Dimethylformamide → 6-aminopyrimidine-4-carbonitrile
Reaction equation
Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH2:8])[CH:3]=1.CCOC(C)=O.[CH3:15][N:16](C=O)C>[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>[NH2:8][C:4]1[N:5]=[CH:6][N:7]=[C:2]([C:15]#[N:16])[CH:3]=1Participants
6
Conditions
- Temperature
- 120 °C
Procedure
A mixture of 6-chloropyrimidin-4-amine (3.0 g, 23 mmol), zinc (II) cyanide (5.4 g, 46 mmol) and tetrakis(triphenylphosphine)palladium(0) (1.3 g, 1.2 mmol) in dry DMF (50 mL) was heated to 120° C. under nitrogen atmosphere for 15 hours. EtOAc (100 mL) was added and the insoluble precipitate was removed by filtration. The filtrate was diluted with water (100 mL), and extracted with EtOAc (3×50 mL). The combined organic extract was washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by reverse phase column chromatography, eluting with a 0-60% gradient of CH3CN in 0.5% NH4HCO3 to give the desired product as a pale yellow solid (0.6 g, 21% yield). LCMS (ESI) m/z: 121.2 [M+H+].
Workup
- customthe insoluble precipitate was removed by filtration
- additionThe filtrate was diluted with water (100 mL)
- extractionextracted with EtOAc (3×50 mL)
- extractionThe combined organic extract
- washwas washed with brine
- dry with materialdried over Na2SO4
- concentrationconcentrated under reduced pressure
- customThe residue was purified by reverse phase column chromatography
- washeluting with a 0-60% gradient of CH3CN in 0.5% NH4HCO3
Sources & evidence
- ORD record
- ord-5ce384df26f943ba93e52c10f464377b
- Source dataset
- uspto-grants-2014_04
- Patent number
- US08697708B2
Reaction notes
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