Malononitrile → HCID 86653539, compound

Temperature

60 °C

2-Methylthio-4,6-dichloropyrimidine (1b) (10 g, 51.27 mmoles) was suspended in 150 mL of dry THF along with malononitrile (3.72 g, 56.14 mmoles) and trans-dichloro-bis(triphenylphosphine)palladium (II) (2.0 g, 2.85 mmoles). The reaction mixture was purged with a stream of nitrogen gas for five minutes with rapid stirring before the cautious portion wise addition of sodium hydride (60% oil dispersion, 6.15 g, 154 mmoles). Note that the reaction is exothermic and THF starts to reflux upon addition of NaH. Nitrogen purging was continued throughout the addition. Upon completion of the sodium hydride addition, the nitrogen purge was ceased and the reaction mixture was placed into a pre-heated oil bath at ˜70° C. The reaction mixture was heated under a blanket of nitrogen for 2 hours or until complete (color changes from a yellow to orange brown). The reaction was cooled and cautiously quenched with 30 mL of aq. 1N HCl solution and when gas formation ceased the majority of the solvent was removed under reduced pressure. The concentrated mixture was diluted with aq. 0.25 N HCl solution with stirring and the orange brown precipitate was collected via suction filtration, washed with water and vacuum-dried. The crude cake was transferred to a round bottomed flask containing acetonitrile (250 mL) and stirred vigorously for one hour. The precipitate was isolated via suction filtration, washed with acetonitrile and cautiously washed with DCM. The cake was then re-suspended in acetonitrile, warmed to ˜60° C., allowed to cool while stirring, and re-isolated via suction filtration and vacuum-dried. 8.81 g of a pale yellow solid was obtained (77% yield).

1. customThe reaction mixture was purged with a stream of nitrogen gas for five minutes
2. additionNitrogen purging was continued throughout the addition
3. customthe nitrogen purge
4. customthe reaction mixture was placed into a pre-heated oil bath at ˜70° C
5. temperatureThe reaction mixture was heated under a blanket of nitrogen for 2 hours
6. temperatureThe reaction was cooled
7. customcautiously quenched with 30 mL of aq. 1N HCl solution and when gas formation
8. customwas removed under reduced pressure
9. additionThe concentrated mixture was diluted with aq. 0.25 N HCl solution
10. filtrationthe orange brown precipitate was collected via suction filtration
11. washwashed with water
12. customvacuum-dried
13. customThe crude cake was transferred to a round bottomed flask
14. additioncontaining acetonitrile (250 mL)
15. stirringstirred vigorously for one hour
16. customThe precipitate was isolated via suction filtration
17. washwashed with acetonitrile
18. washcautiously washed with DCM
19. temperatureto cool
20. stirringwhile stirring
21. customre-isolated via suction filtration
22. customvacuum-dried

ORD record

ord-8ed721cea7944b63ba5ddf09515a1ea5

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08937064B2