Triethylamine → 10-Methylbenzo[f][1,7]naphthyridin-5-amine

HRID 340254Notes

Reaction equation

HRID 340254 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[CH:6]2)#[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:24](CC)CC)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.CN(C=O)C>[CH3:6][C:5]1[C:4]2=[C:13]3[C:14](=[C:20]([NH2:21])[N:24]=[C:3]2[CH:11]=[CH:10][CH:9]=1)[N:15]=[CH:16][CH:17]=[CH:18]3.[NH:8]1[C:9]2[C:5](=[CH:4][C:3]([C:1]#[C:2][C:17]3[CH:18]=[C:13]([Cl:12])[C:14]([C:20]#[N:21])=[N:15][CH:16]=3)=[CH:11][CH:10]=2)[CH:6]=[CH:7]1

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 27696993,5-Dichloro-2-cyanopyridineHCID 178425855-Ethynyl-1H-indole

Product 2

HCID 5821372010-Methylbenzo[f][1,7]naphthyridin-5-amineYield 4%HCID 668923115-((1H-indol-5-yl)ethynyl)-3-chloropicolinonitrile

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a round bottom flask capped with septa was added 5-ethynyl-1H-indole (from the previous step) (1.1 eq), 3,5-dichloropicolinonitrile (1 eq.), triethylamine (5 eq.), and anhydrous DMF (0.2 M). Vacuumed and nitrogen flushed for three times. CuI (0.05 eq.) and bis(triphenylphosphine)dichloro-palladium(II) (0.05 eq) were added. 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 5-((1H-indol-5-yl)ethynyl)-3-chloropicolinonitrile.

Workup

  1. customTo a round bottom flask capped with septa
  2. customVacuumed and nitrogen flushed for three times
  3. customThe septum was replaced with a refluxing condenser
  4. customUpon completion of the reaction

Sources & evidence

ORD record
ord-4f2e3c0dc8f34e288d0541d07784e4f1
Source dataset
uspto-grants-2014_11
Patent number
US08895577B2

Reaction notes

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