6-Bromo-5-methyl-2-pyridinamine

To a stirred solution of 2-bromo-3-methylpyridine-1-oxide (18g) and pyridine (3OmL) in acetonitrile (l8OmL) at about 71°C, was added a solution of methanesulfonic anhydride (33.31g) in acetonitrile (4OmL). The reaction mixture was stirred for about 90mm at about the same temperature and acetonitrile (3 OmL) was added to it. The reaction mixturewas cooled to about 10°C to about 15°C and ethanolamine (58.59g) was added to it. The reaction mixture was stirred for about 1 3h at about room temperature and water and ethyl acetate were added to it. The two layers were separated and the organic layer was washed with water and saturated brine solution, dried and concentrated under reduced pressure at about 45°C. The residue was purified by column chromatography (25-30 percent ethyl acetate in hexane). Yield: big (56percent)‘H NIVIR (300IVIHz, CDC13): ö 7.24-7.22 (d, J8.1 Hz, 1H), 6.39-6.36 (d, J=8.4 Hz, 1H), 4.27 (brs, 2H), 2.21 (s, 3H)IR: 3365, 3200, 2915, 1636, 1601, 1475, 1374, 1058, 820 cmMass [M+Hfb: 187.053.4 g of chloride IA was added to 10 ml of phosphorus tribromide and heated to 140 degrees.After 6 hours of reaction, the TLC reaction was complete, dropped to ambient temperature, and slowly added to crushed ice.Add 40percent sodium hydroxide to adjust the pH to 10, a large amount of solids are precipitated, filtered, and the filter cake is washed with 20 ml of water.The product IB 4g was obtained in a yield of 91percent.To a stirred solution of 2-bromo-3-methyl pyridine-1-oxide (25g) and pyridine (42g) in acetonitrile (250mL) at about 70°C, was added a solution of trifluoromethanesulfonic anhydride (55g) in acetonitrile (5OmL). The reaction mixture was stirred for about lh atabout the same temperature. The mixture was cooled to about 10°C to about 15°C and ethanolamine (80.52g) was added to it. The reaction mixture was stirred for about 3h at about room temperature and water and ethyl acetate were added to it. The two layers were separated and the organic layer was washed with saturated brine solution, dried and concentrated under reduced pressure at about 40°C. The residue was purified by columnchromatography (15-20percent ethyl acetate in hexane). Yield: 4g (16percent)‘H NIVIR (300IVIHz, CDC13): ö 7.26-7.24 (d, J8.lOHz, 1H), 6.42-6.39 (d, J8.4Hz, 1H), 4.28 (brs, 2H), 2.22 (s, 3H)‘3CNMR(400MHz, CDC13): 156.52, 141.56, 140.50, 122.99, 107.26, 20.58 IR: 3364, 3199, 2913, 1635, 1601, 1373, 1058, 819 cm4—Amino-2-bromo-3-methyl pyridine (3g) was obtained which was eluted at 25-30percent ethyl acetate in hexane.‘H NIVIR (300IVIHz, CDC13): ö 7.82-7.80 (d, J5.4Hz, 1H), 6.48-6.46 (d, J 5.4Hz, 1H), 4.35 (brs, 2H), 2.21 (s, 3H)‘3CNMR(400MHz, CDC13): 152.70, 146.94, 145.05, 116.88, 109.25, 15.73A mixture of 6-bromo 5-methyl pyridine N-oxide (1 .2 g) and Pyridine (2.06 mL) in acetonitrile (4.8 mL) was heated to 70°C and a solution of methane sulfonic anhydride (1 .667 g in 2.4 mL of acetonitrile) was added to it drop wise over a period of 20 minutes. The reaction mixture was stirred for 1 hour at 70°C and allowed to cool to 30°C. Ethanol amine (3.851 mL) was added drop wise over 10 minutes under nitrogen atmosphere at 30°C and stirred the reaction mixture for 15 hours at the same temperature. The reaction mixture was quenched with water (15 mL) and extracted with ethyl acetate (3 x 20 mL). The combined organic solution was dried over sodium sulfate and concentrated under reduced pressure to obtain crude product. The crude product was purified by column chromatography using 60-120 mesh and 20-30percent ethyl acetate / hexane as eluent to obtain 0.32 g of 6-bromo 5-methyl pyridin-2-amine with 93.41 percent purity by HPLC as a brown solid and 0.34 g of 2-bromo 3-methyl pyridin-4-amine with 97.94percent purity by HPLC as a brown solid.

Molecular Weight:187.04
XLogP3:1.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:185.97926
Monoisotopic Mass:185.97926
Topological Polar Surface Area:38.9
Heavy Atom Count:9
Complexity:97.1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes