Ethyl Acetate → (7-Chloro-imidazo[1,2-c]pyrimidin-2-yl)-carbamic acid ethyl ester

A solution of 4-(2-hydroxyethyl)morpholine (2.77 g, 21.1 mmol) in dry tetrahydrofuran (5 mL) was added to a refluxing suspension of sodium hydride (557 mg, 23.2 mmol) in tetrahydrofuran (50 mL). This mixture was heated at reflux temperature for 3 h., then 2,5-dibromopyridine (1; 5.00 g, 21.1 mmol) added as a solid (portion wise). The resulting mixture was then heated at reflux for 15 h. After allowing the reaction mixture to cool, it was diluted with ethyl acetate (200 mL), then washed with water (200 mL). The water fraction was back-extracted with ethyl acetate (100 mL). The combined ethyl acetate fractions were washed with water (2×200 mL), then brine (100 mL) and dried over sodium sulfate. The drying agent was removed by filtration and the resultant liquor was concentrated under reduced pressure. The resulting yellow oil was purified by chromatography on silica gel (100% dichloromethane gradient to 10% methanol/dichloromethane). Compound 2 was isolated as a yellow oil (yield: 5.06 g, 84%);

1. temperatureThis mixture was heated
2. temperatureat reflux temperature for 3 h.
3. temperatureThe resulting mixture was then heated
4. temperatureat reflux for 15 h
5. temperatureto cool
6. washwashed with water (200 mL)
7. extractionThe water fraction was back-extracted with ethyl acetate (100 mL)
8. washThe combined ethyl acetate fractions were washed with water (2×200 mL)
9. dry with materialbrine (100 mL) and dried over sodium sulfate
10. customThe drying agent was removed by filtration
11. concentrationthe resultant liquor was concentrated under reduced pressure
12. customThe resulting yellow oil was purified by chromatography on silica gel (100% dichloromethane gradient to 10% methanol/dichloromethane)

ORD record

ord-b27881be484143269102ea42b9ba4c54

Source dataset

uspto-grants-2009_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07563788B2