4-Fluoroaniline → HCID 59853019, compound

HRID 1670241Notes

Reaction equation

HRID 1670241 reaction equation
Cl[C:2]1[N:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16](=[O:18])[CH3:17])=[CH:11][C:10]=2[F:19])[CH:5]=[CH:4][N:3]=1.[F:20][C:21]1[CH:27]=[CH:26][C:24]([NH2:25])=[CH:23][CH:22]=1.[O:28]1CCOCC1>CO>[CH3:6][OH:8].[NH4+:3].[OH-:28].[F:19][C:10]1[CH:11]=[C:12]([NH:15][C:16](=[O:18])[CH3:17])[CH:13]=[CH:14][C:9]=1[O:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:25][C:24]2[CH:26]=[CH:27][C:21]([F:20])=[CH:22][CH:23]=2)[N:7]=1

Participants

6

Reactant 3

HCID 97314-FluoroanilineHCID 312751,4-DioxaneHCID 59852996HCID 59852996, compound

Product 2

HCID 21894508Ammonium hydroxide methanolHCID 59853019HCID 59853019, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of N-(4-(2-chloropyrimidin-4-yloxy)-3-fluorophenyl)acetamide (100 mg, 0.36 mmol), 4-fluoroaniline (Aldrich, 40 mg, 0.36 mmol), and 1,4-dioxane (3 mL) was heated at reflux for 2 h. The mixture was concentrated in vacuo and the residue triturated with ether to give a gray solid. The product was dissolved in MeOH, treated with silica gel (150 mg) and the mixture concentrated to dryness. The compound was concentrated down on silica gel and applied to a silica gel column and eluted first with EtOAc then with 100:1 MeOH/NH4OH in CH2Cl2 to give the title compound (40 mg, 31%) as a white solid. 1H NMR (DMSO-d6) δ 10.19 (s, 1H), 9.61 (s, 1H), 8.33 (d, 1H, J=5.6 Hz), 7.71 (d, 1H, J=12.7 Hz), 7.40 (s, 2H), 7.30-7.26 (m, 2H), 6.86 (dd, 2H, J=8.3, 8.3 Hz), 6.50 (d, 1H, J=5.4 Hz), 2.05 (s, 3H); MS (ESI+) m/z 357.13 (M+H)+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2 h
  3. concentrationThe mixture was concentrated in vacuo
  4. customthe residue triturated with ether
  5. customto give a gray solid
  6. additiontreated with silica gel (150 mg)
  7. concentrationthe mixture concentrated to dryness
  8. concentrationThe compound was concentrated down on silica gel
  9. washeluted first with EtOAc

Sources & evidence

ORD record
ord-f7d98e0974434d55adc691959d7d9847
Source dataset
uspto-grants-2011_08
Patent number
US07989477B2

Reaction notes

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