Inert atmosphere;
To a so[ution of 3.50 g (11.2 mmo[) 5,10-dioxo-5H,1OH-diimidazo[1,5-a:1?,S?-d]pyrazine-1,6-dicarbony[ dich[oride (Intermediate 001) in 60 mL THF were added 3.10 g (22.4 mmo[) <strong>[14916-65-5]6-nitropyridin-3-amine</strong> and 5.00 mL N,N-diisopropy[ethy[amine. The resu[ting mixture was stirred for 1 hour at room temperature under an argon atmosphere.
4-chlorobenzaldehyde (84.3 g, 0.6 mol) <strong>[14916-65-5]5-amino-2-nitropyridine</strong> (70.0 g, 0.5 mol) and acetic acid (7.2 g, 0.12 mol) were dissolved in ethanol (350 ml) and stirred at room temperature for 1 hour. The reaction system was heated to reflux and TLC was detected.After completion of the reaction, the reaction solution was cooled to room temperature and then filtered, and the filter cake was washed with ethanol (100 mL x 3)The crude oil was recrystallized to give yellow solid compound 28 (104.6 g, yield 80%).
Dichloromethane 10 ml, <strong>[14916-65-5]2-nitro 5-aminopyridine</strong> (200 mg, 1.4 mmol) starting material 1 and ethyl 4-bromo-2-oxo-butyrate (280 ml, 1.4 mmol) were added to a 50 ml reaction flask at room temperature. The magnetic stirring reaction was performed for 1 to 2 hours, and the solvent was concentrated under reduced pressure. The residue was dissolved with 10 ml of ethanol and specifically ethanol, and the mixture was heated under reflux for 3 h. The reaction was completely checked by TLC.The reaction solution was allowed to cool to room temperature and concentrated under reduced pressure to remove the ethanol.The residue was washed with saturated sodium hydrogencarbonate solution and the aqueous layer was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate overnight, suction filtered and concentrated, and the residue was separated using silica gel column chromatography to give Intermediate 2 as a yellow solid.MS calculated 235, found 236 [M+l].
Intermediate V-1 was synthesized through the reaction of <strong>[14916-65-5]5-amino-2-nitropyridine</strong> with sodium azide and orthoformate and subsequent reduction with hydrogen in the presence of palladium hydroxide/activated carbon