Dimethylformamide → 4-Methylpyrimidine-2-carbonitrile
Reaction equation
Cl[C:2]1[N:7]=[C:6]([CH3:8])[CH:5]=[CH:4][N:3]=1.[CH3:9][N:10](C=O)C>CCOC(C)=O.[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([C:9]#[N:10])[N:7]=1Participants
6
Conditions
- Temperature
- 110 °C
Procedure
A mixture of 2-chloro-4-methylpyrimidine (725 mg, 5.63 mmol, 1 eq), zinccyanide (396 mg, 3.38 mmol, 0.6 eq) and tetrakis(triphenylphosphine)palladium(0) (716 mg, 0.562, 0.1 eq) in DMF (10 ml) was heated at 110° C. under nitrogen for 1 hr. The mixture was cooled to r.t., diluted with EtOAc and washed twice with 2N ammonium hydroxide (50 ml). The organic layer was washed with brine (20 ml) dried over sodium sulphate and concentrated in vacuum to provide the crude mixture. The crude product was then purified by column chromatography (30% EtOAc in Hexane) to afford 4-methylpyrimidine-2-carbonitrile Yield: 380 mg (56%). 1H NMR (400 MHz, CDCl3): δ2.61 (s, 3H), 7.36 (d, 1H, J=5.2 Hz), 8.66 (d, 1H, J=5.2 Hz),
Workup
- temperatureThe mixture was cooled to r.t.
- washwashed twice with 2N ammonium hydroxide (50 ml)
- washThe organic layer was washed with brine (20 ml)
- dry with materialdried over sodium sulphate
- concentrationconcentrated in vacuum
- customto provide the crude mixture
- customThe crude product was then purified by column chromatography (30% EtOAc in Hexane)
Sources & evidence
- ORD record
- ord-ccb6952bc7e64854a102a3c0ef7fbe3d
- Source dataset
- uspto-grants-2014_05
- Patent number
- US08722688B2
Reaction notes
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