Dimethylformamide → 3-Chloro-5-[2-(4-methoxy-2-methylphenyl)ethynyl]-2-pyridinecarbonitrile

HRID 2167633Notes

Reaction equation

[C:1]([C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][C:4]=1[CH3:11])#[CH:2].[Cl:12][C:13]1[C:14]([C:20]#[N:21])=[N:15][CH:16]=[C:17](Cl)[CH:18]=1.C(N(CC)CC)C.CN(C=O)C>[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CCOC(C)=O>[Cl:12][C:13]1[C:14]([C:20]#[N:21])=[N:15][CH:16]=[C:17]([C:2]#[C:1][C:3]2[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][C:4]=2[CH3:11])[CH:18]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a round bottom flask capped with septa was added 1-ethynyl-4-methoxy-2-methylbenzene (1.1 eq), 3,5-dichloropicolinonitrile (1 eq.), triethylamine (5 eq.), and anhydrous DMF (0.2 M). The mixture was degassed (vacuum) and nitrogen flushed three times. CuI (0.05 eq.) and bis(triphenylphosphine)dichloro-palladium(II) (0.05 eq) were added and the septum was replaced with a refluxing condenser and the flask was heated at 60° C. overnight under nitrogen atmosphere. Upon completion of the reaction as monitored by TLC, the content of the flask was loaded onto a large silica gel column pretreated with hexanes. Flash chromatography (silica gel, hexanes:EtOAc (1:4%)) afforded the product 3-chloro-5-((4-methoxy-2-methylphenyl)ethynyl)picolinonitrile (B-1).

Workup

customTo a round bottom flask capped with septa
customThe mixture was degassed (vacuum) and nitrogen
customflushed three times
customthe septum was replaced with a refluxing condenser
customUpon completion of the reaction

Sources & evidence

ORD record: ord-3d13521280584e91917287db51313778
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09045470B2

Reaction notes

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