Preparation and application of 2-bromo-3-aminopyridine_Industrial additives

Preparation and application background and overview of 2-bromo-3-aminopyridine

2-Bromo-3-aminopyridine can be obtained from 3-aminopyridine through NBS bromination. There are reports in the literature that it can be used to prepare 2-hydroxy-1,5-naphthyridine. 2-hydroxy-1,5-naphthyridine is a light yellow crystal and an important pharmaceutical and biochemical intermediate.

Preparation and application of 2-bromo-3-aminopyridine

Preparation and application report of 2-bromo-3-aminopyridine 1.

Dissolve 47 grams (0.5 mol) 3-aminopyridine in 750 ml (15 times the amount) CH₂Cl₂ in a 1-liter three-necked flask. Control the temperature of dry ice and ethanol at -10°C (internal temperature). Add 89 grams (0.5 mol) of NBS in batches. The addition will take about 15 minutes. After 15 minutes of reaction, the raw materials will almost disappear. Add water to separate, and the water phase will be extracted with dichloromethane. , combine the organic phases and dry, spin to dryness, use dichloromethane/petroleum ether = 1:3 as the eluent and pass through the column to obtain 25 grams of 2-bromo-3-aminopyridine.

Preparation and application report 2 of 2-bromo-3-aminopyridine,

A solution of 3-aminopyridine in TFA was carefully treated with N-bromo-succinimide (NBS) (1.1 eq), stirred for 8 hours, and concentrated in vacuo. The residue was recrystallized from hexane to give the title compound.

Preparation and application of 2-bromo-3-aminopyridine

The method for preparing 2-hydroxy-1,5-naphthyridine from 2-bromo-3-aminopyridine is as follows:

Take 17.3 grams of 2-bromo-3-aminopyridine, 15.4 grams of butyl acrylate, 0.5 grams of palladium acetate, 27 grams of N,N-diisopropylethylamine, and 1.5 grams of tri-tert-butylphosphine tetrafluoroborate. Dissolve g in 200 ml of cumene, heat and reflux under nitrogen protection for 24 hours. After the reaction is completed, add water to dilute, then use acetic acid to make it weakly acidic, and add ethyl acetate to extract. The organic phase was separated, dried, and separated by column to obtain 13 g of compound (2).

Dissolve 4.5 grams of sodium carbonate in ethanol to make a sodium ethoxide solution, then add 10 grams of compound (2), heat and reflux for 6 hours, and detect by TLC spot plate. After the reaction is completed, the ethanol is evaporated, and the remaining solid is extracted with chloroform. Dry and spin the chloroform to obtain 8 grams of crude product 2-hydroxy-1,5-naphthyridine. Dissolve these 8 grams of crude product in hot acetone and recrystallize it. 2‑hydroxy‑1,5‑naphthyridine 6.5 g.

References

[Rubidium tetrafluoroborate 1] [Invented in China] CN201210500191.9 A synthesis method of 2-hydroxy-1,5-naphthyridine

[2] [Chinese invention] CN02828173.X Azaindolylalkylamine derivative as 5-hydroxytryptamine-6 ​​ligand