4-Methoxy cinnamic acid → N-[2-(4-Chloro-2-methoxyphenyl)-4-methylthiazol-5-yl]-3-(4-methoxyphenyl)acrylamide

HRID 1498952Notes

Reaction equation

HRID 1498952 reaction equation
[CH3:1][O:2][C:3]1[CH:13]=[CH:12][C:6]([CH:7]=[CH:8][C:9]([OH:11])=O)=[CH:5][CH:4]=1.S(Cl)(Cl)=O.[NH2:18][C:19]1[S:23][C:22]([C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:25]=2[O:31][CH3:32])=[N:21][C:20]=1[CH3:33]>N1C=CC=CC=1>[Cl:30][C:27]1[CH:28]=[CH:29][C:24]([C:22]2[S:23][C:19]([NH:18][C:9](=[O:11])[CH:8]=[CH:7][C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:13][CH:12]=3)=[C:20]([CH3:33])[N:21]=2)=[C:25]([O:31][CH3:32])[CH:26]=1

Participants

5

Reactant 3

HCID 132454-Methoxy cinnamic acidHCID 24386Thionyl ChlorideHCID 686418935-Amino-2-(4-chloro-2-methoxyphenyl)-4-methylthiazole

Product 1

HCID 77387369N-[2-(4-Chloro-2-methoxyphenyl)-4-methylthiazol-5-yl]-3-(4-methoxyphenyl)acrylamideYield 13%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

4-Methoxycinnamic acid (178 mg, 1.0 mmol) and thionyl chloride (480 mg, 4.0 mmol) were heated under reflux for 2 hours. The excess thionyl chloride was distilled off. The resulting residue was dissolved in pyridine (1 ml). Under an ice cooling, the resulting solution was added to a solution of 5-amino-2-(4-chloro-2-methoxyphenyl)-4-methylthiazole (254 mg, 1.0 mmol) prepared in the Step 28-1-2 in pyridine (4 ml). After the removal of the ice bath, the mixture was stirred for 16 hours at a room temperature. To the mixture, 3.5% hydrochloric acid was added, and the resulting mixture was subjected to extraction with chloroform. The extract was washed with water. The washed product was dried over anhydrous magnesium sulfate, and the solvent was distilled off. The resulting residue was purified by silica gel column chromatography (chloroform:methanol=30:1) to give the title compound (54 mg, 13%).

Workup

  1. temperatureunder reflux for 2 hours
  2. distillationThe excess thionyl chloride was distilled off
  3. dissolutionThe resulting residue was dissolved in pyridine (1 ml)
  4. customAfter the removal of the ice bath
  5. additionTo the mixture, 3.5% hydrochloric acid was added
  6. extractionthe resulting mixture was subjected to extraction with chloroform
  7. washThe extract was washed with water
  8. dry with materialThe washed product was dried over anhydrous magnesium sulfate
  9. distillationthe solvent was distilled off
  10. customThe resulting residue was purified by silica gel column chromatography (chloroform:methanol=30:1)

Sources & evidence

ORD record
ord-1aa6afc00a204a6eaaf7b1857ad70693
Source dataset
uspto-grants-2015_12
Patent number
US09200008B2

Reaction notes

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