Triethylamine → 1-(5-Acetamido-2-chloro-4-fluorophenyl)-3-(2-propynyl)urea

HRID 1480

Reaction equation

HRID 1480 reaction equation
[NH2:1][C:2]1[C:3]([Cl:13])=[CH:4][C:5]([F:12])=[C:6]([CH:11]=1)[NH:7][C:8](=[O:10])[CH3:9].C(N(CC)CC)C.[C:21]1([O:27]C(Cl)=O)C=CC=CC=1.[CH2:31]([NH2:34])[C:32]#[CH:33]>O1CCCC1.O.C(OCC)(=O)C>[C:8]([NH:7][C:6]1[C:5]([F:12])=[CH:4][C:3]([Cl:13])=[C:2]([NH:1][C:21]([NH:34][CH2:31][C:32]#[CH:33])=[O:27])[CH:11]=1)(=[O:10])[CH3:9]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 239041PropargylamineHCID 11769584N-(5-amino-4-chloro-2-fluorophenyl)acetamide

Product 1

HCID 538737111-(5-Acetamido-2-chloro-4-fluorophenyl)-3-(2-propynyl)urea

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 5'-amino-4'-chloro-2'-fluoroacetanilide (11.25 g, 55.6 mmol), and triethylamine (7.70 mL, 55.6 mmol) in tetrahydrofuran is added dropwise to a stirred solution of phenylchloroformate (8.70 mL, 69.4 mmol) in tetrahydrofuran while maintaining the reaction mixture temperature at 25°-30° C. After the addition is complete, the reaction mixture is stirred at room temperature for 75 minutes, and poured into ethyl acetate. The organic mixture is washed sequentially with water, saturated sodium hydrogen carbonate solution and brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo to obtain a tan solid. A solution of the solid in tetrahydrofuran is treated with propargylamine (9.52 mL, 139 mmol), refluxed for 1 hour, and poured into water. The aqueous mixture is filtered to obtain a solid which is washed sequentially with water, 0.5N hydrochloric acid and water, and dried overnight to give the title product as a beige solid.

Workup

  1. temperaturewhile maintaining the reaction mixture temperature at 25°-30° C
  2. additionAfter the addition
  3. washThe organic mixture is washed sequentially with water, saturated sodium hydrogen carbonate solution and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customto obtain a tan solid
  7. temperaturerefluxed for 1 hour
  8. filtrationThe aqueous mixture is filtered
  9. customto obtain a solid which
  10. washis washed sequentially with water, 0.5N hydrochloric acid and water
  11. customdried overnight

Sources & evidence

ORD record
ord-5a556d937a384abda5eb0822445fcd79
Source dataset
uspto-grants-1998_03
Patent number
US05726126

Linked notes

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