Potassium Carbonate → 7-[2-(4-acetylpiperazin-1-yl)ethoxy]-4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazoline

HRID 916446Notes

Reaction equation

HRID 916446 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][N:7]([CH2:10][CH2:11][O:12][C:13]2[CH:22]=[C:21]3[C:16]([C:17](Cl)=[N:18][CH:19]=[N:20]3)=[CH:15][C:14]=2[O:24][CH3:25])[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[F:26][C:27]1[C:35]([OH:36])=[CH:34][CH:33]=[C:32]2[C:28]=1[CH:29]=[C:30]([CH3:37])[NH:31]2.C(=O)([O-])[O-].[K+].[K+]>CN(C)C(=O)C.CC(C)=O.FC1C(O)=CC=C2C=1C=C(C)N2.C(=O)([O-])[O-].[K+].[K+]>[C:1]([N:4]1[CH2:9][CH2:8][N:7]([CH2:10][CH2:11][O:12][C:13]2[CH:22]=[C:21]3[C:16]([C:17]([O:36][C:35]4[C:27]([F:26])=[C:28]5[C:32](=[CH:33][CH:34]=4)[NH:31][C:30]([CH3:37])=[CH:29]5)=[N:18][CH:19]=[N:20]3)=[CH:15][C:14]=2[O:24][CH3:25])[CH2:6][CH2:5]1)(=[O:3])[CH3:2]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 103520364-fluoro-2-methyl-1H-indol-5-olHCID 589602407-[2-(4-Acetylpiperazin-1-yl)ethoxy]-4-chloro-6-methoxyquinazoline

Product 1

HCID 117522547-[2-(4-acetylpiperazin-1-yl)ethoxy]-4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazolineYield 60.5%

Reagents, catalysts & solvents 4

HCID 11430Potassium CarbonateCatalystHCID 103520364-fluoro-2-methyl-1H-indol-5-olCatalystHCID 180AcetoneSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 7-[2-(4-acetylpiperazin-1-yl)ethoxy]-4-chloro-6-methoxyquinazoline (12.24 g, 33.5 mmol), 4-fluoro-5-hydroxy-2-methylindole (5.54 g, 33.5 mmol), (prepared as described for the starting material in Example 1), and potassium carbonate (4.64 g, 33.5 mmol) was heated in N,N-dimethylacetamide (150 ml) at 85° C. for 4 hours. 4-Fluoro-5-hydroxy-2-methylindole (33 mg, 0.2 mmol) and potassium carbonate (108 mg, 57%) were added and the mixture heated for a further 1 hour at 85° C. and then stirred at ambient temperature overnight. The mixture was filtered and concentrated under reduced pressure. The residue was purified by column chromatography eluting with methylene chloride/methanol (95/5) to give a white solid which was suspended in acetone (150 ml) and heated at reflux for 1 hour. After cooling the mixture was filtered and the solid dried in air to give 7-[2-(4-acetylpiperazin-1-yl)ethoxy]-4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazoline (10 g, 60%) as a white solid.

Workup

  1. custom(prepared
  2. filtrationThe mixture was filtered
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by column chromatography
  5. washeluting with methylene chloride/methanol (95/5)
  6. customto give a white solid which
  7. temperatureheated
  8. temperatureat reflux for 1 hour
  9. temperatureAfter cooling the mixture
  10. filtrationwas filtered
  11. customthe solid dried in air

Sources & evidence

ORD record
ord-7d68095e9c5640aa814c2fecc287372e
Source dataset
uspto-grants-2007_09
Patent number
US07268230B2

Reaction notes

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