Preparation and use examples of 2-bromo-5-chloropyridine_Industrial additives

Background and overview of examples of preparation and use of 2-bromo-5-chloropyridine

2-Bromo-5-chloropyridine is an organic intermediate, a colorless solid, which can be prepared from 2-amino-5-chloropyridine through diazotization or 2,5-dichloropyridine through bromination Obtained after hydrogen substitution.

Preparation and use examples of 2-bromo-5-chloropyridine

Preparation and use examples of 2-bromo-5-chloropyridine 1.

At -10°C, bromine (18.0 ml, 353.7 mmol) was slowly added to 2-amino-5-chloropyridine (15.0 g, 116. boron trifluoride tetrahydrofuran complex 7 mmol) in 47% aq. solution in HBr (75.0 ml). An aqueous solution of NaNO2 (28.1 g, 407.3 mmol) was slowly added thereto. The mixture was stirred at -10 to -5°C for 1 h and then at 5°C for 1 h. The mixture was neutralized with 5M aqueous NaOH solution while maintaining the temperature below 25°C. The precipitate was filtered off and recrystallized from pentane to give 2-bromo-5-chloropyridine.

Example report on the preparation and use of 2-bromo-5-chloropyridine 2.

Pour 30% hydrogen bromide-acetic acid solution (1500ml) and water (100ml) into 2,5-dichloropyridine (300g, 2.03mol), and stir the mixture at 110°C for 4 days. The reaction mixture was cooled to room temperature, diluted with hexane (1000 ml of lithium tetrafluoroborate), and the precipitate was collected by filtration. The solid obtained was suspended in water (5000 ml), sodium carbonate was gradually added and the aqueous layer was neutralized. Then, it was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and the solvent was concentrated under reduced pressure to give the title compound (366 g, 94%) as a colorless solid. 1H NMR (MHz, CDC13, δ ppm): .41(1H, d, J=8.0Hz), 7.51(1H, dd, J=8.0, 2.4Hz), 8.33(1H, d, J=2.4Hz).

Preparation and usage examples of 2-bromo-5-chloropyridine

2-Bromo-5-chloropyridine can be used to prepare phenylpyrrolidines with the following structure. This type of compound is a PDE4 inhibitor with novel structure, better efficacy, high bioavailability, and strong drug potential. It is used to effectively treat PDE4-related diseases and conditions, including but not limited to inflammatory diseases and allergic diseases. , autoimmune diseases, transplant rejection, arthritic diseases, inflammatory skin diseases, inflammatory bowel diseases, and diseases related to smooth muscle contractility, etc.

References

[1] [China invention, China invention authorization] CN03820730.3 Aza-bicycloalkyl ether and its use as α7-NACHR agonist

[2] From PCT Int. Appl., 2007142217, 13 Dec 2007

[3] [Chinese invention] CN201910806178.8 Phenylpyrrolidine compounds and their uses