Cyanoacetic acid → 2-Cyano-N-(2,4-dimethoxybenzyl)-N-[2-(3-fluorobenzoyl)-4-methoxyphenyl]acetamide

HRID 640715Notes

Reaction equation

HRID 640715 reaction equation
[C:1]([CH2:3][C:4](O)=[O:5])#[N:2].P(Cl)(Cl)(Cl)(Cl)Cl.[CH3:13][O:14][C:15]1[CH:39]=[C:38]([O:40][CH3:41])[CH:37]=[CH:36][C:16]=1[CH2:17][NH:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][C:20]=1[C:27]([C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([F:35])[CH:30]=1)=[O:28]>ClCCl>[C:1]([CH2:3][C:4]([N:18]([CH2:17][C:16]1[CH:36]=[CH:37][C:38]([O:40][CH3:41])=[CH:39][C:15]=1[O:14][CH3:13])[C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][C:20]=1[C:27](=[O:28])[C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([F:35])[CH:30]=1)=[O:5])#[N:2]

Participants

5

Reactant 3

HCID 9740Cyanoacetic acidHCID 24819Phosphorus pentachlorideHCID 68659721{2-[(2,4-Dimethoxybenzyl)amino]-5-methoxyphenyl}(3-fluorophenyl)methanone

Product 1

HCID 686597692-Cyano-N-(2,4-dimethoxybenzyl)-N-[2-(3-fluorobenzoyl)-4-methoxyphenyl]acetamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of cyanoacetic acid (43.0 mg, 0.511 mmol) in 1 mL of dichloromethane at room temperature was added PCl5 (106 mg, 0.511 mmol). The mixture was heated to reflux for 10 minutes. A solution of {2-[(2,4-dimethoxybenzyl)amino]-5-methoxyphenyl}(3-fluorophenyl)methanone (101 mg, 0.255 mmol) in 1 mL dichloromethane was added, and the reaction was refluxed for an additional 1.5 hours. The reaction was partitioned between EtOAc and saturated NaHCO3 solution, and the organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The titled product was isolated as a yellow foam (117 mg, 99% yield) which was used in the next step without further purification. Proton NMR for the product was consistent with the titled compound. ESI+ MS: 463.2 [M+H]+.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 10 minutes
  3. temperaturethe reaction was refluxed for an additional 1.5 hours
  4. customThe reaction was partitioned between EtOAc and saturated NaHCO3 solution
  5. washthe organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7bb2f2801a554389a3ee466bb34998fa
Source dataset
uspto-grants-2010_04
Patent number
US07692017B2

Reaction notes

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