6-Bromo-5-chloro-2-pyridinamine

To a stirred solution of compound LXIII (20 g; 115.54 mmol) in acetonitrile (360m1) was added N-chlorosuccinimide (17 g, 127.0 mmol) portionwise at 0°C. The resultant solution was stirred at 90°C for 18 h. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with brine solution and dried over anhydrous Na2504, filtered and evaporated under reduced pressure to obtain the crude compound, which was purified by column chromatography using 18percent ethyl acetate in hexane to afford 6-bromo-5- chloropyridin-2-amine as off white solid (LXIV; 18 g; 75percent yield). ‘H NMR (400 MHz, CDC13) 6 7.42-7.40 (d, J =8.8 Hz, 1H), 6.38-6.36 (d, J =8.8 Hz, 1H), 4.63 (bs, 2H). MS (M+1): 206.92 (LCMS Purity 96percent).6-bromo-5-chloropyridin-2-amine [00403] A solution of 2-amino-6-bromopyridine (1000 mg, 5.78 mmol) and Nchlorosuccinimide (771 mg, 5.78 mmol) in ACN (23 mL) was heated for 18 h at 80 °C. The cooled mixture was diluted with EtOAc (70 mL) and sat. NaHCO3 (30 mL). The aqueous layer was extracted with EtOAc (3x3OmL), the combined organic layers were washed with brine (20 mL), dried (MgSO4), and concentrated under reduce pressure. The residue was purified by Si02 chroamatography (Hex/EtOAc 0 to 50percent gradient), affording the title compound (890 mg, 4.29 mmol, 74percent) as a white solid.The title compound was prepared analogous to the literature procedure (W02015/97122). Asolution of 6-bromopyridin-2-amine (20.0 g, 115.60 minol) and N-chlorosuccinimide (15.43 g, 115.60 minol) in acetonitrile (250 mL) was heated at 80°C for 16 h. Reaction mixture was cooled, concentrated under reduced pressure. The residue was diluted with sat. NaHCO3 solution (100 mL) and extracted with EtOAc thrice. The combined organic portion was washed with brine, dried over anhydrous Na2SO4, and concentrated under reduce pressure. The crudeproduct mass was stirred with hexane, the solid separated was collected by filtration and dried in vacuo to yield the title compound as an off white solid (16.0 g, 61percent). LC/MS, ESl-MS():210.9.A stirring solution of 6-bromo-2-pyridinamine (15 g, 87 mmol, Sigma- Aldrich, St. Louis, MO), acetonitrile (170 mL), and N-chlorosuccinimide (14 g, 100 mmol) was heated at reflux under a nitrogen atmosphere. After 18 h, the reaction mixture was concentrated and the residue was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The layers were separated, and the organic layer was washed sequentially with saturated aqueous sodium bicarbonate and brine, dried (sodium sulfate), and filtered. Silica gel (45 g) was added to the filtrate, and the volatiles were removed under a vacuum. The residue was subjected to flash chromatography on silica gel (gradient elution; 6: 1 to 4: 1 hexane-ethyl acetate). The isolated material was dissolved with dichloromethane, silica gel (25 g) was added to the solution, and the volatiles were removed under a vacuum. The residue was subjected to flash chromatography on silica gel (2: 1 dichloromethane-pentane) to give 6-bromo-5- chloro-2-pyridinamine (9.8 g) as a colorless solid.Stepf: 6-Bromo-5-chloropyridin-2-amine; To a solution of methyl 6-bromo-5-chloropyridin-2-ylcarbamate (1.1 g, 4.1 mmol) in methanol (50 mL) was added KOH (700 mg, 13 mmol) at room temperature. The mixture was heated at reflux for 2 hr. The reaction mixture was diluted with water and extracted with ethyl acetate (20 mL x 3). The combined organic layers were dried over anhydrous Na

Molecular Weight:207.45
XLogP3:2.2
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