Water → HCID 53957884, compound

HRID 2182571Notes

Reaction equation

HRID 2182571 reaction equation
[Br:1][CH2:2][CH2:3]Br.[Cl:5][C:6]1[CH:25]=[CH:24][C:9]([NH:10][C:11]2C3C(=CC(O)=C(OC)C=3)N=CN=2)=[C:8]([F:26])[CH:7]=1.[C:27](=[O:30])([O-])[O-].[K+].[K+].O.C[N:35]([CH:37]=[O:38])[CH3:36]>>[Br:1][CH2:2][CH2:3][O:30][C:27]1[CH:24]=[C:9]2[C:8]([C:37]([O:38][CH2:11][NH:10][C:9]3[CH:24]=[CH:25][C:6]([Cl:5])=[CH:7][C:8]=3[F:26])=[N:35][CH:36]=[N:10]2)=[CH:7][CH:6]=1

Participants

6

Reactant 5

HCID 962WaterHCID 6228DimethylformamideHCID 78391,2-DibromoethaneHCID 11430Potassium CarbonateHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 53957884HCID 53957884, compoundYield 54%

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 titurated with ether, collected by filtration, washed with ether and dried under vacuum to give 7-(2-bromoethoxy)-4-(4-chloro-2-fluoroanilino) 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. filtrationcollected by filtration
  6. washwashed with ether
  7. customdried under vacuum

Sources & evidence

ORD record
ord-761965732d3044ef9637ba235fce1728
Source dataset
uspto-grants-2005_05
Patent number
US06897210B2

Reaction notes

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