Tetrahydrofuran → 4-[(3-Aminopyridin-2-yl)amino]-2-fluorobenzonitrile

HRID 2272708Notes

Reaction equation

[F:1][C:2]1[CH:9]=[C:8]([NH:10][C:11]2[C:16]([N+:17]([O-])=O)=[CH:15][CH:14]=[CH:13][N:12]=2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].O1CCCC1.[Cl-].[NH4+]>[Zn].O>[NH2:17][C:16]1[C:11]([NH:10][C:8]2[CH:7]=[CH:6][C:3]([C:4]#[N:5])=[C:2]([F:1])[CH:9]=2)=[N:12][CH:13]=[CH:14][CH:15]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 2-fluoro-4-[(3-nitropyridin-2-yl)amino]benzonitrile (C14) (5.4 g, 21 mmol) in a 1:1 mixture of tetrahydrofuran and water (40 mL) was added ammonium chloride (8.9 g, 170 mmol), followed by zinc (10.8 g, 165 mmol). The mixture was stirred at 60° C. for 30 minutes, whereupon it was filtered through a pad of Celite. The organic layer from the filtrate was diluted with ethyl acetate, washed with saturated aqueous ammonium chloride solution, dried over sodium sulfate, filtered, and concentrated in vacuo; the residue was washed with heptane to afford the product as a brown solid. Yield: 4.2 g, 18 mmol, 86%. LCMS m/z 229.1 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 8.68 (br s, 1H), 7.82 (dd, J=13.6, 2.0 Hz, 1H), 7.66 (dd, J=8.4, 8.3 Hz, 1H), 7.61 (dd, J=4.8, 1.6 Hz, 1H), 7.37 (dd, J=8.8, 2.0 Hz, 1H), 7.03 (dd, J=7.8, 1.6 Hz, 1H), 6.82 (dd, J=7.8, 4.8 Hz, 1H), 5.24 (br s, 2H).

Workup

filtrationwas filtered through a pad of Celite
additionThe organic layer from the filtrate was diluted with ethyl acetate
washwashed with saturated aqueous ammonium chloride solution
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
washthe residue was washed with heptane

Sources & evidence

ORD record: ord-a428dd050141435690309d4815bba1e0
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09120788B2

Reaction notes

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