Water → 2-Aminoisonicotinonitrile

HRID 1848113Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH2:8])[CH:3]=1.O.[CH3:10][N:11](C=O)C>[C-]#N.[C-]#N.[Zn+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[NH2:8][C:4]1[CH:3]=[C:2]([CH:7]=[CH:6][N:5]=1)[C:10]#[N:11]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 4-bromopyridin-2-amine (4.9 g, 28.5 mmol), Zn(CN)2 (5.0 g, 42.5 mmol), Pd2(dba)3 (1.3 g, 1.4 mmol) and dppf (1.6 g, 2.8 mmol) in DMF (150 mL) was stirred at 100° C. under nitrogen atmosphere for 1.5 h. The mixture was cooled to rt and water (500 mL) was added. The mixture was extracted with EtOAc (300 mL×3). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 10:1 to 2:1 petroleum ether/EtOAc to afford 2-aminoisonicotinonitrile as a light yellow solid (2.7 g, 80%). 1H NMR (300 MHz, CDCl3) δ 8.19 (d, J=5.1 Hz, 1H), 6.82 (d, J=4.8 Hz, 1H), 6.69 (d, J=0.9 Hz, 1H), 4.72 (br s, 2H). LCMS (ESI) m/z 120 (M+H)+.

Workup

temperatureThe mixture was cooled to rt
extractionThe mixture was extracted with EtOAc (300 mL×3)
washThe combined organic layers were washed with brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe residue was purified by silica gel chromatography
washeluting with 10:1 to 2:1 petroleum ether/EtOAc

Sources & evidence

ORD record: ord-43c0e7801fc146e1b0aabd0a73506c3a
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08952058B2

Reaction notes

Loading…