Aniline → 2-Propenoic acid, 2-cyano-3-(phenylamino)-, ethyl ester, (E)-

HRID 1357487Notes

Reaction equation

HRID 1357487 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:8]([O:10][C:11](=[O:19])[C:12](=[CH:15]OCC)[C:13]#[N:14])[CH3:9]>N1C=CC=CC=1>[CH2:8]([O:10][C:11](=[O:19])[C:12](=[CH:15][NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:13]#[N:14])[CH3:9]

Participants

4

Reactant 2

HCID 6115AnilineHCID 789432-Propenoic acid, 2-cyano-3-ethoxy-, ethyl ester

Product 1

HCID 51025632-Propenoic acid, 2-cyano-3-(phenylamino)-, ethyl ester, (E)-Yield 50%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

0.91 ml (10 mmol) of aniline and 1.69 g (10 mmol of ethyl(ethoxymethylene)cyanoacetate were dissolved in 10 ml of pyridine and heated under reflux. After 3 h pyridine was removed under vacuum, and the residue was purified by chromatography (silica gel column, eluent 1% methanol in dichloromethane). 1.08 g (50%) of ethyl(anilinomethylene)cyanoacetate were obtained. The compound was cyclized by heating in a biphenyl/phenyl ether mixture. After cooling a precipitate was filtered and washed with diethyl ether to give 4-hydroxyquinoline-3-carbonitrile (49%). Following the procedure outlined in Step 3 of Example 1, but substituting 4-hydroxyquinoline-3-carbonitrile for 9-(10H)acridone, 4-chloro-3-cyanoquinoline (90%) was obtained, which was reacted with 4-(4-methylpiperazin-1-yl)aniline (according to the procedure of Step 4 in Example 1), to afford the title compound with 12% yield (overall yield 3%).

Workup

  1. temperatureheated
  2. temperatureunder reflux
  3. customAfter 3 h pyridine was removed under vacuum
  4. customthe residue was purified by chromatography (silica gel column, eluent 1% methanol in dichloromethane)

Sources & evidence

ORD record
ord-a4b53589555e4d10aeb7df75fbee4165
Source dataset
uspto-grants-2003_07
Patent number
US06593324B2

Reaction notes

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