Triethylamine → N-(2-{[3-Chloro-4-(2-methylbenzoyl)phenyl]amino}phenyl)-2-phenoxy-acetamide

HRID 1797315Notes

Reaction equation

HRID 1797315 reaction equation
[O:1]([CH2:8][C:9]([OH:11])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)(Cl)=O.[Cl:16][C:17]1[CH:22]=[C:21]([NH:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[NH2:30])[CH:20]=[CH:19][C:18]=1[C:31]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[CH3:39])=[O:32].C(N(CC)CC)C.C([O-])(O)=O.[Na+]>CN(C=O)C.C1(C)C=CC=CC=1.C(Cl)Cl.CCOC(C)=O>[Cl:16][C:17]1[CH:22]=[C:21]([NH:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[NH:30][C:9](=[O:11])[CH2:8][O:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH:20]=[CH:19][C:18]=1[C:31](=[O:32])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[CH3:39]

Participants

10

Reactant 5

HCID 8471TriethylamineHCID 19188Phenoxyacetic AcidHCID 24386Thionyl ChlorideHCID 516892Sodium BicarbonateHCID 98191574-(2-Aminophenylamino)-2-chloro-2'-methylbenzophenone

Product 1

HCID 22174546N-(2-{[3-Chloro-4-(2-methylbenzoyl)phenyl]amino}phenyl)-2-phenoxy-acetamide

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2-phenoxyacetic acid (75 mg, 0.49 mmol), thionylchloride (72 μL, 1.0 mmol) and one drop of DMF in toluene (2.0 mL) was refluxed for 30 min. The reaction mixture was concentrated in vacuo and the resulting crude acid chloride was dissolved in dry DCM (2.0 ml). The solution was added slowly to a cooled (0° C.) solution of {2-chloro-4-[(2-aminophenyl)amino]phenyl}(2-methylphenyl)methanone (0.150 g, 0.45 mmol) (disclosed in WO 98/32730) and triethylamine (135 mg, 1.33 mmol) in dry DCM (5.0 ml). The solution was allowed to reach room temperature. The reaction mixture was stirred for 3 h and then poured into a mixture of NaHCO3 (aq.) and EtOAc. The aqueous phase was extracted with more EtOAc (×2). The combined organic phases were washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified by flash chromatography using DCM as the eluent to afford the title compound as a yellow oil.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionthe resulting crude acid chloride was dissolved in dry DCM (2.0 ml)
  3. additionThe solution was added slowly to
  4. customto reach room temperature
  5. extractionThe aqueous phase was extracted with more EtOAc (×2)
  6. washThe combined organic phases were washed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-5f7a2f31d13140938ec7c3ab6db5d0f5
Source dataset
uspto-grants-2006_04
Patent number
US07034015B2

Reaction notes

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