2,5-Dichloro-3-nitropyridine

Light yellow crystalline powder

5-Chloro-3-nitro-2-pyridinamine (5.0 g, 28.8 mmol) was dissolved in cone. HCI (50 mL) and cooled to -10 5-chloro-3-nitropyridine-2-amine 10.0g of (57.6 mmol) was dissolved in concentrated hydrochloric acid 100 mL, and stirred at -10 ° C.. Here, sodium nitrite 9.94g of (144 mmol) Yuki dropwise over 30 minutes a liquid obtained by dissolving water 20 mL, after the addition, the mixture was stirred 1 hour at 0 ° C.. By adding 1N aqueous sodium hydroxide solution to the reaction solution and pH 9, and extracted with ethyl acetate. Insolubles were removed by filtration, the organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. Filtered and the filtrate was evaporated under reduced pressure to give the title compound 6.50g of (58.5percent yield) as a solid.5-chloro-3-nitropyridine-2-amine 10.0g of (57.6 mmol) was dissolved in concentrated hydrochloric acid 100 mL, and stirred at -10 ° C.. Here, sodium nitrite 9.94g of (144 mmol) add dropwise over 30 minutes a liquid obtained by dissolving water 20 mL, after the addition, the mixture was stirred 1 hour at 0 ° C.. By adding 1N aqueous sodium hydroxide solution to the reaction solution and pH 9, and extracted with ethyl acetate. Insolubles were removed by filtration, the organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. Filtered and the filtrate was evaporated under reduced pressure to give the title compound 6.50g of (58.5percent yield) as a solid.(Step 1) (+/-)-9-[Acetyl-(3, 5-bis-trifluoromethylbenzyl)amino]-3-chloro-2-methoxy-6, 7, 8, 9- tetrahydro-pyrido[3, 2-b]azepine-5-carboxylic acid isopropyl ester; Step 1;. Preparation of 5-Chloro-3-nitro-pyridine-2-carbonitrile; Add 3-nitro-5-chloro-pyridin-2-ol (3.9 g, 22.3 mmol) to a mixture of phosphorous oxychloride (4.17 mL) and dimethylformamide (10 mL). Heat the resulting mixture at 110 C for 30 min. Cool the reaction mixture to room temperature and pour onto ice- water. Add sodium bicarbonate slowly until neutralization occurs and extract with ethyl acetate. Dry the organic layer over anhydrous sodium sulfate, filter, and remove the solvent under reduced pressure. Dissolve the residue in N-methyl pyrrolidinone (4 mL), add copper (I) cyanide (2.39 g, 26.7 mmol) and heat at 160 C for 15 min. Cool the reaction mixture to room temperature and pour onto ice water and ethyl acet ate. Add a saturated solution of sodium bicarbonate, separate the organic layer, and extract the aqueous layer with ethyl acetate. Dry the combined organic layers over sodium sulfate, filter, and concentrate under reduced pressure. Purify the residue using silica gel chromatography, eluting with ethyl acetate/hexanes 1: 3 to afford the title cornpound (1.01 g, 26%). H-NMR (CDC13, 300 MHz) : No. 8.61 (s, 1H), 8.95 (s, 1H).5-Chloro-3-nitro-2-pyridinamine (5.0 g, 28.8 mmol) was dissolved in cone. HCI (50 mL) and cooled to -10 0C in an ice-salt bath. Sodium nitrite (4.97 g, 72 mmol) in water (10 mL) was added dropwise to the cooled solution over 1 h and stirred at 0 C for 1 h longer. The reaction mixture was cooled to -10 0C in an ice-salt bath and neutralized with 2N sodium hydroxide to pH 9.0 keeping the temperature below 0 0C. EtOAc (150 mL) was added and the mixture was filtered. The organic layer was separated, dried over sodium sulfate and concentrated in vacuo to afford the title compound as 3.36 g (60% yield) of a light brown solid; 1H NMR (cfe-DMSO) delta 8.62 (d, 1 H, 2.5 Hz), 8.26 (d, 1 H, 2.2 Hz).5-chloro-3-nitropyridine-2-amine 10.0g of (57.6 mmol) was dissolved in concentrated hydrochloric acid 100 mL, and stirred at -10 C.. Here, sodium nitrite 9.94g of (144 mmol) Yuki dropwise over 30 minutes a liquid obtained by dissolving water 20 mL, after the addition, the mixture was stirred 1 hour at 0 C.. By adding 1N aqueous sodium hydroxide solution to the reaction solution and pH 9, and extracted with ethyl acetate. Insolubles were removed by filtration, the organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. Filtered and the filtrate was evaporated under reduced pressure to give the title compound 6.50g of (58.5% yield) as a solid.5-chloro-3-nitropyridine-2-amine 10.0g of (57.6 mmol) was dissolved in concentrated hydrochloric acid 100 mL, and stirred at -10 C.. Here, sodium nitrite 9.94g of (144 mmol) add dropwise over 30 minutes a liquid obtained by dissolving water 20 mL, after the addition, the mixture was stirred 1 hour at 0 C.. By adding 1N aqueous sodium hydroxide solution to the reaction solution and pH 9, and extracted with ethyl acetate. Insolubles were removed by filtration, the organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. Filtered and the filtrate was evaporated under reduced pressure to give the title compound 6.50g of (58.5% yield) as a solid.(Step 1) 2, 5-Dichloro-3-nitropyridine 5-Chloro-3-nitropyridin-2-amine (10.0 g, 57.6 mmol) was dissolved in concentrated hydrochloric acid (100 mL), and the solution was stirred at -10C. A solution of sodium nitrite (9.94 g, 144 mmol) dissolved in water (20 mL) was added dropwise thereto over 30 minutes. After the completion of the addition, the mixture was stirred at 0C for 1 hour. The pH of the reaction solution was adjusted to 9 by the addition of a 1 N aqueous sodium hydroxide solution, followed by extraction with ethyl acetate. Insoluble matter was removed by filtration, and the organic layer was washed with saturated saline and then dried over anhydrous magnesium sulfate. After filtration, the solvent in the filtrate was distilled off under reduced pressure to obtain the title compound (6.50 g, yield: 58.5%) as a solid. 1H-NMR (CDCl3) delta: 8.60 (1H, d, J = 2.9 Hz), 8.24 (1H, d, J = 2.6 Hz).Preparation of Compound 14A ; To a stirred solution of tert-butyl nitrite (55.2 ml, 466 mmol) and anhydrous Cu(II)Cl2 (50.0 g, 372 mmol) in CH3CN (500 mL), maintained at 70 C., was added

Molecular Weight:192.98
XLogP3:2.3
Hydrogen Bond Acceptor Count:3
Exact Mass:191.9493327
Monoisotopic Mass:191.9493327
Topological Polar Surface Area:58.7
Heavy Atom Count:11
Complexity:161
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes