Preparation and application of 3-bromo-4-hydroxy-5-nitropyridine_Industrial additives

Preparation and application background and overview of 3-bromo-4-hydroxy-5-nitropyridine

3-Bromo-4-hydroxy-5-nitropyridine can be used as a pharmaceutical synthesis intermediate. It can be prepared by reacting 3-nitropyridin-4-ol as a raw material with acetic acid and bromine. It can be used to prepare other An intermediate: 3-bromo-Ndifluorophenylboronic acid-cyclopropyl-5-nitropyridin-4-amine.

Preparation and application of 3-bromo-4-hydroxy-5-nitropyridine

To a solution of 3-nitropyridin-4-ol (20g, 142.76mmol, 1eq.) in 50% aqueous acetic acid (250mL), bromine (113g, 713mmol, 5eq.) was added dropwise, and the resulting The mixture was stirred at room temperature for 20 hours, and the resulting precipitate was filtered and washed with water to obtain 25 g of the intermediate 3-bromo-4-hydroxy-5-nitropyridine.

Preparation and application of 3-bromo-4-hydroxy-5-nitropyridine

3-Bromo-4-hydroxy-5-nitropyridine can be used to prepare the compound 3-bromo-N-cyclopropyl-5-nitropyridin-4-amine: at room temperature, to 3-bromo-4 To a suspension of -hydroxy-5-nitropyridine (25 g, 114.16 mol) in toluene (50 mL) was added POCl₃ (50 mL). The mixture was slowly heated to 100°C and stirred at 100°C overnight. The mixture was cooled to room temperature and concentrated. Ice water was carefully added to the resulting residue, and the resulting mixture was extracted with ethyl acetate. The organic layer was separated, washed with water and brine, dried with anhydrous Na₂SO₄ and evaporated to obtain 25g of intermediate benzylpyridine 3- Bromo-4-chloro-5-nitropyridine. To a solution of the intermediate 3-bromo-4-chloro-5-nitropyridine (25 g, 105.29 mmol, 1 eq.) in ethanol (250 mL) was added cyclopropylamine (9.02 g, 157.93 mmol, 1.5 eq.). The solution was warmed to 80°C for 4 hours. The solvent was evaporated and water added. The resulting mixture was extracted with dichloromethane (3×50 mL). The organic layer was washed with brine, dried over MgSO₄ and concentrated. 26 g of 3-bromo-N-cyclopropyl-5-nitropyridin-4-amine were obtained.

References

[1]CN104507916 – 4-substituted 1,3-dihydro-2H-benzimidazole-2-one derivatives substituted with benzimidazole as an antiviral agent for respiratory syncytial virus