Water → 6-(4-Aminophenyl)-2-chloronicotinonitrile

HRID 556440Notes

Reaction equation

HRID 556440 reaction equation
[Cl:1][C:2]1[N:9]=[C:8](Cl)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[NH2:11][C:12]1[CH:17]=[CH:16][C:15](B(O)O)=[CH:14][CH:13]=1.C(=O)(O)[O-].[Na+].O>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:8]2[CH:7]=[CH:6][C:3]([C:4]#[N:5])=[C:2]([Cl:1])[N:9]=2)=[CH:14][CH:13]=1

Participants

7

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 27346154-Aminophenylboronic acidHCID 126055382,6-Dichloropyridine-3-carbonitrile

Product 1

HCID 597666616-(4-Aminophenyl)-2-chloronicotinonitrile

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

2.89 mmol (500 mg) of 2,6-dichloronicotinonitrile and 3.18 mmol (551 mg, 1.1 eq.) of 4-aminophenylboronic acid are dissolved under an inert atmosphere in 33.3 ml of dioxane. 680 mg (8.09 mmol, 2.8 eq.) of sodium bicarbonate and then 8.3 ml of water are subsequently added. The mixture is stirred for 5 minutes under an inert atmosphere and then 334 mg (0.29 mmol, 0.1 eq.) of tetrakis(triphenylphosphine)palladium are added. The reaction mixture is brought to reflux (100° C.) for 2 hours and is then cooled to ambient temperature. The reaction medium is filtered and then extracted four times with ethyl acetate. The organic phases are combined, washed twice with a saturated aqueous sodium chloride solution, dried with magnesium sulphate, and concentrated. A yellow solid is then obtained. This crude is purified on a column of 90 g of silica, with an eluent gradient of 20% to 50% of ethyl acetate in heptane. The expected product is obtained in the form of a yellow solid (531 mg).

Workup

  1. temperatureis then cooled to ambient temperature
  2. filtrationThe reaction medium is filtered
  3. extractionextracted four times with ethyl acetate
  4. washwashed twice with a saturated aqueous sodium chloride solution
  5. dry with materialdried with magnesium sulphate
  6. concentrationconcentrated
  7. customA yellow solid is then obtained
  8. customThis crude is purified on a column of 90 g of silica, with an eluent gradient of 20% to 50% of ethyl acetate in heptane

Sources & evidence

ORD record
ord-60d6c8bb752f4a0cb2afe80a881b23b6
Source dataset
uspto-grants-2011_11
Patent number
US08058290B2

Reaction notes

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