Malononitrile → 2-Amino-6-methyl-4-(tetrahydro-2H-pyran-2-yl)pyridine-3,5-dicarbonitrile

HRID 1873580Notes

Reaction equation

[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[CH:7]=O.[C:9](#[N:13])[CH2:10][C:11]#[N:12].[NH2:14]/[C:15](/[CH3:19])=[CH:16]\[C:17]#[N:18].C[O-].[Na+]>C(O)C>[NH2:12][C:11]1[C:10]([C:9]#[N:13])=[C:7]([CH:2]2[CH2:3][CH2:4][CH2:5][CH2:6][O:1]2)[C:16]([C:17]#[N:18])=[C:15]([CH3:19])[N:14]=1

Participants

Conditions

Temperature: 0 °C

Procedure

870 mg (7.62 mmol) of tetrahydro-2H-pyran-2-carbaldehyde, 504 mg (7.62 mmol) of malononitrile and 626 mg (7.62 mmol) of 3-aminocrotononitrile are dissolved in 8.4 ml of dry ethanol. The solution is cooled to 0° C., and 412 mg (7.62 mmol) of sodium methoxide are added a little at a time. The reaction mixture is then warmed to RT and stirred for 10 min. The mixture is then heated at reflux for 10 h. After cooling, the brown precipitate formed is filtered off with suction, washed three times with a total of 100 ml of ethanol and then dried at 50° C. under reduced pressure. The product is used without further purification for the next reaction. Purification may be carried out by preparative HPLC (column: YMC GEL ODS-AQ S-5, 15 μm; mobile phase gradient: acetonitrile/water 10:90→95:5).

Workup

temperatureThe reaction mixture is then warmed to RT
temperatureThe mixture is then heated
temperatureat reflux for 10 h
temperatureAfter cooling
customthe brown precipitate formed
filtrationis filtered off with suction
washwashed three times with a total of 100 ml of ethanol
customdried at 50° C. under reduced pressure
customThe product is used without further purification for the next reaction
customPurification

Sources & evidence

ORD record: ord-a32baf7113914c44a6da69bb00cf6964
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08304412B2

Reaction notes

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