6-Bromo-2-nitro-pyridin-3-ol

3-Hydroxy-2-nitropyridine (20 g, 0.143 mole) was dissolved in methanol (400 mL) and a solution of 25percent sodium methoxide in methanol (33 mL, 0.13 mole) was added at room temperature. The mixture was stirred for 30 min, then was cooled to 0 Preparation 3; Preparation of 3-Oxo-3, 4-dihydro-2/-/-pyridoF3, 2-d1f 1 , 41oxazine-6-carboxaldehvde; (a) 2-Bromo-5-hydroxy-6-nitropyridine; 3-Hydroxy-2-nitropyridine (20 g, 0.143 mole) was dissolved in methanol (400 ml_) and a solution of 25percent sodium methoxide in methanol (33 ml_, 0.13 mole) was added at - room temperature. The mixture was stirred for 30 min, then was cooled to 0 Preparation 3; Preparation of 3-Oxo-3.4-dihydro-2H-pyrido[3, 2-biπ , 41oxazine-6-carboxaldehyde; a) 2-Bromo-5-hydroxy-6-nitropyridine; 3-Hydroxy-2-nitropyridine (20 g, 0.143 mole) was dissolved in methanol (400 ml_) and a solution of 25percent sodium methoxide in methanol (33 ml_, 0.13 mole) was added at room temperature. The mixture was stirred for 30 min, then was cooled to 0 3-Hydroxy-2-nitropyridine (20 g, 0.143 mole) was dissolved in methanol (400 mL) and a solution of 25percent sodium methoxide in methanol (33 mL, 0.13 mole) was added at room temperature. The mixture was stirred for 30 min, then was cooled to 0 3-Hydroxy-2-nitropyridine (20 g, 0.143 mole) was dissolved in methanol (400 mL) and a solution of 25percent sodium methoxide in methanol (33 mL, 0.13 mole) was added at room temperature. The mixture was stirred for 30 min, then was cooled to 0 °C, and EPO Preparation 3; Preparation of 3-Oxo-3, 4-dihydro-2H-pyrido[3, 2-b][1, 4]oxazine-6-carboxaldehyde; a) 2-Bromo-5-hydroxy-6-nitropyridine; 3-Hydroxy-2-nitropyridine (20 g, 0.143 mole) was dissolved in methanol (400 mL) and a solution of 25percent sodium methoxide in methanol (33 mL, 0.13 mole) was added at room temperature. The mixture was stirred for 30 min, then was cooled to 0° C., and bromine (7.2 mL, 0.14 mole) was added slowly. The reaction was stirred at 0° C. for 30 min, then was quenched with glacial AcOH (2.5 mL). The solvent was removed in vacuo to afford material (30 g, 96percent), which was used without further purification. MS (ES) m/z219.0 (M+H)3-Hydroxy-2-nitropyridine (20 g, 0.143 mole) was dissolved in methanol (400 ml) and a solution of 25percent sodium methoxide in methanol (33 ml, 0.13 mol) was added at room temperature. The mixture was stirred for 30 minutes, then cooled to 0 °C, and bromine (7.2 ml, 0.14 mol) was added slowly. The reaction was then stirred at 0 °C for 30 minutes, then was quenched with glacial AcOH (2.5 ml). The solvent was removed in vacuo to afford material (30 g, 96percent), which was used without further purification. MS (+ve ion electrospray) m/z 219 (MH+).3-Hydroxy-2-nitropyridine (20 g, 0.143 mole) was dissolved in methanol (400 [ML)] and a solution of 25percent sodium methoxide in methanol (33 mL, 0.13 mole) was added at room temperature. The mixture was stirred for 30 min, then was cooled to [0 °C, ] and bromine (7. [2] mL, 0.14 mole) was added slowly. The reaction was then stirred at [0 °C] for 30 min, then was quenched with glacial [ACOH] (2.5 mL). The solvent was removed in vacuo to afford material (30 g, 96percent), which was used without further purification. MS (ES) [NIEZ 219.] 0 [(M + H)] +.3-Hydroxy-2-nitropyridine (20 g, 0.143 mol) was dissolved in methanol (400 mL) and a solution of 25percent sodium methoxide in methanol (33 mL, 0.13 mol) was added at room temperature. The mixture was stirred for 30 min, then was cooled to 0 degree;C, and bromine (7.2 mL, 0.14 mol) was added slowly. The reaction was then stirred at 0 degree;C for 30 min, then was quenched with glacial AcOH (2.5 mL). The solvent was removed in vacuo to afford material (30 g, 96percent), which was used without further purification. MS (ES) m/z 219.0 (M + H)+.3-Hydroxy-2-nitropyridine (20 g, 0.143 mole) was dissolved in methanol (400 ml) and a solution of 25percent sodium methoxide in methanol (33 ml, 0.13 mole) was added at room temperature. The mixture was stirred for 30 min, then was cooled to 0 °C, and bromine (7.2 ml, 0.14 mole) was added slowly. The reaction was then stirred at 0 °C for 30 min, then was quenched with glacial AcOH (2.5 ml). The solvent was removed in vacuo to afford material (30 g, 96percent), which was used without further purification. MS (ES) m/z 219.0 (M + H) +.Preparation 16; Preparation of 3-Oxo-3, 4-dihvdro-2/-/-pyridor3, 2-jb1H , 41oxazine-6-carboxaldehyde; a) 2-Bromo-5-hydroxy-6-nitropyridine; 3-Hydroxy-2-nitropyridine (20 g, 0.143 mole) was dissolved in methanol (400 mL) and a solution of 25percent sodium methoxide in methanol (33 mL, 0.13 mole) was added at room temperature. The mixture was stirred for 30 min, then was cooled to 0 °C, and bromine (7.2 mL, 0.14 mole) was added slowly. The reaction was stirred at 0 0C for 30 min, then was quenched with glacial AcOH (2.5 ml_). The solvent was removed in vacuo to afford material (30 g, 96percent), which was used without further purification. MS (ES) m/z 219.0 (M + H)+.Preparation 10; Preparation of 3-Oxo-3.4-dihvdro-2H-pvrido[3.2-foiri , 41oxazine-6-carboxalde; a) 2-Bromo-5-hydroxy-6-nitropyridine; 3-Hydroxy-2-nitropyridine (20 g, 0.143 mole) was dissolved in methanol (400 ml)and a solution of 25percent sodium methoxide in methanol (33 mL, 0.13 mole) was added atroom temperature. The mixture was stirred for 30 min, then was cooled to 0 °C, andbromine (7.2 mL, 0.14 mole) was added slowly. The reaction was stirred at 0 °C for 30mm, irien was quenuneu wiui yiauitil AcOH (2.5 mL). The solvent was removed in vacuato afford material (30 g, 96percent), which was used without further purification.MS(ES)m/z219.0(M + H)+.; Preparation 11; Preparation of 7-chloro-3-oxo-3, 4-dihydro-2/-/-1.4-benzoxazine-6-carbaldehyde; a) 2-Bromo-5-hydroxy-6-nitropyridine; 3-Hydroxy-2-nitropyridine (20 g, 0.143 mole) was dissolved in methanol (400 ml)and a solution of 25percent sodium methoxide in methanol (33 mL, 0.13 mole) was added atroom temperature. The mixture was stirred for 30 min, then was cooled to 0 °C, andbromine (7.2 mL, 0.14 mole) was added slowly. The reaction was stirred at 0 °C for 30min, then was quenched with glacial AcOH (2.5 mL). The solvent was removed in vacuato afford material (30 g, 96percent), which was used without further purification.MS(ES)m/z219.0(M + H)+.Preparation 5; Preparation of 3-Oxo-3.4-dihvdro-2H-pvridof3.2-/?in , 41oxazine-6-carboxaldehvde; (a) 2-Bromo-5-hydroxy-6-nitropyridine; 3-Hydroxy-2-nitropyridine (20 g, 0.143 mole) was dissolved in methanol (400 mL) and a solution of 25percent sodium methoxide in methanol (33 mL, 0.13 mole) was added at room temperature. The mixture was stirred for 30 min, then was cooled to 0 °C, and bromine (7.2 mL, 0.14 mole) was added slowly. The reaction was stirred at 0 °C for 30 min, then was quenched with glacial AcOH (2.5 mL). The solvent was removed in vacuo to afford material (30 g, 96percent), which was used without further purification: MS (ES) m/z 219.0 (M + H)a) 2-Bromo-5-hydroxy-6-nitropyridine3-Hydroxy-2-nitropyridine (20 g, 0.143 mole) was dissolved in methanol (400 mL) and a solution of 25percent sodium methoxide in methanol (33 mL, 0.13 mole) was added at room temperature. The mixture was stirred for 30 min, then was cooled to 0 0C, and bromine (7.2 mL, 0.14 mole) was added slowly. The reaction was stirred at 0 0C for 30 min, then was quenched with glacial AcOH (2.5 mL). The solvent was removed in vacuo to afford material (30 g, 96percent), which was used without further purification. MS (ES) m/z219.0 (M + H)+.3-Hydroxy-2-nitropyridine (20 g, 0.143 mole) was dissolved in methanol (400 ml_) and a solution of 25percent sodium methoxide in methanol (33 mL, 0.13 mole) was added at room temperature. The mixture was stirred for 30 min, then was cooled to 0 0C, and bromine (7.2 mL, 0.14 mole) was added slowly. The reaction was stirred at 0 0C for 30 min, then was quenched with glacial AcOH (2.5 mL). The solvent was removed in vacuo to afford material (30 g, 96percent), which was used without further purification. MS (ES) m/z219.0 (M + H)+.3-Hydroxy-2-nitropyridine (20 g, 0.143 mole) was dissolved in methanol (400 mL) and a solution of 25percent sodium methoxide in methanol (33 mL, 0.13 mole) was added at room temperature. The mixture was stirred for 30 min, and then was cooled to 0 3-Hydroxy-2-nitropyridine (50 g, 357 mmol) was dissolved in 900 mL of N, N-dimethylformamide. N-bromosuccinimide (82.57 g, 464 mmol) was slowly added thereto and stirred at room temperature for 12 hours. After the reaction was completed, the solution was concentrated using a rotary evaporator, and then extracted twice with distilled water and dichloromethane.The precipitate was formed using methyl alcohol and distilled water and filtered to obtain a mixture of compound 1 and dibrominated compound (67.5 g, Y = 86.4percent) in an 8: 2 ratio.(Synthesis of Compounds I-113 and 1-144) [Show Image]Step 1 A solution of 2-nitropyridin-3-ol (6) (16.0 g, 114 mmol) in dimethylformamide (120 mL) was cooled to 0°C, and then N-bromosuccinimide (26.4 g, 1.48 mmol) was gradually added thereto. The solution was then stirred at 0 °C for 1 hour, and at room temperature for another 2 hours. The reaction solution was concentrated in vacuo, and then the residue was washed with diethyl ether. The filtrate was poured to aqueous saturated sodium bicarbonate, followed by extraction with diethyl ether. The organic layer was washed sequentially with water and saturated brine, then dried with anhydrous magnesium sulfate, and concentrated in vacuo to yield the subject compound (7) (15.5 g, 62percent) as a white powder.A solution of 3-hydroxy-2-nitropyridine (176.0 g, 1.256 mol) in aqueous sodiumhydroxide (74.0 mL of 50percent NaOH in 1.94 L water, 1.40 mol) was cooled at 3.3 °C whiledibromantin (198.5 g, 0.694 mol) was added portion-wise over 58 minutes maintaining reaction temperature at or below 4 °C. The reaction mixture was then allowed to warm to room temperature overnight. The reaction was quenched with acetic acid (80.0 mL, 1.34 mol), and the resulting slurry was stirred at room temperature for 4 h. The solids werecollected by filtration, washed with water (3 x 300 mL), and then vacuum-dried (35°C) overnight to give 148.3 g (54percent) of 2-bromo-5-hydroxy-6-nitropyridine as a yellow solid with a purity of 97.8percent (LC).A solution of 2-nitropyridin-3-ol (15 g, 104 mmol) in DMF (189 mL) was cooled to 0°C then N- bromosuccinimide (24 g, 135 mmol) was added gradually over 25 minutes. The solution was stirred at 0°C for an additional 15 minutes and then the mixture was allowed to warm to RT, and stirred over night. The reaction mixture was concentrated in vacuo and purified by column chromatography using 100percent CHCompound I-1 (5 g, 35.7 mmol) was added to a clean and dry reaction flask, Dissolved in 50 mL of methanol, After replacing the nitrogen three times, Sodium methoxide (2.89 g, 53.5 mmol)In methanol (15 mL) was added dropwise to the reaction system, The reaction was stirred at room temperature for 30 min.The reaction was then cooled to 0 ° C, Bromine (6.3 g, 39.4 mmol) was added dropwise, The temperature of the reaction system was controlled at 0-5 ° CUnder the conditions of reaction 4h;(CH2Cl2: CH3OH = 25: 1), the reaction was quenched with a small amount of 10percent aqueous sodium sulfite solution, the reaction system was cooled to -15C, and the yellow solid was stirred, After filtration, the filter cake was washed with ice methanol (2 x 5 mL), dried, A yellow solid was the target product I-2 (4.2 g, 53percent).Under an atmosphere of nitrogen, a solution of CH3ONa (2.89 g, 53.5 mmol) in CH3OH (15 mL) was added dropwise to a solution of2-nitropyridin-3-ol (16) (5 g, 35.7 mmol) in CH3OH (50 mL) and themixture was stirred at RT for 30 min. After the reaction systemcooling to 0 C, Br2 (6.3 g, 39.4 mmol) was added dropwise withstirring. After 16 was consumed, the mixture was quenched byadding a solution of 10percent Na2SO3 and then cooled to 15 C. Yellowsolid was precipitated, filtered and washed with cold CH3OH. Thetitle compound was obtained as a yellow solid (4.2 g, 53percent). 1H NMR(400 MHz, DMSO) d 7.85 (d, J 8.64 Hz, 1H), 7.66 (d, J 8.64 Hz, 1H); MS (M H): m/z 216.97.At 0 °C, BrTo a solution of A-25 (10 g, 71.38 mmol) in methanol (200 mL) was added CH

Molecular Weight:218.99
XLogP3:2.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Exact Mass:217.93270
Monoisotopic Mass:217.93270
Topological Polar Surface Area:78.9
Heavy Atom Count:11
Complexity:160
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes