Dimethylformamide → HCID 22478209, compound

HRID 2182525Notes

Reaction equation

HRID 2182525 reaction equation
[O:1]1[CH2:5][CH2:4][O:3][CH2:2]1.[Cl:6][C:7]1[CH:26]=[CH:25][C:10]([NH:11][C:12]2[C:21]3[C:16](=[CH:17][C:18](O)=[C:19]([O:22][CH3:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)=[C:9]([F:27])[CH:8]=1.[C:28](=[O:31])([O-])[O-].[K+].[K+].[CH3:34]N(C=O)C>>[Cl:6][C:7]1[CH:26]=[CH:25][C:10]([NH:11][C:12]2[C:21]3[C:16](=[CH:17][C:18]([O:31][CH2:28][CH2:34][CH:2]4[O:3][CH2:4][CH2:5][O:1]4)=[C:19]([O:22][CH3:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)=[C:9]([F:27])[CH:8]=1

Participants

5

Reactant 4

HCID 6228Dimethylformamide2×HCID 11430Potassium CarbonateHCID 125861,3-DioxolaneHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 22478209HCID 22478209, compoundYield 107%

Conditions

Temperature
100 °C

Procedure

A solution of 242-bromoethyl)-1,3-dioxolane (258 mg, 1.4 mmol) in DMF (0.5 ml) was added to a mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (329 mg, 1.02 mmol) and potassium carbonate (264 mg, 2 mmol) in DMF (2 ml). The mixture was heated at 100° C. for 3 hours and allowed to cool. The volatiles were removed by evaporation, and the residue partitioned between aqueous sodium hydrogen carbonate solution and methylene chloride. The organic phase was separated and passed through phase separating paper. The solvent was removed by evaporation, and the residue was purified by column chromatography eluting with methylene chloride/methanol (95/5) to give 4-(4-chloro-2-fluoroanilino)-7-(2(1,3-dioxolan-2-yl)ethoxy)-6-methoxyquinazoline (71 mg, 107%).

Workup

  1. temperatureto cool
  2. customThe volatiles were removed by evaporation
  3. customthe residue partitioned between aqueous sodium hydrogen carbonate solution and methylene chloride
  4. customThe organic phase was separated
  5. customseparating paper
  6. customThe solvent was removed by evaporation
  7. customthe residue was purified by column chromatography
  8. washeluting with methylene chloride/methanol (95/5)

Sources & evidence

ORD record
ord-80bc342df173435b90657dbe7f658067
Source dataset
uspto-grants-2005_05
Patent number
US06897210B2

Reaction notes

Loading…