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

HRID 1422936Notes

Reaction equation

[Cu][C:2]#[N:3].Br[C:5]1[C:6]([Cl:17])=[CH:7][N:8]=[C:9]2[C:14]=1[N:13]=[C:12]([O:15][CH3:16])[CH:11]=[CH:10]2.[Cl-].[NH4+]>CN(C)C=O>[Cl:17][C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:5]=1[C:2]#[N:3])=[N:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=2

Participants

Conditions

Temperature: 130 °C

Procedure

Copper(I) 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-361a027e7b6b4fc486e238988e3a0ea9
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08927541B2

Reaction notes

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