Dimethylformamide → 3-(2,4-Dimethylpyridin-3-yloxy)-5-(pyridin-2-ylthio)picolinonitrile

HRID 1511075Notes

Reaction equation

[NH:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]1=[S:7].Br[C:9]1[CH:10]=[C:11]([O:17][C:18]2[C:19]([CH3:25])=[N:20][CH:21]=[CH:22][C:23]=2[CH3:24])[C:12]([C:15]#[N:16])=[N:13][CH:14]=1.CN(C=O)C.[H-].[Na+]>O>[CH3:25][C:19]1[C:18]([O:17][C:11]2[C:12]([C:15]#[N:16])=[N:13][CH:14]=[C:9]([S:7][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)[CH:10]=2)=[C:23]([CH3:24])[CH:22]=[CH:21][N:20]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Pyridin-2(1H)-thione (0.768 g, 6.90 mmol) and 5-bromo-3-(2,4-dimethylpyridin-3-yloxy)picolinonitrile (2.00 g, 6.58 mmol) were added to DMF (12 mL) and cooled to 0° C. 95% Sodium hydride (0.174 g, 6.90 mmol) was slowly added and the reaction was warmed to ambient temperature and stirred overnight. The reaction mixture was poured into water (100 mL) and stirred for 30 minutes. A cloudy milky solution that was not filterable resulted. The reaction was extracted twice with ethyl acetate. The combined organic layers were washed twice with water and brine, dried, and concentrated. The residue was purified over silica gel (2:3 to 0:1 hexane:ethyl acetate) to afford 3-(2,4-dimethylpyridin-3-yloxy)-5-(pyridin-2-ylthio)picolinonitrile (2.03 g, 6.07 mmol, 92.3% yield) as a white powder.

Workup

temperaturethe reaction was warmed to ambient temperature
stirringstirred for 30 minutes
extractionThe reaction was extracted twice with ethyl acetate
washThe combined organic layers were washed twice with water and brine
customdried
concentrationconcentrated
customThe residue was purified over silica gel (2:3 to 0:1 hexane:ethyl acetate)

Sources & evidence

ORD record: ord-76342b4b6d9742f09bf7d27b8a4dd8fb
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08212045B2

Reaction notes

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