Sulfuric Acid → 2-Bromo-6-methyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-amine

D4 (978 mg, 6 mmol) was dissolved in acetic acid (10 ml) containing 2M sulphuric acid (2 ml). Bromine (0.31 ml, 6 mmol) was added dropwise with stirring over a period of approximately 25 min. After 2 h, the precipitated solid was removed by filtration and washed with ether to give a pale yellow solid which was dissolved in water. The solution was basified with 2M NaOH and extracted with ethyl acetate. The combined extracts were washed with brine, dried (MgSO4) and evaporation in vacuo gave the crude product as a pale yellow solid (444 mg). The above filtrate from the reaction mixture was concentrated by evaporation in vacuo, diluted with water and made basic with 2M sodium hydroxide. The mixture was extracted with dichloromethane and the extract dried (MgSO4) and evaporated to give a crude brown solid which was purified by chromatography on silica gel eluting with dichloromethane:methanol:aq. ammonia (0.880) (ratio 19:1:0.1). The title compound was obtained as a white solid (248 mg).

1. waitAfter 2 h
2. customthe precipitated solid was removed by filtration
3. washwashed with ether
4. customto give a pale yellow solid which
5. extractionextracted with ethyl acetate
6. washThe combined extracts were washed with brine
7. customdried
8. custom(MgSO4) and evaporation in vacuo
9. customgave the crude product as a pale yellow solid (444 mg)
10. concentrationThe above filtrate from the reaction mixture was concentrated by evaporation in vacuo
11. additiondiluted with water
12. extractionThe mixture was extracted with dichloromethane
13. dry with materialthe extract dried (MgSO4)
14. customevaporated
15. customto give a crude brown solid which
16. customwas purified by chromatography on silica gel eluting with dichloromethane

ORD record

ord-ac639d87c4e54884bcbf56602f8b3263

Source dataset

uspto-grants-2001_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06245778B1