Potassium Carbonate → 6-Methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)4-(quinolin-7-yloxy)quinazoline

HRID 454160Notes

Reaction equation

HRID 454160 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].[OH:31][C:32]1[CH:41]=[C:40]2[C:35]([CH:36]=[CH:37][CH:38]=[N:39]2)=[CH:34][CH:33]=1.[OH-].[Na+]>CN(C=O)C>[CH3:13][O:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][C:8]=1[O:14][CH2:15][CH2:16][CH2:17][N:18]1[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]1)[N:5]=[CH:4][N:3]=[C:2]2[O:31][C:32]1[CH:41]=[C:40]2[C:35]([CH:36]=[CH:37][CH:38]=[N:39]2)=[CH:34][CH:33]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 112450614-Chloro-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazolineHCID 1354268667-Hydroxyquinoline

Product 1

HCID 98254556-Methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)4-(quinolin-7-yloxy)quinazolineYield 39%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-chloro-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazoline (200 mg, 0.57 mmol), potassium carbonate (106 mg, 0.77 mmol) and 7-hydroxyquinoline (111 mg, 0.76 mmol) in DMF (7 ml) was stirred at 100° C. for 5 hours and allowed to cool to ambient temperature. The reaction mixture was treated with 1.0 N aqueous sodium hydroxide solution (40 ml) and allowed to stir at ambient temperature for a few minutes. The reaction mixture was extracted 4 times with ethyl acetate and the organic extracts washed with water and brine. The organic extracts were dried over magnesium sulphate, filtered and the solvent removed by evaporation. The residue was triturated with ether/isohexane, filtered and dried to give 6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)-4-(quinolin-7-yloxy)quinazoline (102 mg, 39%).

Workup

  1. temperatureto cool to ambient temperature
  2. stirringto stir at ambient temperature for a few minutes
  3. extractionThe reaction mixture was extracted 4 times with ethyl acetate
  4. washthe organic extracts washed with water and brine
  5. dry with materialThe organic extracts were dried over magnesium sulphate
  6. filtrationfiltered
  7. customthe solvent removed by evaporation
  8. customThe residue was triturated with ether/isohexane
  9. filtrationfiltered
  10. customdried

Sources & evidence

ORD record
ord-d6fc256f85b24cd5ae662ecdb541a959
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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