Tetrahydrofuran → 6-Bromo-2-methoxypyrido[3,2-d]pyrimidine

Temperature

40 °C

A 3-necked roundbottom flask purged and maintained with an inert atmosphere of nitrogen was charged with 2,6-dibromopyrido[3,2-d]pyrimidine (10.7 g, 37.04 mmol). To this was added tetrahydrofuran (500 ml) and methanol (150 ml). A solution of sodium (89 mg, 3.87 mmol, 0.10 equiv) in methnaol (60 ml) was then added dropwise with stirring, while warming to a temperature of 40° C. The resulting solution was allowed to react, with stirring, for 1.5 hours while the temperature was maintained at 40° C. The reaction progress was monitored by TLC. The reaction mixture was then quenched by adding 1.5 L of water. The mixture was concentrated under reduced pressure. The resulting slurry was filtered and the solids collected. The solids were then dissolved in 2 L of ethyl acetate. The resulting mixture was washed once with 500 ml of brine. The organic layer was dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified recrystallization from 2:1 tetrahydrofuran:methanol to afford the title compound.

1. customA 3-necked roundbottom flask purged
2. temperaturemaintained with an inert atmosphere of nitrogen
3. customto react
4. stirringwith stirring, for 1.5 hours while the temperature
5. temperaturewas maintained at 40° C
6. customThe reaction mixture was then quenched
7. additionby adding 1.5 L of water
8. concentrationThe mixture was concentrated under reduced pressure
9. filtrationThe resulting slurry was filtered
10. customthe solids collected
11. dissolutionThe solids were then dissolved in 2 L of ethyl acetate
12. washThe resulting mixture was washed once with 500 ml of brine
13. dry with materialThe organic layer was dried over magnesium sulfate
14. filtrationfiltered
15. concentrationconcentrated under reduced pressure
16. customThe resulting residue was purified
17. customrecrystallization from 2:1 tetrahydrofuran

ORD record

ord-fef56fb1e5544357a6b8db01396e42cc

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08344144B2