2-Amino-3-hydroxy-5-chloropyridine

A suspension of 6-chlorooxazolo[4, 5-b]pyridin-2(3H)-one (6.Og, 35.3mmol) in 10percent NaOH solution (200mL) was stirred at 130 00 for 16h. TLC showed the reaction to be complete. The reaction mixture was cooled to rt , neutralized with 6.0 N HCI and extracted with EtOAc (3x200mL). The organic layer was washed with brine (200mL), dried (Na2SO4), filtered and concentrated under reduced pressure to afford 2-amino-5-chloropyridin-3-ol as a brown solid. Yield: 4.Og (80percent); 1H NMR (400 MHz, DMSO-d6): 10.03 (bs, 1H), 7.41 (d, J= 2.1 Hz, 1H), 6.82 (d, J= 2.1 Hz, 1H), 5.68 (bs, 2H); MS (ESl+) for CHNOS m/z 145.13 [M+H].General procedure: 59.7 g of 5-chloro-3[(2, 6-difluorobenzyl)oxy] -2-nitropyridine (Example 13A; 199 mmol, 1 equivalent) were initially charged in 600 ml of ethanol, 34.4 g of iron powder (616 mmol, 3.1 equivalents) were added and the mixture was heated to the boil. 152 ml of concentrated hydrochloric acid were slowly added dropwise, and the mixture was heated at reflux for a thrther 30 mm. The reaction mixture was cooled and stirred into an ice/water mixture. The resulting mixture was adjusted to pH 5 using sodium acetate, the crystals were filtered oil with suction and air-dried and then dried under reduced pressure at 500 C. 52.7 g (98percent of theory) of the title compound were obtained.General procedure: Example 11A 2-Amino-5-fluoropyridin-3-ol 5.6 g of 5-fluoro-2-nitropyridin-3-ol (Example 10A; 36 mmol) were dissolved in 2 l of ethanol, a catalytic amount of palladium on activated carbon (10percent) was added and the mixture was hydrogenated under hydrogen standard pressure for 16 h. The mixture was filtered off through kieselguhr and the filtrate was concentrated (product batch 1). The residue was rinsed with methanol until the colour of the filtrate was no longer yellowish. The filtrate was concentrated, giving a second product batch. This gave a total of 4.26 g (85percent of theory) of the title compound.To a stirred solution of 4 (1.45 g, 10.0 mmol) , cesium carbonate (6.52 g, 20.0 mmol) in acetone (50 mL) was added 259 (3.24 g, 20 mmol) . The resulting mixture was refluxed for overnight. After cooling, the reaction mixture was poured into brine and extracted with ethyl acetate. The combined organic layers were dried by anhydrous sodium sulfate and concentrated in vacuum. The residue was purified by column chromatography to give the desired product as yellow solid (1.65 g, 61%) .General procedure: To the solvent of acetone (30 mL) was added 7 (1.86g, 6.18mmol) , 4 (896mg, 6.18mmol) and CsCO3(2.619g, 8.03mmol) . The resulting mixture was heated to 60and refluxed for 16h. The reaction mixture was concentrated in vacuo, purified by column chromatography and dried in vacuo to give yellow solid 8 (810mg, 37.5%) .To the solvent of acetone (30 mL) was added 7 (1.86g, 6.18mmol) , 4 (896mg, 6.18mmol) and CsCO3(2.619g, 8.03mmol) . The resulting mixture was heated to 60and refluxed for 16h. The reaction mixture was concentrated in vacuo, purified by column chromatography and dried in vacuo to give yellow solid 8 (810mg, 37.5%) .

Molecular Weight:144.56
XLogP3:0.8
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Exact Mass:144.0090405
Monoisotopic Mass:144.0090405
Topological Polar Surface Area:59.1
Heavy Atom Count:9
Complexity:101
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes