2-Propenoic acid, 2-cyano-3-ethoxy-, ethyl ester → 2-Cyano-3-(6-methyl-pyridin-3-ylamino)-acrylic acid ethyl ester

HRID 968711Notes

Reaction equation

HRID 968711 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][C:5]([CH3:8])=[CH:6][CH:7]=1.[CH2:9]([O:11][C:12](=[O:20])[C:13](=[CH:16]OCC)[C:14]#[N:15])[CH3:10]>C1(C)C=CC=CC=1>[CH2:9]([O:11][C:12](=[O:20])[C:13]([C:14]#[N:15])=[CH:16][NH:1][C:2]1[CH:3]=[N:4][C:5]([CH3:8])=[CH:6][CH:7]=1)[CH3:10]

Participants

4

Reactant 2

HCID 789432-Propenoic acid, 2-cyano-3-ethoxy-, ethyl esterHCID 2433135-Amino-2-methylpyridine

Product 1

HCID 7219982-Cyano-3-(6-methyl-pyridin-3-ylamino)-acrylic acid ethyl esterYield 65.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 3-amino-6-picoline (ChemPacific, 15.00 g, 138.70 mmol), in toluene (400 mL) was added ethyl(ethoxymethylene)-cyano-acetate (Aldrich, 98%, 35.88 g, 208.00 mol), and the reaction mixture was refluxed for 4 hrs. The reaction mixture was concentrated and the solid was collected by filtration to give 2-cyano-3-(6-methyl-pyridin-3-ylamino)-acrylic acid ethyl ester (21.0 g). The filtrate was concentrated and the residue was then purified by Biotage column, eluting with a gradient of 30-75% AcOEt in nHex to give 2-cyano-3-(6-methyl-pyridin-3-ylamino)-acrylic acid ethyl ester (7.6 g, total yield: 28.6 g, 89.0%) which was used in the next step without further purification.

Workup

  1. temperaturethe reaction mixture was refluxed for 4 hrs
  2. concentrationThe reaction mixture was concentrated
  3. filtrationthe solid was collected by filtration

Sources & evidence

ORD record
ord-79dedd885e6b4d18a10eab682fe021f4
Source dataset
uspto-grants-2007_12
Patent number
US07304074B2

Reaction notes

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