Cyanide → 3-Chloro-6-methoxy-[1,5]naphthyridine-4-carbonitrile

HRID 633789Notes

Reaction equation

[C-:1]#[N:2].Br[C:4]1[C:5]([Cl:16])=[CH:6][N:7]=[C:8]2[C:13]=1[N:12]=[C:11]([O:14][CH3:15])[CH:10]=[CH:9]2.[Cl-].[NH4+]>CN(C)C=O>[Cl:16][C:5]1[CH:6]=[N:7][C:8]2[C:13]([C:4]=1[C:1]#[N:2])=[N:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=2

Participants

Conditions

Temperature: 130 °C

Procedure

CoppeeI cyanide (39.3 g, 0.44 mol, 1.2 eq) is added at room temperature to a stirred solution of 8-bromo-7-chloro-2-methoxy-[1,5]naphthyridine (100 g, 0.37 mol, 1.0 eq) in N,N-dimethylformamide (1.5 L). After 8 hours stirring at 130° C., the reaction mixture is cooled down to room temperature and treated with a saturated ammonium chloride aqueous solution (1.5 L). The aqueous layer is separated and extracted with ethyl acetate (2×1.5 L). The combined organic layers are dried over sodium sulfate, filtered and concentrated to give a residue that is washed with ethanol (20 mL) to afford 3-chloro-6-methoxy-[1,5]naphthyridine-4-carbonitrile as an off-white solid (49.5 g, 62% yield).

Workup

temperaturethe reaction mixture is cooled down to room temperature
customThe aqueous layer is separated
extractionextracted with ethyl acetate (2×1.5 L)
dry with materialThe combined organic layers are dried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customto give a residue that
washis washed with ethanol (20 mL)

Sources & evidence

ORD record: ord-bab5d201091a423a9f608504d3e374b1
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09321788B2

Reaction notes

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