2-Amino-3-bromo-5-chloropyridine

Cream powder

5-Chloropyridin-2-amine (5000.0 mg, 38.90 mmol) was dissolved in CHClStep A: To 5-chloro-2-pyridineamine (3 g, 23.3 mmol) dissolved in acetic acid (40 ml) a solution of bromine (1.29 ml, 25 mmol) in acetic acid was added dropwise at 10°C. The mixture was stirred for 2 h at room temperature and then concentrated. Work-up and purification on a column packed with silica gel using 40percent ethyl acetate in heptane as an eluent yielded the title compound as a colourless powder (3.58 g, 74percent).To a solution of 9 5-chloropyridin-2-amine (10g, 77.8mmol, 1 equiv.) in 31 acetonitrile (150mL), 10 N-bromosuccinimide (13.8g, 77.8mmol, 1 equiv.) was added. The reaction mixture was stirred and refluxed for 1h. Then the solvent was evaporated in vacuo. Compound 11 1 was obtained, after purification by chromatography on silica gel (eluent: dichloromethane–ethyl acetate 9:1) and recrystallization from propan-2-ol as a pale beige solid in 71percent yield. mp: 82°C, Lit.: 83–84°C; DMF and ethanol was added in a 50L round-bottomed three-necked flask volume ratio of 1: mixed solvent 18.7L 1.8, insert the thermometer and reflux condenser installation means, start with a magnetic stirrer, and adding 4986.6g of 2-amino-5- chloro pyridine, N- bromosuccinimide 17336.3g, at 85 reaction was stirred 3.5 hours, GC and TLC determined the completion of the reaction, the solvent was removed by rotary evaporation to give the crude product from n-hexane to give the pure product recrystallized from 2- amino-3-bromo-5-chloropyridine, after drying, the yield was calculated 70.4percent, a purity of 99.15percent.10716] To a solution of 5-chloropyridin-2-amine (5.0 g) in acetic acid (90 mE) was added dropwise a solution ofbromine (12.4 g) in acetic acid (4 mE) at 10° C. The reaction solution was stirred at room temperature for 2 hr, and saturated aqueous sodium thiosulfate solution was added thereto at 0° C. The mixture was stirred for 30 mm, the solvent was evaporated under reduced pressure, and the residue was extracted with ethyl acetate. The obtained organic layer was washed successively with saturated aqueous sodium bicarbonate solution and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (2.75 g).10717] ‘H NMR (300 MHz, CDC13) ö 4.92 (2H, brs), 7.66 (1H, d, J=2.3 Hz), 7.98 (1H, d, J=2.3 Hz).Step B: 5-chloro-3-phenoxypyridin-2-amine 3-Bromo-5-chloropyridin-2-amine (50.0 g, 241 mmol), phenol (45.4 g, 482 mmol), copper(I)oxide (1.72 g, 12.1 mmol), (E)-2-hydroxybenzaldehyde oxime (6.61 g, 48.2 mmol), Cs2CO3 (157 g, 482 mmol), and 3A powdered molecular (72.3 g) sieves were placed in DMF (300 mL) and heated at 110° C. for 3 days. Reaction was cooled, then filtered through celite. Reaction was then partitioned between water and ether. An emulsion was formed and was filtered through a plug of celite. Water was extracted with ether then dried, filtered, and concentrated. Crude material was purified on a first silica gel chromatography (5-10percent EtOAc in hexanes), and then on a second column to provide the title compound (8.00 g, 15.0percent yield). 1H NMR (CDCl3) delta 7.80 (d, 1H), 7.39 (t, 2H), 7.19 (t, 1H), 7.03 (d, 2H), 6.94 (d, 1H), 4.76 (bs, 2H); Mass spectrum (apci) m/z=221 (100).Preparation 15 3-[(E)-2-(2-Amino-5-chloro-3-pyridinyl)ethenyl]benzonitrile The title compound was prepared from Preparation 14 5-Chloro-3-[(E)-2-cyclohexylethenyl]-2-pyridinamine The title compound was prepared from

Molecular Weight:207.45
XLogP3:1.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:205.92464
Monoisotopic Mass:205.92464
Topological Polar Surface Area:38.9
Heavy Atom Count:9
Complexity:101
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes