Dimethyl Sulfate → HCID 22449396, compound

Sodium hydride (9.72 g, 60%, 243 mmol) was added portionwise to a cooled (5° C.) solution of malononitrile (7.9 g, 120 mmol) in tetrahydrofuran (75 ml), and the mixture stirred for 20 minutes. A solution of 2-pyrazinecarbonyl chloride (J. Med. Chem. 1992, 35, 1214) (17.1 g, 120 mmol) in tetrahydrofuran (250 ml) was added dropwise so as to maintain the internal temperature below 10° C., and the mixture then stirred at room temperature for an hour. Dimethyl sulphate (18.16 g, 144 mmol) was added, the mixture heated under reflux for 3 hours, allowed to cool, triethylamine (58.5 ml, 420 mmol) and ethyl hydrazine oxalate (18 g, 120 mmol) added and the reaction mixture heated under reflux for 18 hours. The solvent was decanted from the cooled reaction mixture and the residual brown gum extracted with dichloromethane (2×150 ml). The combined organic solutions were evaporated under reduced pressure and the crude product purified by column chromatography on silica gel, using ethyl acetate:hexane (50:50) as eluant to afford the title compound, (1.2 g).

1. temperatureto maintain the internal temperature below 10° C.
2. stirringthe mixture then stirred at room temperature for an hour
3. temperaturethe mixture heated
4. temperatureunder reflux for 3 hours
5. temperatureto cool
6. temperaturethe reaction mixture heated
7. temperatureunder reflux for 18 hours
8. customThe solvent was decanted from the cooled reaction mixture
9. extractionthe residual brown gum extracted with dichloromethane (2×150 ml)
10. customThe combined organic solutions were evaporated under reduced pressure
11. customthe crude product purified by column chromatography on silica gel

ORD record

ord-700d25a5eb6143eca92c0e69643427a4

Source dataset

uspto-grants-2002_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06407114B1