Cyanoacetic acid → HCID 69607388, compound

HRID 1244085Notes

Reaction equation

HRID 1244085 reaction equation
P(Cl)(Cl)(Cl)(Cl)Cl.[C:7]([CH2:9][C:10](O)=[O:11])#[N:8].[CH2:13]([O:15][C:16]([C:18]1[C:22]([C:23]2[CH:28]=[C:27]([CH3:29])[CH:26]=[C:25]([CH3:30])[CH:24]=2)=[CH:21][S:20][C:19]=1[NH2:31])=[O:17])[CH3:14]>C(Cl)Cl.CN(C=O)C>[CH2:13]([O:15][C:16]([C:18]1[C:22]([C:23]2[CH:24]=[C:25]([CH3:30])[CH:26]=[C:27]([CH3:29])[CH:28]=2)=[CH:21][S:20][C:19]=1[NH:31][C:10](=[O:11])[CH2:9][C:7]#[N:8])=[O:17])[CH3:14]

Participants

6

Reactant 3

HCID 9740Cyanoacetic acidHCID 24819Phosphorus pentachlorideHCID 69607364HCID 69607364, compound

Product 1

HCID 69607388HCID 69607388, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×

Procedure

To a stirred suspension of PCl5 (0.74 g, 3.5 mmol) in CH2Cl2 (10 mL) was added a solution of cyanoacetic acid (0.3 g, 3.5 mmol) in CH2Cl2 (5 mL) and DMF (1 mL) dropwise via syringe at room temperature and the reaction mixture was heated at reflux for 1 hour. The reaction was cooled to room temperature and a solution of 2-Amino-4-(3,5-dimethyl-phenyl)-thiophene-3-carboxylic acid ethyl ester (0.78 g, 2.8 mmol) in CH2Cl2 (5 mL) was added via canula over 5 minutes. The reaction was then heated at reflux for 2.5 h, cooled to 0° C. and quenched by slow addition of sat. aq. Na2CO3 (10 mL) until basic (pH 9–10). The mixture was extracted with ethyl acetate (3×30 mL) and the combined organic layers were washed with water (25 mL), brine (15 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to provide the title compound as a yellow solid. MS (ESI) m/e 341.0 (M−H); 1H NMR (300 MHz, CDCl3): δ ppm 12.02 (s, 1H), 7.26 (s, 1H), 6.97 (s, 1H), 6.91 (s, 2H), 6.67 (s, 1H), 4.15 (q, 4H, J=7.12), 3.68 (s, 2H), 2.33 (s, 6H), 0.98 (t, 3H, J=7.12).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux for 1 hour
  3. temperatureThe reaction was then heated
  4. temperatureat reflux for 2.5 h
  5. temperaturecooled to 0° C.
  6. customquenched by slow addition of sat. aq. Na2CO3 (10 mL) until basic (pH 9–10)
  7. extractionThe mixture was extracted with ethyl acetate (3×30 mL)
  8. washthe combined organic layers were washed with water (25 mL), brine (15 mL)
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-82f54bc7b4b049378390902fd884248f
Source dataset
uspto-grants-2006_10
Patent number
US07119205B2

Reaction notes

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