Report background and overview of several preparation methods of 5-amino-2-bromopyridine
5-Amino-2-bromopyridine Also called 6-bromopyridin-3-amine, it can be obtained by reducing the nitro group of 2-bromo-5-nitropyridine. The reducing agent can be selected from iron powder; 6-bromo Pyridin-3-amine can also be obtained by bromination of 3-aminopyridine.
Several preparation methods of 5-amino-2-bromopyridine reported
Report on several preparation methods of 5-amino-2-bromopyridine 1.
To a mixture of 2-bromo-5-nitropyridine (502 mg, 2.47 mmol) in EtOH/THF/H2O/NH4Cl (saturated) (5.0 mL, 4:4:1:1 v/v) was added Fe powder (1.40g, 25.1mmol) and the mixture was heated to 80°C overnight. The reaction mixture was filtered through a small pad of Celite/MgSO4 mixture (1:1) using EtOAc. The crude product was concentrated and purified by ISCO (SiO2, 0-50% ethyl acetate in hexanes) to give the product as a brown solid (411 mg, 96.1% yield).
1H NMR (MHz, CDCl3 tetrahydrofuran) δ7.84 (dd, J＝3.1, 0.5Hz, 1H), 7.21 (dd, J＝8.5, 0.6Hz, 1H), 6.87 (dd, J＝8.5, 3.1 Hz,1H),3.73(br s,2H). 13C NMR (101MHz, C difluorophenylboronic acid DCl3) δ 142.1, 137.1, 129.6, 127.8, 124.7. LCMS: m/z [M+2H]+ = 175.2, RT = 0.92 minutes. HPLC conditions: Column: XBridge C18, 3.5 μm, 4.6 × 30 mm; Gradient: 5% B in 0.2 minutes; 5% to 100% B in 1.8 minutes; 100% B in 1 minute; 3 mL/minute. Eluent A: Milli-Q H2O+10mM ammonium formate pH: 3.8; Eluent B: acetonitrile.
Report 2 on several preparation methods of 5-amino-2-bromopyridine,
To a solution of 2-bromo-5-nitropyridine (2.03g, 10mmol) in ethanol (48mL), add iron powder (2.8g, 50mmol), concentrated hydrochloric acid (1.9mL), and water (9.1mL) in sequence. The system was reacted under reflux for 5 hours, cooled, and filtered. The filtrate was concentrated and adjusted to pH ≈ 7-8. It was extracted with dichloromethane, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 1.58 g of a reddish-brown solid with a yield of 91.3%.
Report 3 on several preparation methods of 5-amino-2-bromopyridine,
Add acetonitrile (250ml) and 3-aminopyridine (20g, 0.212mol) to the reaction flask in sequence, and stir to dissolve. Slowly add N-bromosuccinimide (38g, 0.212mol) under ice bath conditions, stir for 15 minutes, remove the ice bath, and react overnight at room temperature in the dark. Spin off the solvent under reduced pressure, dissolve the concentrate with ethyl acetate and water, filter the insoluble matter and extract and separate the liquids. After washing the organic phase with water and brine, add anhydrous sodium sulfate and dry. Filter, spin off the solvent, and pass through the column to obtain compound 11, an orange solid, 7.4 g, yield 20.2%. 1HNMR (Hz, CDCl3): δ (ppm) 7.86-7.87 (1H, d), 7.21-7.22 (1H, d), 6.87-6.90 (1H, m).
References
[1] [Invented in China] CN201780041926.7 compound and its use for reducing uric acid levels
[2] [Invented in China] CN201010132837.3 Heterocyclic imidazole phospholipid kinase inhibitor
[3] [China invention, China invention authorization] CN201380039519.4 Bicyclic substituted pyrimidine compounds
