Dimethylformamide → 6-Amino-5-methoxy-nicotinonitrile

HRID 525990Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([O:9][CH3:10])[C:5]([NH2:8])=[N:6][CH:7]=1.[CH3:11][N:12](C)C=O>C(OCC)(=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:5]1[N:6]=[CH:7][C:2]([C:11]#[N:12])=[CH:3][C:4]=1[O:9][CH3:10]

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 5-bromo-3-methoxy-pyridin-2-amine (3.00 g, 14.8 mmol) in N,N-dimethylformamide (55 mL) under a nitrogen atmosphere was added zinc (II) cyanide (2.78 g, 23.6 mmol) and tetrakis(triphenylphosphine)palladium(0) (2.06 g, 1.77 mmol). The reaction mixture was stirred at 100° C. for 4 h. The reaction mixture was diluted with ethyl acetate and washed successively with a saturated solution of ammonium hydroxide and brine. The phases were separated. The organic phases was dried over sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent: ethyl acetate/cyclohexane 1:5) to give 6-amino-5-methoxy-pyridine-3-carbonitrile (1.2 g, 54% yield). 1H NMR (400 MHz, CDCl3): 7.99 (s, 1H), 6.99 (s, 1H), 3.88 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): 152.83, 144.58, 141.27, 118.32, 115.52, 97.66, 55.65. LC-MS (Method B): RT 0.69, 150 (M+H+)

Workup

washwashed successively with a saturated solution of ammonium hydroxide and brine
customThe phases were separated
dry with materialThe organic phases was dried over sodium sulfate
concentrationconcentrated
customThe residue was purified by column chromatography on silica gel (eluent: ethyl acetate/cyclohexane 1:5)

Sources & evidence

ORD record: ord-ff5d2d387b65476986dfd8b49b36d56e
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09345244B2

Reaction notes

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