3,3-Dianilino-1-[2,6-dichloro-4-(trifluoromethyl)-3-pyridinyl]-2-propen-1-one → 2-anilino-7-chloro-1-phenyl-5-trifluoromethyl-1,8-naphthyridin-4(1H)-one

HRID 2214987Notes

Reaction equation

HRID 2214987 reaction equation
[NH:1]([C:8]([NH:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[CH:9][C:10]([C:12]1[C:13](Cl)=[N:14][C:15]([Cl:22])=[CH:16][C:17]=1[C:18]([F:21])([F:20])[F:19])=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC([O-])(C)C.[K+]>O1CCOCC1>[NH:1]([C:8]1[N:24]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:13]2[C:12]([C:10](=[O:11])[CH:9]=1)=[C:17]([C:18]([F:21])([F:19])[F:20])[CH:16]=[C:15]([Cl:22])[N:14]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 219481843,3-Dianilino-1-[2,6-dichloro-4-(trifluoromethyl)-3-pyridinyl]-2-propen-1-oneHCID 23665647Potassium tert-butoxide

Product 1

HCID 219481692-anilino-7-chloro-1-phenyl-5-trifluoromethyl-1,8-naphthyridin-4(1H)-oneYield 95%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of 3,3-dianilino-1-[2,6-dichloro-4-(trifluoromethyl)-3-pyridinyl]-2-propen-1-one (12.9 g, 28.5 mmol) and t-BuOK (28.5 mL, 28.5 mmol, 1M in THF) in dioxane (200 mL) was heated at reflux overnight. The reaction was cooled, concentrated in vacuo, treated with saturated NH4Cl and extracted with EtOAc (3×). The combined organic extracts were washed with brine, dried over MgSO4, and concentrated in vacuo. Silica gel flash chromatography of the residue using 6:1 Hex:EtOAc provided 2-anilino-7-chloro-1-phenyl-5-(trifluoromethyl)-1,8-naphthyridin-4(1H)-one (11.2 g, 95%) as an off-white solid: LCMS RT: 3.00 min, MH+: 416.7, Rf=0.25 (3:1 Hex:EtOAc). This transformation can be accomplished by using the combination of other aprotic solvents such as DMF, and THF with other bases such as NaH.

Workup

  1. temperaturewas heated
  2. temperatureat reflux overnight
  3. temperatureThe reaction was cooled
  4. concentrationconcentrated in vacuo
  5. additiontreated with saturated NH4Cl
  6. extractionextracted with EtOAc (3×)
  7. washThe combined organic extracts were washed with brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4e45d44e824e4937aa7699ead39de221
Source dataset
uspto-grants-2006_09
Patent number
US07109196B2

Reaction notes

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