反应详情

5-Bromo-2-chloro-3-pyridinamine [commercially available] (10 g, 48.2 mmol) was dissolved in pyridine (75 ml) and methanesulfonyl chloride (7.46 ml, 96 mmol) added, and the mixture stirred overnight. Further methanesulfonyl chloride (2.1 ml) was added and the reaction stirred at room temperature for 5 h. A further portion of methanesulfonyl chloride (2.1 ml) was added and the mixture stirred at room temperature overnight. The pH was adjusted to ˜pH6 by the addition of 2M hydrochloric acid. The mixture was then extracted with dichloromethane (2×150 ml) the combined organic layers were dried using a hydrophobic frit and the solvent removed in vacuo. The residue was suspended in methanol (200 ml) and 2M sodium hydroxide (50 ml) added. The mixture was stirred for 1 h and then the solvent removed in vacuo. The residue was dissolved in water (250 ml) and extracted with dichloromethane (150 ml). The aqueous layer was then acidified and the resulting precipitate collected by filtration. The solid was air dried overnight to give the title compound as an off white solid (13.45 g).

1. stirringthe reaction stirred at room temperature for 5 h
2. stirringthe mixture stirred at room temperature overnight
3. extractionThe mixture was then extracted with dichloromethane (2×150 ml) the combined organic layers
4. customwere dried
5. customthe solvent removed in vacuo
6. addition2M sodium hydroxide (50 ml) added
7. stirringThe mixture was stirred for 1 h
8. customthe solvent removed in vacuo
9. dissolutionThe residue was dissolved in water (250 ml)
10. extractionextracted with dichloromethane (150 ml)
11. filtrationthe resulting precipitate collected by filtration
12. customdried overnight