1-Acetylpiperazine → 7-(2-(4-Acetylpiperazin-1-yl)ethoxy)-4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochloride

HRID 547219Notes

Reaction equation

HRID 547219 reaction equation
Br[CH2:2][CH2:3][O:4][C:5]1[CH:14]=[C:13]2[C:8]([C:9]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=3[F:23])=[N:10][CH:11]=[N:12]2)=[CH:7][C:6]=1[O:24][CH3:25].[C:26]([N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1)(=[O:28])[CH3:27]>C(Cl)Cl.C(OCC)(=O)C>[ClH:22].[C:26]([N:29]1[CH2:34][CH2:33][N:32]([CH2:2][CH2:3][O:4][C:5]2[CH:14]=[C:13]3[C:8]([C:9]([NH:15][C:16]4[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=4[F:23])=[N:10][CH:11]=[N:12]3)=[CH:7][C:6]=2[O:24][CH3:25])[CH2:31][CH2:30]1)(=[O:28])[CH3:27]

Participants

4

Reactant 2

HCID 837951-AcetylpiperazineHCID 187534227-(2-Bromoethoxy)-4-(4-chloro-2-fluoroanilino)6-methoxyquinazoline

Product 1

HCID 187534357-(2-(4-Acetylpiperazin-1-yl)ethoxy)-4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochlorideYield 170.2%

Reagents, catalysts & solvents 1

HCID 21226138Dichloromethane ethylacetateSolvent

Procedure

7-(2-Bromoethoxy)-4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline (150 mg, 0.35 mmol) and 1-acetylpiperazine (135 mg, 1 mmol) were heated together at 140° C. for 10 minutes. The mixture was allowed to cool and was dissolved in a mixture of methylene chloride/ethyl acetate. The solution was washed with water, and then brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (9/1). The purified product was dissolved in methylene chloride and 2.9M ethereal hydrogen chloride was added. The precipitate was collected by filtration, washed with ether and dried under vacuum to give 7-(2-(4-acetylpiperazin-1-yl)ethoxy)-4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochloride (152 mg, 79%).

Workup

  1. temperatureto cool
  2. washThe solution was washed with water
  3. dry with materialbrine, dried (MgSO4)
  4. customthe solvent removed by evaporation
  5. customThe residue was purified by column chromatography
  6. washeluting with methylene chloride/methanol (9/1)
  7. dissolutionThe purified product was dissolved in methylene chloride
  8. addition2.9M ethereal hydrogen chloride was added
  9. filtrationThe precipitate was collected by filtration
  10. washwashed with ether
  11. customdried under vacuum

Sources & evidence

ORD record
ord-c4a4404476fd4419bff6ad594133cf3e
Source dataset
uspto-grants-2011_05
Patent number
USRE042353E1

Reaction notes

Loading…