4-Amino-2-chloro-3-nitropyridine

Yellow solid

2-ChloiO-4-nitroaminopyridine (10.0 g, mol) was carefully dissolved in 100 mL of concentrated sulfuric acid at room temperature and heated 100 3b) [1208] A solution of L-1 (20.00 g, 103.64 mmol, 1.00 eq) in ethanolic NH3 (600 ml of absolute ethanol saturated at 5°C with dry NH3) was stirred at rt for 7h. Then, the reaction solution was concentrated in vacuum to get a residue. The residue was triturated with boiling chloroform (120 ml). The resulting insoluble solid was filtered and dried in vacuum. Crystallization of this material from EA (200 ml) gave L-2 (7.20 g, 41.62 mmol, 40percent yield) as a brown solid.Potassium nitrate (7.86 g, 0.0784 mol) was added portionwise to 2-chloro-4-aminopyridine (10.00 g, 0.078 mol) in concentrated sulfuric acid (80 mL) at 0 ° C, and the reaction was continued at 0 ° C for 1 hour. After completion, the reaction solution was poured into crushed ice, concentrated aqueous ammonia was added to adjust the pH to 3, stirred for 15 minutes, filtered, and a solid was collected. Add solid to concentrated sulfuric acid (80mL), heat to 80 ° C for 5 hours, cool, pour the reaction solution into crushed ice, add concentrated ammonia to adjust the pH to 3, stir for 15 minutes, filter, collect solids, through silica gel column Chromatographic purification, Elution with ethyl acetate/petroleum gradient (10-20percent) gave product ( 6.00 g, 44percent).In a reactor with a stirring, thermometer, and reflux system, Add 60 kg of tetrahydrofuran, 7.5 kg (107 mol) of 3-aminopropionitrile, 17.5 kg (100 mol) of trichloronitroethylene, 0.1 kg of DBU, The reaction was stirred at 50-55 C for 4 hours and then cooled to 30-40 C.30.5 kg (220 mol) of potassium carbonate was added, and the reaction was stirred at 55-60 C for 3 hours.It was then cooled to 20-25 C, filtered, and the filter cake was washed with 20 kg of tetrahydrofuran.The filtrate was combined, the solvent was distilled off, and 45 kg of isopropanol was added to the residue.0.5 kg of activated carbon, decolorized at 55-60 C for 1 hour, filtered while hot, recrystallized, Filtered, dried, Obtained 16.2 kg of pale yellow solid To a solution of the pyridine 3 (300 mg, 1.73 mmol) [51] in absolute ethanol (10 mL) were added triethylamine (0.5 mL, 3.58 mmol) and the aniline 6 (500 mg, 1.99 mmol) [45] and the mixture was heated at reflux for 8 h. The solvent was vacuum evaporated, water was added to the residue and the precipitate was filtered, washed with water, dried and purified using silica gel column chromatography (dichloromethane) to give pure 7 (440 mg, 65%). M.p. =159-160 C (EtOAc/n-hexane). 1H NMR (400 MHz, DMSO-d6) delta 10.39 (s, 1H, NH), 8.20 (s, 2H, NH2), 7.91 (d, J = 2.4 Hz, 1H, H-20), 7.69 (d, J = 5.9 Hz, 1H, H-6), 7.46 (m, 2H, H-60 , H-500), 7.30 (m, 2H, H-200 , H-600), 7.17 (m, 2H, H-50 , H-400), 6. 30 (d, J = 5.9 Hz, 1H, H-5), 5.22 (s, 2H, CH2). 13C NMR (151 MHz, DMSO-d6) delta 162.99, 161.37 (C-300), 153.04 (C-2), 151.53 (C-4), 149.88 (C-6), 149.58 (C-40), 139.71, 139.66 (C-100), 133.10 (C-10), 130.55, 130.49 (C-500), 124.30 (C-20), 123.26 (C-600), 122.50 (C-60), 121.05 (C-30), 116.50 (C-3), 114.71, 114.57 (C-400), 114.27 (C-50), 114.03, 113.89 (C-200), 103.77 (C-5), 69.35 (CH2).

Molecular Weight:173.56
XLogP3:1.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Exact Mass:172.9992041
Monoisotopic Mass:172.9992041
Topological Polar Surface Area:84.7
Heavy Atom Count:11
Complexity:160
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes