Water → 7-(2-Bromoethoxy)-4-(4-chloro-2-fluoroanilino)6-methoxyquinazoline

HRID 1838595Notes

Reaction equation

HRID 1838595 reaction equation
[Br:1][CH2:2][CH2:3]Br.[Cl:5][C:6]1[CH:25]=[CH:24][C:9]([NH:10][C:11]2[C:20]3[C:15](=[CH:16][C:17]([OH:23])=[C:18]([O:21][CH3:22])[CH:19]=3)[N:14]=[CH:13][N:12]=2)=[C:8]([F:26])[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[Br:1][CH2:2][CH2:3][O:23][C:17]1[CH:16]=[C:15]2[C:20]([C:11]([NH:10][C:9]3[CH:24]=[CH:25][C:6]([Cl:5])=[CH:7][C:8]=3[F:26])=[N:12][CH:13]=[N:14]2)=[CH:19][C:18]=1[O:21][CH3:22]

Participants

6

Reactant 4

HCID 962WaterHCID 78391,2-DibromoethaneHCID 11430Potassium CarbonateHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 187534227-(2-Bromoethoxy)-4-(4-chloro-2-fluoroanilino)6-methoxyquinazolineYield 54%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1,2-Dibromoethane (5.4 ml, 62 mmol) was added to a mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (5 g, 15.6 mmol), (prepared as described for the starting material in Example 2), and potassium carbonate (8.6 g, 62 mmol) in DMF (50 ml) and the mixture stirred for 18 hours at ambient temperature. Water was added and the resulting precipitate was collected by filtration. The solid was purified by chromatography on neutral alumina eluting with methylene chloride/methanol (95/5). The semi-purified product was repurified by chromatography on silica eluting with methylene chloride/methanol (97/3). The purified product was triturated with ether, collected by filtration, washed with ether and dried under vacuum to give 7-(2-bromoethoxy)-4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline (3.58 g, 54%).

Workup

  1. custom(prepared
  2. filtrationthe resulting precipitate was collected by filtration
  3. customThe solid was purified by chromatography on neutral alumina eluting with methylene chloride/methanol (95/5)
  4. customThe semi-purified product was repurified by chromatography on silica eluting with methylene chloride/methanol (97/3)
  5. customThe purified product was triturated with ether
  6. filtrationcollected by filtration
  7. washwashed with ether
  8. customdried under vacuum

Sources & evidence

ORD record
ord-703e6273a2394c119fdc042949fb0107
Source dataset
uspto-grants-2004_01
Patent number
US06673803B2

Reaction notes

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